Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer

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Despite advancements in treatment, the disease remains a leading cause of cancer-related deaths among women globally. Chemoradiation utilizing cisplatin has been the cornerstone therapy for locally advanced cervical cancer. Prognostic biomarkers, including hematological parameters, have emerged as valuable tools in guiding treatment decisions and predicting outcomes. Methodology Data from patients treated between January 2021 and June 2022 were analyzed. Demographic information, histopathology, pre-treatment blood parameters, treatment details, and response assessments were collected. The parameters assessed included hemoglobin levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and eosinophil albumin ratio (EAR). Receiver operating characteristic (ROC) curve analysis was conducted to determine optimal cut-off values for these biomarkers. Results Of the 140 patients included, the majority had squamous cell carcinoma (92%) and were at stage II or III. Complete response to treatment was observed in 86.4% of patients. Non-responders demonstrated significantly higher levels of hemoglobin, NLR, and EAR, along with lower PNI levels compared to responders. ROC analysis revealed cut-off values for hemoglobin (< 9.5), NLR ( 289.26), PNI (< 37.67), and EAR (< 49.63) associated with treatment response. Conclusion The study highlights the potential utility of pre-treatment blood parameters as predictive markers for treatment response in locally advanced cervical cancer. Lower hemoglobin, higher NLR, and EAR, along with reduced PNI, were associated with poorer treatment outcomes. Integration of these biomarkers into clinical practice could aid in treatment planning and improve patient outcomes. Further validation and prospective studies are warranted to establish the role of these biomarkers in guiding personalized treatment strategies for cervical cancer patients. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-118/v1", "name": "Pre-treatment blood parameters as an economical predictive marker..." } } ] } Home Browse Pre-treatment blood parameters as an economical predictive marker... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Krishna A, N V, Shada F et al. Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.12688/f1000research.160308.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] Abhishek Krishna https://orcid.org/0000-0002-9318-7024 1 , Vishnumaya N 1 , Fathima Shada 1 , [...] Pooja MS 1 , Dilson Lobo https://orcid.org/0000-0002-9222-863X 1 , Athiyamaan MS https://orcid.org/0000-0003-4691-9728 1 , Challapalli Srinivas 1 , Sourjya Banerjee 1 , Johan Sunny 1 , Paul Simon 1 Abhishek Krishna https://orcid.org/0000-0002-9318-7024 1 , Vishnumaya N 1 , [...] Fathima Shada 1 , Pooja MS 1 , Dilson Lobo https://orcid.org/0000-0002-9222-863X 1 , Athiyamaan MS https://orcid.org/0000-0003-4691-9728 1 , Challapalli Srinivas 1 , Sourjya Banerjee 1 , Johan Sunny 1 , Paul Simon 1 PUBLISHED 21 Jan 2025 Author details Author details 1 Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, India Abhishek Krishna Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation Vishnumaya N Roles: Data Curation, Resources, Validation, Writing – Review & Editing Fathima Shada Roles: Data Curation, Formal Analysis, Investigation, Writing – Review & Editing Pooja MS Roles: Investigation, Methodology, Validation, Writing – Review & Editing Dilson Lobo Roles: Conceptualization, Investigation, Methodology, Validation, Writing – Original Draft Preparation Athiyamaan MS Roles: Data Curation, Investigation, Visualization, Writing – Review & Editing Challapalli Srinivas Roles: Resources, Writing – Review & Editing Sourjya Banerjee Roles: Investigation Johan Sunny Roles: Investigation, Validation Paul Simon Roles: Supervision OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. Abstract Background Cervical cancer poses a significant public health challenge, particularly in low and middle-income countries. Despite advancements in treatment, the disease remains a leading cause of cancer-related deaths among women globally. Chemoradiation utilizing cisplatin has been the cornerstone therapy for locally advanced cervical cancer. Prognostic biomarkers, including hematological parameters, have emerged as valuable tools in guiding treatment decisions and predicting outcomes. Methodology Data from patients treated between January 2021 and June 2022 were analyzed. Demographic information, histopathology, pre-treatment blood parameters, treatment details, and response assessments were collected. The parameters assessed included hemoglobin levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and eosinophil albumin ratio (EAR). Receiver operating characteristic (ROC) curve analysis was conducted to determine optimal cut-off values for these biomarkers. Results Of the 140 patients included, the majority had squamous cell carcinoma (92%) and were at stage II or III. Complete response to treatment was observed in 86.4% of patients. Non-responders demonstrated significantly higher levels of hemoglobin, NLR, and EAR, along with lower PNI levels compared to responders. ROC analysis revealed cut-off values for hemoglobin (< 9.5), NLR ( 289.26), PNI (< 37.67), and EAR (< 49.63) associated with treatment response. Conclusion The study highlights the potential utility of pre-treatment blood parameters as predictive markers for treatment response in locally advanced cervical cancer. Lower hemoglobin, higher NLR, and EAR, along with reduced PNI, were associated with poorer treatment outcomes. Integration of these biomarkers into clinical practice could aid in treatment planning and improve patient outcomes. Further validation and prospective studies are warranted to establish the role of these biomarkers in guiding personalized treatment strategies for cervical cancer patients. READ ALL READ LESS Keywords Keywords: Cervical cancer, chemoradiation, prognostic markers, pre-treatment blood parameters, treatment response. Corresponding Author(s) Dilson Lobo ( [email protected] ) Close Corresponding author: Dilson Lobo Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Krishna A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Krishna A, N V, Shada F et al. Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.12688/f1000research.160308.1 ) First published: 21 Jan 2025, 14 :118 ( https://doi.org/10.12688/f1000research.160308.1 ) Latest published: 15 Apr 2025, 14 :118 ( https://doi.org/10.12688/f1000research.160308.