Peripheral Blood Lymphocyte and Eosinophil Dynamics with Chemotherapy and Pembrolizumab in Cervical Cancer

Peripheral Blood Lymphocyte and Eosinophil Dynamics with Chemotherapy and Pembrolizumab in Cervical Cancer | 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 Peripheral Blood Lymphocyte and Eosinophil Dynamics with Chemotherapy and Pembrolizumab in Cervical Cancer Sho Sato, Masahiro Kagabu, Ami Jo, Haruka Otsuka, Ayaka Kitamura, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7964240/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jan, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted 5 You are reading this latest preprint version Abstract Background Cervical cancer poses a significant global health burden, particularly in its metastatic and recurrent forms, for which treatment options are limited. Although immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes, predictive markers for efficacy are still undefined. This retrospective study investigated changes in peripheral blood eosinophil and lymphocyte counts as potential prognostic indicators in patients with metastatic or recurrent cervical cancer undergoing pembrolizumab-based therapy. Methods Forty-one patients treated with pembrolizumab plus taxane-platinum chemotherapy (± bevacizumab) were analyzed. Peripheral blood eosinophil and lymphocyte counts were measured before and three weeks after treatment initiation. Statistical analyses included Kaplan–Meier curves, Cox regression, and log-rank tests. Results Immune-related adverse events ≥ Grade 2 emerged as a significant independent factor associated with prolonged progression-free survival (PFS) in this cohort (p = 0.014). Patients with decreased eosinophil count ratios post-treatment demonstrated longer PFS, particularly among those with recurrence and those who had received prior radiotherapy (p < 0.001). Conversely, increased lymphocyte count ratios correlated with improved PFS in patients undergoing primary treatment (p = 0.018). Conclusion Changes in peripheral eosinophil and lymphocyte counts following pembrolizumab initiation may serve as predictive indicators of treatment efficacy in specific cervical cancer subgroups. Incorporating these hematologic parameters could help optimize patient selection and therapeutic strategies. Further research is needed to clarify their role as predictive markers of pembrolizumab efficacy in cervical cancer. cervical cancer immune checkpoint inhibitor white blood cell differential counts Figures Figure 1 Figure 2 Figure 3 Introduction Cervical cancer is the fourth most common cancer worldwide, with 661,021 new cases and nearly 348,189 deaths reported in 2022 [ 1 ]. Metastatic cervical cancer has a poor prognosis, with a 5-year overall survival (OS) rate of only 19%. Thus, the development of effective treatment strategies is imperative [ 2 ]. Recently, the KEY-NOTE826 trial, a phase 3 double-blind study evaluating pembrolizumab combined with chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer, demonstrated that pembrolizumab significantly improved progression-free survival (PFS) and OS compared with placebo [ 3 ]. However, many aspects of the efficacy and prognostic implication of immune checkpoint inhibitors (ICIs) remain unknown, and identifying predictive markers of efficacy is essential to optimize their clinical application. In clinical practice, blood tests, such as the complete blood count (CBC), are important for cancer management [ 4 ], providing valuable insights into treatment response. The utility of blood tests in predicting the efficacy of ICIs across multiple malignancies has been reported. Recently, white blood cell differential counts, and increased lymphocyte or eosinophil counts, have emerged as markers of favorable treatment outcomes in patients with cancer receiving pembrolizumab. Patients receiving pembrolizumab who exhibit higher baseline lymphocyte counts or favorable lymphocyte ratios tend to show better treatment outcomes. In cohorts with advanced urothelial carcinoma, increases in total lymphocytes and improvements in ratios (e.g., decreased neutrophil-to-lymphocyte ratio or increased CD4/CD8 ratio) coincided with clinical benefits [ 5 ]. Recent evidence also suggest that eosinophil count is associated with the therapeutic efficacy of ICIs in melanoma [ 6 ], lung cancer [ 7 , 8 ], and urothelial carcinoma [ 9 ]. However, only a few studies have been conducted on the relationship between changes in peripheral blood leukocyte counts before and after pembrolizumab treatment and the effects of pembrolizumab in patients with cervical cancer. In this study, we focused on changes in peripheral lymphocyte and eosinophil counts pre-treatment and post-treatment to clarify the relationship between these changes and clinical outcomes of pembrolizumab plus taxane-platinum chemotherapy in metastasis and recurrent cervical cancer. Patients and Methods Patients This retrospective study was reviewed and approved by the Institutional Review Board of Iwate Medical University (Iwate, Japan; approval no. MH2024027). Forty-one patients diagnosed with stage IVB cervical cancer according to the International Federation of Gynecology and Obstetrics [FIGO 2018] classification or with cervical cancer recurrence who received pembrolizumab plus taxane-platinum combination chemotherapy (with or without bevacizumab) at Iwate Medical University Hospital between January 2023 and December 2024 were included in this study. Measure of peripheral lymphocyte and eosinophil counts Peripheral lymphocyte and eosinophil counts were measured at the same time as the CBC before initial pembrolizumab initiation and three weeks after. Results were obtained from patient medical records. The ratio of peripheral lymphocyte and eosinophil counts before initial pembrolizumab initiation and three weeks later, we defined as the ratio of neutrophil count and lymphocyte count, respectively. Statistical analysis Differences between patient groups were assessed using the chi-square test and paired t-test. Prognosis was evaluated using the Kaplan–Meier method, and significant differences between groups were investigated using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived based on a stratified Cox regression model. Analyses were performed using GraphPad Prism version 10 (GraphPad Software, San Diego, CA, USA). All reported p-values were two-sided, and P < 0.05 was considered statistically significant. Results Patient characteristics Forty-one patients with cervical cancer were included in this study: 24 (58.5%) had squamous cell carcinoma (SCC) and 17 (41.5%) had non-SCC. Of the total, 16 (39.0%) received primary treatment, and 25 (61.0%) were treated for recurrence. Histories of radiotherapy and chemotherapy were reported 21 (51.2%) and 12 (29.3%) patients, respectively. During ICI treatment, 30 patients (73.2%) experienced immune-related adverse events (irAEs) of less than grade 2 and 11 patients (26.8%) experienced irAEs of grade ≥ 2. Regarding the best treatment response, eight patients (19.5%) achieved complete response, 19 (46.3%) had partial response, eight (19.5%) showed stable disease, and six (14.6%) had progressive disease. (Table 1 ) Table 1 Characteristics of the study population. Factor N (%) Age* (Median: 51) < 51 21 (51.2) ≥ 51 20 (48.8) Treatment timing Primary 16 (39.0) Recurrence 25 (61.0) Histology SCC 24 (58.5) Non-SCC 17 (41.5) Prior RT Yes 21 (51.2) No 20 (48.8) Prior CT Yes 12 (29.3) No 29 (70.7) Combination with Bev Yes 23 (56.1) No 18 (43.9) irAE Yes 11 (26.8) No 30 (73.2) Best response CR 8 (19.5) PR 19 (46.4) SD 8 (19.5) PD 6 (14.6) *range:32–79 Bev; bevacizumab, CR; complete response, CT; chemotherapy, irAE; immune-related adverse events, PR; partial response, PD; progressive disease, RT; radiotherapy, SCC; squamous cell carcinoma, SD; stable disease Factors for better PFS in patients with Pembrolizumab treatment Table 2 shows the results of the evaluation of factors that improve PFS in patients with cervical cancer treated with pembrolizumab. The median follow-up time was 13 months (range 2–29). Table 2 The Univariate and Multivariate analyses of the factors associated with the progression-free survival in patients who received pembrolizumab treatment. Factor Univariate Multivariate HR (95%CI) p value HR (95%CI) p value Age < 51 1 ≥51 1.212 (0.558–2.672) 0.626 Treatment timing Primary Recurrence 1 1.727 (0.781–4.082) 0.189 Histological type SCC nonSCC 1 1.215 (0.551–2.640) 0.622 Prior RT No Yes 1 1.149 (0.527–2.508) 0.724 Prior CT No Yes 1 1.762 (0.714–3.976) 0.189 Bev No Yes 1 0.419 (0.187–0.910) 0.029 1 0.484 (0.214–1.061) 0.072 irAE ≥ Grade 2 No Yes 1 0.231 (0.067–0.614) 0.008 1 0.254 (0.073–0.684) 0.014 WBC ratio Decreased Increased 1 1.112 (0.496–2.417) 0.790 Lymph ratio Decreased Increased 1 0.683 (0.312–1.493) 0.333 Eosi ratio Decreased Increased 1 2.131 (0.870–4.774) 0.077 Bev; bevacizumab, CRP; C-reactive protein, CT; chemotherapy, Eosi; eosinophils, irAE; immune-related adverse events, Lymph; Lymphocytes, RT; radiotherapy, SCC; squamous cell carcinoma, WBC; white blood cells, 95% CI; 95% confidence interval To identify factors associated with PFS in this cohort, clinicopathological features, including peripheral blood lymphocyte count, eosinophil count, and PFS, were analyzed using Cox regression analysis. Univariate analysis of the relationship between these features and PFS revealed that bevacizumab use (p = 0.029, HR: 0.419, 95% CI: 0.187–0.910) and grade > 2 irAE (p = 0.008, HR: 0.231, 95% CI: 0.067–0.614) were significant predictors of better prognosis. Multivariate analysis confirmed grade > 2 irAE (p = 0.014, HR: 0.254, 95% CI: 0.073–0.684) as an independent prognostic factor for PFS. Relationship of eosinophil and lymphocyte count ratio changes pre- and post-pembrolizumab treatment with prognosis Although no statistically significant differences were observed, patients with a decreased eosinophil count ratio tended to have a longer PFS than patients with an increased eosinophil count ratio (p = 0.072, Fig. 1 A). Similarly, patients with an increased lymphocyte count ratio tended to have a longer PFS than patients with a decreased lymphocyte count ratio (p = 0.321, Fig. 1 C). However, no such associations were observed for OS (Fig. 1 B and 1 D). As shown in Fig. 2 A, although the difference did not reach statistical significance, there was a trend toward longer progression-free survival (PFS) in the primary-disease group among patients with a decreased eosinophil count ratio (p = 0.236). In contrast, in the recurrent group (Fig. 2 B, p = 0.0002) and in patients with a history of radiotherapy (Fig. 2 C, p = 0.0001), patients with a decreased eosinophil count ratio showed significantly longer PFS compared with patients with a increased eosinophil count ratio.. However, as shown in Fig. 3 , only patients who received primary treatment with an increased lymphocyte count ratio tended to have a longer PFS than those with a decreased lymphocyte count ratio (Fig. 3 A, p = 0.018). The opposite trend was observed in patients with recurrent disease or a history of radiotherapy, with no statistically significant differences observed in either case. Figure 3 B and 3 C). Supplementary Tables 1 and 2 summarize the associations between clinicopathological features and eosinophil and lymphocyte count ratios, respectively. No statistically significant differences were observed in clinicopathological features. Discussion We analyzed the relationships between clinicopathological features, including peripheral blood lymphocyte count and eosinophil count, and PFS using Cox regression analysis to determine whether our patient characteristics were similar to those previously reported. In our study, bevacizumab use and grade ≥ 2 irAEs were associated with significantly better prognosis in the univariate analysis, and grade 2 irAEs were confirmed as independent prognostic factors for PFS in the multivariate analysis. A recent report further supports pembrolizumab plus chemotherapy, with or without bevacizumab, as the standard of care for patients with persistent, recurrent, or metastatic cervical cancer [ 10 ]. Other recent studies have also suggested a correlation between irAEs and the efficacy of pembrolizumab in patients with various cancers [ 11 , 12 ]. Das et al. reported that irAE onset is an indicator of immune activation and may be associated with antitumor effects [ 13 ]. Our cohort reflets these factors. Peripheral differential white blood cell count may serve as a biomarker for ICI treatment [ 14 – 16 ]. However, only a few reports exist on this relationship in cervical cancer. Therefore, we performed a prognostic analysis of eosinophil and lymphocyte counts and examined intergroup differences using the Kaplan–Meier method and the log-rank test. Patients with higher eosinophil ratios before pembrolizumab treatment tended to have shorter PFS compared with those with lower ratios. This trend was particularly significant in patients with recurrence or a history of radiation therapy. Patients with higher lymphocyte ratios tended to have longer PFS, and this trend was particularly evident in patients with initial disease; however, the opposite trend was observed in patients with recurrent disease or a history of radiation therapy, with no statistically significant differences observed in either case. Increased peripheral blood eosinophil count has been associated with improved pembrolizumab efficacy across several cancers, as indicated by both baseline and post-treatment measurements. In advanced urothelial carcinoma, two studies suggest that decreased relative eosinophil count at three weeks predicts worse OS [ 9 ], whereas one study suggests that a post-treatment relative count of at least 4.8% is linked to improved survival [ 17 ]. In metastatic melanoma, a baseline relative eosinophil count ≥ 1.5% is associated with favorable OS [ 18 ]. In the present study, unlike previous reports on other cancers, patients with higher eosinophil count ratios before and after pembrolizumab treatment tended to have shorter PFS compared with those with lower ratios. This may be owing to differences in clinical backgrounds between these studies. In our study, pembrolizumab was administered in combination with chemotherapy to patients with cervical cancer according to the KEY-NOTE826 trial [ 3 ]. By contrast, in other studies on ureteral cancer [ 9 , 17 ] and melanoma [ 18 ] treated with pembrolizumab monotherapy, an association was observed between increased eosinophil count and pembrolizumab efficacy. Osawa et al. also reported differences between pembrolizumab therapy combined with chemotherapy and pembrolizumab monotherapy, reporting an association only with pembrolizumab monotherapy [ 8 , 7 ]. Their suggested reason is that bone marrow suppression caused by antitumor drugs leads to complex changes in peripheral blood cells [ 7 ]. Over half of patients in the present study had a history of radiotherapy. Reports have shown that pelvic radiotherapy is strongly associated with bone marrow suppression and hematologic toxicity in patients receiving concurrent chemoradiotherapy for rectal and cervical cancers [ 19 – 21 ], and have identified correlations between radiation dose and volume parameters and acute bone marrow suppression. Specifically, the volume of pelvic bone receiving low-to-moderate doses was significantly associated with higher grades of bone marrow suppression [ 22 ]. This phenomenon may also lead to complex changes in peripheral blood cells, similar to the bone marrow suppression caused by antitumor drugs. Recent studies have shown a significant relationship between eosinophil count and cervical cancer. Higher pretreatment eosinophil levels and increased post-pre-radiotherapy eosinophil ratios were associated with worse PFS and OS in patients with cervical squamous cell carcinoma patients [ 23 ]. The reason for this is unclear, but it is possible that patients with cervical cancer who have undergone radiation therapy experience changes in peripheral blood eosinophil counts that differ from those observed in patients with other types of cancer. Moreover, in the present study, log-rank test showed a significant prolongation of PFS in the low-eosinophil group of patients with a history of radiation therapy. Several reports have shown that PFS is significantly longer with elevated pre-post treatment peripheral lymphocyte counts in patients with advanced non-small cell lung cancer treated with ICIs, including ICIs combined with chemotherapy [ 24 , 25 ]. In the present study, although no significant differences were observed in all cases, patients whose lymphocyte counts increased before and after treatment tended to have longer PFS. This tendency was particularly evident in patients with no prior treatment history, with a statistically significant difference. However, this tendency was not observed in patients with a history of radiation therapy or recurrence. This study has several limitations. First, it was a single-center study with a limited number of cases. A multicenter study with a large number of patients and long-term analysis is necessary to investigate the association between changes in peripheral blood leukocyte fractions and pembrolizumab use in cervical cancer. Second, further studies are needed to clarify the differences in the effects of pembrolizumab