Neoadjuvant Sintilimab Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Study

Neoadjuvant Sintilimab Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Study | 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 Neoadjuvant Sintilimab Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Study Congcong Wang, Lulu XU, Zeyu LIU, Fenge JIANG, Jiannan LIU, Ping SUN, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4580244/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Immunotherapy has demonstrated promise in treating advanced esophageal cancer, yet evidence on neoadjuvant immunotherapy for locally advanced cases remains limited. This study aimed to assess the efficacy and safety of immunotherapy combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: A retrospective review of 54 patients undergoing radical esophageal cancer surgery following neoadjuvant immunotherapy combined with chemotherapy was conducted. The treatment regimen consisted of sintilimab (200mg) with albumin paclitaxel (100 mg/m2 on days 1 and 8) and cisplatin (75 mg/m2 on day 1) every 3 weeks. Efficacy and safety were evaluated, alongside peripheral blood lymphocyte subpopulation counts and clinicopathological characteristics to identify predictive factors of neoadjuvant efficacy. Results: All 54 patients underwent surgery, with 53(98.1%) achieving R0 resection. Pathological complete response (pCR) was observed in 22(40.7%) patients. The overall response rate (ORR) was 83.3% (45/54) and the DCR was 100.00% (54/54). A significant association between pCR and CD4+/CD8+ ratio and frequency of CD4+ T cell (p = 0.01, p = 0.01) was identified. Conclusions: Neoadjuvant immunochemotherapy combining sintilimab with chemotherapy resulted in favorable clinical outcomes in locally advanced ESCC, accompanied by well tolerability. Peripheral blood CD4+/CD8+ ratio and frequency of CD4+ T cell emerged as promising predictive biomarkers for treatment efficacy. Neoadjuvant immunochemotherapy Sintilimab Lymphocyte subpopulation Pathological complete response locally advanced ESCC Introduction Esophageal cancer ranks as the seventh most common malignancy worldwide [ 1 ]. This disease is primarily categorized into two histologic subtypes: esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC). ESCC is the predominant subtype in Eastern Asia and Sub-Saharan Africa, representing over 90% of cases in these regions [ 2 – 3 ]. At diagnosis, the majority of patients present with locally advanced disease, and the five-year survival rates for those treated with surgery alone at stages II-III range from only 20.6–34% [ 4 ]. The pressing need to enhance resection rates and improve long-term survival has led to increased emphasis on a multidisciplinary approach, integrating neoadjuvant therapy with surgical management. Currently, there is no consensus on a standard protocol for neoadjuvant therapy in ESCC, and the choice between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy remains a subject of debate [ 5 – 6 ]. Immunotherapy, particularly with immune checkpoint inhibitors (ICIs), has shown significant promise in the treatment of advanced or metastatic ESCC and is now broadly implemented in clinical practice [ 7 ]. Key studies such as KEYNOTE-181[ 8 ], ATTRACTION-3[ 9 ], and ESCORT [ 10 ] have demonstrated the superiority of ICIs over chemotherapy in the second-line treatment setting. Further pivotal trials, including KEYNOTE-590[ 11 ], CheckMate-648[ 12 ], ESCORT 1st [ 13 ], and ORIENT-15[ 14 ], have positioned immunotherapy at the forefront of the treatment paradigm for advanced ESCC. Ongoing investigations into neoadjuvant immunotherapy for locally advanced ESCC, such as the NICE [ 15 ] and KEYSTONE-001[ 16 ] studies, have reported favorable outcomes in terms of efficacy and safety, alongside high rates of pathological response and R0 resection rates. Despite these advancements, responses to neoadjuvant therapy among esophageal cancer patients are highly variable. Currently, there are no universally accepted treatment regimens or biomarkers for assessing efficacy in the predominant patient population. Peripheral blood lymphocyte subpopulations, crucial components of the immune response, have been identified as potential biomarkers. Emerging research emphasizes the importance of maintaining a dynamic equilibrium among these subpopulations for effective immune function. This study aims to assess the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy for treating locally advanced ESCC in a real-world context, while also exploring the potential of peripheral blood lymphocyte