Second Primary Malignancies in Patients with Solid Tumors: The Prognostic Role of Magnesium Depletion Score

Second Primary Malignancies in Patients with Solid Tumors: The Prognostic Role of Magnesium Depletion Score | 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 Second Primary Malignancies in Patients with Solid Tumors: The Prognostic Role of Magnesium Depletion Score Neslihan Özyurt, Müge Sönmez This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7491473/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: Second primary malignancies (SPMs) have become an increasingly recognized clinical entity in modern oncology as advances in treatment prolong survival. This study aimed to investigate the incidence of SPMs in patients with solid tumors, to evaluate associated demographic and clinical factors, and to examine the potential prognostic role of the Magnesium Depletion Score (MDS). Methods: This retrospective cohort study included 1,027 patients diagnosed with solid tumors between 2010 and 2023, with complete follow-up data available. Patients were stratified according to the presence of SPM. Demographic, clinical, and lifestyle variables were compared. Survival analyses were performed using the Kaplan–Meier method, and risk factors associated with SPM were assessed using univariable logistic regression. Results: SPMs were identified in 7.1% of patients. Patients with SPMs were more frequently diagnosed at earlier stages (28.8% stage I) and had significantly longer overall survival compared to those without SPMs (median OS: 7.89 vs. 2.52 years; p < 0.05). Logistic regression analysis revealed that former smoking (OR = 1.99), presence of diabetes (OR = 1.78), and each one-unit increase in MDS (OR = 1.59) were significantly associated with SPM development. Advanced stage at initial diagnosis was inversely associated with the likelihood of SPM occurrence. Conclusion: SPMs are more commonly observed in patients diagnosed at an earlier stage and with longer survival. MDS may serve as a potential biomarker for predicting SPM risk. These findings highlight the importance of long-term follow-up and metabolic assessment in cancer survivors. Second primary neoplasms Neoplasms Magnesium depletion score Prognosis Survival analysis Figures Figure 1 Figure 2 Introduction Advances in cancer therapies have significantly prolonged survival in many patients ( 1 ). While this represents a major achievement in oncology, it has also introduced new clinical challenges. One such issue is the occurrence of second primary malignancies (SPMs), which are detected during the treatment or follow-up of index cancer cases ( 2 ). SPMs are defined as new malignant neoplasms that develop independently of the initial primary tumor. Epidemiological studies describe SPMs as tumors arising in different anatomical sites and/or belonging to different histological or morphological subgroups ( 3). Although their diagnostic criteria and biological mechanisms have been studied for decades, clinical management remains challenging. The reported incidence of SPMs varies between 0.7% and 11.7% ( 4 ) and this rate increases with longer follow-up durations ( 5 ). The risk also differs by primary cancer type, ranging from about 1% in primary liver cancer to as high as 16% in primary bladder cancer ( 6 ). Multiple factors contribute to the development of SPMs. Genetic predisposition, through mutations in BRCA1/2, p16/CDKN2A, and DNA repair genes, can increase susceptibility ( 7 ). Lifestyle factors, particularly smoking and alcohol consumption, contribute via cumulative carcinogenic exposure ( 8 , 9 ). Prior treatments such as radiotherapy and chemotherapy further elevate the risk by inducing free radical production, cytokine-mediated inflammatory responses, and telomere damage ( 10 ). Comorbidities such as diabetes, obesity ( 11 ), and chronic inflammatory conditions, as well as metabolic alterations such as magnesium deficiency, also play a role. Environmental and occupational exposures (e.g., radon, asbestos industry) and oncogenic infections (EBV, HPV, Helicobacter pylori ) further contribute to SPM pathogenesis ( 12 ). Altogether, these factors represent a multidimensional network that shapes the individual patient’s risk profile. Within this network, clinically accessible biomarkers have attracted increasing attention. Among them, magnesium (Mg²⁺) has emerged as a potential factor of interest in cancer development and prognosis ( 13 , 14 ). Magnesium is essential for numerous physiological processes including neuronal transmission, muscle contraction, cardiovascular function, energy metabolism, and protein and nucleic acid synthesis, thereby maintaining cellular homeostasis ( 15 ). Its absorption and excretion can be influenced by alcohol consumption (reducing intake and increasing renal excretion), long-term proton pump inhibitor (PPI) therapy (reducing TRPM6 activity and absorption), and diuretic use (enhancing renal excretion) ( 16 , 17 ). Renal function also plays a key role in regulating magnesium filtration, reabsorption, and excretion ( 17 ). The Magnesium Depletion Score (MDS) combines these clinical parameters—alcohol intake, PPI and diuretic use, and renal function—into a simple scoring system to assess magnesium status. By integrating such factors, MDS has been proposed as a useful biomarker for predicting disease risk associated with magnesium deficiency and may be relevant in the early identification of conditions such as cancer ( 18 ). Magnesium deficiency or dysregulation has been associated with a range of diseases, including cardiovascular disease, diabetes, hypertension, and osteoporosis ( 19 ). More recently, its role in tumor development has gained attention, as magnesium has been shown to regulate cytotoxic T lymphocytes (CD8 + T cells) and influence antitumor immunity ( 20 ), as well as to maintain genomic stability and regulate apoptosis ( 14 ). Magnesium status can be assessed by serum magnesium concentration, magnesium tolerance testing, or MDS. Serum magnesium, however, is tightly regulated and may not accurately reflect total body magnesium deficiency. It is also dynamic and influenced by hydration, laboratory methods, and circadian variations. Because the majority of magnesium is stored in bone and intracellular compartments, serum levels alone are insufficient to reflect true magnesium status. The magnesium tolerance test is costly and not feasible in routine practice ( 21 ). In contrast, MDS provides a practical, clinically applicable tool that more reliably reflects systemic magnesium status. MDS incorporates simple parameters such as diabetes, hypertension, and diuretic use, which contribute to magnesium loss, and has been associated with cardiovascular disease and all-cause mortality. However, its association with cancer remains poorly investigated ( 18 ). In this study, we aimed to investigate the incidence of SPMs in a large cohort of patients with solid tumors and to evaluate associated clinical and demographic factors, as well as the prognostic role of MDS. Our goal was to raise clinical awareness and to highlight potential early warning biomarkers in the management of cancer survivors. Methods This retrospective descriptive cohort study was conducted on 1,027 patients with solid tumors who were followed and treated at the Medical Oncology Clinic of Ordu University Training and Research Hospital between 2010 and 2023. Eligible patients were those with histopathologically confirmed solid malignancies, who had been followed for at least 6 months, and whose clinical and laboratory data were fully available. The definition of second primary malignancy (SPM) was based on the Warren and Gates criteria ( 22 ). Accordingly, patients with two or more malignant tumors were included if each tumor exhibited malignant histology, developed in distinct anatomical sites, and could not be considered as a metastasis or recurrence of the index tumor. In line with the literature, SPMs were further classified as synchronous or metachronous. Synchronous tumors were defined as those diagnosed within 6 months of the initial primary tumor, whereas metachronous tumors were those diagnosed more than 6 months after the initial diagnosis ( 23 ). Data collected from patient records included demographic variables (age, sex, occupation, place of residence), clinical characteristics (BMI, ECOG performance status, comorbidities), lifestyle factors (smoking history), laboratory findings (components of the Magnesium Depletion Score [MDS]), primary tumor site, stage, family history, and survival outcomes. All data were anonymized to ensure patient confidentiality. The study was approved by the Ethics Committee of Ordu University Faculty of Medicine (Date: June 2, 2025; Decision No: 2025/212). Written informed consent was waived due to the retrospective design of the study. The MDS is a simple tool designed to estimate magnesium deficiency and was calculated by summing four risk factors: Diuretic use : 1 point for current use, 0 points otherwise. Proton pump inhibitor (PPI) use : 1 point for current use, 0 points otherwise. Renal function : eGFR ≥ 90 mL/min/1.73 m² = 0 points; eGFR < 90 but ≥ 60 = 1 point; eGFR 2 drinks/day in men or > 1 drink/day in women, scored as 1 point; all other categories (never, rare, mild, or moderate consumption) scored as 0. In this cohort, the MDS was calculated as described above, with scores ranging from 0 to 5. Statistical Analysis All data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Demographic and clinical characteristics, tumor and pathological findings, diagnostic and surgical procedures, treatment outcomes, and survival data of patients with solid tumors were summarized. Categorical variables were presented as frequencies (n) and percentages (%), while continuous variables were expressed as mean ± standard deviation, median, minimum, and maximum values. The normality of data distribution was assessed using skewness and kurtosis coefficients, with values within the range of ± 1.96 considered to indicate normal distribution. Comparisons between groups according to the presence of second primary malignancy (SPM) were performed using the Chi-square test for categorical variables. Post-hoc comparisons were conducted with the Bonferroni test, and groups showing significant differences were labeled with distinct superscript letters. For continuous variables, comparisons between groups were performed using either the Independent Samples t-test or the Mann–Whitney U