and changes in eosinophil counts between cervical cancer and other cancers. In conclusion, among patients with cervical cancer treated with pembrolizumab in combination with chemotherapy, a trend toward longer PFS was observed in those whose post-treatment eosinophil counts were lower than their pre-treatment levels, particularly among patients with a history of radiotherapy. Further studies are warranted to determine whether this finding could serve as a predictive biomarker of pembrolizumab efficacy in cervical cancer. Declarations Competing interests The authors declare that they have no competing interests. Ethical approval and consent to participate This study was performed in accordance with the Declaration of Helsinki and was reviewed and approved by the Institutional Review Board of Iwate Medical University (Approval No. MH2024027). Author contributions SS and MK conceived and designed the study. SS, MK, and TB performed the experiments. SS, MK, DS, HO, and YC analyzed the data. AJ, HO, AK, MM, NJ, ET, YK, TN, and TS prepared the materials. SS, MK and TB drafted the manuscript. SS and MK confirmed the authenticity of all raw data. All the authors have read and approved the final manuscript. Acknowledgments We are grateful to all patients, their families, oncologists, allied healthcare professionals, and research assistants who participated in this study. Data availability statement The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74 (3):229-263. doi:10.3322/caac.21834 Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A (2025) Cancer statistics, 2025. CA: A Cancer Journal for Clinicians 75 (1):10-45. doi:https://doi.org/10.3322/caac.21871 Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yañez E, Gümüş M, Olivera Hurtado de Mendoza M, Samouëlian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ (2021) Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med 385 (20):1856-1867. doi:10.1056/NEJMoa2112435 Holub K, Biete A (2019) Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients. Clin Transl Oncol 21 (7):836-844. doi:10.1007/s12094-018-1991-4 Kadono Y, Kawaguchi S, Nohara T, Shigehara K, Izumi K, Kamijima T, Seto C, Takano A, Yotsuyanagi S, Nakagawa R, Miyagi T, Aoyama S, Asahi H, Fukuda R, Mizokami A (2021) Blood Cell Count Biomarkers Predicting Efficacy of Pembrolizumab as Second-line Therapy for Advanced Urothelial Carcinoma. Anticancer Res 41 (3):1599-1606. doi:10.21873/anticanres.14921 Wendlinger S, Wohlfarth J, Kreft S, Siedel C, Kilian T, Dischinger U, Heppt MV, Wistuba-Hamprecht K, Meier F, Goebeler M, Schadendorf D, Gesierich A, Kosnopfel C, Schilling B (2022) Blood Eosinophils Are Associated with Efficacy of Targeted Therapy in Patients with Advanced Melanoma. Cancers (Basel) 14 (9). doi:10.3390/cancers14092294 Osawa H, Shiozawa T, Okauchi S, Sasatani Y, Ohara G, Sato S, Miyazaki K, Kodama T, Kagohashi K, Satoh H, Hizawa N (2021) Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients. Cancer Diagn Progn 1 (5):485-490. doi:10.21873/cdp.10065 Osawa H, Shiozawa T, Okauchi S, Miyazaki K, Kodama T, Kagohashi K, Nakamura R, Satoh H, Hizawa N (2021) Association between time to treatment failure and peripheral eosinophils in patients with non-small cell lung cancer treated with immune checkpoint inhibitors. Pol Arch Intern Med 131 (10). doi:10.20452/pamw.16049 Furubayashi N, Minato A, Negishi T, Sakamoto N, Song Y, Hori Y, Tomoda T, Harada M, Tamura S, Miura A, Komori H, Kuroiwa K, Seki N, Fujimoto N, Nakamura M (2022) Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab. Cancer Manag Res 14:1641-1651. doi:10.2147/cmar.S360473 Lorusso D, Colombo N, Dubot C, Cáceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Olivera M, Samouëlian V, Castonguay V, Arkhipov A, Li K, Toker S, Tekin C, Tewari KS, Monk BJ (2025) Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study. Ann Oncol 36 (1):65-75. doi:10.1016/j.annonc.2024.10.002 Noguchi S, Suminaga K, Kaki T, Kawachi H, Fukao A, Terashita S, Horikawa S, Ikeue T, Sugita T (2020) Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer. Lung Cancer (Auckl) 11:53-57. doi:10.2147/lctt.S254146 Kobayashi K, Suzuki K, Hiraide M, Aoyama T, Yokokawa T, Shikibu S, Hashimoto K, Iikura Y, Sato H, Sugiyama E, Tajima M, Hama T (2020) Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma. Oncology 98 (4):237-242. doi:10.1159/000505340 Das S, Johnson DB (2019) Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer 7 (1):306. doi:10.1186/s40425-019-0805-8 Alessi JV, Ricciuti B, Alden SL, Bertram AA, Lin JJ, Sakhi M, Nishino M, Vaz VR, Lindsay J, Turner MM, Pfaff K, Sharma B, Felt KD, Rodig SJ, Gainor JF, Awad MM (2021) Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer. J Immunother Cancer 9 (11). doi:10.1136/jitc-2021-003536 Yanazume S, Kobayashi Y, Kirita Y, Kitazono I, Nagata C, Kozai A, Tanimoto A, Kobayashi H (2025) A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab. J Obstet Gynaecol Res 51 (1):e16182. doi:10.1111/jog.16182 Morimoto H, Tsujikawa T, Miyagawa-Hayashino A, Kimura A, Saburi S, Murakami N, Kitamoto K, Mukudai S, Nagao H, Saya S, Ogi H, Konishi E, Itoh K, Hirano S (2024) Neutrophil-to-lymphocyte ratio associates with nutritional parameters, intratumoral immune profiles, and clinical outcomes of pembrolizumab in head and neck squamous cell carcinoma. Head Neck 46 (8):1956-1964. doi:10.1002/hed.27671 Furubayashi N, Minato A, Negishi T, Sakamoto N, Song Y, Hori Y, Tomoda T, Tamura S, Kuroiwa K, Seki N, Fujimoto N, Nakamura M (2021) The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab. Cancer Manag Res 13:8049-8056. doi:10.2147/cmar.S333823 Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, Simeone E, Mangana J, Schilling B, Di Giacomo AM, Brenner N, Kähler K, Heinzerling L, Gutzmer R, Bender A, Gebhardt C, Romano E, Meier F, Martus P, Maio M, Blank C, Schadendorf D, Dummer R, Ascierto PA, Hospers G, Garbe C, Wolchok JD (2016) Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clin Cancer Res 22 (22):5487-5496. doi:10.1158/1078-0432.Ccr-16-0127 Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Racca P, Morino M, Numico G, Ricardi U (2017) Hematologic toxicity in anal cancer patients during combined chemo-radiation: a radiation oncologist perspective. Expert Rev Anticancer Ther 17 (4):335-345. doi:10.1080/14737140.2017.1288104 Zhang B-Z, Li Y, Xu L-M, Chai Y-L, Qu C, Cao Y-J, Wang J, Hou H-L, Zhang J (2023) The relationship between the radiation dose of pelvic-bone marrow and lymphocytic toxicity in concurrent chemoradiotherapy for cervical cancer. Radiation Oncology 18 (1):12. doi:10.1186/s13014-023-02205-8 Konnerth D, Gaasch A, Zinn A, Rogowski P, Rottler M, Walter F, Knoth J, Sturdza A, Oelmann J, Grawe F, Bodensohn R, Belka C, Corradini S (2024) Hematologic Toxicity and Bone Marrow-Sparing Strategies in Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review. Cancers (Basel) 16 (10). doi:10.3390/cancers16101842 Kumar T, Schernberg A, Busato F, Laurans M, Fumagalli I, Dumas I, Deutsch E, Haie-Meder C, Chargari C (2019) Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation. Cancer Manag Res 11:6285-6297. doi:10.2147/cmar.S195989 Zhu J, Wang H, Gao MJ, Li YF, Huang YQ, Shi JP, Wang WJ (2019) Prognostic values of lymphocyte and eosinophil counts in resectable cervical squamous cell carcinoma. Future Oncol 15 (30):3467-3481. doi:10.2217/fon-2018-0879 Qin A, Street L, Cease K, Viglianti BL, Warren EH, Zhao L, Ramnath N (2017) Clinical Determinants of Durable Clinical Benefit of Pembrolizumab in Veterans With Advanced Non-Small-Cell Lung Cancer. Clin Lung Cancer 18 (5):559-564. doi:10.1016/j.cllc.2017.01.012 Lee YJ, Park YS, Lee HW, Park TY, Lee JK, Heo EY (2022) Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer. Scientific Reports 12 (1):626. doi:10.1038/s41598-021-04630-9 Cite Share Download PDF Status: Published Journal Publication published 22 Jan, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted Editorial decision: Major revisions 17 Nov, 2025 Reviewers agreed at journal 29 Oct, 2025 Reviewers invited by journal 29 Oct, 2025 Editor assigned by journal 29 Oct, 2025 First submitted to journal 27 Oct, 2025 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-7964240","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":536796733,"identity":"8f38b231-17ef-45bd-b27b-0d794b9a6aa4","order_by":0,"name":"Sho Sato","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYDACCQaGwz8MbORA7AMPiNTC+JihIs0YrCWBSC3MxgxnDiU2gDhEaZGf3XxMurDtQPr8sMMPgbbYyek2ENBicOdYmvTMtju5G2+nGQC1JBubHSCkRSLHTIK37VnuxtkJIC0HErcR0iI/A6zlcLrh7PQPxGlhuJFjbMxz5nCCvHQOkbYY3EhLfDijIs1wg3ROwYEEAyL8Ij8j+cCBDwY28vKz0zd/+FBhJ0dQC8I6sEoDYpWDrWsgRfUoGAWjYBSMKAAA4g1KsJdmyqUAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-5628-7141","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":true,"prefix":"","firstName":"Sho","middleName":"","lastName":"Sato","suffix":""},{"id":536796734,"identity":"6a601fd0-87f8-42e7-ad43-20df42aef53e","order_by":1,"name":"Masahiro