Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data

Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data Noiver Graciano, Lucelly López, Yeidy Vallejo, Juan Flórez, Carlos A. Rodriguez This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6377607/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Cisplatin and radiotherapy have been the standard treatment for locally advanced squamous cell carcinoma of the head and neck (LAHNSC) for over 20 years. Achieving a cumulative cisplatin dose ≥200 mg/m 2 has been associated with improved overall survival (OS); however, this target is often not met in clinical practice. Methods This retrospective cohort study was conducted at Instituto de Cancerología Las Américas (Medellín, Colombia) from 2014-2024. Demographic and clinical factors were analyzed to evaluate the relationship between ineffective cisplatin doses (<200 mg/m 2 ) and OS. Survival analysis was performed using the log-rank test and Kaplan-Meier curves. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR), and a Poisson regression model to calculate relative risks (RR). Results 326 patients were included. OS was longer in patients receiving ≥200 mg/m 2 of cisplatin (median 72.4 vs. 31.8 months), with an HR of 1.46 (95% CI 0.98–2.18, p=0.064). Multivariable analysis showed that an ineffective dose was associated with increased mortality (HR 1.54, 95% CI 1.00–2.37, p=0.049). Factors associated with worse OS included low functional status, primary oral carcinoma, subsidized health insurance, and leukocytosis. Patients with low body mass index, hypertension, male sex, or GFR <60 mL/min/1.73 m 2 were at higher risk of receiving an ineffective dose. Acute kidney injury during treatment doubled this risk. Conclusions This real-world study supports that failure to achieve a cisplatin dose ≥200 mg/m 2 increases mortality in LAHNSC. Identifying high-risk patients and optimizing management strategies are essential to improve treatment outcomes. head and neck neoplasms chemoradiotherapy cisplatin mortality prognostic factors Figures Figure 1 Figure 2 Figure 3 BACKGROUND With the exception of locally advanced head and neck squamous cell carcinoma (LAHNSC) of the oral cavity, where surgery is the primary therapeutic option, the concurrent use of cisplatin and radiotherapy (Cis/RT) has been the standard treatment for over 20 years [1,2]. In surgically treated patients, the EORTC 22931 and RTOG 9501 studies indicated that Cis/RT reduces mortality by 30% in patients with positive margins (<1 mm) and extracapsular nodal extension [3]. The MACH-NC meta-analysis concluded that the combination of platinum-based chemotherapy and radiotherapy in LAHNSC provides an overall survival (OS) benefit of 6.5% at 5 years and 3.6% at 10 years [4]. However, the optimal dose schedule of cisplatin remains debatable, with high variability in clinical practice. In 2016, Strojan et al. suggested that a cumulative cisplatin dose of 200 mg/m 2 or higher significantly impacts OS [5]. Despite the survival benefit of achieving a cumulative cisplatin dose ≥200 mg/m 2 , the frequency with which this target is reached in controlled clinical trials (CCTs) of definitive and adjuvant Cis/RT is 91-92.6% and 66-84%, respectively [1,2,6,7]. However, in observational studies, these rates drop to 46-76% and 50%, respectively [8–10]. The primary reasons for failing to achieve the minimum effective dose are acute toxicities, the most significant of which include mucositis (45%), leukopenia (42%), nausea/vomiting (16%), and acute kidney injury (AKI) (8%) [1]. Unfortunately, in LAHNSC, there are no evidence-based clinical factors that reliably predict the occurrence of these toxicities. The main clinical variables used in practice to determine whether a patient is unsuitable for cisplatin include impaired renal, auditory, or hematologic function, as well as poor performance status [11,12]. Given these considerations, this study aimed to evaluate the effect of an ineffective cisplatin dose, defined as a cumulative dose <200 mg/m 2 , on mortality in patients with LAHNSC and to identify diagnostic factors that contribute to this outcome, using real-world data. METHODS A retrospective cohort study was conducted, including all patients aged >18 years with a diagnosis of locally advanced head and neck squamous cell carcinoma (LAHNSC) who received at least one dose of concurrent cisplatin and radiotherapy (Cis/RT), either as definitive treatment or adjuvant therapy, at the Instituto de Cancerología, Clínica Las Américas-AUNA (IDCLA-AUNA) in Medellín, Colombia, between January 1, 2014, and January 1, 2024. Clinical staging was determined according to the 7th edition of the American Joint Committee on Cancer (AJCC) criteria, using staging imaging such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET), and included only stages III to IVB (12). The diagnosis of LAHNSC was confirmed through pathology reports, including p16 positivity by immunohistochemistry in patients with oropharyngeal cancer. Cases of p16-positive LAHNSC with an unknown primary site were treated as oropharyngeal carcinoma [13]. Patients with sinonasal or nasopharyngeal carcinomas, cutaneous squamous cell carcinomas, synchronous or metachronous active neoplasms, those treated with carboplatin, those who had received induction chemotherapy, those with incomplete data, or those who did not provide informed consent were excluded. The decision to perform surgery was made by head and neck surgeons, while the indication for Cis/RT was determined by clinical oncologists and radiation oncologists at IDCLA-AUNA. Controversial cases were discussed in the institutional multidisciplinary tumor board. All patients received radiotherapy with definitive intent (70 Gy/35 fractions) or adjuvant intent (60–66 Gy/30–33 fractions) over a period of less than 8 weeks (98.5% of patients). Until 2020, 3D conformal radiotherapy was used, and intensity-modulated radiotherapy (IMRT) was implemented thereafter. The administered doses or volumes were not modified based on p16 positivity [14]. Data were collected from the institutional registry, specifically the Head and Neck Cancer module, which is maintained in a RedCap database containing all clinical records of patients treated at the institution. Any inconsistencies or missing data identified by the investigators were verified against the clinical records at IDCLA and corrected or completed for analysis. Figure 1 illustrates the patient selection flowchart. Exposures and Outcomes The primary exposure variable was the cumulative cisplatin dose (<200 mg/m 2 vs. ≥200 mg/m 2 ). Independent variables considered at the time of diagnosis (first or second contact with the IDC specialist) included: age, sex, type of health insurance (contributory or subsidized), alcohol consumption, smoking, diabetes mellitus (DM), hypertension (HTN), macrovascular disease (e.g., cerebral, coronary, or peripheral arterial thrombosis), body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, diagnostic imaging modality, primary tumor site (oral, oropharyngeal, hypopharyngeal/laryngeal), TNM staging, hemoglobin levels, platelet count, leukocyte count, and glomerular filtration rate (GFR) calculated using the CKD-EPI formula. Treatment-related variables included the intent of Cis/RT, cisplatin administration frequency, radiotherapy technique, and the development of moderate to severe acute kidney injury (AKI) as defined by common terminology criteria for adverse events (CTCAE) 5.0 criteria [15]. Strategies to improve adherence and reduce toxicity were employed for all patients, including hydration, magnesium supplementation, diuretics (furosemide, mannitol), weekly dietitian evaluation, nutritional supplementation if necessary, weight monitoring at each visit, mucositis management, and reactive placement of nasogastric or gastrostomy tubes in patients who lost oral intake [12,16]. The primary outcome variable was overall survival (OS), calculated from the date of the first Cis/RT dose to the date of death from any cause or the last institutional contact with the patient. Death dates were verified using the National Civil Registry records as of June 30, 2024. The secondary objective was to evaluate diagnostic factors associated with an ineffective cisplatin dose (<200 mg/m 2 ). The primary exposure variables were those described at diagnosis, and the outcome variable was failure to achieve a cumulative cisplatin dose of 200 mg/m 2 . Data Analysis To describe the study population, summary measures were obtained. For clinical variables and follow-up intervals, measures of central tendency and dispersion were used, depending on the results of the Shapiro-Wilk test (mean and standard deviation or median and interquartile range, depending on whether the normality assumption was met). Qualitative variables, such as DM, HTN, and staging, were presented as absolute frequencies and percentages. Only patients with LAHNSC who received Cis/RT were included in the analysis. To estimate OS for the entire LAHNSC cohort, survival time was calculated from the first cisplatin dose to death from any cause. Right censoring was applied for patients who were alive (not listed in national death records) and lost to follow-up, with the end of follow-up defined as the last contact with any specialist in outpatient consultation or hospitalization at Clínica Las Américas. Administrative censoring was applied to all patients alive as of June 30, 2024. Survival analyses were performed to determine the association between the primary exposure (ineffective dose) and OS using the log-rank test and Kaplan-Meier curves. A Cox proportional hazards model was used to adjust for diagnostic and treatment variables described previously. Hazard ratios (HR) with confidence intervals (CI) were estimated, and the proportional hazards assumption was verified. A p-value <0.05 was considered statistically significant. To assess the association between an ineffective dose and diagnostic characteristics, the c 2 test, Fisher's exact test, or likelihood ratio test was used. For quantitative variables such as age or GFR, the Mann-Whitney U test was applied, considering a p-value ≤0.1 as significant in the bivariate analysis. Crude and adjusted relative risks (RR) with 95% confidence intervals were estimated using a Poisson regression model, with a p-value <0.05 considered significant. An initial model (Model 1) included variables collected at diagnosis, and a second model (Model 2) incorporated the development of AKI. Statistical analyses were performed using Jamovi 2.6.17 and R 4.4.1, with libraries such as psych, Epi, foreign, lmtest, sandwich (for Poisson regression with robust errors), survival and survminer (for survival models and adjusted graphs). RESULTS Clinical and Tumor Characteristics at Diagnosis and Treatment During the study period (2014–2024), 326 patients met the eligibility criteria. The median age was 62 years (IQR 55–68), with the majority being male (71%), smokers (65%), and covered by contributory health insurance (87%). At diagnosis, many patients were overweight or obese (45%) and had an ECOG performance status of 1 (57%). The most common primary tumor sites were the oropharynx (42%) and larynx (29%), with stage IVA being the most prevalent (49%). Renal function impairment (KDIGO stages G2 and G3) was frequent (44.2%), as was thrombocytosis (20%), while leukocytosis (12%) and auditory toxicity (4.3%) were less common. Cis/RT was administered with definitive intent in 67% of cases, using a tri-weekly cisplatin schedule in 90% of patients and 3D radiotherapy in 63% (Table 1). Association of Ineffective Dose with Increased Mortality The median follow-up for the cohort was 23.8 months (IQR 12.9–49.2, range 2.2–97.9 months), with a median overall survival (OS) of 20 months (IQR 10.9–45.7) and a mortality rate of 42%. Seven deaths (2.15%) occurred during treatment. In unadjusted data, OS was higher in the group receiving ≥200 mg/m 2 of cisplatin (median 72.4 vs. 31.8 months), with a non-significant trend toward increased mortality risk in those receiving <200 mg/m 2 (HR 1.46, 95% CI 0.98–2.18, p=0.064). The 1-, 3-, and 5-year OS rates for the ≥200 mg/ m 2 group were 82%, 62.2%, and 52.5%, respectively, compared to 72.9%, 49.2%, and 45.5% for the <200 mg/ m 2 group. In the bivariate analysis, considering a significance threshold of p≤0.1, 12 out of 22 characteristics were associated with OS. The most significant risk factors for mortality were age between 50–70 years (HR 2.31, 95% CI 1.22–4.37, p=0.01), subsidized health insurance (HR 2.36, 95% CI 1.54–3.61, p<0.001), and ECOG performance status of 2 (HR 2.72, 95% CI 0.98–7.57, p=0.055) (Table 1). In the multivariate analysis, only six variables were associated with increased mortality. Since categorized age did not meet the proportional hazards assumption, it was not assigned an HR but was included as a stratification variable for model adjustment. In