test, depending on data distribution. Survival analyses were performed using the Kaplan–Meier method, and differences between groups were assessed with the log-rank (Mantel–Cox) test. Univariable logistic regression analysis was used to identify factors associated with the presence of SPM. A p-value of < 0.05 was considered statistically significant, with p < 0.01 regarded as highly significant. Results A total of 1,027 patients with solid tumors were included in the study. Of these, 56.2% were male and 43.8% female, with a mean age at diagnosis of 62.8 ± 12.9 years. No significant differences were observed between patients with and without SPM in terms of age and sex. Similarly, no significant differences were found regarding place of residence, body mass index (BMI), or performance status. The mean follow-up time was 7.1 ± 5.9 years (range: 0–30 years). While 92.9% of patients did not develop SPM, 7.1% (n = 73) were diagnosed with an SPM. Among these, 65 cases (6.3%) were metachronous and 8 cases (0.8%) synchronous. Of the 73 patients with SPM, 71 (97.3%) developed a single second primary, whereas two and three distinct SPMs were identified in one patient each (1.4%). The most common SPM sites were breast (n = 13, 17.8%), prostate (n = 11, 15.1%), colorectal (n = 9, 12.3%), and bladder (n = 9, 12.3%). Less frequent SPMs included lung (n = 6, 8.2%), hematologic malignancies (n = 7, 9.6%), skin (n = 3, 4.1%), thyroid (n = 3, 4.1%), head and neck (n = 3, 4.1%), and other solid tumors. The distribution of SPMs by tumor type and stage is shown in Fig. 1 . (Fig. 1 here) Regarding lifestyle and comorbidity factors, the proportion of former smokers was significantly higher among patients with SPM compared to those without (39.7% vs. 23.7%; p = 0.009). Although patients with SPM had higher cumulative smoking exposure (pack-years: 50.2 ± 24.1 vs. 46.8 ± 32.7), this difference only approached statistical significance (p = 0.053). Diabetes was also more prevalent in patients with SPM (27.4% vs. 17.5%; p = 0.035). Mean MDS scores were significantly higher in patients with SPM than in those without (1.85 ± 0.84 vs. 1.48 ± 0.87; p < 0.001). The distribution of demographic, clinical, and lifestyle variables according to SPM status is presented in Table 1 . (Table 1 here) Table 1 Comparison of clinical and demographic characteristics according to the presence of second primary malignancy (SPM) Presence of SPM Total (n:1027) No SPM (n:954) SPM (n:73) n % n % n % p-value Sex Male 577 56.2 536 56.2 41 56.2 1.000 Female 450 43.8 418 43.8 32 43.8 Age at diagnosis < 65 years 554 53.9 511 53.6 43 58.9 0.447 ≥ 65 years 473 46.1 443 46.4 30 41.1 Occupation Housewife 432 42.1 401 42.0 31 42.5 0.715 Farmer 182 17.7 170 17.8 12 16.4 Worker 214 20.8 195 20.4 19 26.0 Tradesman 86 8.4 82 8.6 4 5.5 Officer 68 6.6 64 6.7 4 5.5 Fisherman 16 1.6 16 1.7 0 0.0 Unemployed 29 2.8 26 2.7 3 4.1 Residence Urban 767 74.7 709 74.3 58 79.5 0.405 Rural 260 25.3 245 25.7 15 20.5 Blood group 0 Positive 118 11.5 112a 11.7 6a 8.2 0.001** A Positive 156 15.2 144a 15.1 12a 16.4 B Positive 58 5.6 52a 5.5 6a 8.2 AB Positive 22 2.1 18a 1.9 4b 5.5 0 Negative 20 1.9 15a 1.6 5b 6.8 A Negative 21 2.0 17a 1.8 4b 5.5 B Negative 5 0.5 4a 0.4 1a 1.4 Unknown 627 61.1 592a 62.1 35b 47.9 Smoking status Never 430 41.9 404a 42.3 26a 35.6 0.009* Current 342 33.3 324a 34.0 18a 24.7 Former 255 24.8 226a 23.7 29b 39.7 BMI Underweight 34 3.3 31 3.2 3 4.1 0.950 Normal 304 29.6 284 29.8 20 27.4 Overweight 382 37.2 355 37.2 27 37.0 Obese 307 29.9 284 29.8 23 31.5 ECOG score I 387 37.7 357 37.4 30 41.1 0.740 II 565 55.0 528 55.3 37 50.7 III 75 7.3 69 7.2 6 8.2 Diabetes Absent 840 81.8 787a 82.5 53b 72.6 0.035* Present 187 18.2 167a 17.5 20b 27.4 COPD Absent 938 91.3 869 91.1 69 94.5 0.431 Present 89 8.7 85 8.9 4 5.5 Hypertension Absent 627 61.1 590 61.8 37 50.7 0.078 Present 400 38.9 364 38.2 36 49.3 Coronary artery disease Absent 873 85.0 813 85.2 60 82.2 0.597 Present 154 15.0 141 14.8 13 17.8 Mean.±S.D. Med. (Min.-Max.) Mean.±S.D. Med. (Min.-Max.) Mean.±S.D. Med. (Min.-Max.) p Age (years) t 62.79 ± 12.85 63 (17–95) 62.77 ± 12.91 64 (17–95) 63.05 ± 12.11 62 (32–86) 0.855 Smoking (pack-years) z 47.08 ± 32.12 40 (3–435) 46.81 ± 32.72 40 (3–435) 50.23 ± 24.13 45 (15–140) 0.053 BMI z 27.21 ± 5.4 27 (15–53) 27.22 ± 5.41 27 (15–53) 27.07 ± 5.39 27 (16–52) 0.989 MDS score t 1.5 ± 0.87 1 (0–5) 1.48 ± 0.87 1 (0–5) 1.85 ± 0.84 2 (0–4) 0.000** SPM: second primary malignancy; BMI: body mass index; MDS: magnesium depletion score; COPD: chronic obstructive pulmonary disease. S.D.: Standard deviation. Med.: Median. Min.: Minimum. Max.: Maximum. *p < 0.05. * p < 0.01. χ²: Chi-square test (categorical variables). t: Independent Samples t-test. z: Mann–Whitney U test. Superscript letters indicate significant differences between groups. The most common primary tumor types were lung (23.8%), breast (22.0%), gastric (7.9%), and colorectal (7.4%). Compared with patients without SPM, those with SPM more frequently had bladder, prostate, and renal cancers as their initial primary tumors (p < 0.05). Stage distribution also showed a striking difference: 28.8% of patients with SPM were diagnosed at stage I compared with only 11.4% in patients without SPM (p 0.05). No significant associations were found regarding cancer history in first-, second-, or third-degree relatives (p > 0.05). The distribution of diagnosis, stage, family history, and survival characteristics according to SPM status is summarized in Table 2 . (Table 2 here) Table 2 Comparison of diagnosis. stage. family history. and survival characteristics according to the presence of second primary malignancy (SPM). Variables Presence of SPM Total (n:1027) No SPM (n:954) SPM (n:73) n % n % n % p-value Diagnosis Lung 244 23.8 229a 24.0 15a 20.5 0.006* Breast 226 22.0 211a 22.1 15a 20.5 Stomach 81 7.9 78a 8.2 3a 4.1 Colon 76 7.4 69a 7.2 7a 9.6 Prostate 65 6.3 59a 6.2 6a 8.2 Rectum 60 5.8 58a 6.1 2b 2.7 Brain 46 4.5 44a 4.6 2b 2.7 Uterus 40 3.9 38a 4.0 2a 2.7 Bladder 31 3.0 25a 2.6 6a 8.2 Ovary 21 2.0 21a 2.2 0a 0.0 Thymoma 19 1.9 18a 1.9 1a 1.4 Pancreas 18 1.8 18a 1.9 0b 0.0 Kidney 16 1.6 11a 1.2 5a 6.8 Cervix 16 1.6 15a 1.6 1a 1.4 Gallbladder 15 1.5 13a 1.4 2a 2.7 Sarcoma 14 1.4 13a 1.4 1a 1.4 Testis 7 0.7 7a 0.7 0a 0.0 Skin 6 0.6 5a 0.5 1a 1.4 Malignant melanoma 6 0.6 4a 0.4 2a 2.7 NET 6 0.6 6a 0.6 0a 0.0 Liver 4 0.4 4a 0.4 0a 0.0 Larynx 4 0.4 3a 0.3 1a 1.4 Appendix 2 0.2 2a 0.2 0a 0.0 Esophagus 2 0.2 1a 0.1 1b 1.4 Parotid 1 0.1 1a 0.1 0a 0.0 Thyroid 1 0.1 1a 0.1 0a 0.0 Stage at diagnosis I 130 12.7 109a 11.4 21b 28.8 0.000** II 151 14.7 139a 14.6 12a 16.4 III 370 36.0 351a 36.8 19a 26.0 IV 376 36.6 355a 37.2 21a 28.8 Family history Absent 429 41.8 405 42.5 24 32.9 0.140 Present 598 58.2 549 57.5 49 67.1 First-degree relative with cancer *** Present 501 83.8 458 83.4 43 87.8 0.558 Absent 97 16.2 91 16.6 6 12.2 Second-/third-degree relative with cancer*** Present 201 33.6 189 34.4 12 24.5 0.210 Absent 397 66.4 360 65.6 37 75.5 > 3 relatives with cancer Present 40 3.9 35 3.7 5 6.8 0.298 Absent 987 96.1 919 96.3 68 93.2 Mortality Alive 411 40.0 371a 38.9 40b 54.8 0.011* Deceased 616 60.0 583a 61.1 33b 45.2 Mean.±S.D. Med. (Min.-Max.) Mean.±S.D. Med. (Min.-Max.) Mean.±S.D. Med. (Min.-Max.) p Number of first-degree relatives with cancer (Mann–Whitney U test) 1.33 ± 0.63 1 (0–4) 1.34 ± 0.64 1 (0–4) 1.23 ± 0.48 1 ( 1 – 3 ) 0.366 Overall survival (years) (Mann–Whitney U test) 2.87 ± 3.13 1.9 (0.03–24.08) 2.72 ± 2.84 1.81 (0.03–24.08) 4.84 ± 5.34 2.8 (0.16–22.24) 0.000** SPM: second primary malignancy; OS: overall survival; NET: neuroendocrine tumor. S.D: Standard deviation. Med.: Median. Min.: Minimum. Max.: Maximum. *p < 0.05, **p < 0.01. χ²: Chi-square test (categorical variables), z: Mann–Whitney U test (continuous variables). Superscript letters indicate significant differences between groups. *Analysis performed on 598 patients. In survival analysis, overall survival was significantly longer in patients with SPM. Median OS was 2.52 years in patients without SPM, compared with 7.89 years in those with SPM (p < 0.05). Kaplan–Meier survival curves clearly demonstrated this difference (Fig. 2 ). (Fig. 2 here) Logistic regression analysis identified former smoking (OR = 1.99; 95% CI: 1.15–3.47; p = 0.015), diabetes (OR = 1.78; 95% CI: 1.04–3.05; p = 0.037), and each one-unit increase in MDS score (OR = 1.59; 95% CI: 1.23–2.07; p < 0.001) as independent risk factors for SPM. Furthermore, advanced stage at initial diagnosis was inversely associated with SPM development: patients with stage II, III, or IV disease had a significantly lower risk compared with those diagnosed at stage I (Table 3 ). (Table 3 here) MDS was strongly associated with SPM presence (p < 0.05; R²=0.029), with each unit increase in the score conferring an approximately 1.6-fold higher risk of developing an SPM. Table 3 Results of univariate logistic regression analysis for potential predictors of second primary malignancy (SPM) Predictor variable B S.E. p Exp(B)/ Odds ratio 95% CI for Exp(B) R 2 Smoking status 0.010** 0.021 Smoking status ( 1 ) -0.15 0.32 0.641 0.86 0.47 1.60 Smoking status ( 2 ) 0.69 0.28 0.015* 1.99 1.15 3.47 Diabetes (DT) 0.58 0.28 0.037* 1.78 1.04 3.05 0.010 Hypertension (HT) 0.46 0.24 0.061 1.58 0.98 2.54 0.008 MDS score 0.47 0.13 0.000** 1.59 1.23 2.07 0.029 Stage at diagnosis 0.000** 0.039 Stage at diagnosis ( 2 ) -0.80 0.38 0.036* 0.45 0.21 0.95 Stage at diagnosis ( 3 ) -1.27 0.34 0.000** 0.28 0.15 0.54 Stage at diagnosis ( 4 ) -1.18 0.33 0.000** 0.31 0.16 0.58 *p < 0.05. ** p < 0.01; Exp(B): Odds Ratio (OR); R²: Coefficient of determination. Discussion In this study, conducted on a large cohort of patients with solid tumors followed at the Medical Oncology Clinic of Ordu University Training and Research Hospital, the incidence of SPMs was found to be 7.1%. This rate falls within the range of 2–17% previously reported in the literature ( 24 ). Amer et al. ( 22 ) reported in a large series evaluating multiple primary malignancies that breast, prostate, and colorectal cancers were the most frequent tumors, both as first and second primaries. Similarly, in our cohort, breast, prostate, and colorectal cancers were among the most common SPMs, with bladder cancer also observed at a notable frequency. In contrast, their study emphasized that poor-prognosis tumors such as pancreatic and hepatocellular carcinoma rarely developed SPMs. Our findings also showed that patients with SPMs were diagnosed at earlier stages and had significantly longer overall