Kagabu","email":"","orcid":"https://orcid.org/0000-0003-0926-1015","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Kagabu","suffix":""},{"id":536796735,"identity":"16c09226-3812-4fa0-98f0-24c69fea4dcd","order_by":2,"name":"Ami Jo","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Ami","middleName":"","lastName":"Jo","suffix":""},{"id":536796736,"identity":"36d33c53-5fc9-4d49-9b46-c5a07297fa41","order_by":3,"name":"Haruka Otsuka","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Haruka","middleName":"","lastName":"Otsuka","suffix":""},{"id":536796737,"identity":"d184ff39-94af-4a30-9950-cb54b56c0200","order_by":4,"name":"Ayaka Kitamura","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Ayaka","middleName":"","lastName":"Kitamura","suffix":""},{"id":536796738,"identity":"baad315a-d4c6-4559-95e0-ed6abdf4edb6","order_by":5,"name":"Miku Musashi","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Miku","middleName":"","lastName":"Musashi","suffix":""},{"id":536796739,"identity":"34d3a186-1dbb-47a6-9f2f-bb9acb01c1f9","order_by":6,"name":"Nanako Jonai","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Nanako","middleName":"","lastName":"Jonai","suffix":""},{"id":536796740,"identity":"ba97855d-f2bf-4951-bbee-27faf83807fe","order_by":7,"name":"Yohei Chiba","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Yohei","middleName":"","lastName":"Chiba","suffix":""},{"id":536796741,"identity":"7718869d-c3b4-44fc-8205-38ee668e6c31","order_by":8,"name":"Eriko Takatori","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Eriko","middleName":"","lastName":"Takatori","suffix":""},{"id":536796742,"identity":"de66a372-75d2-4c03-888c-b059bb7d31e7","order_by":9,"name":"Yoshitaka Kaido","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Yoshitaka","middleName":"","lastName":"Kaido","suffix":""},{"id":536796743,"identity":"57f3ca62-5a0a-4d91-afb8-cf71be6f5a42","order_by":10,"name":"Takayuki Nagasawa","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Nagasawa","suffix":""},{"id":536796744,"identity":"96b8fbce-bd57-4770-a258-15c7f0653edc","order_by":11,"name":"Tadahiro Shoji","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Tadahiro","middleName":"","lastName":"Shoji","suffix":""},{"id":536796745,"identity":"26ce41e3-6470-4d7f-bc46-ba3308fae771","order_by":12,"name":"Tsukasa Baba","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Tsukasa","middleName":"","lastName":"Baba","suffix":""}],"badges":[],"createdAt":"2025-10-28 07:06:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7964240/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7964240/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10147-026-02960-0","type":"published","date":"2026-01-22T15:58:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":95655068,"identity":"8ee76fbb-fd36-4a0a-9df4-5d8dddf29764","added_by":"auto","created_at":"2025-11-11 16:14:16","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":103666,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/48115184230dbf3b4c267294.tif"},{"id":95654702,"identity":"5a8b1b0b-dd38-4636-8f4f-715ae894b73a","added_by":"auto","created_at":"2025-11-11 16:12:46","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82832,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/3e84e3079d679890ea53a45c.tif"},{"id":95654897,"identity":"94a6d424-ca02-45e8-a191-25d1d1829611","added_by":"auto","created_at":"2025-11-11 16:13:42","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21471,"visible":true,"origin":"","legend":"","description":"","filename":"Table1Charactics.docx","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/0754745d735e037ee109cff2.docx"},{"id":95565646,"identity":"029cb339-0f3c-45e9-ab15-4189fe42127b","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":24186,"visible":true,"origin":"","legend":"","description":"","filename":"Table2AllPFSv2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/2d20565ad40a8e7826de520e.docx"},{"id":95565643,"identity":"0d191248-d9ae-4af5-b5ae-780ad2f81715","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81966,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/1545fd03cccdb6340741e0e9.tif"},{"id":95654610,"identity":"6bc3e9d7-e9c5-4fb8-9d3a-4736526c93e5","added_by":"auto","created_at":"2025-11-11 16:12:33","extension":"xml","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":14849,"visible":true,"origin":"","legend":"","description":"","filename":"ijcoIJCOD2501312.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/8bdff404fd978ae17edc3978.xml"},{"id":95654849,"identity":"a882b01e-ab4e-46dc-8c6e-84d2fe182789","added_by":"auto","created_at":"2025-11-11 16:13:19","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1142,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD250131214847.go.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/c1b377bfeac72bb36c887644.xml"},{"id":95565649,"identity":"0db48683-3d11-4938-a911-820eb357180a","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":846,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD2501312Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/1926ff249fcc8747464293ee.xml"},{"id":95565656,"identity":"a9f4ddb1-80cd-4894-a536-f090220eaa59","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":98692,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD25013120enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/aa1fc7d2f8276b792ef7f197.xml"},{"id":95655633,"identity":"e9f091d4-98e8-4573-a781-ebf76d5609c9","added_by":"auto","created_at":"2025-11-11 16:16:36","extension":"tif","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":103666,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/ee274c78ba5b4352b2983061.tif"},{"id":95654513,"identity":"578b2653-fd22-450c-a90b-45b8f5ec6b91","added_by":"auto","created_at":"2025-11-11 16:12:16","extension":"tif","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":82832,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/0c6a061ee2b2d9623b262f38.tif"},{"id":95655001,"identity":"bcddaab1-164b-4e25-8401-6e65a5372c57","added_by":"auto","created_at":"2025-11-11 16:14:01","extension":"tif","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81966,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/bb4924466352ea0a8c14094d.tif"},{"id":95654902,"identity":"0fc97a41-efe3-440e-8bc3-0de029f46c2d","added_by":"auto","created_at":"2025-11-11 16:13:45","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":22706,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/d475a1ca58c17b6cd92040cc.png"},{"id":95655265,"identity":"43f07027-ca40-40d2-a276-0ac73870d68e","added_by":"auto","created_at":"2025-11-11 16:14:57","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17831,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/4dd1ef8d7363a6296bd58350.png"},{"id":95654525,"identity":"8deeeb4a-cff6-465c-8e64-327097b11e74","added_by":"auto","created_at":"2025-11-11 16:12:22","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18018,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/efe2f640b60fc1bdebe5120e.png"},{"id":95565655,"identity":"171d9178-3299-4586-9edf-bc178cf22b71","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"xml","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97011,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD25013120structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/c9d996075d3db3ce335b59ed.xml"},{"id":95565651,"identity":"804b34d3-abb2-477f-942c-001bda5d8d4b","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"html","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":105041,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/b9282d7570043e6069424668.html"},{"id":95565637,"identity":"5052ae7e-3f34-44c1-92aa-a6c7b12433a1","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":165965,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for progression free survival (PFS) and overall survival (OS) by clinicopathological factors. A and B: eosinophil count ratio, C and D: lymphocytes count ratio\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/4258c80dfda735488d91d806.png"},{"id":95565636,"identity":"4eee8ef3-33de-4515-a471-e18ccf56a3ef","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":118386,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for progression free survival (PFS) by eosinophil count ratio. A: Primary cases, B: Recurrence cases, and C: Cases with past radiation