this model, receiving an ineffective cisplatin dose significantly increased mortality (HR 1.54, 95% CI 1.00–2.37, p=0.049), as did leukocytosis, oral cavity tumors, and poor functional status, with the latter being the strongest predictor of mortality (HR 3.25, 95% CI 1.13–9.34, p=0.029) (Table 2, Figure 2). Subsidized health insurance also significantly increased mortality risk. As shown in Figure 2F, the deleterious impact of an ineffective dose was more pronounced in this population, with the ≥200 mg/m 2 group failing to achieve the same mortality reduction benefit as the contributory insurance group. Diagnostic Characteristics Associated with Ineffective Cisplatin Dose A cumulative dose of 70 years (32% vs. 14%), diabetes mellitus (20% vs. 11%), hypertension (53% vs. 33%), macrovascular disease (12% vs. 5.3%), and GFR <75 mL/min/1.73 m 2 (23% vs. 11%). Acute kidney injury (AKI) was also more frequent in this group (42% vs. 20%). Conversely, patients who received an effective dose had a higher proportion of normal BMI (50% vs. 40%), ECOG 0 (42% vs. 35%), and hemoglobin >11 g/dL (85% vs. 75%). No significant differences were observed between the groups in terms of tri-weekly vs. weekly cisplatin administration (90% vs. 89%), definitive intent of Cis/RT (67% vs. 63%), or 3D radiotherapy technique (63% vs. 63%) (Table 3). The bivariate analysis of diagnostic characteristics associated with an ineffective dose identified 8 out of 17 candidate variables. Among these, low BMI and hypertension doubled the risk of receiving an ineffective dose, while KDIGO stage G3 renal disease increased the risk nearly fourfold. Similarly, a GFR <75 mL/min at diagnosis doubled the risk (Table 3). In the multivariate analysis (Model 1), hypertension (RR 1.77, 95% CI 1.24–2.30, p=0.034) and KDIGO stage G3 (RR 3.46, 95% CI 1.31–3.03, p=0.014) were significantly associated with an increased risk of receiving an ineffective dose, with borderline significance for low BMI and male sex. In Model 2, which included the development of AKI during Cis/RT, the previous findings were confirmed. Male sex became a significant risk factor (RR 1.75, 95% CI 1.22–2.27, p=0.038), and patients who developed AKI had double the risk of receiving <200 mg/m² of cisplatin compared to those without AKI (Table 4). A stratified analysis of the probability of receiving an ineffective dose in patients with multiple risk factors revealed that patients with low BMI, KDIGO stage G3 renal function, and male sex had an approximately 80% probability of not achieving 200 mg/m 2 , compared to 75% for women with the same risk factors (Figures 3A and 3B). Additionally, patients with low BMI, hypertension, and AKI had a 75% probability of not achieving 200 mg/m 2 , compared to 55% in those without AKI (Figures 3C and 3D). DISCUSSION Concurrent cisplatin and radiotherapy (Cis/RT) is currently considered the standard therapeutic approach for locally advanced squamous cell carcinoma of the head and neck (LAHNSC), supported by decades of scientific evidence demonstrating its efficacy in tumor control and improved survival outcomes [6,7,17]. Studies suggest an inverse relationship between mortality and the cumulative dose of cisplatin administered, emphasizing the importance of achieving optimal doses to maximize clinical benefits (5,18). Evidence from meta-analyses, randomized controlled trials (RCTs), and observational studies indicates that a cumulative cisplatin dose of ≥200 mg/m 2 is ideal for optimizing therapeutic outcomes [5,18–21]. Our real-world data study, supported by multivariate analysis, validates this concept by showing a significant increase in mortality among patients who fail to achieve this dose. It is important to note that achieving a cumulative cisplatin dose of ≥200 mg/m 2 is not the sole determinant of mortality. A key finding of our research is the significant impact of health insurance type on patient survival. Figure 2F illustrates that, in patients with subsidized insurance, the relationship between administered dose and mortality is neither clear nor consistent, unlike in patients with contributory insurance, where this relationship is more defined. This phenomenon may be linked to socioeconomic factors associated with subsidized insurance, such as nutritional status, educational level, family support, and limited access to specialized healthcare personnel. Similar observations have been reported in other studies, highlighting the influence of social determinants on clinical outcomes [22,23]. While our study was not designed to evaluate socioeconomic factors, it raises valuable hypotheses for future research. Although the primary tumor site does not appear to significantly influence the ability to achieve a therapeutic dose, our findings indicate that tumors originating in the oral cavity are associated with an adjusted mortality rate approximately 2.5 times higher. This result aligns with previous research, suggesting the presence of specific biological or clinical factors that may contribute to the unfavorable prognosis in these patients [24]. Additionally, we identified that leukocytosis and poor functional status are significantly associated with reduced overall survival (OS), findings that have also been documented in other studies [19,25,26]. Despite efforts in RCTs, a significant proportion of patients continue to receive ineffective doses of cisplatin due to treatment-related toxicities. In our study, this issue affected nearly one in five patients. Attempts to optimize cisplatin administration schedules and doses have not shown a positive impact on compliance rates, as interruptions and acute toxicities persist. Furthermore, we found no significant differences between weekly and tri-weekly cisplatin administration in terms of OS or the likelihood of administering ineffective doses [18,19]. These results suggest inadequate patient selection for cisplatin treatment, with some patients deemed eligible who, in reality, are not [27–29]. Unlike other malignancies, patients with LAHNSC often begin treatment with a high prevalence of weight loss, oral intake difficulties, and multiple comorbidities. These factors contribute to reduced tolerance to treatment-related toxicities [27,28]. In this context, adherence to the Cis/RT regimen is significantly impacted when nutritional, geriatric, social, and comorbidity factors are inadequately assessed, which is not uncommon [29]. This situation is further exacerbated by the lack of specific criteria developed for LAHNSC populations to identify patients unsuitable for cisplatin treatment. A clear example is the suggested glomerular filtration rate (GFR) threshold for withholding cisplatin (<60 mL/min/1.73 m 2 ), which is based on extrapolations from its use in genitourinary or gastrointestinal malignancies [27,30]. To our knowledge, our study is the first in an LAHNSC population to demonstrate that patients with a GFR <60 mL/min/1.73 m 2 who are offered Cis/RT have a more than threefold increased risk of failing to achieve an effective dose, suggesting that cisplatin should not be administered to these patients. Similarly, in patients with multiple risk factors for developing acute kidney injury (AKI), such as the use of potentially nephrotoxic antihypertensives (e.g., ACE inhibitors, angiotensin II receptor blockers, and diuretics), KDIGO stage G2 renal function, and low body mass index (BMI), continuous and intensive monitoring is recommended, as the development of AKI significantly increases the likelihood of receiving an ineffective dose (Figures 3C and 3D). To our knowledge, this study presents the largest cohort of Latin American patients with LAHNSC in a real-world data study, evaluating the impact of chemoradiotherapy and cumulative cisplatin dose in this population, with over 10 years of follow-up. This study provides a detailed analysis of various demographic, clinical, and therapeutic variables at diagnosis, as well as clinically relevant outcomes. Unlike other studies that combine different histology, include metastatic patients, lack OS data, use varied chemotherapy regimens, or fail to detail cumulative cisplatin doses, our work offers a more specific and rigorous approach [31–33]. Our study has several limitations. One of the main limitations is the relatively short follow-up period, which reduces the ability to evaluate the impact of other variables, such as sex, staging, or weight loss, which have been described in the literature as influential factors in OS [9,24,34]. The retrospective nature of the study complicates the inclusion of outcomes such as local or distant recurrences in many patients, as some follow-ups were not completed at our institution. Additionally, many patients lacked p16 testing, preventing the evaluation of this variable's impact on the studied outcomes. Finally, in cases where an effective dose was not administered, the precise causes remained unclear, whether due to toxicities, social issues, or continuity in social security coverage. CONCLUSIONS In conclusion, our real-world data study validates the importance of achieving an effective cisplatin dose ≥200 mg/m 2 to improve OS, as well as other factors such as leukocytosis, primary tumor site, and functional status. Furthermore, it highlights diagnostic characteristics that affect the likelihood of achieving this cumulative cisplatin dose. Identifying specific characteristics in LAHNSC patients is crucial to avoid exposing them to toxic treatments that do not provide the expected benefit. These findings deserve prospective and multicentric validation. Abbreviations LAHNSC: Locally advanced squamous cell carcinoma of the head and neck OS: Overall survival HR: Hazard ratio RR: Relative risk CI: Confidence interval Cis/RT: Cisplatin and radiotherapy CCTs: Controlled clinical trials AKI: Acute kidney injury IDCLA-AUNA: Instituto de Cancerología, Clínica las Américas-AUNA AJCC: American Joint Committee on Cancer CT: Computed tomography MRI: Magnetic resonance imaging PET: Positron emission tomography IMRT: Intensity-modulated radiotherapy DM: Diabetes mellitus HTN: Hypertension BMI: Body mass index ECOG: Eastern Cooperative Oncology Group GFR: Glomerular filtration rate CKD-EPI: Chronic Kidney Disease-Epidemiology Collaboration CTCAE: Common terminology criteria for adverse events KDIGO: Kidney Disease: Improving Global Outcomes IQR: Interquartile range RCTs: Randomized clinical trials ACE: Angiotensin-converting enzyme Declarations Ethics approval and consent to participate The study complied with the principles of the Declaration of Helsinki and was approved by the Instituto de Cancerología Las Américas-AUNA Ethics Committee (Act 217-2024). According to Resolution 8430 of 1993 of Colombia’s Ministry of Health this observational retrospective study was classified as low risk (https://www.minsalud.gov.co/sites/rid/lists/bibliotecadigital/ride/de/dij/resolucion-8430-de-1993.pdf). All the patients signed the institutional informed consent to authorize the use of their clinical data for scientific research. Consent for publication Not applicable. Availability of data and materials The datasets used and analysed in the study are not publicly available due to the institutional policies of Instituto de Cancerología Las Américas-AUNA, but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests related to this work. Funding The publication of this work was supported by an unconditional grant from Merck. The company did not have any participation in conceptualization, design, data collection, data analysis or preparation of the manuscript. Authors’ contributions NG, LL and CAR conceived and designed the study. The data were collected by NG and YV. Data analysis was performed by NG, LL and CAR. All authors contributed to the results presentation and discussion. NG wrote the first draft of the paper, all authors read and commented on previous versions of the article and approved the final manuscript. Acknowledgements Not applicable. References Adelstein DJ, Li Y, Adams GL, Wagner H, Kish JA, Ensley JF, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003;21:92–8. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–8. Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al. 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J Clin Oncol. 2006;24:3095–100. Sichero L, Tagliabue M, Mota G, Ferreira S, Nunes RAL, Castañeda CA, et al. Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16INK4a status. Head Neck. 2022;44:122–33. Aragón N, Ordoñez D, Urrea MF, Holguín J, Collazos P, García LS, et al. Head and neck cancer in Cali, Colombia: Population-based study. Community Dent Oral Epidemiol. 2022;50:292–9. Chedid HM, Lehn CN, Rapoport A, Amar A, Franzi SA. Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy. Braz J Otorhinolaryngol. 