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction Cervical cancer continues to be a substantial public health problem, especially in low and middle income countries with inadequate healthcare resources. According to the GLOBOCAN 2020 report, there were 604,000 new cases of cervical cancer worldwide in 2020, with approximately 90% of deaths occurring in countries belonging to low and lower middle income category. 1 Cervical carcinoma is the 9 th most commonly diagnosed cancer in globally in women and the second most commonly diagnosed malignancy in women in India. 1 , 2 In India, the majority of patients (80.9%) present at an advanced stage. 3 Concurrent chemoradiation (CCRT) utilizing cisplatin has been the gold standard therapeutic regimen for locally advanced cervical cancer over the last two decades. 4 Prognostic markers are pivotal in cancer management, guiding treatment decisions and aiding in the prediction of disease outcomes, thus profoundly impacting patient care and therapeutic strategies. In recent studies, various prognostic and predictive biomarkers have been identified in cervical cancer, and these biomarkers have improved the understanding of the disease and refining the treatment strategies. 5 Systemic inflammation has shown to play a critical role in cancer development and progression. IN nervical malignancy, increased systemic inflammation correlates with adverse clinical prognoses, attributed to cellular proliferation, neovascularization, resistance to therapy, and metastatic dissemination. 6 Simple hematological indicators such as neutrophil counts, lymphocyte counts, and platelet counts, as well as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum albumin, and their combined values, can be used to indirectly identify systemic inflammation. Several studies have reported that low hemoglobin, high NLR and PLR and low Prognostic Nutritional Index correspond to an unfavorable prognosis, increased distant metastasis, and poor response to chemotherapy and radiation therapy. 7 – 11 Hematological parameters can be easily analysed from the complete blood count reports, which invariably are done in all patients undergoing diagnostic evaluation of cervical cancer. Hence, pretreatment blood parameters represent an economical tool for predicting response to treatment in locally advanced cervical carcinoma patients. This study was conducted to assess the feasibility of utilizing pre-treatment blood parameters as markers to predict treatment response in patients with locally advanced cervical cancer. Methods The participants included patients aged 18 or older with confirmed histopathological cervical cancer, who had completed the prescribed chemoradiation and brachytherapy treatment, and had a minimum follow-up of 3 months. Informed consent for participation in the study was obtained. Excluded were patients with metastatic or recurrent cervical cancer, incomplete treatment, lack of relevant data, hematological/cardiovascular diseases, prior malignancies, advanced kidney Issues, allergic asthma, and active infections. The study was started after approval from the Institution Ethics Committee, Kasturba Medical College, Mangalore (IEC KMC MLR 05/2023/228 dated 18th May 2023). Data was collected by retrospectively of cases of locally advanced cervical cancer treated with chemoradiation at the hospital between January 2021 and June 2022, adhering to inclusion and exclusion criteria. Patient & Demographic information including age, stage of the disease, histopathology, pre-treatment Hemoglobin, Total Leucocyte counts, Differential Leucocyte Counts, Platelet Counts, Serum Albumin levels, treatment parameters, and response assessments were recorded from the hospital medical records. Response to treatment was assessed based on RECIST 1.1 criteria using MRI scans at 3 months after completion of treatment. 12 The response was recorded either as Complete Response, Partial Response, Stable Disease or Progressive Disease. Additionally, everyone who had a complete response were classified as a complete responder (CR), and everyone else who had a partial response, a stable disease, or a progressive disease was classified as a non-responder (NR). The parameters analyzed included Hemoglobin levels, Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Nutritional Index (PNI), and Eosinophil Albumin Ratio (EAR) and were calculated as below 11 , 13 – 15 Neutrophil − to − Lymphocyte Ratio ( NLR ) = Absolute Neutrophil Counts / Absolute Lymphocyte Counts Platelet − to − Lymphocyte Ratio ( PLR ) = Platelet Count / Absolute Lymphocyte Count Prognostic Nutritional Index = 10 ∗ Serum Albumin ( gm / dl ) + 0.005 ∗ Absolute lymphocyte count Eosinophil Albumin Ratio ( EAR ) = Absolute Eosinophil Count / Serum Albumin ( gm / dl ) Statistics Demographic data were analyzed using descriptive statistics, with continuous variables represented as mean and standard deviation (SD), while categorical variables were expressed as percentages (%). The comparison between responder and non-responder groups was conducted using the student t-test to assess the means of different parameters. Receiver Operating Characteristic (ROC) curve analysis was employed to determine the area under the curve (AUC) for hemoglobin levels, Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Prognostic Nutritional Index (PNI), and Eosinophil Albumin Ratio (EIR) in relation to the response to chemoradiation. The ROC curve facilitated the identification of optimal cut-off thresholds for these predictive biomarkers and evaluated their sensitivity and specificity values. Group comparisons were carried out using the Chi-square test, with statistical significance set at a p value of <0.05. All analyses were performed using Jamovi version 2.3. 16 Results A total of 140 patients who satisfied the study’s inclusion requirements were assessed. 