therapy\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/9311b75a3467556f76572ee3.png"},{"id":95565642,"identity":"e84b591c-bd9c-4c4d-b2ac-50aa3d68282a","added_by":"auto","created_at":"2025-11-10 16:17:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":119441,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier curves for progression free survival (PFS) by the lymphocytes count ratio. A: Primary cases, B: Recurrence cases, and C: Cases with past radiation therapy\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/8ccf94ea44fe1868740f6b90.png"},{"id":101151846,"identity":"206c3c0b-a946-447d-b00c-8b71910a8481","added_by":"auto","created_at":"2026-01-26 16:06:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1244324,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7964240/v1/13292797-eb4d-41be-8244-9d526da06024.pdf"}],"financialInterests":"","formattedTitle":"Peripheral Blood Lymphocyte and Eosinophil Dynamics with Chemotherapy and Pembrolizumab in Cervical Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical cancer is the fourth most common cancer worldwide, with 661,021 new cases and nearly 348,189 deaths reported in 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Metastatic cervical cancer has a poor prognosis, with a 5-year overall survival (OS) rate of only 19%. Thus, the development of effective treatment strategies is imperative [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecently, the KEY-NOTE826 trial, a phase 3 double-blind study evaluating pembrolizumab combined with chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer, demonstrated that pembrolizumab significantly improved progression-free survival (PFS) and OS compared with placebo [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, many aspects of the efficacy and prognostic implication of immune checkpoint inhibitors (ICIs) remain unknown, and identifying predictive markers of efficacy is essential to optimize their clinical application.\u003c/p\u003e\u003cp\u003eIn clinical practice, blood tests, such as the complete blood count (CBC), are important for cancer management [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], providing valuable insights into treatment response. The utility of blood tests in predicting the efficacy of ICIs across multiple malignancies has been reported. Recently, white blood cell differential counts, and increased lymphocyte or eosinophil counts, have emerged as markers of favorable treatment outcomes in patients with cancer receiving pembrolizumab.\u003c/p\u003e\u003cp\u003ePatients receiving pembrolizumab who exhibit higher baseline lymphocyte counts or favorable lymphocyte ratios tend to show better treatment outcomes. In cohorts with advanced urothelial carcinoma, increases in total lymphocytes and improvements in ratios (e.g., decreased neutrophil-to-lymphocyte ratio or increased CD4/CD8 ratio) coincided with clinical benefits [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Recent evidence also suggest that eosinophil count is associated with the therapeutic efficacy of ICIs in melanoma [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], lung cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and urothelial carcinoma [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, only a few studies have been conducted on the relationship between changes in peripheral blood leukocyte counts before and after pembrolizumab treatment and the effects of pembrolizumab in patients with cervical cancer.\u003c/p\u003e\u003cp\u003eIn this study, we focused on changes in peripheral lymphocyte and eosinophil counts pre-treatment and post-treatment to clarify the relationship between these changes and clinical outcomes of pembrolizumab plus taxane-platinum chemotherapy in metastasis and recurrent cervical cancer.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003e This retrospective study was reviewed and approved by the Institutional Review Board of Iwate Medical University (Iwate, Japan; approval no. MH2024027). Forty-one patients diagnosed with stage IVB cervical cancer according to the International Federation of Gynecology and Obstetrics [FIGO 2018] classification or with cervical cancer recurrence who received pembrolizumab plus taxane-platinum combination chemotherapy (with or without bevacizumab) at Iwate Medical University Hospital between January 2023 and December 2024 were included in this study.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMeasure of peripheral lymphocyte and eosinophil counts\u003c/h3\u003e\n\u003cp\u003ePeripheral lymphocyte and eosinophil counts were measured at the same time as the CBC before initial pembrolizumab initiation and three weeks after. Results were obtained from patient medical records. The ratio of peripheral lymphocyte and eosinophil counts before initial pembrolizumab initiation and three weeks later, we defined as the ratio of neutrophil count and lymphocyte count, respectively.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDifferences between patient groups were assessed using the chi-square test and paired t-test. Prognosis was evaluated using the Kaplan\u0026ndash;Meier method, and significant differences between groups were investigated using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived based on a stratified Cox regression model. Analyses were performed using GraphPad Prism version 10 (GraphPad Software, San Diego, CA, USA). All reported p-values were two-sided, and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003eForty-one patients with cervical cancer were included in this study: 24 (58.5%) had squamous cell carcinoma (SCC) and 17 (41.5%) had non-SCC. Of the total, 16 (39.0%) received primary treatment, and 25 (61.0%) were treated for recurrence. Histories of radiotherapy and chemotherapy were reported 21 (51.2%) and 12 (29.3%) patients, respectively.\u003c/p\u003e\u003cp\u003eDuring ICI treatment, 30 patients (73.2%) experienced immune-related adverse events (irAEs) of less than grade 2 and 11 patients (26.8%) experienced irAEs of grade\u0026thinsp;\u0026ge;\u0026thinsp;2. Regarding the best treatment response, eight patients (19.5%) achieved complete response, 19 (46.3%) had partial response, eight (19.5%) showed stable disease, and six (14.6%) had progressive disease. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\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\u003eCharacteristics of the study population.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge* (Median: 51)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;51\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (51.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; 51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20 (48.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment timing\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (39.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecurrence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (61.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24 (58.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-SCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17 (41.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrior RT\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (51.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20 (48.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrior CT\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12 (29.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e29 (70.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCombination with Bev\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (56.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (43.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eirAE\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (26.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30 (73.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBest response\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (19.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19 (46.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (19.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (14.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e*range:32\u0026ndash;79\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eBev; bevacizumab, CR; complete response, CT; chemotherapy, irAE; immune-related adverse events, PR; partial response, PD; progressive disease, RT; radiotherapy, SCC; squamous cell carcinoma, SD; stable disease\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eFactors for better PFS in patients with Pembrolizumab treatment\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the results of the evaluation of factors that improve PFS in patients with cervical cancer treated with pembrolizumab. The median follow-up time was 13 months (range 2\u0026ndash;29).