2010;76:225–30. Capuano G, Grosso A, Gentile PC, Battista M, Bianciardi F, Di Palma A, et al. Influence of weight loss on outcomes in patients with head and neck cancer undergoing concomitant chemoradiotherapy. Head Neck. 2008;30:503–8. Tables Table 1. Baseline Characteristics, Treatments and Bivariate Analysis of Mortality Risk Characteristic Total N(%) = 326 Alive N(%) = 189 (58) Dead N(%) = 137(42) HR (95% CI), p-value Age in years, median (IQR) 62 (55-68) 60 (54-67) 64 (57-67) Categorized Age in years 70 57 (17) 27 (14) 30 (22) 2.31 (1.22-4.37), 0.010 Men 230 (71) 128 (68) 102 (74) 1.43 (0.97-2.11), 0.067 Subsidized health insurance 42 (13) 15 (7,9) 27 (20) 2.36 (1.54-3.61), <0.001 Alcohol 82 (25) 54 (29) 28 (20) 0.74 (0.49-1.13), 0.166 Tobacco 211 (65) 121 (64) 90 (66) 1.01 (0.71-1.43), 0.972 Diabetes 40 (12) 22 (12) 18 (13) 1.10 (0.67-1.81), 0.705 Hypertension 119 (37) 58 (31) 61 (45) 1.51 (1.07-2.11), 0.018 Macrovascular Diseases* 21 (6.4) 10 (5.3) 11 (8,0) 1.36 (0.73-2.53), 0.326 BMI Normal 156 (48) 90 (48) 66 (48) Low 23 (7.1) 8 (4.2) 15 (11) 2.01 (1.14-3.53), 0.015 Overweight/Obese 147 (45) 91 (48) 56 (41) 0.80 (0.56-1.15), 0.231 ECOG 0 133 (41) 86 (46) 47 (34) 1 187 (57) 101 (53) 86 (63) 1.40 (0.98-1.99), 0.066 2 6 (1.8) 2 (1.1) 4 (2.9) 2.72 (0.98-7.57), 0.055 Diagnostic Imaging CT/MRI (vs PET) 278 (85) 157 (83) 121 (88) 1.01 (0.60-1.71), 0.963 Primary Tumor Oropharyngeal 137 (42) 94 (50) 43 (31) Oral 84 (25.8) 41 (22) 43 (31) 2.09 (1.37-3.20), 0.001 Hypopharyngeal/Laryngeal 105 (32.2) 54 (29) 51 (37) 1.70 (1.13-2.55), 0.011 Tumor Stage III 98 (30) 62 (33) 36 (26) IVA 159 (49) 94 (50) 65 (47) 1.14 (0.76-1.71), 0.536 IVB 69 (21) 33 (17) 36 (26) 1.76 (1.11-2.80), 0.017 Hemoglobin g/dL median (RIQ) 13.4 (11.9- 14.5) 13.4 (12-14.7) 13.3 (11.7- 14.4) Hemoglobin 450,000/µL 66 (20) 44 (23) 22 (16) 0.74 (0.47-1.17.), 0.193 Leukocytes/µL median (IQR) 6635 (4280- 8260) 6040 (4000- 7700) 7000 (4560- 8989) Leukocytes >10,000/µL 38 (12) 14 (7,4) 24 (18) 1.67 (1.07-2.59), 0.023 Initial GFR (ml/min/1.73 m 2 ) 92 (81-99) 89 (80-98) 95 (84-101) KDIGO stage G1 182(55.8) 91 (48) 91 (66) G2 136(41.7) 94 (50) 42 (31) 0.60 (0.42-0.87), 0.006 G3 8(2.5) 4 (2.1) 4 (2.9) 1.22 (0.45-3.32), 0.701 GFR <75 (ml/min/1.73 m 2 ) 43 (13) 29 (15) 14 (10) 0.82 (0.47-1.43), 0.494 Positive p16 83 (89) 67 (93) 16 (76) Unknown p16 233 117 116 AKI during treatment 79 (24) 42 (22) 37 (27) 1.06 (0.73-1.55), 0.746 Intention of treatment Definitive 217 (67) 132 (70) 85 (62) Adjuvant 109 (33) 57 (30) 52 (38) 1.44 (1.02-2.03), 0.041 Cisplatin dosing frequency** Every 3 weeks 292 (90) 164 (87) 128 (93) Weekly 34 (10) 25 (13) 9 (6.6) 0.89 (0.45-1.75), 0.730 Total Cisplatin dose (mg/m 2 ) ≥200 266 (81.5) 160 (85) 106 (77) <200 60 (18.5) 29 (15) 31 (23) 1.46 (0.98-2.18), 0.064 RT technique IMRT 120 (37) 89 (47) 31 (23) 3D 206 (63) 100 (53) 106 (77) 1.23 (0.81-1.86), 0.341 * Macrovascular diseases include cerebrovascular, coronary and peripheral arterial disease. **Cisplatin dosing schedules: 3-weekly 100 mg/m 2 for up to three doses or weekly 40 mg/m 2 for up to seven doses. RIQ: interquartile range; ECOG: Eastern Cooperative Oncology Group; PET: Positron Emission Tomography; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; TNM: Tumor, Node, Metastasis; QT: chemotherapy; RT: radiotherapy; IMRT: Intensity-Modulated Radiation Therapy; GFR: glomerular filtration rate calculated by CKD-EPI formula; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines. Table 2. Multivariate Analysis of Mortality Risk* Variable Crude HR (95% CI), p-value Adjusted HR (95% CI), p-value Total Cisplatin dose <200 vs ≥200 1.46 (0.98-2.18), 0.064 1.54 (1.00-2.37), 0.049 Oral vs Oropharyngeal 2.09 (1.37-3.20), 0.001 2.46 (1.58-3.81), <0.001 Hypopharyngeal/Laryngeal vs Oropharyngeal 1.7 (1.13-2.55), 0.011 1.36 (0.89-2.08), 0.157 Subsidized vs Contributory insurance 2.36 (1.54-3.61), <0.001 2.44 (1.55-3.81), <0.001 ECOG 1 vs 0 1.4 (0.98-1.99), 0.066 1.30 (0.90-1.89), 0.162 ECOG 2 vs 0 2.72 (0.98-7.57), 0.055 3.25 (1.13-9.34), 0.029 Leukocytes ≥10000/µL vs <10000/µL 1.67 (1.07-2.59), 0.023 1.90 (1.20-3.02), 0.007 HR: Hazard Ratio; CI confidence interval; ECOG: Eastern Cooperative Oncology Group; *Age, not meeting the proportional hazards assumption, was included only as a stratification variable in the adjustment of the Cox regression model. Table 3. Characteristics at the Time of Diagnosis and Risk of NOT ACHIEVING 200 mg/m² of Accumulated Cisplatin Characteristic <200 N = 60 (18.5%) ≥200 N = 266 (81.5%) <200 n/N(%) RR* (95% CI), p-value* Categorized Age in years 70 19 (32) 38 (14) 19/57 (33.33) 1.70 (0.88-3.32), 0.131 Men 36 (60) 194 (73) 36/230 (15.65) 1.60 (0.99-2.51), 0.050 Subsidized health insurance 11 (18) 31 (12) 11/42 (26.19) 1.52 (0.75-2.81), 0.211 Alcohol 17 (28) 65 (24) 17/82 (20.73) 1.17 (0.69-1.90), 0.530 Tobacco 40 (67) 171 (64) 40/211 (18.96) 1.09 (0.68-1.81), 0.730 Diabetes 12 (20) 28 (11) 12/40 (30) 1.79 (0.98-2.94), 0.035 Hypertension 32 (53) 87 (33) 32/119 (26.89) 1.99 (1.26-3.16), 0.003 Macrovascular Diseases 7 (12) 14 (5.3) 7/21 (33.33) 1.92 (0.89-3.38), 0.050 BMI Normal 24 (40) 132 (50) 24/156 (15.38) Low 7 (12) 16 (6.0) 7/23 (23.38) 1.99 (0.87-3.82), 0.063 Overweight/Obese 29 (48) 118 (44) 29/147 (14.38) 1.28 (0.79-2.12), 0.322 ECOG 0 21 (35) 112 (42) 21/133 (13.38) 1 38 (63) 149 (56) 38/187 (18.38) 1.29 (0.80-2.13), 0.307 2 1 (1.7) 5 (1.9) 1/6 (6.38) 1.06 (0.06-3.87), 0.954 Diagnostic Imaging PET 5 (8,3) 43 (16) 5/48 (48,38) CT/MR 55 (92) 223 (84) 55/278 (27.38) 1.90 (0.90-5.24), 0.145 Primary Tumor Oropharyngeal 19 (32) 65 (24) 19/84 (84.38) Oral 22 (37) 115 (43) 22/137 (13.38) 0.71 (0.41-1.25), 0.223 Laryngeal 17 (28) 76 (29) 17/93 (93.38) 0.81 (0.45-1.45), 0.475 Hypopharyngeal 2 (3.3) 10 (3.8) 2/12 (12.38) 0.74 (0.13-2.13), 0.652 Tumor Stage III 14 (23) 84 (32) 14/98 (98.38) IVA 29 (48) 130 (49) 29/159 (15.38) 1.28 (0.73-2.38), 0.240 IVB 17 (28) 52 (20) 17/69 (69.38) 1.76 (0.91-3.33), 0.093 Hemoglobin 450,000/µL 16 (27) 50 (19) 16/66 (66.38) 1.43 (0.83-2.31), 0.163 Leukocytes >10,000/µL 2 (3.3) 36 (14) 2/38 (38.38) 3.83 (1.27-22.77), 0.055 KDIGO stage G1 29 (48.3) 153 (57.5) 29/182 (15.90) G2 26 (43.3) 110 (41.4) 26/136 (19.12) 1.20 (0.7- 2.04), 0.500 G3 5 (8.3) 3 (1.1) 5/8 (62.50) 3.92 (1.33- 9.29), 0.005 GFR <75 (ml/min/1.73 m 2 ) 14 (23) 29 (11) 14/43 (43.38) 2.00 (1.15-3.21), 0.007 RR: Relative Risk; CI: Confidence Interval; RIQ: interquartile range; HTN: Arterial Hypertension; BMI: Body Mass Index; ECOG: Eastern Cooperative Oncology Group; PET: Positron Emission Tomography; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; TNM: Tumor, Node, Metastasis; QT: chemotherapy; RT: radiotherapy; IMRT: Intensity-Modulated Radiation Therapy; GFR: glomerular filtration rate estimated by CKD-EPI formula; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines;* RR, CI 95% and p value calculated using Poisson regression. Table 4. Multivariate Analysis of the Probability of NOT ACHIEVING 200 mg/m² of Accumulated Cisplatin Variable Crude RR 95% CI p- value Adjusted RR* 95% CI p-value Adjusted RR* 95% CI p-value Model 1 (variables at time of diagnosis only) Model 2 (variables at time of diagnosis + AKI) HTN vs No HTN 1.97 1.8-3.32 0.008 1.77 1.24-2.30 0.034 1.64 1.11-2.18 0.069 KDIGO stage 2 vs 1 1.20 0.70- 2.04 0.500 1.08 0.53-1.62 0.787 0.99 0.44-1.54 0.973 KDIGO stage 3 vs 1 3.92 1.33- 9.29 0.005 3.46 2.48-4.45 0.014 3.16 2.16-4.16 0.024 Low BMI vs Normal 1.98 0.79-4.36 0.110 2.17 1.31-3.03 0.076 2.30 1.44-3.16 0.058 BMI Overweight/Obese vs Normal 1.28 0.75-2.22 0.368 1.21 0.66-1.77 0.496 1.13 0.58-1.69 0.658 Men vs Women 1.60 0.94-2.66 0.076 1.65 1.13-2.17 0.060 1.75 1.22-2.27 0.038 AKI vs No AKI 2.23 1.32-3.71 0.002 2.07 1.54-2.60 0.008 RR: Relative Risk; HTN: Arterial Hypertension; BMI: Body Mass Index; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines; AKI: Acute Kidney Failure; * RR calculated using Poisson regression with robust errors. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6377607","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":464808512,"identity":"e0e36729-e2c6-4623-bdbb-998a25fcb346","order_by":0,"name":"Noiver Graciano","email":"","orcid":"","institution":"Instituto de Cancerología Las Américas- AUNA","correspondingAuthor":false,"prefix":"","firstName":"Noiver","middleName":"","lastName":"Graciano","suffix":""},{"id":464808514,"identity":"e9fedbae-a447-40d3-a01d-088f8fd2f8d1","order_by":1,"name":"Lucelly López","email":"","orcid":"","institution":"Universidad Pontificia Bolivariana","correspondingAuthor":false,"prefix":"","firstName":"Lucelly","middleName":"","lastName":"López","suffix":""},{"id":464808516,"identity":"3296b0ad-ca66-4526-96a0-af912d4fbc45","order_by":2,"name":"Yeidy Vallejo","email":"","orcid":"","institution":"Instituto de Cancerología Las Américas- AUNA","correspondingAuthor":false,"prefix":"","firstName":"Yeidy","middleName":"","lastName":"Vallejo","suffix":""},{"id":464808518,"identity":"28bfa2bb-eaba-4b49-b8d0-834f51a7af1e","order_by":3,"name":"Juan Flórez","email":"","orcid":"","institution":"Instituto de Cancerología Las Américas- AUNA","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Flórez","suffix":""},{"id":464808520,"identity":"a8b97163-f3ce-4a63-b777-d32529a46de9","order_by":4,"name":"Carlos A. Rodriguez","email":"data:image/png;base64,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","orcid":"","institution":"Universidad de Antioquia","correspondingAuthor":true,"prefix":"","firstName":"Carlos","middleName":"A.","lastName":"Rodriguez","suffix":""}],"badges":[],"createdAt":"2025-04-04 16:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6377607/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6377607/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83897417,"identity":"d0d6359a-9fa9-4df9-aa1b-0b1e83082cc5","added_by":"auto","created_at":"2025-06-04 08:57:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62812,"visible":true,"origin":"","legend":"\u003cp\u003ePatient inclusion flowchart\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6377607/v1/f752961721616aaec9606c85.jpg"},{"id":83897419,"identity":"a8499c3a-99d1-4a2d-94df-bae49e83f7c0","added_by":"auto","created_at":"2025-06-04 08:57:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":390842,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival adjusted in the model presented in Table 2 for LAHNSC treated with concurrent cisplatin and radiotherapy. (A) OS for accumulated cisplatin dose ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e vs. \u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e. (B) OS according to tumor site. (C) OS according to ECOG performance status. (D) OS according to leukocyte count at diagnosis. (E) OS according to health insurance. (F) Mortality risk based on accumulated dose of cisplatin, stratified by health insurance. OS: overall survival; HR: hazard ratio; CI: confidence interval; p: p value; ECOG: Eastern Cooperative Oncology Group\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6377607/v1/5033e51dbb0014d3513b95fb.jpg"},{"id":83897418,"identity":"ff2cca9e-c8ac-47cb-b31f-09e83f8bfd6c","added_by":"auto","created_at":"2025-06-04 08:57:40","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232598,"visible":true,"origin":"","legend":"\u003cp\u003eProbability of achieving an ineffective dose of cisplatin in patients with LAHNSC. (A) and (B): Effect of sex, KDIGO stage of renal function, and BMI. (C) and (D): Effect of BMI and HTN in patients with AKI during treatment. BMI: body mass index; HTN: arterial hypertension; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines; AKI: Acute Kidney Injury.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6377607/v1/047f94c3cee8b0db4f0a4d3e.jpg"},{"id":87303837,"identity":"37e4e148-2bed-487b-a8d9-c72ac531ff45","added_by":"auto","created_at":"2025-07-22 13:53:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1947366,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6377607/v1/00a464e7-b0f5-4317-b9ef-1b6e7064b041.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eWith the exception of locally advanced head and neck squamous cell carcinoma (LAHNSC) of the oral cavity, where surgery is the primary therapeutic option, the concurrent use of cisplatin and radiotherapy (Cis/RT) has been the standard treatment for over 20 years [1,2]. In surgically treated patients, the EORTC 22931 and RTOG 9501 studies indicated that Cis/RT reduces mortality by 30% in patients with positive margins (\u0026lt;1 mm) and extracapsular nodal extension [3]. The MACH-NC meta-analysis concluded that the combination of platinum-based chemotherapy and radiotherapy in LAHNSC provides an overall survival (OS) benefit of 6.5% at 5 years and 3.6% at 10 years [4]. However, the optimal dose schedule of cisplatin remains debatable, with high variability in clinical practice. In 2016, Strojan et al. suggested that a cumulative cisplatin dose of 200 mg/m\u003csup\u003e2\u003c/sup\u003e or higher significantly impacts OS [5].