survival. This suggests that SPMs are more likely to arise in patients who survive longer and remain under regular surveillance. Indeed, longer survival associated with earlier-stage diagnosis may provide sufficient time for the development of additional malignancies. Similar observations have been reported in the literature, where SPMs were found to occur more frequently among patients diagnosed at early stages ( 25 ) and in populations with extended survival ( 26 ). These findings support our conclusion that SPMs are particularly common in patients with early-stage disease and longer survival. One of the novel findings of our study was the identification of “former smoking” as an independent risk factor for SPM development. Similarly, previous studies have reported that former smokers have approximately a 1.4-fold higher risk of developing SPMs compared with never-smokers ( 27 ). Data from the American Cancer Society also demonstrate that while the risk of first and second primaries in former smokers is lower than in current smokers, it remains significantly higher compared with never-smokers ( 28 ). This observation may reflect the cumulative carcinogenic effect of smoking, while also being attributable to the fact that patients who quit smoking often belong to longer-surviving cohorts. Diabetes was another independent risk factor identified in our study. Chronic inflammation, oxidative stress, and metabolic dysfunction are well-established mechanisms through which diabetes may predispose to cancer development. This mechanistic link has been clearly demonstrated in the literature ( 29 – 32 ), and our results confirm that diabetes significantly increases the risk of SPMs. Family history of cancer is another recognized risk factor for multiple primary malignancies. Studies have shown that individuals carrying predisposition genes, such as BRCA1/2, or those with Lynch syndrome are more likely to develop SPMs and tend to be diagnosed at younger ages ( 33 – 36 ). In our study, although family history of cancer was more common among patients with SPMs, this association did not reach statistical significance. This may be due to the relatively limited sample size or the retrospective nature of family history documentation. Nevertheless, given the well-established role of hereditary predisposition, further prospective studies with larger cohorts are warranted. A particularly original contribution of our study was the significant association between MDS and the development of SPMs. This simple clinical scoring system—comprising alcohol consumption, diuretic and proton pump inhibitor use, and renal function—has been primarily studied in the context of cardiovascular mortality ( 37 ), In our cohort, however, a one-unit increase in MDS was associated with a 1.6-fold higher risk of developing SPMs. This finding is consistent with the established role of magnesium in DNA repair, oxidative stress regulation, and immune function Magnesium deficiency may promote pro-inflammatory and pro-oncogenic processes within the tumor microenvironment, thereby facilitating the development of secondary primaries. Supporting this, Gong et al. ( 18 ), in a large-scale NHANES analysis, reported that higher MDS was significantly associated with the prevalence of prostate cancer. Similarly, our results suggest that MDS is an independent risk factor for SPMs, underscoring its potential importance in cancer biology. It should also be noted that in our study, MDS was evaluated at the time of diagnosis and found to be associated with SPM development. However, magnesium deficiency is not limited to baseline assessment; it is also a clinically relevant issue during oncologic therapy. Platinum compounds, anti-EGFR inhibitors, and various chemotherapeutic agents are well known to induce hypomagnesemia, which may negatively affect treatment response, prognosis, and quality of life ( 38 ). For this reason, we believe that magnesium status should be regularly monitored not only during treatment but also in cancer survivors, and that patients with alcohol consumption or uncontrolled PPI use should be counseled regarding lifestyle modification and avoidance of unnecessary medications. Our survival analysis demonstrated that patients with SPMs had significantly longer survival compared with those without. Although this may initially appear paradoxical, similar findings have been reported in the literature. Amer (2014) and Coyte (2006), among others, emphasized that SPMs are more frequently seen in long-term survivors and may thus appear as a surrogate marker of favorable prognosis. Similarly, Wu et al. ( 39 ), in a SEER-based analysis of 241,805 patients with non-small cell lung cancer diagnosed between 2004 and 2014, showed that patients with SPMs had significantly higher 5-year survival compared with those with a single primary tumor (p = 0.029) ( 39 ). Our results are consistent with these findings, supporting the interpretation that SPMs predominantly occur in long-surviving patients. This study has several limitations. First, due to its retrospective design, the data are observational and potential confounders may not have been fully accounted for. Additionally, MDS was calculated using clinical parameters rather than biochemical magnesium levels. Given the retrospective, single-center design of this study, the findings should be interpreted with caution and warrant validation in larger, multicenter prospective cohorts. Nonetheless, the large sample size, long follow-up period, and detailed analysis of SPMs represent notable strengths of our study. In conclusion, this study demonstrated the incidence and associated factors of SPMs in patients with solid tumors and identified MDS as an independent predictor of SPM development. Our findings emphasize the importance of long-term follow-up in cancer survivors and suggest that MDS, as a simple and accessible biomarker, may be incorporated into clinical decision-making in the future. Conclusion Our study demonstrated that SPMs developed in 7.1% of patients with solid tumors, particularly among long-term survivors diagnosed at early stages. Former smoking, diabetes, and elevated MDS scores independently increased the risk of SPMs. While SPMs remain a major cause of mortality in cancer survivors ( 40 ), they should be interpreted as a marker of prolonged survival rather than improved prognosis. MDS, as an accessible clinical score, holds potential for integration into survivorship care to stratify patients at higher risk and to guide long-term monitoring. Abbreviations BMI : Body mass index CI : Confidence interval ECOG : Eastern Cooperative Oncology Group eGFR : Estimated glomerular filtration rate MDS : Magnesium Depletion Score NHANES : National Health and Nutrition Examination Survey OR : Odds ratio OS : Overall survival PPI : Proton pump inhibitor SPM : Second primary malignancy Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Ordu University Faculty of Medicine (Date: 02/06/2025; Decision No: 2025/212). The requirement for written informed consent was waived due to the retrospective design of the study. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to ethical issues but are available from the corresponding author, Dr. Neslihan Özyurt (email: [email protected] ), on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Authors’ contributions NÖ: study conception, data collection, analysis, manuscript drafting. MS: data collection, interpretation, critical revision. Both authors read and approved the final manuscript. Acknowledgements The authors sincerely thank all healthcare staff at Ordu University Training and Research Hospital for their invaluable support in patient care and data collection. We also express our gratitude to the patients and their families for their trust and contribution to this study. References Wood ME, Vogel V, Ng A, Foxhall L, Goodwin P, Travis LB. Second malignant neoplasms: assessment and strategies for risk reduction. J Clin Oncol. 2012;30(30):3734-45. Shah SA, Riaz U, Zahoor I, Jalil A, Zubair M. Carcinoma multiplex. J Coll Physicians Surg Pak. 2013;23(4):290-2. 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Lötscher J, i Líndez A-AM, Kirchhammer N, Cribioli E, Attianese GMPG, Trefny MP, et al. Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Cell. 2022;185(4):585-602. e29. Arnaud MJ. Update on the assessment of magnesium status. British Journal of Nutrition. 2008;99(S3):S24-S36. Friedrich RE. Primary and second primary cancer in 649 patients with malignancies of the maxillofacial region. Anticancer research. 2007;27(4A):1805-18. Amer MH. Multiple neoplasms, single primaries, and patient survival. Cancer Management and research. 2014:119-34. Wu H, Jiang Y, He M, Xu X, Jiang H. Multiple primary tumors in a patient with non‑small‑cell lung cancer harboring mutations in ERCC6 and LYL1: A case report. Oncology Letters. 2024;29(1):63. Huang X, Kong Y, Wu T, Meng Z, Kang M. Clinical and survival differences between second primary and first primary nasopharyngeal carcinoma in a retrospective study. 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The relationship between diabetes mellitus and cancers and its underlying mechanisms. Frontiers in Endocrinology. 2022;13:800995. Olatunde A, Nigam M, Singh RK, Panwar AS, Lasisi A, Alhumaydhi FA, et al. Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs. Cancer cell international. 2021;21(1):499. Molina-Montes E, Pérez-Nevot B, Pollán M, Sánchez-Cantalejo E, Espín J, Sánchez M-J. Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: a systematic review and meta-analysis. The Breast. 2014;23(6):721-42. Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. Journal of clinical oncology. 2010;28(5):893-901. Salati SA, Alkhezzi A, Elmuttalut MA, Memon MM, Memon M. Multiple Primary Malignant Tumours. Journal of Analytical Oncology. 2023;12:77-83. Power RF, Doherty DE, Parker I, Gallagher DJ, Lowery MA, Cadoo KA. Modifiable risk factors and risk of colorectal and endometrial cancers in Lynch syndrome: A systematic review and meta-analysis. JCO precision oncology. 2024;8:e2300196. Ye L, Zhang C, Duan Q, Shao Y, Zhou J. Association of magnesium depletion score with cardiovascular disease and its association with longitudinal mortality in patients with cardiovascular disease. Journal of the American Heart Association. 2023;12(18):e030077. Sambataro D, Scandurra G, Scarpello L, Gebbia V, Dominguez LJ, Valerio MR. A Practical Narrative Review on the Role of Magnesium in Cancer Therapy. Nutrients. 