53.5 years old was the median age. Adenocarcinoma was the second most common histology observed in 11 (8%) individuals, whereas squamous cell carcinoma was the most prevalent histology in 129 (92%) of the patients. The most common stage was Stage 2 seen in 64 (45.7%) of the patients followed by Stage III in 51 (36.4%) of patients. Out of the 140 patients, 121 (86.4%) were seen to be complete responders and 19 (13.6%) were classified as non-responders. The comparison of patient characteristics between the complete responder (CR) and non-responder (NR) cohorts is depicted in Table 1 . The comparison of the pre-treatment blood parameters between the complete responders (CR) and non-responder (NR) cohorts is given in Table 2 . Table 1. Patient characteristics (EBRT-External Beam Radiation Therapy). Patient characteristics Complete responders Non-responders P N=121 N=19 Age (Median) 54 years 51 years 0.567 Stage I 5 (4.1%) 1(5.3%) 0.445 II 58 (47.9%) 8 (42.1%) 0.334 III 46 (38.1%) 8 (42.1%) 0.225 IVA 12 (9.9%) 2 (10.5%) 0.450 Histology Squamous Cell Carcinoma 119(96.6%) 14 (84.3%) 0.120 Adenocarcinoma 5 (3.4%) 3 (15.7%) 0.09 EBRT 50Gy in 25# 86 (71.1%) 14 (73.6%) 0.786 46 Gy in 23 # 35 (28.9%) 5 (26.4%) 0.775 Brachytherapy ICRT 7.5 Gy x 3 # 96 (79.3%) 16 (84.2%) 0.453 ICRT 7 Gy x 4 # 25 (20.7%) 3 (15.8%) 0.334 Chemotherapy Cisplatin 108 (89.2%) 17 (89.4%) 0.998 Carboplatin 11 (9.1%) 1 (5.3%) 0.567 No 2 (1.75 1 (5.3%) 0.445 Table 2. Pretreatment hematological parameters in both the groups (NLR-Neutrophil to Lymphocyte Ratio; PLR-Platelet to Lymphocyte Ratio; PNI-Prognostic Nutritional Index; EAR-Eosinophil to Albumin Ratio). Hematological parameters Complete responders Non responders P Hemoglobin (gm/dl) Range 8.1-13.2 7-11.5 Mean 10.9 ± 1.03 9.4 ± 1.34 <0.001 NLR Range 0.86-9.60 2.43-9.89 Mean 2.77 ± 1.79 4.60 ± 2.21 <0.001 PLR Range 64.7-1344 62.2-2435 Mean 353 ± 305 578 ± 602 0.113 PNI Range 24.5-58.1 29.9-43.3 0.041 Mean 41.9 ± 5.12 37.0 ± 4 EAR Range 1.03-474 18.7-786 Mean 53.8 ± 14.3 90 ± 27.1 <0.001 The patients categorized as non-responders manifested significantly elevated pre treatment levels of Hemoglobin, NLR and EAR in contrast to responders. However, the Platelet-to-Lymphocyte Ratio (PLR) mean values, although higher in the non-responders group, did not attain statistical significance. Non-responder patients exhibited markedly diminished Prognostic Nutritional Index (PNI) levels compared to complete responders. The mean values for Hemoglobin, NLR, PLR, PNI, and EAR were 10.9 ± 1.03, 2.77 ± 1.79, 353 ± 305, 41.9 ± 5.12, and 53.8 ± 14.3, respectively, in the complete responders group, while in the non-responders group, they were 9.4 ± 1.34, 2.43-9.89, 578 ± 602, 37.0 ± 4, and 90 ± 27.1. Further details are provided in Table 2 . To determine the ideal cut-off value for pretreatment hemoglobin, NLR, PLR, PNI, and EAR, a ROC curve analysis was performed ( Table 3 ). It was shown that the hemoglobin cut-off value was < 9.5 (AUC: 0.509; 95% CI), with 38.3% specificity and 68.42% sensitivity ( Figure 1 ). As can be observed in Figure 2 , the NLR cut-off was found to be < 2.98 (AUC:0.796; 95% CI), with 89.47% sensitivity and 68.6% specificity. The PLR cut-off was 52.63% sensitive and 39.67% specific, with an AUC-0.454; 95% CI of ≤ 289.26 as shown in Figure 3 . The PNI cut-off was < 37.67 (AUC-0.226; 95% CI), with a sensitivity of 47.37% and a specificity of 20.66% ( Figure 4 ). The EAR cut-off was < 49.63 (AUC-0.791; 95% CI) with a sensitivity of 78.9% and a specificity of 71.9% ( Figure 5 ). The non-responder group exhibited a notably higher proportion of patients compared to the responders group when using the calculated cut-off values from the ROC analysis ( Table 4 ). Table 3. Cut off points for all parameters (NLR-Neutrophil to Lymphocyte Ratio; PLR-Platelet to Lymphocyte Ratio; PNI-Prognostic Nutritional Index; EAR-Eosinophil to Albumin Ratio). Parameters Hb NLR PLR PNI EAR Area Under Curve 0.509 0.796 0.454 0.226 0.791 Sensitivity 68.42 89.47 52.63 47.37 78.9 Specificity 38.54 68.6 39.67 20.66 71.9 Cut off Value 9.5 2.98 289.26 37.67 49.63 Figure 1. ROC curve for hemoglobin. Figure 2. ROC curve for NLR. Figure 3. ROC curve for PLR. Figure 4. ROC curve for PNI. Figure 5. ROC curve for EAR. Table 4. Comparative analysis of CR and NR using the cut-off for all parameters (NLR-Neutrophil to Lymphocyte Ratio; PLR-Platelet to Lymphocyte Ratio; PNI-Prognostic Nutritional Index; EAR-Eosinophil to Albumin Ratio). Parameters Complete responders N=121 Non-responders N=19 p Hemoglobin ≤9.5 10 10 9.5 111 9 NLR ≤2.98 85 7 0.004 >2.98 36 12 PLR ≤289.26 48 11 0.134 >289.26 73 8 PNI ≤37.67 26 10 0.003 >37.67 95 9 EAR ≤49.63 86 4 0.001 >49.63 35 15 Discussion The symbiotic relationship between inflammation and cancer is deeply rooted in the history of oncology. 17 From Rudolf Virchow’s observations in the 19th century linking chronic inflammation to cancer development to contemporary research unveiling the molecular mechanisms underlying this association, the connection has been a focal point of scientific inquiry. 18 Early studies highlighted the role of inflammatory mediators in promoting carcinogenesis, while subsequent investigations elucidated the complex interplay between inflammatory cells, cytokines, and tumor cells in the tumor microenvironment. 19 Despite fluctuations in scientific interest over time, recent advances in cancer immunology and molecular biology have reignited enthusiasm for exploring the inflammatory pathways driving tumor progression. Inflammatory mediators, including interleukins, tumor necrosis factor-alpha (TNF-α), and prostaglandins, modulate the behavior of cancer cells and surrounding stromal cells. Additionally, proteins, such as C Reactive protein (CRP), serum amyloid A (SAA) and other markers serve as biomarkers of systemic inflammation and are associated with poor prognosis in cancer patients. 18 , 19 While these biomarkers have been thoroughly investigated across different cancer types, their routine availability for clinical testing is limited due to cost and accessibility constraints. Instead, hematological parameters, readily accessible through routine blood tests, offer valuable insights into the inflammatory status of cancer patients. 8 Pretreatment hematological parameters indirectly provide us with an idea about the state of inflammation in the cancer patient and offer an economical alternative. 8 As pretreatment blood parameters are routinely conducted in all patients planned for treatment, it provides us with an opportunity to prognosticate the patient from the outset. Changes in the composition of peripheral blood, including alterations in leukocyte subsets, platelet count, and erythrocyte sedimentation rate (ESR), reflect systemic inflammation and may serve as prognostic and predictive markers in cancer. Among these parameters, increased NLR and PLR have been associated with advanced disease stage, aggressive tumor behavior, and reduced survival in various malignancies, including cervical cancer. 20 The Prognostic Nutritional Index is another recent parameter that has been identified to be correlating with outcomes in cancer. By incorporating serum albumin levels, reflecting nutritional status, and absolute lymphocyte counts, representing immune competence, PNI provides valuable insights into the host’s ability to mount an effective anti-tumor response and tolerate aggressive therapies. 