\u003c/p\u003e\n\u003cp\u003eDespite the survival benefit of achieving a cumulative cisplatin dose \u0026ge;200 mg/m\u003csup\u003e2\u003c/sup\u003e, the frequency with which this target is reached in controlled clinical trials (CCTs) of definitive and adjuvant Cis/RT is 91-92.6% and 66-84%, respectively \u0026nbsp;[1,2,6,7]. However, in observational studies, these rates drop to 46-76% and 50%, respectively [8\u0026ndash;10].\u003c/p\u003e\n\u003cp\u003eThe primary reasons for failing to achieve the minimum effective dose are acute toxicities, the most significant of which include mucositis (45%), leukopenia (42%), nausea/vomiting (16%), and acute kidney injury (AKI) (8%) [1]. Unfortunately, in LAHNSC, there are no evidence-based clinical factors that reliably predict the occurrence of these toxicities. The main clinical variables used in practice to determine whether a patient is unsuitable for cisplatin include impaired renal, auditory, or hematologic function, as well as poor performance status [11,12].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven these considerations, this study aimed to evaluate the effect of an ineffective cisplatin dose, defined as a cumulative dose \u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e, on mortality in patients with LAHNSC and to identify diagnostic factors that contribute to this outcome, using real-world data.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eA retrospective cohort study was conducted, including all patients aged \u0026gt;18 years with a diagnosis of locally advanced head and neck squamous cell carcinoma (LAHNSC) who received at least one dose of concurrent cisplatin and radiotherapy (Cis/RT), either as definitive treatment or adjuvant therapy, at the Instituto de Cancerología, Clínica Las Américas-AUNA (IDCLA-AUNA) in Medellín, Colombia, between January 1, 2014, and January 1, 2024. Clinical staging was determined according to the 7th edition of the American Joint Committee on Cancer (AJCC) criteria, using staging imaging such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET), and included only stages III to IVB (12). The diagnosis of LAHNSC was confirmed through pathology reports, including p16 positivity by immunohistochemistry in patients with oropharyngeal cancer. Cases of p16-positive LAHNSC with an unknown primary site were treated as oropharyngeal carcinoma [13].\u003c/p\u003e\n\u003cp\u003ePatients with sinonasal or nasopharyngeal carcinomas, cutaneous squamous cell carcinomas, synchronous or metachronous active neoplasms, those treated with carboplatin, those who had received induction chemotherapy, those with incomplete data, or those who did not provide informed consent were excluded.\u003c/p\u003e\n\u003cp\u003eThe decision to perform surgery was made by head and neck surgeons, while the indication for Cis/RT was determined by clinical oncologists and radiation oncologists at IDCLA-AUNA. Controversial cases were discussed in the institutional multidisciplinary tumor board. All patients received radiotherapy with definitive intent (70 Gy/35 fractions) or adjuvant intent (60–66 Gy/30–33 fractions) over a period of less than 8 weeks (98.5% of patients). Until 2020, 3D conformal radiotherapy was used, and intensity-modulated radiotherapy (IMRT) was implemented thereafter. The administered doses or volumes were not modified based on p16 positivity [14].\u003c/p\u003e\n\u003cp\u003eData were collected from the institutional registry, specifically the Head and Neck Cancer module, which is maintained in a RedCap database containing all clinical records of patients treated at the institution. Any inconsistencies or missing data identified by the investigators were verified against the clinical records at IDCLA and corrected or completed for analysis. Figure 1 illustrates the patient selection flowchart.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExposures and Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary exposure variable was the cumulative cisplatin dose (\u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e vs. ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e). Independent variables considered at the time of diagnosis (first or second contact with the IDC specialist) included: age, sex, type of health insurance (contributory or subsidized), alcohol consumption, smoking, diabetes mellitus (DM), hypertension (HTN), macrovascular disease (e.g., cerebral, coronary, or peripheral arterial thrombosis), body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, diagnostic imaging modality, primary tumor site (oral, oropharyngeal, hypopharyngeal/laryngeal), TNM staging, hemoglobin levels, platelet count, leukocyte count, and glomerular filtration rate (GFR) calculated using the CKD-EPI formula. Treatment-related variables included the intent of Cis/RT, cisplatin administration frequency, radiotherapy technique, and the development of moderate to severe acute kidney injury (AKI) as defined by common terminology criteria for adverse events (CTCAE) 5.0 criteria [15].\u003c/p\u003e\n\u003cp\u003eStrategies to improve adherence and reduce toxicity were employed for all patients, including hydration, magnesium supplementation, diuretics (furosemide, mannitol), weekly dietitian evaluation, nutritional supplementation if necessary, weight monitoring at each visit, mucositis management, and reactive placement of nasogastric or gastrostomy tubes in patients who lost oral intake [12,16].\u003c/p\u003e\n\u003cp\u003eThe primary outcome variable was overall survival (OS), calculated from the date of the first Cis/RT dose to the date of death from any cause or the last institutional contact with the patient. Death dates were verified using the National Civil Registry records as of June 30, 2024.\u003c/p\u003e\n\u003cp\u003eThe secondary objective was to evaluate diagnostic factors associated with an ineffective cisplatin dose (\u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e). The primary exposure variables were those described at diagnosis, and the outcome variable was failure to achieve a cumulative cisplatin dose of 200 mg/m\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo describe the study population, summary measures were obtained. For clinical variables and follow-up intervals, measures of central tendency and dispersion were used, depending on the results of the Shapiro-Wilk test (mean and standard deviation or median and interquartile range, depending on whether the normality assumption was met). Qualitative variables, such as DM, HTN, and staging, were presented as absolute frequencies and percentages. Only patients with LAHNSC who received Cis/RT were included in the analysis.\u003c/p\u003e\n\u003cp\u003eTo estimate OS for the entire LAHNSC cohort, survival time was calculated from the first cisplatin dose to death from any cause. Right censoring was applied for patients who were alive (not listed in national death records) and lost to follow-up, with the end of follow-up defined as the last contact with any specialist in outpatient consultation or hospitalization at Clínica Las Américas. Administrative censoring was applied to all patients alive as of June 30, 2024.\u003c/p\u003e\n\u003cp\u003eSurvival analyses were performed to determine the association between the primary exposure (ineffective dose) and OS using the log-rank test and Kaplan-Meier curves. A Cox proportional hazards model was used to adjust for diagnostic and treatment variables described previously. Hazard ratios (HR) with confidence intervals (CI) were estimated, and the proportional hazards assumption was verified. A p-value \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003eTo assess the association between an ineffective dose and diagnostic characteristics, the\u0026nbsp;c\u003csup\u003e2\u003c/sup\u003e test, Fisher's exact test, or likelihood ratio test was used. For quantitative variables such as age or GFR, the Mann-Whitney U test was applied, considering a p-value ≤0.1 as significant in the bivariate analysis. Crude and adjusted relative risks (RR) with 95% confidence intervals were estimated using a Poisson regression model, with a p-value \u0026lt;0.05 considered significant. An initial model (Model 1) included variables collected at diagnosis, and a second model (Model 2) incorporated the development of AKI. Statistical analyses were performed using Jamovi 2.6.17 and R 4.4.1, with libraries such as psych, Epi, foreign, lmtest, sandwich (for Poisson regression with robust errors), survival and survminer (for survival models and adjusted graphs).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eClinical and Tumor Characteristics at Diagnosis and Treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the study period (2014–2024), 326 patients met the eligibility criteria. The median age was 62 years (IQR 55–68), with the majority being male (71%), smokers (65%), and covered by contributory health insurance (87%). At diagnosis, many patients were overweight or obese (45%) and had an ECOG performance status of 1 (57%). The most common primary tumor sites were the oropharynx (42%) and larynx (29%), with stage IVA being the most prevalent (49%). Renal function impairment (KDIGO stages G2 and G3) was frequent (44.2%), as was thrombocytosis (20%), while leukocytosis (12%) and auditory toxicity (4.3%) were less common. Cis/RT was administered with definitive intent in 67% of cases, using a tri-weekly cisplatin schedule in 90% of patients and 3D radiotherapy in 63% (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation of Ineffective Dose with Increased Mortality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up for the cohort was 23.8 months (IQR 12.9–49.2, range 2.2–97.9 months), with a median overall survival (OS) of 20 months (IQR 10.9–45.7) and a mortality rate of 42%. Seven deaths (2.15%) occurred during treatment. In unadjusted data, OS was higher in the group receiving ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e of cisplatin (median 72.4 vs. 31.8 months), with a non-significant trend toward increased mortality risk in those receiving \u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e (HR 1.46, 95% CI 0.98–2.18, p=0.064). The 1-, 3-, and 5-year OS rates for the ≥200 mg/ m\u003csup\u003e2\u003c/sup\u003e group were 82%, 62.2%, and 52.5%, respectively, compared to 72.9%, 49.2%, and 45.5% for the \u0026lt;200 mg/ m\u003csup\u003e2\u003c/sup\u003e group.\u003c/p\u003e\n\u003cp\u003eIn the bivariate analysis, considering a significance threshold of p≤0.1, 12 out of 22 characteristics were associated with OS. The most significant risk factors for mortality were age between 50–70 years (HR 2.31, 95% CI 1.22–4.37, p=0.01), subsidized health insurance (HR 2.36, 95% CI 1.54–3.61, p\u0026lt;0.001), and ECOG performance status of 2 (HR 2.72, 95% CI 0.98–7.57, p=0.055) (Table 1).\u003c/p\u003e\n\u003cp\u003eIn the multivariate analysis, only six variables were associated with increased mortality. Since categorized age did not meet the proportional hazards assumption, it was not assigned an HR but was included as a stratification variable for model adjustment. In this model, receiving an ineffective cisplatin dose significantly increased mortality (HR 1.54, 95% CI 1.00–2.37, p=0.049), as did leukocytosis, oral cavity tumors, and poor functional status, with the latter being the strongest predictor of mortality (HR 3.25, 95% CI 1.13–9.34, p=0.029) (Table 2, Figure 2). Subsidized health insurance also significantly increased mortality risk. As shown in Figure 2F, the deleterious impact of an ineffective dose was more pronounced in this population, with the ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e group failing to achieve the same mortality reduction benefit as the contributory insurance group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Characteristics Associated with Ineffective Cisplatin Dose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA cumulative dose of \u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e was administered to 18.5% of patients. Compared to those who received an effective dose, this group had a higher prevalence of age \u0026gt;70 years (32% vs. 14%), diabetes mellitus (20% vs. 11%), hypertension (53% vs. 33%), macrovascular disease (12% vs. 5.3%), and GFR \u0026lt;75 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e (23% vs. 11%). Acute kidney injury (AKI) was also more frequent in this group (42% vs. 20%). Conversely, patients who received an effective dose had a higher proportion of normal BMI (50% vs. 40%), ECOG 0 (42% vs. 35%), and hemoglobin \u0026gt;11 g/dL (85% vs. 75%). No significant differences were observed between the groups in terms of tri-weekly vs. weekly cisplatin administration (90% vs. 89%), definitive intent of Cis/RT (67% vs. 63%), or 3D radiotherapy technique (63% vs. 63%) (Table 3).\u003c/p\u003e\n\u003cp\u003eThe bivariate analysis of diagnostic characteristics associated with an ineffective dose identified 8 out of 17 candidate variables. Among these, low BMI and hypertension doubled the risk of receiving an ineffective dose, while KDIGO stage G3 renal disease increased the risk nearly fourfold. Similarly, a GFR \u0026lt;75 mL/min at diagnosis doubled the risk (Table 3).