2025;17(14):2272. Wu B, Cui Y, Tian J, Song X, Hu P, Wei S. Effect of second primary cancer on the prognosis of patients with non-small cell lung cancer. Journal of Thoracic Disease. 2019;11(2):573. Oeffinger KC, Baxi SS, Friedman DN, Moskowitz CS, editors. Solid tumor second primary neoplasms: who is at risk, what can we do? Seminars in oncology ; 2013: Elsevier. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7491473","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":525791759,"identity":"302512e1-23f2-4187-8a48-d123f6dc690e","order_by":0,"name":"Neslihan Özyurt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYDCCAyCiQCIBSBqAmHJgwQcEtRggtBiDBRMIa2GAa0lsAJH4tPDdPnvw4Q8Dizz+2c0bH36puZM+P+zwQ6AtdnK6Ddi1SJ7LSzbmMZAolrhzrNhY5tiz3I230wyAWpKNzQ5g12JwhsdMGuiXxIYbOWbSEmyHczfOTgBpOZC4DbcW858/gFrmg7X8O5xuODv9AyEtZgxAhyVuAGqR/Nh2OEFeOge/LZJneIylQVo23kgrNmbsO2y4QTqn4ECCAW6/8J3hMfz4o6Iucd6N5I0Pf3w7LC8/O33zhw8VdnK4tKAAZh6QU8EqDYhQDgKMP4CEfAORqkfBKBgFo2DEAAD+PWaUIzcWBAAAAABJRU5ErkJggg==","orcid":"","institution":"Ordu University Training and Research Hospital","correspondingAuthor":true,"prefix":"","firstName":"Neslihan","middleName":"","lastName":"Özyurt","suffix":""},{"id":525791763,"identity":"3aad9eaa-112e-4626-967f-5336c6b293b3","order_by":1,"name":"Müge Sönmez","email":"","orcid":"","institution":"Ordu University Training and Research 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16:38:01","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":163072,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7491473/v1/91f4f44c2db79ebc80a2f88f.html"},{"id":93062652,"identity":"09993299-749c-4861-bccf-44004e15bd16","added_by":"auto","created_at":"2025-10-08 16:38:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":81491,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of second primary malignancy (SPM) and related characteristics.\u003cbr\u003e\n(A) Frequency of SPM among patients with solid tumors.\u003cbr\u003e\n(B) Distribution of SPM according to tumor stage at diagnosis.\u003cbr\u003e\n(C) Distribution of single, metachronous, and synchronous tumors.\u003c/p\u003e","description":"","filename":"Figure1BMC.png","url":"https://assets-eu.researchsquare.com/files/rs-7491473/v1/21392df74bd2c0994f759c86.png"},{"id":93062589,"identity":"c9114553-7569-42c1-bd31-f8105d0c7204","added_by":"auto","created_at":"2025-10-08 16:38:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":76902,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier survival curves demonstrating the impact of second primary malignancy (SPM) on overall survival (OS).\u003c/p\u003e","description":"","filename":"Figure2BMC.png","url":"https://assets-eu.researchsquare.com/files/rs-7491473/v1/c703d43eb1c289fe6aecb7b4.png"},{"id":96183306,"identity":"f1e4da91-acfb-4330-ad0a-f97dfe764beb","added_by":"auto","created_at":"2025-11-18 12:54:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1409897,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7491473/v1/80450055-6b18-4bd3-8025-754f96008dc4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Second Primary Malignancies in Patients with Solid Tumors: The Prognostic Role of Magnesium Depletion Score","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAdvances in cancer therapies have significantly prolonged survival in many patients (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). While this represents a major achievement in oncology, it has also introduced new clinical challenges. One such issue is the occurrence of second primary malignancies (SPMs), which are detected during the treatment or follow-up of index cancer cases (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSPMs are defined as new malignant neoplasms that develop independently of the initial primary tumor. Epidemiological studies describe SPMs as tumors arising in different anatomical sites and/or belonging to different histological or morphological subgroups ( 3). Although their diagnostic criteria and biological mechanisms have been studied for decades, clinical management remains challenging. The reported incidence of SPMs varies between 0.7% and 11.7% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) and this rate increases with longer follow-up durations (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The risk also differs by primary cancer type, ranging from about 1% in primary liver cancer to as high as 16% in primary bladder cancer (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMultiple factors contribute to the development of SPMs. Genetic predisposition, through mutations in BRCA1/2, p16/CDKN2A, and DNA repair genes, can increase susceptibility (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Lifestyle factors, particularly smoking and alcohol consumption, contribute via cumulative carcinogenic exposure (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Prior treatments such as radiotherapy and chemotherapy further elevate the risk by inducing free radical production, cytokine-mediated inflammatory responses, and telomere damage (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Comorbidities such as diabetes, obesity (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), and chronic inflammatory conditions, as well as metabolic alterations such as magnesium deficiency, also play a role. Environmental and occupational exposures (e.g., radon, asbestos industry) and oncogenic infections (EBV, HPV, \u003cem\u003eHelicobacter pylori\u003c/em\u003e) further contribute to SPM pathogenesis (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Altogether, these factors represent a multidimensional network that shapes the individual patient\u0026rsquo;s risk profile.\u003c/p\u003e\u003cp\u003eWithin this network, clinically accessible biomarkers have attracted increasing attention. Among them, magnesium (Mg\u0026sup2;⁺) has emerged as a potential factor of interest in cancer development and prognosis (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Magnesium is essential for numerous physiological processes including neuronal transmission, muscle contraction, cardiovascular function, energy metabolism, and protein and nucleic acid synthesis, thereby maintaining cellular homeostasis (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Its absorption and excretion can be influenced by alcohol consumption (reducing intake and increasing renal excretion), long-term proton pump inhibitor (PPI) therapy (reducing TRPM6 activity and absorption), and diuretic use (enhancing renal excretion) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Renal function also plays a key role in regulating magnesium filtration, reabsorption, and excretion (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The Magnesium Depletion Score (MDS) combines these clinical parameters\u0026mdash;alcohol intake, PPI and diuretic use, and renal function\u0026mdash;into a simple scoring system to assess magnesium status. By integrating such factors, MDS has been proposed as a useful biomarker for predicting disease risk associated with magnesium deficiency and may be relevant in the early identification of conditions such as cancer (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMagnesium deficiency or dysregulation has been associated with a range of diseases, including cardiovascular disease, diabetes, hypertension, and osteoporosis (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). More recently, its role in tumor development has gained attention, as magnesium has been shown to regulate cytotoxic T lymphocytes (CD8\u0026thinsp;+\u0026thinsp;T cells) and influence antitumor immunity (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), as well as to maintain genomic stability and regulate apoptosis (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMagnesium status can be assessed by serum magnesium concentration, magnesium tolerance testing, or MDS. Serum magnesium, however, is tightly regulated and may not accurately reflect total body magnesium deficiency. It is also dynamic and influenced by hydration, laboratory methods, and circadian variations. Because the majority of magnesium is stored in bone and intracellular compartments, serum levels alone are insufficient to reflect true magnesium status. The magnesium tolerance test is costly and not feasible in routine practice (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In contrast, MDS provides a practical, clinically applicable tool that more reliably reflects systemic magnesium status.\u003c/p\u003e\u003cp\u003eMDS incorporates simple parameters such as diabetes, hypertension, and diuretic use, which contribute to magnesium loss, and has been associated with cardiovascular disease and all-cause mortality. However, its association with cancer remains poorly investigated (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn this study, we aimed to investigate the incidence of SPMs in a large cohort of patients with solid tumors and to evaluate associated clinical and demographic factors, as well as the prognostic role of MDS. Our goal was to raise clinical awareness and to highlight potential early warning biomarkers in the management of cancer survivors.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e This retrospective descriptive cohort study was conducted on 1,027 patients with solid tumors who were followed and treated at the Medical Oncology Clinic of Ordu University Training and Research Hospital between 2010 and 2023. Eligible patients were those with histopathologically confirmed solid malignancies, who had been followed for at least 6 months, and whose clinical and laboratory data were fully available.\u003c/p\u003e\u003cp\u003eThe definition of second primary malignancy (SPM) was based on the Warren and Gates criteria (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Accordingly, patients with two or more malignant tumors were included if each tumor exhibited malignant histology, developed in distinct anatomical sites, and could not be considered as a metastasis or recurrence of the index tumor. In line with the literature, SPMs were further classified as synchronous or metachronous. Synchronous tumors were defined as those diagnosed within 6 months of the initial primary tumor, whereas metachronous tumors were those diagnosed more than 6 months after the initial diagnosis (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eData collected from patient records included demographic variables (age, sex, occupation, place of residence), clinical characteristics (BMI, ECOG performance status, comorbidities), lifestyle factors (smoking history), laboratory findings (components of the Magnesium Depletion Score [MDS]), primary tumor site, stage, family history, and survival outcomes. All data were anonymized to ensure patient confidentiality. The study was approved by the Ethics Committee of Ordu University Faculty of Medicine (Date: June 2, 2025; Decision No: 2025/212). Written informed consent was waived due to the retrospective design of the study.