\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\u003eThe Univariate and Multivariate analyses of the factors associated with the progression-free survival in patients who received pembrolizumab treatment.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" 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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnivariate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMultivariate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR (95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHR (95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt; 51\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e\u0026ge;51\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.212 (0.558\u0026ndash;2.672)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.626\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTreatment timing\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003cp\u003eRecurrence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1.727 (0.781\u0026ndash;4.082)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.189\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistological type\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSCC\u003c/p\u003e\u003cp\u003enonSCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1.215 (0.551\u0026ndash;2.640)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.622\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrior RT\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo\u003c/p\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1.149 (0.527\u0026ndash;2.508)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrior CT\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo\u003c/p\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1.762 (0.714\u0026ndash;3.976)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.189\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBev\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo\u003c/p\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0.419 (0.187\u0026ndash;0.910)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0.484 (0.214\u0026ndash;1.061)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.072\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eirAE\u0026thinsp;\u0026ge;\u0026thinsp;Grade 2\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNo\u003c/p\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0.231 (0.067\u0026ndash;0.614)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0.254 (0.073\u0026ndash;0.684)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWBC ratio\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDecreased\u003c/p\u003e\u003cp\u003eIncreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1.112 (0.496\u0026ndash;2.417)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.790\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph ratio\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDecreased\u003c/p\u003e\u003cp\u003eIncreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e0.683 (0.312\u0026ndash;1.493)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEosi ratio\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDecreased\u003c/p\u003e\u003cp\u003eIncreased\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e2.131 (0.870\u0026ndash;4.774)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eBev; bevacizumab, CRP; C-reactive protein, CT; chemotherapy, Eosi; eosinophils, irAE; immune-related adverse events, Lymph; Lymphocytes, RT; radiotherapy, SCC; squamous cell carcinoma, WBC; white blood cells, 95% CI; 95% confidence interval\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTo identify factors associated with PFS in this cohort, clinicopathological features, including peripheral blood lymphocyte count, eosinophil count, and PFS, were analyzed using Cox regression analysis. Univariate analysis of the relationship between these features and PFS revealed that bevacizumab use (p\u0026thinsp;=\u0026thinsp;0.029, HR: 0.419, 95% CI: 0.187\u0026ndash;0.910) and grade\u0026thinsp;\u0026gt;\u0026thinsp;2 irAE (p\u0026thinsp;=\u0026thinsp;0.008, HR: 0.231, 95% CI: 0.067\u0026ndash;0.614) were significant predictors of better prognosis. Multivariate analysis confirmed grade\u0026thinsp;\u0026gt;\u0026thinsp;2 irAE (p\u0026thinsp;=\u0026thinsp;0.014, HR: 0.254, 95% CI: 0.073\u0026ndash;0.684) as an independent prognostic factor for PFS.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRelationship of eosinophil and lymphocyte count ratio changes pre- and post-pembrolizumab treatment with prognosis\u003c/h3\u003e\n\u003cp\u003eAlthough no statistically significant differences were observed, patients with a decreased eosinophil count ratio tended to have a longer PFS than patients with an increased eosinophil count ratio (p\u0026thinsp;=\u0026thinsp;0.072, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Similarly, patients with an increased lymphocyte count ratio tended to have a longer PFS than patients with a decreased lymphocyte count ratio (p\u0026thinsp;=\u0026thinsp;0.321, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). However, no such associations were observed for OS (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, although the difference did not reach statistical significance, there was a trend toward longer progression-free survival (PFS) in the primary-disease group among patients with a decreased eosinophil count ratio (p\u0026thinsp;=\u0026thinsp;0.236).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn contrast, in the recurrent group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB, p\u0026thinsp;=\u0026thinsp;0.0002) and in patients with a history of radiotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC, p\u0026thinsp;=\u0026thinsp;0.0001), patients with a decreased eosinophil count ratio showed significantly longer PFS compared with patients with a increased eosinophil count ratio.. However, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, only patients who received primary treatment with an increased lymphocyte count ratio tended to have a longer PFS than those with a decreased lymphocyte count ratio (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, p\u0026thinsp;=\u0026thinsp;0.018). The opposite trend was observed in patients with recurrent disease or a history of radiotherapy, with no statistically significant differences observed in either case. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Supplementary Tables\u0026nbsp;1 and 2 summarize the associations between clinicopathological features and eosinophil and lymphocyte count ratios, respectively. No statistically significant differences were observed in clinicopathological features.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe analyzed the relationships between clinicopathological features, including peripheral blood lymphocyte count and eosinophil count, and PFS using Cox regression analysis to determine whether our patient characteristics were similar to those previously reported. In our study, bevacizumab use and grade\u0026thinsp;\u0026ge;\u0026thinsp;2 irAEs were associated with significantly better prognosis in the univariate analysis, and grade 2 irAEs were confirmed as independent prognostic factors for PFS in the multivariate analysis. A recent report further supports pembrolizumab plus chemotherapy, with or without bevacizumab, as the standard of care for patients with persistent, recurrent, or metastatic cervical cancer [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Other recent studies have also suggested a correlation between irAEs and the efficacy of pembrolizumab in patients with various cancers [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Das et al. reported that irAE onset is an indicator of immune activation and may be associated with antitumor effects [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Our cohort reflets these factors.\u003c/p\u003e\u003cp\u003ePeripheral differential white blood cell count may serve as a biomarker for ICI treatment [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, only a few reports exist on this relationship in cervical cancer. Therefore, we performed a prognostic analysis of eosinophil and lymphocyte counts and examined intergroup differences using the Kaplan\u0026ndash;Meier method and the log-rank test. Patients with higher eosinophil ratios before pembrolizumab treatment tended to have shorter PFS compared with those with lower ratios. This trend was particularly significant in patients with recurrence or a history of radiation therapy. Patients with higher lymphocyte ratios tended to have longer PFS, and this trend was particularly evident in patients with initial disease; however, the opposite trend was observed in patients with recurrent disease or a history of radiation therapy, with no statistically significant differences observed in either case.