21 Low PNI values have been consistently associated with poor prognosis, including decreased survival and increased susceptibility to treatment-related complications, across various malignancies, including cervical cancer. In the context of cancer treatment, adequate tissue oxygenation is essential for optimizing the efficacy of therapeutic interventions, including chemotherapy, radiation therapy, and immunotherapy. Low pre-treatment hemoglobin levels, indicative of anemia, have been consistently associated with reduced treatment tolerance, increased risk of treatment-related complications, and poorer outcomes in cancer patients. 8 Furthermore, anemia is often a consequence of underlying disease burden, inflammation, and bone marrow suppression, all of which may influence treatment response. The eosinophil-to-albumin ratio (EAR) is a less explored yet potentially insightful biomarker in the realm of cancer research and inflammation. Eosinophils can release various pro-inflammatory cytokines, chemokines, and cytotoxic granule proteins, influencing tumor growth, angiogenesis, and immune surveillance. On the other hand, albumin, a ubiquitous plasma protein, serves as a marker of nutritional status, inflammation, and disease severity. Therefore, the EAR could reflect the balance between eosinophil-mediated anti-tumor immunity and systemic inflammation in patients with cancer. The findings of our study underscore the potential of hematological parameters as non-invasive biomarkers for risk stratification, treatment selection, and prognostic evaluation in cancer patients. Furthermore, changes in these parameters during the course of treatment may serve as dynamic indicators of treatment response and disease progression, enabling timely therapeutic interventions and personalized patient management strategies. The observed differences in pre-treatment hematological parameters between responders and non-responders in this study may be attributed to several underlying biological mechanisms. Elevated levels of hemoglobin in responders could reflect better oxygenation and tissue perfusion, which are crucial for enhancing the efficacy of cancer treatment modalities such as chemotherapy and radiation therapy. Conversely, lower hemoglobin levels in non-responders may indicate underlying anemia, which is associated with reduced treatment tolerance and impaired oxygen delivery to tumor tissues, potentially compromising treatment efficacy. The higher neutrophil to lymphocyte ratio (NLR) observed in non-responders suggests an imbalance between pro-inflammatory and anti-tumor immune responses. Neutrophils, as key effectors of the innate immune system, can promote tumor progression through various mechanisms, including the release of proinflammatory cytokines and suppression of anti-tumor immune responses. Conversely, lymphocytes play a critical role in tumor surveillance and cytotoxic activity against cancer cells. Therefore, an elevated NLR may reflect a state of heightened inflammation and immunosuppression, which could contribute to treatment resistance and disease progression in non-responders. Similarly, the elevated eosinophil-to-lymphocyte ratio (EAR) in non-responders may indicate a dysregulated immune response characterized by increased eosinophilic inflammation. Eosinophils have been implicated in promoting tissue remodeling, angiogenesis, and tumor growth in various cancer types. Thus, a higher EAR may reflect an inflammatory microenvironment conducive to tumor progression and treatment resistance. The lack of significant differences in platelet-to-lymphocyte ratio (PLR) between responders and non-responders could be attributed to the multifactorial nature of platelet function in cancer. While platelets are known to contribute to tumor progression through mechanisms such as angiogenesis and metastasis, their role in modulating treatment response may vary depending on tumor type and treatment regimen. Additionally, other factors such as concurrent medications or comorbidities may influence platelet levels and treatment outcomes, potentially confounding the observed associations. The low prognostic nutritional index (PNI) levels in non-responders may reflect underlying malnutrition and systemic inflammation, which are known predictors of poor treatment response and survival in cancer patients. Malnutrition compromises immune function and treatment tolerance, thereby reducing the effectiveness of cancer therapy. Additionally, systemic inflammation can promote tumor progression and resistance to therapy through various molecular pathways. Overall, the observed differences in pre-treatment hematological parameters between responders and non-responders likely reflect underlying differences in tumor biology, host immune response, and systemic inflammation. These findings underscore the potential utility of hematological parameters as prognostic markers for predicting treatment response and guiding individualized therapeutic strategies in patients with cervical cancer. Despite the promising findings regarding the prognostic and predictive value of hematological parameters in cervical cancer, several challenges remain. Standardization of the cut-off values for Hb, NLR, PLR, EAR, PNI and other blood parameters across studies is essential to ensure consistency and reproducibility of results. Moreover, larger prospective studies with a long-term follow-up are needed to validate the utility of these biomarkers in clinical practice. Additionally, elucidating the underlying mechanisms linking inflammation and cancer progression will provide insights into novel therapeutic strategies targeting the inflammatory microenvironment. Conclusion The research emphasizes the predictive significance of pre-treatment blood parameters in cases with locally advanced cervical cancer. These results have the potential to improve treatment plans and, in turn, patient outcomes. To make these metrics standard tools in clinical practice, more investigation and validation are necessary. The study emphasizes the need of further research in the field of cervical cancer management because of its possible influence on treatment response prediction and patient outcomes. Ethics committee approval The study was started after approval from the Institution Ethics Committee, Kasturba Medical College, Mangalore (IEC KMC MLR 05/2023/228 dated 18 th May 2023). This study was approved by the Institutional Review Board under protocol number IEC_KMC_MLR 05/2023/228. Data were collected from cases of locally advanced cervical cancer treated with chemoradiation at the hospital between January 2021 and June 2022. Written informed consent was obtained from all participants. Data availability statement Figshare: Book1 edited with patient identifiers.xlsx DOI: https://doi.org/10.6084/m9.figshare.28060982.v3 . 