\u003c/p\u003e\n\u003cp\u003eIn the multivariate analysis (Model 1), hypertension (RR 1.77, 95% CI 1.24–2.30, p=0.034) and KDIGO stage G3 (RR 3.46, 95% CI 1.31–3.03, p=0.014) were significantly associated with an increased risk of receiving an ineffective dose, with borderline significance for low BMI and male sex. In Model 2, which included the development of AKI during Cis/RT, the previous findings were confirmed. Male sex became a significant risk factor (RR 1.75, 95% CI 1.22–2.27, p=0.038), and patients who developed AKI had double the risk of receiving \u0026lt;200 mg/m² of cisplatin compared to those without AKI (Table 4).\u003c/p\u003e\n\u003cp\u003eA stratified analysis of the probability of receiving an ineffective dose in patients with multiple risk factors revealed that patients with low BMI, KDIGO stage G3 renal function, and male sex had an approximately 80% probability of not achieving 200 mg/m\u003csup\u003e2\u003c/sup\u003e, compared to 75% for women with the same risk factors (Figures 3A and 3B). Additionally, patients with low BMI, hypertension, and AKI had a 75% probability of not achieving 200 mg/m\u003csup\u003e2\u003c/sup\u003e, compared to 55% in those without AKI (Figures 3C and 3D).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eConcurrent cisplatin and radiotherapy (Cis/RT) is currently considered the standard therapeutic approach for locally advanced squamous cell carcinoma of the head and neck (LAHNSC), supported by decades of scientific evidence demonstrating its efficacy in tumor control and improved survival outcomes [6,7,17]. Studies suggest an inverse relationship between mortality and the cumulative dose of cisplatin administered, emphasizing the importance of achieving optimal doses to maximize clinical benefits (5,18). Evidence from meta-analyses, randomized controlled trials (RCTs), and observational studies indicates that a cumulative cisplatin dose of \u0026ge;200 mg/m\u003csup\u003e2\u003c/sup\u003e is ideal for optimizing therapeutic outcomes \u0026nbsp;[5,18\u0026ndash;21]. Our real-world data study, supported by multivariate analysis, validates this concept by showing a significant increase in mortality among patients who fail to achieve this dose.\u003c/p\u003e\n\u003cp\u003eIt is important to note that achieving a cumulative cisplatin dose of \u0026ge;200 mg/m\u003csup\u003e2\u003c/sup\u003e is not the sole determinant of mortality. A key finding of our research is the significant impact of health insurance type on patient survival. Figure 2F illustrates that, in patients with subsidized insurance, the relationship between administered dose and mortality is neither clear nor consistent, unlike in patients with contributory insurance, where this relationship is more defined. This phenomenon may be linked to socioeconomic factors associated with subsidized insurance, such as nutritional status, educational level, family support, and limited access to specialized healthcare personnel. Similar observations have been reported in other studies, highlighting the influence of social determinants on clinical outcomes [22,23]. While our study was not designed to evaluate socioeconomic factors, it raises valuable hypotheses for future research.\u003c/p\u003e\n\u003cp\u003eAlthough the primary tumor site does not appear to significantly influence the ability to achieve a therapeutic dose, our findings indicate that tumors originating in the oral cavity are associated with an adjusted mortality rate approximately 2.5 times higher. This result aligns with previous research, suggesting the presence of specific biological or clinical factors that may contribute to the unfavorable prognosis in these patients [24]. Additionally, we identified that leukocytosis and poor functional status are significantly associated with reduced overall survival (OS), findings that have also been documented in other studies [19,25,26].\u003c/p\u003e\n\u003cp\u003eDespite efforts in RCTs, a significant proportion of patients continue to receive ineffective doses of cisplatin due to treatment-related toxicities. In our study, this issue affected nearly one in five patients. Attempts to optimize cisplatin administration schedules and doses have not shown a positive impact on compliance rates, as interruptions and acute toxicities persist. Furthermore, we found no significant differences between weekly and tri-weekly cisplatin administration in terms of OS or the likelihood of administering ineffective doses [18,19]. These results suggest inadequate patient selection for cisplatin treatment, with some patients deemed eligible who, in reality, are not [27\u0026ndash;29].\u003c/p\u003e\n\u003cp\u003eUnlike other malignancies, patients with LAHNSC often begin treatment with a high prevalence of weight loss, oral intake difficulties, and multiple comorbidities. These factors contribute to reduced tolerance to treatment-related toxicities [27,28]. In this context, adherence to the Cis/RT regimen is significantly impacted when nutritional, geriatric, social, and comorbidity factors are inadequately assessed, which is not uncommon [29]. This situation is further exacerbated by the lack of specific criteria developed for LAHNSC populations to identify patients unsuitable for cisplatin treatment. A clear example is the suggested glomerular filtration rate (GFR) threshold for withholding cisplatin (\u0026lt;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e), which is based on extrapolations from its use in genitourinary or gastrointestinal malignancies [27,30].\u003c/p\u003e\n\u003cp\u003eTo our knowledge, our study is the first in an LAHNSC population to demonstrate that patients with a GFR \u0026lt;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e who are offered Cis/RT have a more than threefold increased risk of failing to achieve an effective dose, suggesting that cisplatin should not be administered to these patients. Similarly, in patients with multiple risk factors for developing acute kidney injury (AKI), such as the use of potentially nephrotoxic antihypertensives (e.g., ACE inhibitors, angiotensin II receptor blockers, and diuretics), KDIGO stage G2 renal function, and low body mass index (BMI), continuous and intensive monitoring is recommended, as the development of AKI significantly increases the likelihood of receiving an ineffective dose (Figures 3C and 3D).\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this study presents the largest cohort of Latin American patients with LAHNSC in a real-world data study, evaluating the impact of chemoradiotherapy and cumulative cisplatin dose in this population, with over 10 years of follow-up. This study provides a detailed analysis of various demographic, clinical, and therapeutic variables at diagnosis, as well as clinically relevant outcomes. Unlike other studies that combine different histology, include metastatic patients, lack OS data, use varied chemotherapy regimens, or fail to detail cumulative cisplatin doses, our work offers a more specific and rigorous approach [31\u0026ndash;33].\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. One of the main limitations is the relatively short follow-up period, which reduces the ability to evaluate the impact of other variables, such as sex, staging, or weight loss, which have been described in the literature as influential factors in OS [9,24,34]. The retrospective nature of the study complicates the inclusion of outcomes such as local or distant recurrences in many patients, as some follow-ups were not completed at our institution. Additionally, many patients lacked p16 testing, preventing the evaluation of this variable\u0026apos;s impact on the studied outcomes. Finally, in cases where an effective dose was not administered, the precise causes remained unclear, whether due to toxicities, social issues, or continuity in social security coverage.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn conclusion, our real-world data study validates the importance of achieving an effective cisplatin dose \u0026ge;200 mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eto improve OS, as well as other factors such as leukocytosis, primary tumor site, and functional status. Furthermore, it highlights diagnostic characteristics that affect the likelihood of achieving this cumulative cisplatin dose. Identifying specific characteristics in LAHNSC patients is crucial to avoid exposing them to toxic treatments that do not provide the expected benefit. These findings deserve prospective and multicentric validation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLAHNSC: Locally advanced squamous cell carcinoma of the head and neck\u003c/p\u003e\n\u003cp\u003eOS: Overall survival\u003c/p\u003e\n\u003cp\u003eHR: Hazard ratio\u003c/p\u003e\n\u003cp\u003eRR: Relative risk\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval\u003c/p\u003e\n\u003cp\u003eCis/RT: Cisplatin and radiotherapy\u003c/p\u003e\n\u003cp\u003eCCTs: Controlled clinical trials\u003c/p\u003e\n\u003cp\u003eAKI: Acute kidney injury\u003c/p\u003e\n\u003cp\u003eIDCLA-AUNA: Instituto de Cancerolog\u0026iacute;a, Cl\u0026iacute;nica las Am\u0026eacute;ricas-AUNA\u003c/p\u003e\n\u003cp\u003eAJCC: American Joint Committee on Cancer\u003c/p\u003e\n\u003cp\u003eCT: Computed tomography\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003ePET: Positron emission tomography\u003c/p\u003e\n\u003cp\u003eIMRT: Intensity-modulated radiotherapy\u003c/p\u003e\n\u003cp\u003eDM: Diabetes mellitus\u003c/p\u003e\n\u003cp\u003eHTN: Hypertension\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index\u003c/p\u003e\n\u003cp\u003eECOG: Eastern Cooperative Oncology Group\u003c/p\u003e\n\u003cp\u003eGFR: Glomerular filtration rate\u003c/p\u003e\n\u003cp\u003eCKD-EPI: Chronic Kidney Disease-Epidemiology Collaboration\u003c/p\u003e\n\u003cp\u003eCTCAE: Common terminology criteria for adverse events\u003c/p\u003e\n\u003cp\u003eKDIGO: Kidney Disease: Improving Global Outcomes\u003c/p\u003e\n\u003cp\u003eIQR: Interquartile range\u003c/p\u003e\n\u003cp\u003eRCTs: Randomized clinical trials\u003c/p\u003e\n\u003cp\u003eACE: Angiotensin-converting enzyme\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study complied with the principles of the Declaration of Helsinki and was approved by the Instituto de Cancerolog\u0026iacute;a Las Am\u0026eacute;ricas-AUNA Ethics Committee (Act 217-2024). According to Resolution 8430 of 1993 of Colombia\u0026rsquo;s Ministry of Health this observational retrospective study was classified as low risk (https://www.minsalud.gov.co/sites/rid/lists/bibliotecadigital/ride/de/dij/resolucion-8430-de-1993.pdf). \u0026nbsp;All the patients signed the institutional informed consent to authorize the use of their clinical data for scientific research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed in the study are not publicly available due to the institutional policies of Instituto de Cancerolog\u0026iacute;a Las Am\u0026eacute;ricas-AUNA, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests related to this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe publication of this work was supported by an unconditional grant from Merck. The company did not have any participation in conceptualization, design, data collection, data analysis or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNG, LL and CAR conceived and designed the study. The data were collected by NG and YV. Data analysis was performed by NG, LL and CAR. All authors contributed to the results presentation and discussion. NG wrote the first draft of the paper, all authors read and commented on previous versions of the article and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAdelstein DJ, Li Y, Adams GL, Wagner H, Kish JA, Ensley JF, et al. 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Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines. Radiother Oncol. 2018;126:3\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eU.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 2017; \u003c/li\u003e\n\u003cli\u003eWu Y, Shi W, Li C, Liu X, Jiang Y, Qiu Y, et al. Managing strategies of chemotherapy and radiotherapy-induced oral mucositis. Cancer Treat Rev. 2025;133:102883. \u003c/li\u003e\n\u003cli\u003eForastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31:845\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eSzturz P, Wouters K, Kiyota N, Tahara M, Prabhash K, Noronha V, et al. Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer. Front Oncol. 2019;9:86. \u003c/li\u003e\n\u003cli\u003eVirk J, Gill J, Fekrmandi F, Iovoli A, Farrugia M, Al-Afif A, et al. Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study. BMC Cancer. 2024;24:838. \u003c/li\u003e\n\u003cli\u003eSteinmann D, Cerny B, Karstens JH, Bremer M. Chemoradiotherapy with weekly cisplatin 40 mg/m(2) in 103 head-and-neck cancer patients: a cumulative dose-effect analysis. Strahlenther Onkol. 