\u003c/p\u003e\u003cp\u003eThe MDS is a simple tool designed to estimate magnesium deficiency and was calculated by summing four risk factors:\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eDiuretic use\u003c/b\u003e: 1 point for current use, 0 points otherwise.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eProton pump inhibitor (PPI) use\u003c/b\u003e: 1 point for current use, 0 points otherwise.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eRenal function\u003c/b\u003e: eGFR\u0026thinsp;\u0026ge;\u0026thinsp;90 mL/min/1.73 m\u0026sup2; = 0 points; eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 but \u0026ge;\u0026thinsp;60\u0026thinsp;=\u0026thinsp;1 point; eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60\u0026thinsp;=\u0026thinsp;2 points.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eAlcohol consumption\u003c/b\u003e: Defined as \u0026gt;\u0026thinsp;2 drinks/day in men or \u0026gt;\u0026thinsp;1 drink/day in women, scored as 1 point; all other categories (never, rare, mild, or moderate consumption) scored as 0.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn this cohort, the MDS was calculated as described above, with scores ranging from 0 to 5.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAll data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Demographic and clinical characteristics, tumor and pathological findings, diagnostic and surgical procedures, treatment outcomes, and survival data of patients with solid tumors were summarized. Categorical variables were presented as frequencies (n) and percentages (%), while continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median, minimum, and maximum values.\u003c/p\u003e\u003cp\u003eThe normality of data distribution was assessed using skewness and kurtosis coefficients, with values within the range of \u0026plusmn;\u0026thinsp;1.96 considered to indicate normal distribution. Comparisons between groups according to the presence of second primary malignancy (SPM) were performed using the Chi-square test for categorical variables. Post-hoc comparisons were conducted with the Bonferroni test, and groups showing significant differences were labeled with distinct superscript letters. For continuous variables, comparisons between groups were performed using either the Independent Samples t-test or the Mann\u0026ndash;Whitney U test, depending on data distribution.\u003c/p\u003e\u003cp\u003eSurvival analyses were performed using the Kaplan\u0026ndash;Meier method, and differences between groups were assessed with the log-rank (Mantel\u0026ndash;Cox) test. Univariable logistic regression analysis was used to identify factors associated with the presence of SPM. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant, with p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 regarded as highly significant.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eA total of 1,027 patients with solid tumors were included in the study. Of these, 56.2% were male and 43.8% female, with a mean age at diagnosis of 62.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9 years. No significant differences were observed between patients with and without SPM in terms of age and sex. Similarly, no significant differences were found regarding place of residence, body mass index (BMI), or performance status. The mean follow-up time was 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 years (range: 0\u0026ndash;30 years). While 92.9% of patients did not develop SPM, 7.1% (n\u0026thinsp;=\u0026thinsp;73) were diagnosed with an SPM. Among these, 65 cases (6.3%) were metachronous and 8 cases (0.8%) synchronous. Of the 73 patients with SPM, 71 (97.3%) developed a single second primary, whereas two and three distinct SPMs were identified in one patient each (1.4%).\u003c/p\u003e\u003cp\u003eThe most common SPM sites were breast (n\u0026thinsp;=\u0026thinsp;13, 17.8%), prostate (n\u0026thinsp;=\u0026thinsp;11, 15.1%), colorectal (n\u0026thinsp;=\u0026thinsp;9, 12.3%), and bladder (n\u0026thinsp;=\u0026thinsp;9, 12.3%). Less frequent SPMs included lung (n\u0026thinsp;=\u0026thinsp;6, 8.2%), hematologic malignancies (n\u0026thinsp;=\u0026thinsp;7, 9.6%), skin (n\u0026thinsp;=\u0026thinsp;3, 4.1%), thyroid (n\u0026thinsp;=\u0026thinsp;3, 4.1%), head and neck (n\u0026thinsp;=\u0026thinsp;3, 4.1%), and other solid tumors. The distribution of SPMs by tumor type and stage is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here)\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eRegarding lifestyle and comorbidity factors, the proportion of former smokers was significantly higher among patients with SPM compared to those without (39.7% vs. 23.7%; p\u0026thinsp;=\u0026thinsp;0.009). Although patients with SPM had higher cumulative smoking exposure (pack-years: 50.2\u0026thinsp;\u0026plusmn;\u0026thinsp;24.1 vs. 46.8\u0026thinsp;\u0026plusmn;\u0026thinsp;32.7), this difference only approached statistical significance (p\u0026thinsp;=\u0026thinsp;0.053). Diabetes was also more prevalent in patients with SPM (27.4% vs. 17.5%; p\u0026thinsp;=\u0026thinsp;0.035). Mean MDS scores were significantly higher in patients with SPM than in those without (1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84 vs. 1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The distribution of demographic, clinical, and lifestyle variables according to SPM status is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of clinical and demographic characteristics according to the presence of second primary malignancy (SPM)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c8\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003ePresence of SPM\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e\u003cem\u003eTotal (n:1027)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003eNo SPM (n:954)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003eSPM (n:73)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e577\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e536\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e56.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e450\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e418\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge at\u003c/p\u003e\u003cp\u003ediagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;65 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e554\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e511\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e53.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e58.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.447\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;65 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e473\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e46.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e41.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eOccupation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHousewife\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e432\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e401\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e42.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.715\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFarmer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e182\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWorker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e214\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e195\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTradesman\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOfficer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFisherman\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnemployed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eResidence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUrban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e767\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e709\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e74.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e79.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e260\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e245\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e20.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBlood group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 Positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e118\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e112a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.001**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA Positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e144a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB Positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e52a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAB Positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 Negative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA Negative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e17a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB Negative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e627\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e61.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e592a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e62.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e35b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSmoking status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e430\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e404a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e26a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e35.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.009*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e342\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e324a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e24.