22 The project contains the following underlying data: • Book1 edited.xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Sung H, Ferlay J, Siegel RL, et al. : Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 May; 71 (3): 209–249. PubMed Abstract | Publisher Full Text 2. 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Ittiamornlert P, Ruengkhachorn I: Neutrophil-lymphocyte ratio as a predictor of oncologic outcomes in stage IVB, persistent, or recurrent cervical cancer patients treated by chemotherapy. BMC Cancer. 2019 Dec; 19 (1): 1. Publisher Full Text 10. Yoshino Y, Taguchi A, Shimizuguchi T, et al. : A low albumin to globulin ratio with a high serum globulin level is a prognostic marker for poor survival in cervical cancer patients treated with radiation based therapy. Int. J. Gynecol. Cancer. 2019 Jan 1; 29 (1): 17–22. PubMed Abstract | Publisher Full Text 11. Haraga J, Nakamura K, Omichi C, et al. : Pretreatment prognostic nutritional index is a significant predictor of prognosis in patients with cervical cancer treated with concurrent chemoradiotherapy. Mol. Clin. Oncol. 2016 Nov 1; 5 (5): 567–574. PubMed Abstract | Publisher Full Text | Free Full Text 12. Schwartz LH, Litière S, De Vries E, et al. : RECIST 1.1—Update and clarification: From the RECIST committee. Eur. J. Cancer. 2016 Jul 1; 62 : 132–137. PubMed Abstract | Publisher Full Text | Free Full Text 13. Faria SS, Fernandes PC Jr, Silva MJ, et al. : The neutrophil-to-lymphocyte ratio: a narrative review. ecancermedicalscience. 2016; 10 : 10. Publisher Full Text 14. Templeton AJ, Ace O, McNamara MG, et al. : Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2014 Jul 1; 23 (7): 1204–1212. PubMed Abstract | Publisher Full Text 15. Guler OC, Onal C, Eralp Y, et al. : The impact of hematological parameters on survival in locally advanced cervical cancer patients treated with definitive radiotherapy. Int. J. Gynecol. Cancer. 2020; 30 (7): 1049–1055. 16. The jamovi project: jamovi (Version 2.3) [Computer Software].2023. Reference Source 17. Singh N, Baby D, Rajguru JP, et al. : Inflammation and cancer. Ann. Afr. Med. 2019 Jul 1; 18 (3): 121–126. PubMed Abstract | Publisher Full Text | Free Full Text 18. Schmidt A, Weber OF: In memoriam of Rudolf virchow: a historical retrospective including aspects of inflammation, infection and neoplasia. InInfection and inflammation: impacts on oncogenesis. Vol. 13 . . Karger Publishers; 2006; pp. 1–15. 19. Allavena P, Sica A, Solinas G, et al. : The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit. Rev. Oncol. Hematol. 2008 Apr 1; 66 (1): 1–9. PubMed Abstract | Publisher Full Text 20. Prabawa IP, Bhargah A, Liwang F, et al. : Pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as a predictive value of hematological markers in cervical cancer. Asian Pac. J. Cancer Prev. 2019; 20 (3): 863–868. PubMed Abstract | Publisher Full Text | Free Full Text 21. Ida N, Nakamura K, Saijo M, et al. : Prognostic nutritional index as a predictor of survival in patients with recurrent cervical cancer. Mol. Clin. Oncol. 2018 Feb 1; 8 (2): 257–263. PubMed Abstract | Publisher Full Text 22. Lobo D: Book1 edited with patient identifiers.xlsx. figshare. [Dataset]. 2024. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 21 Jan 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, India Abhishek Krishna Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation Vishnumaya N Roles: Data Curation, Resources, Validation, Writing – Review & Editing Fathima Shada Roles: Data Curation, Formal Analysis, Investigation, Writing – Review & Editing Pooja MS Roles: Investigation, Methodology, Validation, Writing – Review & Editing Dilson Lobo Roles: Conceptualization, Investigation, Methodology, Validation, Writing – Original Draft Preparation Athiyamaan MS Roles: Data Curation, Investigation, Visualization, Writing – Review & Editing Challapalli Srinivas Roles: Resources, Writing – Review & Editing Sourjya Banerjee Roles: Investigation Johan Sunny Roles: Investigation, Validation Paul Simon Roles: Supervision Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 15 Apr 2025, 14:118 https://doi.org/10.12688/f1000research.160308.2 version 1 Published: 21 Jan 2025, 14:118 https://doi.org/10.12688/f1000research.160308.1 Copyright © 2025 Krishna A et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Krishna A, N V, Shada F et al. Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.12688/f1000research.160308.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 21 Jan 2025 Views 0 Cite How to cite this report: Sequeira L. Reviewer Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r375270 ) The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-375270 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 09 Apr 2025 Lanisha Sequeira , Father Muller Medical College, Mangalore, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.176186.r375270 The authors have done a good work with respect pretreatment prognostic markers in cervical cancers. While most of the points are well written, the following observations would make the paper more robust. Query 1 - Introduction - ... Continue reading READ ALL The authors have done a good work with respect pretreatment prognostic markers in cervical cancers. While most of the points are well written, the following observations would make the paper more robust. Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Radiation Oncology, Gynaecologic Oncology, Cervical Cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sequeira L. Reviewer Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r375270 ) The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-375270 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 25 Apr 2025 Dilson Lobo , Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India 25 Apr 2025 Author Response Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you ... Continue reading Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you for the input. The corrections have been made and we will include recent data in the revised version of the manuscript. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Reply: The study was an ambispective study. We have taken the data both as retrospective and prospective, In patients who had completed the treatment and was on follow up, the data was taken retrospectively. In patients in whom the treatment was the diagnosis was made during our study period, the data was collected prospectively. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Reply: The corrections have been made and will be incorporated in the revised version of the manuscript. Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you for the input. The corrections have been made and we will include recent data in the revised version of the manuscript. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Reply: The study was an ambispective study. We have taken the data both as retrospective and prospective, In patients who had completed the treatment and was on follow up, the data was taken retrospectively. In patients in whom the treatment was the diagnosis was made during our study period, the data was collected prospectively. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Reply: The corrections have been made and will be incorporated in the revised version of the manuscript. Competing Interests: Nil Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 25 Apr 2025 Dilson Lobo , Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India 25 Apr 2025 Author Response Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you ... Continue reading Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you for the input. The corrections have been made and we will include recent data in the revised version of the manuscript. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Reply: The study was an ambispective study. We have taken the data both as retrospective and prospective, In patients who had completed the treatment and was on follow up, the data was taken retrospectively. In patients in whom the treatment was the diagnosis was made during our study period, the data was collected prospectively. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Reply: The corrections have been made and will be incorporated in the revised version of the manuscript. Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you for the input. The corrections have been made and we will include recent data in the revised version of the manuscript. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Reply: The study was an ambispective study. We have taken the data both as retrospective and prospective, In patients who had completed the treatment and was on follow up, the data was taken retrospectively. In patients in whom the treatment was the diagnosis was made during our study period, the data was collected prospectively. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Reply: The corrections have been made and will be incorporated in the revised version of the manuscript. Competing Interests: Nil Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: H Chuwa A. Reviewer Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r367720 ) The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-367720 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 27 Feb 2025 Agapiti H Chuwa , University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176186.r367720 The authors are to be commended for their contribution to the growing body of knowledge on biomarkers for predicting treatment response and prognosis in cancer, an important aspect of clinical oncology. While their efforts are acknowledged, addressing the following observed ... Continue reading READ ALL The authors are to be commended for their contribution to the growing body of knowledge on biomarkers for predicting treatment response and prognosis in cancer, an important aspect of clinical oncology. While their efforts are acknowledged, addressing the following observed issues would enhance the scientific rigour of the article:- 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Gynaecologic oncology, Reproductive physiology, Molecular biology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT H Chuwa A. Reviewer Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r367720 ) The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-367720 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 19 Mar 2025 Dilson Lobo , Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India 19 Mar 2025 Author Response 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records ... Continue reading 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. Response: The study follows an ambispective study design . For the retrospective component, data was obtained from hospital medical records. However, for the prospective component, informed consent was obtained from participants before data collection. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. Response: Since our study includes only patients receiving definitive chemoradiation, most cases of recurrent cervical cancer would have already undergone prior radiotherapy. Given that repeat chemoradiation is generally unlikely in such cases, we excluded recurrent cases to maintain uniformity in our results. This ensures that our findings are specifically applicable to patients receiving first-line chemoradiation. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. Reponse: We will reorder the second sentence in the 'Results' section to emphasize the most significant findings first. Regarding the reporting of continuous variables, while most were presented as means and standard deviations, age was reported as median because it is a more representative measure of central tendency for this variable, considering the distribution of age in our study population 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. Reponse: We will modify the table title to "Patient characteristics between responders and non-responders" for clarity and consistency with the text description. A more detailed analysis will be included. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Response: Table 2 includes both mean and standard deviation values, which will be mentioned in the table for better clarity. 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. Response: The study follows an ambispective study design . For the retrospective component, data was obtained from hospital medical records. However, for the prospective component, informed consent was obtained from participants before data collection. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. Response: Since our study includes only patients receiving definitive chemoradiation, most cases of recurrent cervical cancer would have already undergone prior radiotherapy. Given that repeat chemoradiation is generally unlikely in such cases, we excluded recurrent cases to maintain uniformity in our results. This ensures that our findings are specifically applicable to patients receiving first-line chemoradiation. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. Reponse: We will reorder the second sentence in the 'Results' section to emphasize the most significant findings first. Regarding the reporting of continuous variables, while most were presented as means and standard deviations, age was reported as median because it is a more representative measure of central tendency for this variable, considering the distribution of age in our study population 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. Reponse: We will modify the table title to "Patient characteristics between responders and non-responders" for clarity and consistency with the text description. A more detailed analysis will be included. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Response: Table 2 includes both mean and standard deviation values, which will be mentioned in the table for better clarity. Competing Interests: There is no competing interests. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 19 Mar 2025 Dilson Lobo , Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India 19 Mar 2025 Author Response 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records ... Continue reading 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. Response: The study follows an ambispective study design . For the retrospective component, data was obtained from hospital medical records. However, for the prospective component, informed consent was obtained from participants before data collection. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. Response: Since our study includes only patients receiving definitive chemoradiation, most cases of recurrent cervical cancer would have already undergone prior radiotherapy. Given that repeat chemoradiation is generally unlikely in such cases, we excluded recurrent cases to maintain uniformity in our results. This ensures that our findings are specifically applicable to patients receiving first-line chemoradiation. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. Reponse: We will reorder the second sentence in the 'Results' section to emphasize the most significant findings first. Regarding the reporting of continuous variables, while most were presented as means and standard deviations, age was reported as median because it is a more representative measure of central tendency for this variable, considering the distribution of age in our study population 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. Reponse: We will modify the table title to "Patient characteristics between responders and non-responders" for clarity and consistency with the text description. A more detailed analysis will be included. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Response: Table 2 includes both mean and standard deviation values, which will be mentioned in the table for better clarity. 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. Response: The study follows an ambispective study design . For the retrospective component, data was obtained from hospital medical records. However, for the prospective component, informed consent was obtained from participants before data collection. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. Response: Since our study includes only patients receiving definitive chemoradiation, most cases of recurrent cervical cancer would have already undergone prior radiotherapy. Given that repeat chemoradiation is generally unlikely in such cases, we excluded recurrent cases to maintain uniformity in our results. This ensures that our findings are specifically applicable to patients receiving first-line chemoradiation. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. Reponse: We will reorder the second sentence in the 'Results' section to emphasize the most significant findings first. Regarding the reporting of continuous variables, while most were presented as means and standard deviations, age was reported as median because it is a more representative measure of central tendency for this variable, considering the distribution of age in our study population 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. Reponse: We will modify the table title to "Patient characteristics between responders and non-responders" for clarity and consistency with the text description. A more detailed analysis will be included. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Response: Table 2 includes both mean and standard deviation values, which will be mentioned in the table for better clarity. Competing Interests: There is no competing interests. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 21 Jan 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 15 Apr 25 read read Version 1 21 Jan 25 read read Agapiti H Chuwa , University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania Lanisha Sequeira , Father Muller Medical College, Mangalore, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Sequeira L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Nov 2025 | for Version 2 Lanisha Sequeira , Father Muller Medical College, Mangalore, India 0 Views copyright © 2025 Sequeira L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Approved Competing Interests No competing interests were disclosed. Reviewer Expertise Radiation Oncology, Gynaecologic Oncology, Cervical Cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Sequeira L. Peer Review Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.180510.r378060) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-118/v2#referee-response-378060 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 H Chuwa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Apr 2025 | for Version 2 Agapiti H Chuwa , University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania 0 Views copyright © 2025 H Chuwa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The issues raised in the first version have been adequately addressed by the authors in the revised version. Competing Interests No competing interests were disclosed. Reviewer Expertise Gynaecologic oncology, Reproductive physiology, Molecular biology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) H Chuwa A. Peer Review Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.180510.r378061) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-118/v2#referee-response-378061 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Sequeira L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 09 Apr 2025 | for Version 1 Lanisha Sequeira , Father Muller Medical College, Mangalore, India 0 Views copyright © 2025 Sequeira L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have done a good work with respect pretreatment prognostic markers in cervical cancers. While most of the points are well written, the following observations would make the paper more robust. Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Radiation Oncology, Gynaecologic Oncology, Cervical Cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 25 Apr 2025 Dilson Lobo, Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India Query 1 - Introduction - In the first paragraph, 2020 GLOBOCAN is mentioned. A more recent GLOBOCAN 2022 or any latest studies post 2020 can be included. Reply: Thank you for the input. The corrections have been made and we will include recent data in the revised version of the manuscript. Query 2 - Methods Section - The type of study is not mentioned. Whether it was a retrospective analysis or a prospective one. Reply: The study was an ambispective study. We have taken the data both as retrospective and prospective, In patients who had completed the treatment and was on follow up, the data was taken retrospectively. In patients in whom the treatment was the diagnosis was made during our study period, the data was collected prospectively. Query 3 -Table 1 - The table title is wrongly written. Ideally, the title should be Patient Characteristics between two groups or should be redone for the whole population. Reply: The corrections have been made and will be incorporated in the revised version of the manuscript. View more View less Competing Interests Nil reply Respond Report a concern Sequeira L. Peer Review Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r375270) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-375270 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 H Chuwa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 27 Feb 2025 | for Version 1 Agapiti H Chuwa , University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania 0 Views copyright © 2025 H Chuwa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors are to be commended for their contribution to the growing body of knowledge on biomarkers for predicting treatment response and prognosis in cancer, an important aspect of clinical oncology. While their efforts are acknowledged, addressing the following observed issues would enhance the scientific rigour of the article:- 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Gynaecologic oncology, Reproductive physiology, Molecular biology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 19 Mar 2025 Dilson Lobo, Department of Radiation Oncology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, India 1. Study design : The study design is not clearly stated. The authors should specify the study design (e.g. retrospective case-control) to improve reproducibility. Also, the study used hospital medical records as the primary source of data, but the authors state that informed consent was obtained from each of the participants. Normally, consent would not be necessary for studies that use secondary (stored) data. This part needs to be clarified. Response: The study follows an ambispective study design . For the retrospective component, data was obtained from hospital medical records. However, for the prospective component, informed consent was obtained from participants before data collection. 2. Exclusion of recurrent cases : The exclusion of recurrent cervical cancer cases is questionable. Including them could be valuable for detecting possible recurrence using haematological parameters. Response: Since our study includes only patients receiving definitive chemoradiation, most cases of recurrent cervical cancer would have already undergone prior radiotherapy. Given that repeat chemoradiation is generally unlikely in such cases, we excluded recurrent cases to maintain uniformity in our results. This ensures that our findings are specifically applicable to patients receiving first-line chemoradiation. 3. Results section: The second sentence in the 'Results' section should be reordered to start with the most significant and important findings. Also, the author state that they have reported continuous variables as means and standard deviations, however, the variable "Age" is reported as 'median' in Table1. This part needs to be clarified. Reponse: We will reorder the second sentence in the 'Results' section to emphasize the most significant findings first. Regarding the reporting of continuous variables, while most were presented as means and standard deviations, age was reported as median because it is a more representative measure of central tendency for this variable, considering the distribution of age in our study population 4. Table 1 issues: The text description of Table 1 is inconsistent with the title. The text mentions the comparison of patient characteristics between complete responders (CR) and non-responders (NR), but the table title refers to "Patient characteristics (EBRT-External Beam Radiation Therapy)", which needs to be corrected for clarity. Also, the number of responders and non-responders fluctuates across cancer stages. A more detailed analysis is needed on whether the biomarkers assessed are affected by or related to the disease stage, which could help understand early signs of progression. Reponse: We will modify the table title to "Patient characteristics between responders and non-responders" for clarity and consistency with the text description. A more detailed analysis will be included. 5. Table 2 clarity : The means in Table 2 are unclear. One would expect a single mean value for each category. If the authors intend to report both means and standard deviations, this needs to be clarified, particularly for the PLR values in both responders and non-responders that are abnormally large. Response: Table 2 includes both mean and standard deviation values, which will be mentioned in the table for better clarity. View more View less Competing Interests There is no competing interests. reply Respond Report a concern H Chuwa A. Peer Review Report For: Pre-treatment blood parameters as an economical predictive marker for predicting treatment response in locally advanced cervical cancer [version 1; peer review: 1 approved, 1 approved with reservations] . F1000Research 2025, 14 :118 ( https://doi.org/10.5256/f1000research.176186.r367720) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-118/v1#referee-response-367720 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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