\u003c/p\u003e\u003cp\u003eIncreased peripheral blood eosinophil count has been associated with improved pembrolizumab efficacy across several cancers, as indicated by both baseline and post-treatment measurements. In advanced urothelial carcinoma, two studies suggest that decreased relative eosinophil count at three weeks predicts worse OS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], whereas one study suggests that a post-treatment relative count of at least 4.8% is linked to improved survival [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In metastatic melanoma, a baseline relative eosinophil count\u0026thinsp;\u0026ge;\u0026thinsp;1.5% is associated with favorable OS [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the present study, unlike previous reports on other cancers, patients with higher eosinophil count ratios before and after pembrolizumab treatment tended to have shorter PFS compared with those with lower ratios. This may be owing to differences in clinical backgrounds between these studies. In our study, pembrolizumab was administered in combination with chemotherapy to patients with cervical cancer according to the KEY-NOTE826 trial [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. By contrast, in other studies on ureteral cancer [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and melanoma [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] treated with pembrolizumab monotherapy, an association was observed between increased eosinophil count and pembrolizumab efficacy. Osawa et al. also reported differences between pembrolizumab therapy combined with chemotherapy and pembrolizumab monotherapy, reporting an association only with pembrolizumab monotherapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Their suggested reason is that bone marrow suppression caused by antitumor drugs leads to complex changes in peripheral blood cells [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOver half of patients in the present study had a history of radiotherapy. Reports have shown that pelvic radiotherapy is strongly associated with bone marrow suppression and hematologic toxicity in patients receiving concurrent chemoradiotherapy for rectal and cervical cancers [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and have identified correlations between radiation dose and volume parameters and acute bone marrow suppression. Specifically, the volume of pelvic bone receiving low-to-moderate doses was significantly associated with higher grades of bone marrow suppression [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This phenomenon may also lead to complex changes in peripheral blood cells, similar to the bone marrow suppression caused by antitumor drugs. Recent studies have shown a significant relationship between eosinophil count and cervical cancer. Higher pretreatment eosinophil levels and increased post-pre-radiotherapy eosinophil ratios were associated with worse PFS and OS in patients with cervical squamous cell carcinoma patients [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The reason for this is unclear, but it is possible that patients with cervical cancer who have undergone radiation therapy experience changes in peripheral blood eosinophil counts that differ from those observed in patients with other types of cancer. Moreover, in the present study, log-rank test showed a significant prolongation of PFS in the low-eosinophil group of patients with a history of radiation therapy.\u003c/p\u003e\u003cp\u003eSeveral reports have shown that PFS is significantly longer with elevated pre-post treatment peripheral lymphocyte counts in patients with advanced non-small cell lung cancer treated with ICIs, including ICIs combined with chemotherapy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the present study, although no significant differences were observed in all cases, patients whose lymphocyte counts increased before and after treatment tended to have longer PFS. This tendency was particularly evident in patients with no prior treatment history, with a statistically significant difference. However, this tendency was not observed in patients with a history of radiation therapy or recurrence.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, it was a single-center study with a limited number of cases. A multicenter study with a large number of patients and long-term analysis is necessary to investigate the association between changes in peripheral blood leukocyte fractions and pembrolizumab use in cervical cancer. Second, further studies are needed to clarify the differences in the effects of pembrolizumab and changes in eosinophil counts between cervical cancer and other cancers.\u003c/p\u003e\u003cp\u003eIn conclusion, among patients with cervical cancer treated with pembrolizumab in combination with chemotherapy, a trend toward longer PFS was observed in those whose post-treatment eosinophil counts were lower than their pre-treatment levels, particularly among patients with a history of radiotherapy. Further studies are warranted to determine whether this finding could serve as a predictive biomarker of pembrolizumab efficacy in cervical cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthical approval and consent to participate\u003c/h2\u003e\u003cp\u003e This study was performed in accordance with the Declaration of Helsinki and was reviewed and approved by the Institutional Review Board of Iwate Medical University (Approval No. MH2024027).\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e\u003cp\u003eSS and MK conceived and designed the study. SS, MK, and TB performed the experiments. SS, MK, DS, HO, and YC analyzed the data. AJ, HO, AK, MM, NJ, ET, YK, TN, and TS prepared the materials. SS, MK and TB drafted the manuscript. SS and MK confirmed the authenticity of all raw data. All the authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eWe are grateful to all patients, their families, oncologists, allied healthcare professionals, and research assistants who participated in this study.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74 (3):229-263. doi:10.3322/caac.21834\u003c/li\u003e\n\u003cli\u003eSiegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A (2025) Cancer statistics, 2025. CA: A Cancer Journal for Clinicians 75 (1):10-45. doi:https://doi.org/10.3322/caac.21871\u003c/li\u003e\n\u003cli\u003eColombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Ya\u0026ntilde;ez E, G\u0026uuml;m\u0026uuml;ş M, Olivera Hurtado de Mendoza M, Samou\u0026euml;lian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ (2021) Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med 385 (20):1856-1867. doi:10.1056/NEJMoa2112435\u003c/li\u003e\n\u003cli\u003eHolub K, Biete A (2019) Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients. Clin Transl Oncol 21 (7):836-844. doi:10.1007/s12094-018-1991-4\u003c/li\u003e\n\u003cli\u003eKadono Y, Kawaguchi S, Nohara T, Shigehara K, Izumi K, Kamijima T, Seto C, Takano A, Yotsuyanagi S, Nakagawa R, Miyagi T, Aoyama S, Asahi H, Fukuda R, Mizokami A (2021) Blood Cell Count Biomarkers Predicting Efficacy of Pembrolizumab as Second-line Therapy for Advanced Urothelial Carcinoma. Anticancer Res 41 (3):1599-1606. doi:10.21873/anticanres.14921\u003c/li\u003e\n\u003cli\u003eWendlinger S, Wohlfarth J, Kreft S, Siedel C, Kilian T, Dischinger U, Heppt MV, Wistuba-Hamprecht K, Meier F, Goebeler M, Schadendorf D, Gesierich A, Kosnopfel C, Schilling B (2022) Blood Eosinophils Are Associated with Efficacy of Targeted Therapy in Patients with Advanced Melanoma. Cancers (Basel) 14 (9). doi:10.3390/cancers14092294\u003c/li\u003e\n\u003cli\u003eOsawa H, Shiozawa T, Okauchi S, Sasatani Y, Ohara G, Sato S, Miyazaki K, Kodama T, Kagohashi K, Satoh H, Hizawa N (2021) Absolute Increase in the Number and Proportion of Peripheral Eosinophils Associated With Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer Patients. Cancer Diagn Progn 1 (5):485-490. doi:10.21873/cdp.10065\u003c/li\u003e\n\u003cli\u003eOsawa H, Shiozawa T, Okauchi S, Miyazaki K, Kodama T, Kagohashi K, Nakamura R, Satoh H, Hizawa N (2021) Association between time to treatment failure and peripheral eosinophils in patients with non-small cell lung cancer treated with immune checkpoint inhibitors. Pol Arch Intern Med 131 (10). doi:10.20452/pamw.16049\u003c/li\u003e\n\u003cli\u003eFurubayashi