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFormer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e255\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e226a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e29b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e39.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnderweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.950\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e304\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e284\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e27.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverweight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e382\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e355\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e37.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eObese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e284\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e31.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eECOG score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e387\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e357\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e41.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.740\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e565\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e528\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e55.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e50.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e840\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e81.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e787a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e82.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e72.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.035*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e187\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e167a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e27.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e938\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e91.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e869\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e91.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e94.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e627\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e61.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e590\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e61.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e50.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e364\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e49.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCoronary artery disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e873\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e813\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e85.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e82.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.597\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge (years)\u003csup\u003et\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e62.79\u0026thinsp;\u0026plusmn;\u0026thinsp;12.85\u003c/p\u003e\u003cp\u003e63 (17\u0026ndash;95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e62.77\u0026thinsp;\u0026plusmn;\u0026thinsp;12.91\u003c/p\u003e\u003cp\u003e64 (17\u0026ndash;95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e63.05\u0026thinsp;\u0026plusmn;\u0026thinsp;12.11\u003c/p\u003e\u003cp\u003e62 (32\u0026ndash;86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.855\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSmoking (pack-years)\u003csup\u003ez\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e47.08\u0026thinsp;\u0026plusmn;\u0026thinsp;32.12\u003c/p\u003e\u003cp\u003e40 (3\u0026ndash;435)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e46.81\u0026thinsp;\u0026plusmn;\u0026thinsp;32.72\u003c/p\u003e\u003cp\u003e40 (3\u0026ndash;435)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e50.23\u0026thinsp;\u0026plusmn;\u0026thinsp;24.13\u003c/p\u003e\u003cp\u003e45 (15\u0026ndash;140)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBMI\u003csup\u003ez\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e27.21\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\u003cp\u003e27 (15\u0026ndash;53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e27.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.41\u003c/p\u003e\u003cp\u003e27 (15\u0026ndash;53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e27.07\u0026thinsp;\u0026plusmn;\u0026thinsp;5.39\u003c/p\u003e\u003cp\u003e27 (16\u0026ndash;52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.989\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eMDS score\u003csup\u003et\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\u003cp\u003e1 (0\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e\u003cp\u003e1 (0\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e1.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e\u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eSPM: second primary malignancy; BMI: body mass index; MDS: magnesium depletion score; COPD: chronic obstructive pulmonary disease. S.D.: Standard deviation. Med.: Median. Min.: Minimum. Max.: Maximum.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. *\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.01. χ\u0026sup2;: Chi-square test (categorical variables). t: Independent Samples t-test. z: Mann\u0026ndash;Whitney U test. Superscript letters indicate significant differences between groups.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe most common primary tumor types were lung (23.8%), breast (22.0%), gastric (7.9%), and colorectal (7.4%). Compared with patients without SPM, those with SPM more frequently had bladder, prostate, and renal cancers as their initial primary tumors (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Stage distribution also showed a striking difference: 28.8% of patients with SPM were diagnosed at stage I compared with only 11.4% in patients without SPM (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Family history of cancer was more frequent among patients with SPM (67.1%), although this difference did not reach statistical significance (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No significant associations were found regarding cancer history in first-, second-, or third-degree relatives (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The distribution of diagnosis, stage, family history, and survival characteristics according to SPM status is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of diagnosis. stage. family history. and survival characteristics according to the presence of second primary malignancy (SPM).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c8\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003ePresence of SPM\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e\u003cem\u003eTotal (n:1027)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003eNo SPM (n:954)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003eSPM (n:73)\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDiagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLung\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e244\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e229a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e20.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.006*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBreast\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e226\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e211a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e20.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStomach\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e78a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColon\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e69a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eProstate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e59a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRectum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e58a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBrain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e44a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUterus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBladder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e25a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOvary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThymoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePancreas\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eKidney\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCervix\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGallbladder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSarcoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTestis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSkin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMalignant melanoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNET\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLarynx\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAppendix\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEsophagus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eParotid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThyroid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eStage at diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e109a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e28.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e151\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e139a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e370\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e351a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e36.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e376\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e355a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e28.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily history\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e429\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e32.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.140\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e598\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e549\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e67.