2009;185:682\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eNguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014;32:3858\u0026ndash;66. \u003c/li\u003e\n\u003cli\u003eRohlfing ML, Mays AC, Isom S, Waltonen JD. Insurance status as a predictor of mortality in patients undergoing head and neck cancer surgery. Laryngoscope. 2017;127:2784\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eNaghavi AO, Echevarria MI, Grass GD, Strom TJ, Abuodeh YA, Ahmed KA, et al. Having Medicaid insurance negatively impacts outcomes in patients with head and neck malignancies. Cancer. 2016;122:3529\u0026ndash;37. \u003c/li\u003e\n\u003cli\u003eChang C-L, Yuan KS-P, Wu S-Y. High-dose or low-dose cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer. Head Neck. 2017;39:1364\u0026ndash;70. \u003c/li\u003e\n\u003cli\u003eGouw ZAR, Paul de Boer J, Navran A, van den Brekel MWM, Sonke J-J, Al-Mamgani A. Baseline peripheral blood leukocytosis: Biological marker predicts outcome in oropharyngeal cancer, regardless of HPV-status. Oral Oncol. 2018;78:200\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eRades D, Zwaan I, Idel C, Pries R, Bruchhage KL, Hakim SG, et al. A New Prognostic Instrument for Predicting the Probability of Completion of Cisplatin during Chemoradiation for Head and Neck Cancer. J Pers Med. 2023;13:1120. \u003c/li\u003e\n\u003cli\u003eAhn M-J, D\u0026rsquo;Cruz A, Vermorken JB, Chen J-P, Chitapanarux I, Dang HQT, et al. Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: A literature review. Oral Oncol. 2016;53:10\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eHaddad RI, Harrington K, Tahara M, Szturz P, Le Tourneau C, Salmio S, et al. Managing cisplatin-ineligible patients with resected, high-risk, locally advanced squamous cell carcinoma of the head and neck: Is there a standard of care? Cancer Treat Rev. 2023;119:102585. \u003c/li\u003e\n\u003cli\u003eFalco A, de Oliveira TB, Cacicedo J, Ospina AV, Ticona M\u0026Aacute;, Galindo H, et al. Ibero-American Expert Consensus on Squamous Cell Carcinoma of the Head and Neck Treatment in Patients Unable to Receive Cisplatin: Recommendations for Clinical Practice. Cancer Manag Res. 2021;13:6689\u0026ndash;703. \u003c/li\u003e\n\u003cli\u003eRaj GV, Iasonos A, Herr H, Donat SM. Formulas calculating creatinine clearance are inadequate for determining eligibility for Cisplatin-based chemotherapy in bladder cancer. J Clin Oncol. 2006;24:3095\u0026ndash;100. \u003c/li\u003e\n\u003cli\u003eSichero L, Tagliabue M, Mota G, Ferreira S, Nunes RAL, Casta\u0026ntilde;eda CA, et al. Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16INK4a status. Head Neck. 2022;44:122\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eArag\u0026oacute;n N, Ordo\u0026ntilde;ez D, Urrea MF, Holgu\u0026iacute;n J, Collazos P, Garc\u0026iacute;a LS, et al. Head and neck cancer in Cali, Colombia: Population-based study. Community Dent Oral Epidemiol. 2022;50:292\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eChedid HM, Lehn CN, Rapoport A, Amar A, Franzi SA. Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy. Braz J Otorhinolaryngol. 2010;76:225\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eCapuano G, Grosso A, Gentile PC, Battista M, Bianciardi F, Di Palma A, et al. Influence of weight loss on outcomes in patients with head and neck cancer undergoing concomitant chemoradiotherapy. Head Neck. 2008;30:503\u0026ndash;8. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"690\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Baseline Characteristics, Treatments and Bivariate Analysis of Mortality Risk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.942%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal N(%) = 326\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.942%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlive N(%) = 189 (58)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDead N(%) = 137(42)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI), p-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eAge in years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e62 (55-68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e60 (54-67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e64 (57-67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eCategorized Age in years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e46 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e32 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; 50-70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e223 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e130 (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e93 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.94-2.91), 0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e57 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e27 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e30 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.22-4.37), 0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eMen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e230 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e128 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e102 (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.97-2.11), 0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eSubsidized health insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e42 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e15 (7,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e27 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.54-3.61), \u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eAlcohol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e82 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e54 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e28 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.49-1.13), 0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eTobacco\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e211 (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e121 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e90 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.71-1.43), 0.972\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e40 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e22 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e18 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.67-1.81), 0.705\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e119 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e58 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e61 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.07-2.11), 0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eMacrovascular Diseases*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e21 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e10 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e11 (8,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.73-2.53), 0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; Normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e156 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e90 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e66 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e23 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e8 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e15 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.14-3.53), 0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; Overweight/Obese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e147 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e91 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e56 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.56-1.15), 0.231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e133 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e86 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e47 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e187 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e101 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e86 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.98-1.99), 0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e6 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e2 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e4 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.98-7.57), 0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eDiagnostic Imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; CT/MRI (vs PET)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e278 (85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e157 (83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e121 (88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.60-1.71), 0.963\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003ePrimary Tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; Oropharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e137 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e94 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e43 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Oral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e84 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e41 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e43 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.37-3.20), 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eHypopharyngeal/Laryngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e105 (32.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e54 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e51 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.13-2.55), 0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eTumor Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e98 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e62 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e36 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;IVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e159 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e94 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e65 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.76-1.71), 0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; IVB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e69 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e33 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e36 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.11-2.80), 0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eHemoglobin g/dL median (RIQ)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e13.4 (11.9- 14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e13.4 (12-14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e13.3 (11.7- 14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eHemoglobin \u0026lt;11g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e55 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e35 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e20 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.47-1,22), 0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003ePlatelets/\u0026micro;L median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e261,000 (179,750- 337,000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e241,000 (159,000- 322,000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e285,000 (203,000- 362,000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003ePlatelets \u0026gt;450,000/\u0026micro;L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e66 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e44 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e22 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.47-1.17.), 0.193\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eLeukocytes/\u0026micro;L median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e6635 (4280- 8260)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e6040 (4000- 7700)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e7000 (4560- 8989)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eLeukocytes \u0026gt;10,000/\u0026micro;L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e38 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e14 (7,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e24 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.07-2.59), 0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eInitial GFR (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e92 (81-99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e89 (80-98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e95 (84-101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eKDIGO stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e182(55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e91 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e91 