N, Minato A, Negishi T, Sakamoto N, Song Y, Hori Y, Tomoda T, Harada M, Tamura S, Miura A, Komori H, Kuroiwa K, Seki N, Fujimoto N, Nakamura M (2022) Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab. Cancer Manag Res 14:1641-1651. doi:10.2147/cmar.S360473\u003c/li\u003e\n\u003cli\u003eLorusso D, Colombo N, Dubot C, C\u0026aacute;ceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Ya\u0026ntilde;ez E, G\u0026uuml;m\u0026uuml;ş M, Olivera M, Samou\u0026euml;lian V, Castonguay V, Arkhipov A, Li K, Toker S, Tekin C, Tewari KS, Monk BJ (2025) Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study. Ann Oncol 36 (1):65-75. doi:10.1016/j.annonc.2024.10.002\u003c/li\u003e\n\u003cli\u003eNoguchi S, Suminaga K, Kaki T, Kawachi H, Fukao A, Terashita S, Horikawa S, Ikeue T, Sugita T (2020) Correlation of Immune-Related Adverse Events and Effects of Pembrolizumab Monotherapy in Patients with Non-Small Cell Lung Cancer. Lung Cancer (Auckl) 11:53-57. doi:10.2147/lctt.S254146\u003c/li\u003e\n\u003cli\u003eKobayashi K, Suzuki K, Hiraide M, Aoyama T, Yokokawa T, Shikibu S, Hashimoto K, Iikura Y, Sato H, Sugiyama E, Tajima M, Hama T (2020) Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma. Oncology 98 (4):237-242. doi:10.1159/000505340\u003c/li\u003e\n\u003cli\u003eDas S, Johnson DB (2019) Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer 7 (1):306. doi:10.1186/s40425-019-0805-8\u003c/li\u003e\n\u003cli\u003eAlessi JV, Ricciuti B, Alden SL, Bertram AA, Lin JJ, Sakhi M, Nishino M, Vaz VR, Lindsay J, Turner MM, Pfaff K, Sharma B, Felt KD, Rodig SJ, Gainor JF, Awad MM (2021) Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer. J Immunother Cancer 9 (11). doi:10.1136/jitc-2021-003536\u003c/li\u003e\n\u003cli\u003eYanazume S, Kobayashi Y, Kirita Y, Kitazono I, Nagata C, Kozai A, Tanimoto A, Kobayashi H (2025) A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab. J Obstet Gynaecol Res 51 (1):e16182. doi:10.1111/jog.16182\u003c/li\u003e\n\u003cli\u003eMorimoto H, Tsujikawa T, Miyagawa-Hayashino A, Kimura A, Saburi S, Murakami N, Kitamoto K, Mukudai S, Nagao H, Saya S, Ogi H, Konishi E, Itoh K, Hirano S (2024) Neutrophil-to-lymphocyte ratio associates with nutritional parameters, intratumoral immune profiles, and clinical outcomes of pembrolizumab in head and neck squamous cell carcinoma. Head Neck 46 (8):1956-1964. doi:10.1002/hed.27671\u003c/li\u003e\n\u003cli\u003eFurubayashi N, Minato A, Negishi T, Sakamoto N, Song Y, Hori Y, Tomoda T, Tamura S, Kuroiwa K, Seki N, Fujimoto N, Nakamura M (2021) The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab. Cancer Manag Res 13:8049-8056. doi:10.2147/cmar.S333823\u003c/li\u003e\n\u003cli\u003eWeide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, Simeone E, Mangana J, Schilling B, Di Giacomo AM, Brenner N, K\u0026auml;hler K, Heinzerling L, Gutzmer R, Bender A, Gebhardt C, Romano E, Meier F, Martus P, Maio M, Blank C, Schadendorf D, Dummer R, Ascierto PA, Hospers G, Garbe C, Wolchok JD (2016) Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clin Cancer Res 22 (22):5487-5496. doi:10.1158/1078-0432.Ccr-16-0127\u003c/li\u003e\n\u003cli\u003eFranco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Racca P, Morino M, Numico G, Ricardi U (2017) Hematologic toxicity in anal cancer patients during combined chemo-radiation: a radiation oncologist perspective. Expert Rev Anticancer Ther 17 (4):335-345. doi:10.1080/14737140.2017.1288104\u003c/li\u003e\n\u003cli\u003eZhang B-Z, Li Y, Xu L-M, Chai Y-L, Qu C, Cao Y-J, Wang J, Hou H-L, Zhang J (2023) The relationship between the radiation dose of pelvic-bone marrow and lymphocytic toxicity in concurrent chemoradiotherapy for cervical cancer. Radiation Oncology 18 (1):12. doi:10.1186/s13014-023-02205-8\u003c/li\u003e\n\u003cli\u003eKonnerth D, Gaasch A, Zinn A, Rogowski P, Rottler M, Walter F, Knoth J, Sturdza A, Oelmann J, Grawe F, Bodensohn R, Belka C, Corradini S (2024) Hematologic Toxicity and Bone Marrow-Sparing Strategies in Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review. Cancers (Basel) 16 (10). doi:10.3390/cancers16101842\u003c/li\u003e\n\u003cli\u003eKumar T, Schernberg A, Busato F, Laurans M, Fumagalli I, Dumas I, Deutsch E, Haie-Meder C, Chargari C (2019) Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation. Cancer Manag Res 11:6285-6297. doi:10.2147/cmar.S195989\u003c/li\u003e\n\u003cli\u003eZhu J, Wang H, Gao MJ, Li YF, Huang YQ, Shi JP, Wang WJ (2019) Prognostic values of lymphocyte and eosinophil counts in resectable cervical squamous cell carcinoma. Future Oncol 15 (30):3467-3481. doi:10.2217/fon-2018-0879\u003c/li\u003e\n\u003cli\u003eQin A, Street L, Cease K, Viglianti BL, Warren EH, Zhao L, Ramnath N (2017) Clinical Determinants of Durable Clinical Benefit of Pembrolizumab in Veterans With Advanced Non-Small-Cell Lung Cancer. Clin Lung Cancer 18 (5):559-564. doi:10.1016/j.cllc.2017.01.012\u003c/li\u003e\n\u003cli\u003eLee YJ, Park YS, Lee HW, Park TY, Lee JK, Heo EY (2022) Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer. Scientific Reports 12 (1):626. doi:10.1038/s41598-021-04630-9\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"cervical cancer, immune checkpoint inhibitor, white blood cell differential counts","lastPublishedDoi":"10.21203/rs.3.rs-7964240/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7964240/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCervical cancer poses a significant global health burden, particularly in its metastatic and recurrent forms, for which treatment options are limited. Although immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes, predictive markers for efficacy are still undefined. This retrospective study investigated changes in peripheral blood eosinophil and lymphocyte counts as potential prognostic indicators in patients with metastatic or recurrent cervical cancer undergoing pembrolizumab-based therapy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eForty-one patients treated with pembrolizumab plus taxane-platinum chemotherapy (\u0026plusmn;\u0026thinsp;bevacizumab) were analyzed. Peripheral blood eosinophil and lymphocyte counts were measured before and three weeks after treatment initiation. Statistical analyses included Kaplan\u0026ndash;Meier curves, Cox regression, and log-rank tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eImmune-related adverse events\u0026thinsp;\u0026ge;\u0026thinsp;Grade 2 emerged as a significant independent factor associated with prolonged progression-free survival (PFS) in this cohort (p\u0026thinsp;=\u0026thinsp;0.014). Patients with decreased eosinophil count ratios post-treatment demonstrated longer PFS, particularly among those with recurrence and those who had received prior radiotherapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, increased lymphocyte count ratios correlated with improved PFS in patients undergoing primary treatment (p\u0026thinsp;=\u0026thinsp;0.018).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eChanges in peripheral eosinophil and lymphocyte counts following pembrolizumab initiation may serve as predictive indicators of treatment efficacy in specific cervical cancer subgroups. Incorporating these hematologic parameters could help optimize patient selection and therapeutic strategies. Further research is needed to clarify their role as predictive markers of pembrolizumab efficacy in cervical cancer.\u003c/p\u003e","manuscriptTitle":"Peripheral Blood Lymphocyte and Eosinophil Dynamics with Chemotherapy and Pembrolizumab in Cervical Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 16:16:55","doi":"10.21203/rs.3.rs-7964240/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2025-11-17T22:32:40+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-10-29T11:45:27+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-29T09:49:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-29T05:56:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2025-10-27T20:09:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ce7261fe-dd73-4165-8ded-515d347a8ecf","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:02:59+00:00","versionOfRecord":{"articleIdentity":"rs-7964240","link":"https://doi.org/10.1007/s10147-026-02960-0","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2026-01-22 15:58:13","publishedOnDateReadable":"January 22nd, 2026"},"versionCreatedAt":"2025-11-10 16:16:55","video":"","vorDoi":"10.1007/s10147-026-02960-0","vorDoiUrl":"https://doi.org/10.1007/s10147-026-02960-0","workflowStages":[]},"version":"v1","identity":"rs-7964240","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7964240","identity":"rs-7964240","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}