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFirst-degree relative with cancer ***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e501\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e458\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e83.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e87.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.558\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSecond-/third-degree relative with cancer***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e201\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e189\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.210\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e397\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e360\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e75.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3 relatives with cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.298\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e987\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e96.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e919\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e96.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e93.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e371a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e40b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e54.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.011*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDeceased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e616\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e583a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e61.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e45.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003eMean.\u0026plusmn;S.D.\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMed. (Min.-Max.)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of first-degree relatives with cancer (Mann\u0026ndash;Whitney U test)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e\u003cp\u003e1 (0\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003cp\u003e1 (0\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e\u003cp\u003e1 (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.366\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eOverall survival (years) (Mann\u0026ndash;Whitney U test)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13\u003c/p\u003e\u003cp\u003e1.9 (0.03\u0026ndash;24.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e2.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e\u003cp\u003e1.81 (0.03\u0026ndash;24.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e4.84\u0026thinsp;\u0026plusmn;\u0026thinsp;5.34\u003c/p\u003e\u003cp\u003e2.8 (0.16\u0026ndash;22.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003eSPM: second primary malignancy; OS: overall survival; NET: neuroendocrine tumor. S.D: Standard deviation. Med.: Median. Min.: Minimum. Max.: Maximum.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **p\u0026thinsp;\u0026lt;\u0026thinsp;0.01. χ\u0026sup2;: Chi-square test (categorical variables), z: Mann\u0026ndash;Whitney U test (continuous variables). Superscript letters indicate significant differences between groups. *Analysis performed on 598 patients.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn survival analysis, overall survival was significantly longer in patients with SPM. Median OS was 2.52 years in patients without SPM, compared with 7.89 years in those with SPM (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Kaplan\u0026ndash;Meier survival curves clearly demonstrated this difference (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e here)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eLogistic regression analysis identified former smoking (OR\u0026thinsp;=\u0026thinsp;1.99; 95% CI: 1.15\u0026ndash;3.47; p\u0026thinsp;=\u0026thinsp;0.015), diabetes (OR\u0026thinsp;=\u0026thinsp;1.78; 95% CI: 1.04\u0026ndash;3.05; p\u0026thinsp;=\u0026thinsp;0.037), and each one-unit increase in MDS score (OR\u0026thinsp;=\u0026thinsp;1.59; 95% CI: 1.23\u0026ndash;2.07; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as independent risk factors for SPM. Furthermore, advanced stage at initial diagnosis was inversely associated with SPM development: patients with stage II, III, or IV disease had a significantly lower risk compared with those diagnosed at stage I (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e here) MDS was strongly associated with SPM presence (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; R\u0026sup2;=0.029), with each unit increase in the score conferring an approximately 1.6-fold higher risk of developing an SPM.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eResults of univariate logistic regression analysis for potential predictors of second primary malignancy (SPM)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePredictor variable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003eB\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eS.E.\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eExp(B)/\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eOdds ratio\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e95% CI for Exp(B)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003eR\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.010**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.021\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking status (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.641\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking status (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.015*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes (DT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.037*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension (HT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.061\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMDS score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage at diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage at diagnosis (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.036*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage at diagnosis (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage at diagnosis (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.000**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. ** p\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Exp(B): Odds Ratio (OR); R\u0026sup2;: Coefficient of determination.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn this study, conducted on a large cohort of patients with solid tumors followed at the Medical Oncology Clinic of Ordu University Training and Research Hospital, the incidence of SPMs was found to be 7.1%. This rate falls within the range of 2\u0026ndash;17% previously reported in the literature (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmer et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) reported in a large series evaluating multiple primary malignancies that breast, prostate, and colorectal cancers were the most frequent tumors, both as first and second primaries. Similarly, in our cohort, breast, prostate, and colorectal cancers were among the most common SPMs, with bladder cancer also observed at a notable frequency. In contrast, their study emphasized that poor-prognosis tumors such as pancreatic and hepatocellular carcinoma rarely developed SPMs.\u003c/p\u003e\u003cp\u003eOur findings also showed that patients with SPMs were diagnosed at earlier stages and had significantly longer overall survival. This suggests that SPMs are more likely to arise in patients who survive longer and remain under regular surveillance. Indeed, longer survival associated with earlier-stage diagnosis may provide sufficient time for the development of additional malignancies. Similar observations have been reported in the literature, where SPMs were found to occur more frequently among patients diagnosed at early stages (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) and in populations with extended survival (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). These findings support our conclusion that SPMs are particularly common in patients with early-stage disease and longer survival.\u003c/p\u003e\u003cp\u003eOne of the novel findings of our study was the identification of \u0026ldquo;former smoking\u0026rdquo; as an independent risk factor for SPM development. Similarly, previous studies have reported that former smokers have approximately a 1.4-fold higher risk of developing SPMs compared with never-smokers (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Data from the American Cancer Society also demonstrate that while the risk of first and second primaries in former smokers is lower than in current smokers, it remains significantly higher compared with never-smokers (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). This observation may reflect the cumulative carcinogenic effect of smoking, while also being attributable to the fact that patients who quit smoking often belong to longer-surviving cohorts.\u003c/p\u003e\u003cp\u003eDiabetes was another independent risk factor identified in our study. Chronic inflammation, oxidative stress, and metabolic dysfunction are well-established mechanisms through which diabetes may predispose to cancer development. This mechanistic link has been clearly demonstrated in the literature (\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), and our results confirm that diabetes significantly increases the risk of SPMs.\u003c/p\u003e\u003cp\u003eFamily history of cancer is another recognized risk factor for multiple primary malignancies. Studies have shown that individuals carrying predisposition genes, such as BRCA1/2, or those with Lynch syndrome are more likely to develop SPMs and tend to be diagnosed at younger ages (\u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). In our study, although family history of cancer was more common among patients with SPMs, this association did not reach statistical significance. This may be due to the relatively limited sample size or the retrospective nature of family history documentation. Nevertheless, given the well-established role of hereditary predisposition, further prospective studies with larger cohorts are warranted.