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; G2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e136(41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e94 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e42 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.42-0.87), 0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;G3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e8(2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e4 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e4 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.45-3.32), 0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eGFR \u0026lt;75 (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e43 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e29 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e14 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.47-1.43), 0.494\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003ePositive p16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e83 (89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e67 (93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e16 (76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eUnknown p16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eAKI during treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e79 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e42 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e37 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.73-1.55), 0.746\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eIntention of treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Definitive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e217 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e132 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e85 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; Adjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e109 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e57 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e52 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(1.02-2.03), 0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eCisplatin dosing frequency**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; Every 3 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e292 (90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e164 (87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e128 (93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Weekly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e34 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e25 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e9 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.45-1.75), 0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eTotal Cisplatin dose (mg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e266 (81.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e160 (85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e106 (77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e60 (18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e29 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e31 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.98-2.18), 0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003eRT technique\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; IMRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e120 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e89 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e31 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25.0725%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;3D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e206 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.942%;\"\u003e\n \u003cp\u003e100 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.5072%;\"\u003e\n \u003cp\u003e106 (77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.7971%;\"\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.7391%;\"\u003e\n \u003cp\u003e(0.81-1.86), 0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e* Macrovascular diseases include cerebrovascular, coronary and peripheral arterial disease. **Cisplatin dosing schedules: 3-weekly 100 mg/m\u003csup\u003e2\u003c/sup\u003e for up to three doses or weekly 40 mg/m\u003csup\u003e2\u003c/sup\u003e for up to seven doses. RIQ: interquartile range; ECOG: Eastern Cooperative Oncology Group; PET: Positron Emission Tomography; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; TNM: Tumor, Node, Metastasis; QT: chemotherapy; RT: radiotherapy; IMRT: Intensity-Modulated Radiation Therapy; GFR: glomerular filtration rate calculated by CKD-EPI formula; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 680px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. Multivariate Analysis of Mortality Risk*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude HR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI), p-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted HR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI), p-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eTotal Cisplatin dose \u0026lt;200 vs \u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(0.98-2.18), 0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e1.54\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(1.00-2.37), 0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eOral vs Oropharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(1.37-3.20), 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e2.46\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(1.58-3.81), \u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eHypopharyngeal/Laryngeal vs Oropharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(1.13-2.55), 0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e1.36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(0.89-2.08), 0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eSubsidized vs Contributory insurance \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(1.54-3.61), \u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e2.44\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(1.55-3.81), \u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eECOG 1 vs 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(0.98-1.99), 0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e1.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(0.90-1.89), 0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eECOG 2 vs 0 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(0.98-7.57), 0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e3.25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(1.13-9.34), 0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 259px;\"\u003e\n \u003cp\u003eLeukocytes \u0026ge;10000/\u0026micro;L vs \u0026lt;10000/\u0026micro;L \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(1.07-2.59), 0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e1.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e(1.20-3.02), 0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 680px;\"\u003e\n \u003cp\u003eHR: Hazard Ratio; CI confidence interval; ECOG: Eastern Cooperative Oncology Group; *Age, not meeting the proportional hazards assumption, was included only as a stratification variable in the adjustment of the Cox regression model.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"652\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 652px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3. Characteristics at the Time of Diagnosis and Risk of NOT ACHIEVING 200 mg/m\u0026sup2; of Accumulated Cisplatin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;200 N = 60 (18.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge;200 N = 266 (81.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;200 n/N(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRR*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI), p-value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCategorized Age in years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e9 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e37 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e9/46 (19.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e50-70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e32 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e191 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e32/223 (14.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.73\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.16-0.27), 0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026gt;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e19 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e38 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19/57 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.88-3.32), 0.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e36 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e194 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e36/230 (15.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.60\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.99-2.51), 0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSubsidized health insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e11 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e31 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e11/42 (26.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.52\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.75-2.81), 0.211\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAlcohol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e17 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e65 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e17/82 (20.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.69-1.90), 0.530\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTobacco\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e40 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e171 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e40/211 (18.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.09\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.68-1.81), 0.730\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e12 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e28 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e12/40 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.79\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.98-2.94), 0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e32 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e87 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e32/119 (26.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(1.26-3.16), 0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMacrovascular Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e7 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e14 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e7/21 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.92\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.89-3.38), 0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e24 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e132 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e24/156 (15.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e7 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e16 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e7/23 (23.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.87-3.82), 0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eOverweight/Obese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e29 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e118 (44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29/147 (14.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.79-2.12), 0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 21 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e112 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e21/133 (13.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e38 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e149 (56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e38/187 (18.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.29\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.80-2.13), 0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e1 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e5 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1/6 (6.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.06\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.06-3.87), 0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDiagnostic Imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 5 (8,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e43 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e5/48 (48,38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCT/MR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e55 (92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e223 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e55/278 (27.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.90-5.24), 0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePrimary Tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Oropharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e65 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19/84 (84.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eOral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e22 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e115 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e22/137 (13.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.71\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.41-1.25), 0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLaryngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e17 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e76 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e17/93 (93.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.81\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.45-1.45), 0.475\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHypopharyngeal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e2 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e10 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2/12 (12.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.74\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.13-2.13), 0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTumor Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;14 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e84 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e14/98 (98.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e29 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e130 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29/159 (15.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.73-2.38), 0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;IVB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e17 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e52 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e17/69 (69.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.76\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.91-3.33), 0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHemoglobin \u0026lt;11g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e15 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e40 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e15/55 (55.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.64\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.95-2.65), 0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePlatelets \u0026gt;450,000/\u0026micro;L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e16 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e50 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e16/66 (66.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.43\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.83-2.31), 0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLeukocytes \u0026gt;10,000/\u0026micro;L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e2 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e36 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2/38 (38.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e3.83\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(1.27-22.77), 0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eKDIGO stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e\u0026nbsp; 29 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e153 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29/182 (15.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e26 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e110 (41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e26/136 (19.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(0.7- 2.04), 0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e5 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e3 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e5/8 (62.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e3.92\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(1.33- 9.29), 0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eGFR \u0026lt;75 (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e14 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e29 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e14/43 (43.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e(1.15-3.21), 0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 652px;\"\u003e\n \u003cp\u003eRR: Relative Risk; CI: Confidence Interval; \u0026nbsp;RIQ: interquartile range; HTN: \u0026nbsp;Arterial Hypertension; BMI: Body Mass Index; \u0026nbsp;ECOG: Eastern Cooperative Oncology Group; PET: Positron Emission Tomography; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; TNM: Tumor, Node, Metastasis; QT: chemotherapy; RT: radiotherapy; IMRT: Intensity-Modulated Radiation Therapy; GFR: glomerular filtration rate estimated by CKD-EPI formula; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines;*\u003cstrong\u003e\u0026nbsp;RR, CI 95% and p value calculated using Poisson regression.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"783\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" valign=\"top\" style=\"width: 34.4486%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4. Multivariate Analysis of the Probability of NOT ACHIEVING 200 mg/m\u0026sup2; of Accumulated Cisplatin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude RR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep- value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted RR*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted RR*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 9.4139%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u0026nbsp;\u003c/strong\u003e(variables at time of diagnosis only)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 10.2072%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u0026nbsp;\u003c/strong\u003e(variables at time of diagnosis + AKI)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eHTN vs No HTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.97\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e1.8-3.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.77\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e1.24-2.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.034\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.64\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e1.11-2.18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eKDIGO stage 2 vs 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.20\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e0.70- 2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.08\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e0.53-1.62\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.787\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.99\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e0.44-1.54\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.973\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eKDIGO stage 3 vs 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.92\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e1.33- 9.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.46\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e2.48-4.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.014\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e2.16-4.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eLow BMI vs Normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.98\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e0.79-4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e1.31-3.03\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.076\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e1.44-3.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eBMI Overweight/Obese vs Normal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e0.75-2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e0.66-1.77\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.496\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e0.58-1.69\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.658\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eMen vs Women \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.60\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e0.94-2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.65\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\n \u003cp\u003e1.13-2.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\n \u003cp\u003e0.060\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e1.22-2.27\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.0917%;\"\u003e\n \u003cp\u003eAKI vs No AKI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.8559%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.7021%;\"\u003e\n \u003cp\u003e1.32-3.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.3799%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9136%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.0675%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.4857%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.6492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.07\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 3.9665%;\"\u003e\n \u003cp\u003e1.54-2.60\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 2.2741%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" valign=\"top\" style=\"width: 36.6508%;\"\u003e\n \u003cp\u003eRR: Relative Risk; HTN: \u0026nbsp;Arterial Hypertension; BMI: Body Mass Index; KDIGO Stages: stages of chronic kidney disease according to the Kidney Disease Improving Global Outcomes guidelines; AKI: Acute Kidney Failure; *\u0026nbsp;\u003cstrong\u003eRR calculated using Poisson regression with robust errors.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"head and neck neoplasms, chemoradiotherapy, cisplatin, mortality, prognostic factors","lastPublishedDoi":"10.21203/rs.3.rs-6377607/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6377607/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003cbr\u003e\n\u003c/strong\u003eCisplatin and radiotherapy have been the standard treatment for locally advanced squamous cell carcinoma of the head and neck (LAHNSC) for over 20 years. Achieving a cumulative cisplatin dose ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e has been associated with improved overall survival (OS); however, this target is often not met in clinical practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003cbr\u003e\n\u003c/strong\u003eThis retrospective cohort study was conducted at Instituto de Cancerología Las Américas (Medellín, Colombia) from 2014-2024. Demographic and clinical factors were analyzed to evaluate the relationship between ineffective cisplatin doses (\u0026lt;200 mg/m\u003csup\u003e2\u003c/sup\u003e) and OS. Survival analysis was performed using the log-rank test and Kaplan-Meier curves. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR), and a Poisson regression model to calculate relative risks (RR).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003cbr\u003e\n\u003c/strong\u003e326 patients were included. OS was longer in patients receiving ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e of cisplatin (median 72.4 vs. 31.8 months), with an HR of 1.46 (95% CI 0.98–2.18, p=0.064). Multivariable analysis showed that an ineffective dose was associated with increased mortality (HR 1.54, 95% CI 1.00–2.37, p=0.049). Factors associated with worse OS included low functional status, primary oral carcinoma, subsidized health insurance, and leukocytosis. Patients with low body mass index, hypertension, male sex, or GFR \u0026lt;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e were at higher risk of receiving an ineffective dose. Acute kidney injury during treatment doubled this risk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003cbr\u003e\n\u003c/strong\u003eThis real-world study supports that failure to achieve a cisplatin dose ≥200 mg/m\u003csup\u003e2\u003c/sup\u003e increases mortality in LAHNSC. Identifying high-risk patients and optimizing management strategies are essential to improve treatment outcomes.\u003c/p\u003e","manuscriptTitle":"Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-04 08:57:35","doi":"10.21203/rs.3.rs-6377607/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c182d48f-b2f7-41dc-bd4a-5403de045e85","owner":[],"postedDate":"June 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-22T13:53:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-04 08:57:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6377607","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6377607","identity":"rs-6377607","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}