\u003c/p\u003e\u003cp\u003eA particularly original contribution of our study was the significant association between MDS and the development of SPMs. This simple clinical scoring system\u0026mdash;comprising alcohol consumption, diuretic and proton pump inhibitor use, and renal function\u0026mdash;has been primarily studied in the context of cardiovascular mortality (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), In our cohort, however, a one-unit increase in MDS was associated with a 1.6-fold higher risk of developing SPMs. This finding is consistent with the established role of magnesium in DNA repair, oxidative stress regulation, and immune function Magnesium deficiency may promote pro-inflammatory and pro-oncogenic processes within the tumor microenvironment, thereby facilitating the development of secondary primaries. Supporting this, Gong et al. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), in a large-scale NHANES analysis, reported that higher MDS was significantly associated with the prevalence of prostate cancer. Similarly, our results suggest that MDS is an independent risk factor for SPMs, underscoring its potential importance in cancer biology.\u003c/p\u003e\u003cp\u003eIt should also be noted that in our study, MDS was evaluated at the time of diagnosis and found to be associated with SPM development. However, magnesium deficiency is not limited to baseline assessment; it is also a clinically relevant issue during oncologic therapy. Platinum compounds, anti-EGFR inhibitors, and various chemotherapeutic agents are well known to induce hypomagnesemia, which may negatively affect treatment response, prognosis, and quality of life (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). For this reason, we believe that magnesium status should be regularly monitored not only during treatment but also in cancer survivors, and that patients with alcohol consumption or uncontrolled PPI use should be counseled regarding lifestyle modification and avoidance of unnecessary medications.\u003c/p\u003e\u003cp\u003eOur survival analysis demonstrated that patients with SPMs had significantly longer survival compared with those without. Although this may initially appear paradoxical, similar findings have been reported in the literature. Amer (2014) and Coyte (2006), among others, emphasized that SPMs are more frequently seen in long-term survivors and may thus appear as a surrogate marker of favorable prognosis. Similarly, Wu et al. (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), in a SEER-based analysis of 241,805 patients with non-small cell lung cancer diagnosed between 2004 and 2014, showed that patients with SPMs had significantly higher 5-year survival compared with those with a single primary tumor (p\u0026thinsp;=\u0026thinsp;0.029) (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). Our results are consistent with these findings, supporting the interpretation that SPMs predominantly occur in long-surviving patients.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, due to its retrospective design, the data are observational and potential confounders may not have been fully accounted for. Additionally, MDS was calculated using clinical parameters rather than biochemical magnesium levels. Given the retrospective, single-center design of this study, the findings should be interpreted with caution and warrant validation in larger, multicenter prospective cohorts. Nonetheless, the large sample size, long follow-up period, and detailed analysis of SPMs represent notable strengths of our study.\u003c/p\u003e\u003cp\u003eIn conclusion, this study demonstrated the incidence and associated factors of SPMs in patients with solid tumors and identified MDS as an independent predictor of SPM development. Our findings emphasize the importance of long-term follow-up in cancer survivors and suggest that MDS, as a simple and accessible biomarker, may be incorporated into clinical decision-making in the future.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eOur study demonstrated that SPMs developed in 7.1% of patients with solid tumors, particularly among long-term survivors diagnosed at early stages. Former smoking, diabetes, and elevated MDS scores independently increased the risk of SPMs. While SPMs remain a major cause of mortality in cancer survivors (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), they should be interpreted as a marker of prolonged survival rather than improved prognosis. MDS, as an accessible clinical score, holds potential for integration into survivorship care to stratify patients at higher risk and to guide long-term monitoring.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBMI\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Body mass index\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCI\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Confidence interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eECOG\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Eastern Cooperative Oncology Group\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eeGFR\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Estimated glomerular filtration rate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMDS\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Magnesium Depletion Score\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eNHANES\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eNational Health and Nutrition Examination Survey\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOR\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Odds ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eOS\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Overall survival\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePPI\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Proton pump inhibitor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSPM\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Second primary malignancy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u003cbr\u003e\u003c/em\u003eThis study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Ordu University Faculty of Medicine (Date: 02/06/2025; Decision No: 2025/212). The requirement for written informed consent was waived due to the retrospective design of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u003cbr\u003e\u003c/em\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u003cbr\u003e\u003c/em\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to ethical issues but are available from the corresponding author, Dr. Neslihan \u0026Ouml;zyurt (email: [email protected]), on reasonable request.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u003cbr\u003e\u003c/em\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN\u0026Ouml;: study conception, data collection, analysis, manuscript drafting. MS: data collection, interpretation, critical revision. Both authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u003cbr\u003e\u003c/em\u003eThe authors sincerely thank all healthcare staff at Ordu University Training and Research Hospital for their invaluable support in patient care and data collection. We also express our gratitude to the patients and their families for their trust and contribution to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWood ME, Vogel V, Ng A, Foxhall L, Goodwin P, Travis LB. Second malignant neoplasms: assessment and strategies for risk reduction. \u003cem\u003eJ Clin Oncol.\u003c/em\u003e 2012;30(30):3734-45.\u003c/li\u003e\n\u003cli\u003eShah SA, Riaz U, Zahoor I, Jalil A, Zubair M. 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Solid tumor second primary neoplasms: who is at risk, what can we do? \u003cem\u003eSeminars in oncology\u003c/em\u003e; 2013: Elsevier.\u003c/li\u003e\n\u003c/ol\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":"Second primary neoplasms, Neoplasms, Magnesium depletion score, Prognosis, Survival analysis","lastPublishedDoi":"10.21203/rs.3.rs-7491473/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7491473/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eSecond primary malignancies (SPMs) have become an increasingly recognized clinical entity in modern oncology as advances in treatment prolong survival. This study aimed to investigate the incidence of SPMs in patients with solid tumors, to evaluate associated demographic and clinical factors, and to examine the potential prognostic role of the Magnesium Depletion Score (MDS).\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eThis retrospective cohort study included 1,027 patients diagnosed with solid tumors between 2010 and 2023, with complete follow-up data available. Patients were stratified according to the presence of SPM. Demographic, clinical, and lifestyle variables were compared. Survival analyses were performed using the Kaplan\u0026ndash;Meier method, and risk factors associated with SPM were assessed using univariable logistic regression.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eSPMs were identified in 7.1% of patients. Patients with SPMs were more frequently diagnosed at earlier stages (28.8% stage I) and had significantly longer overall survival compared to those without SPMs (median OS: 7.89 vs. 2.52 years; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Logistic regression analysis revealed that former smoking (OR\u0026thinsp;=\u0026thinsp;1.99), presence of diabetes (OR\u0026thinsp;=\u0026thinsp;1.78), and each one-unit increase in MDS (OR\u0026thinsp;=\u0026thinsp;1.59) were significantly associated with SPM development. Advanced stage at initial diagnosis was inversely associated with the likelihood of SPM occurrence.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eSPMs are more commonly observed in patients diagnosed at an earlier stage and with longer survival. MDS may serve as a potential biomarker for predicting SPM risk. These findings highlight the importance of long-term follow-up and metabolic assessment in cancer survivors.\u003c/p\u003e","manuscriptTitle":"Second Primary Malignancies in Patients with Solid Tumors: The Prognostic Role of Magnesium Depletion Score","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 15:59:40","doi":"10.21203/rs.3.rs-7491473/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":"c842e3bf-69b0-44a9-9fe0-da1e31340724","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-18T12:53:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 15:59:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7491473","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7491473","identity":"rs-7491473","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}