subpopulations as biomarkers for predicting therapy responses. Methods Patients This study enrolled 54 patients from November 2019 to March 2023 who met the following inclusion criteria: histologically confirmed, potentially curable ESCC staged as cT1N1-3M0 or cT2-4aN0-3M0 according to the Union for International Cancer Control TNM Classification, 8th Edition; aged 18–75 years; an ECOG performance status of 0 or 1; at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1; suitability for curative resection; adequate pulmonary and cardiac function; and normal organ function. Patients were excluded if they had a history of autoimmune disease, infectious disease, or other serious medical conditions. Treatments and assessment Patients received 2-4 cycles of neoadjuvant therapy consisting of sintilimab (200 mg every three weeks) combined with chemotherapy, which included albumin-bound paclitaxel (100 mg/m² on days 1 and 8) and cisplatin (75 mg/m² on day 1). The patients were closely monitored for toxic effects using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Complete pathological response (pCR) was defined as the absence of tumor cells in the resected tissue specimen. Tumor response was evaluated via computed tomography (CT) scan, using RECIST version 1.1 criteria. The overall response rate (ORR) was defined as the proportion of patients achieving either a complete response (CR) or a partial response (PR). The disease control rate (DCR) was determined as the proportion of patients with CR, PR, or stable disease (SD). Clinicopathologic data collected included age, sex, underlying diseases, tumor stage and location, lymphocyte subpopulation counts (frequency of CD4+ T cells, frequency of CD8+ T cells, and CD4+/CD8+ ratio), and PD-L1 expression. Peripheral blood was sampled to analyze lymphocyte subpopulation counts before and after neoadjuvant therapy, specifically assessing the frequency of CD4+T cells (CD3+ CD4+ T cells), frequency of CD8+T cells (CD3+ CD8+ T cells), and the CD4+/CD8+ ratio. PD-L1 expression was detected using immunohistochemistry and quantified based on the Combined Positive Score (CPS). PD-L1 expression levels were categorized as negative (CPS < 10) and positive (CPS ≥ 10). Statistical Analysis T-test was utilized for continuous variables and the Fisher exact test for categorical variables, to evaluate the correlation between pCR rates and variables such as age, smoking status, alcohol consumption history, clinical stage, and PD-L1 expression. Data conforming to a normal distribution were presented as mean ± standard deviation and analyzed using independent samples t-tests. P-values reported are two-sided, with a significance threshold set at 0.05. Statistical analyses were performed using SPSS version 23.0. Results Baseline Characteristics Between November 1, 2019, and March 31, 2023, a total of 54 ESCC patients were included for the final analysis. The cohort consisted predominantly of males (n=48) with a median age of 60.6 years (range 45–70 years) (Table 1). The majority were smokers (n=46), drinkers (n=45), and 28 patients had no underlying diseases. Most tumors were located in the middle (57.4%) and distal third (37.0%) of the esophagus, with 42 patients (77.8%) at stage III and 12 (22.2%) at stage IVA. All patients completed at least two cycles of neoadjuvant therapy Efficacy results R0 resection was successfully achieved in 53 of the 54 patients (98.1%). Among those who achieved R0 resection, 22 (40.7%) attained a pCR as shown in Table 3. Out of the 54 patients, 23 attained a CR, 22 saw a PR, and 9 maintained SD. This resulted in an ORR of 83.33% (45 out of 54 patients), with a DCR of 100% across all 54 patients. In addition, association between treatment outcomes and clinicopathological characteristics was examined (Table 5). Peripheral blood lymphocyte subpopulation counts of 48 patients were assessed prior to neoadjuvant therapy. No significant associations were observed regarding gender, smoking history, alcohol consumption, treatment duration, tumor location, clinical stage, or PD-L1 expression. Among these patients, 20 achieved a pCR. Significantly, the CD4+/CD8+ ratio and CD4+ T cell frequency was associated with pCR (p = 0.01 for both). Biomarker analysis Among the 24 patients who underwent peripheral blood lymphocyte subpopulation analysis before and after neoadjuvant therapy, post-treatment assessments revealed notable increases in the frequencies of CD4+ T cells and CD4+/CD8+ ratios, accompanied by a decrease in CD8+ T cell frequency. These alterations were statistically significant (P < 0.05) (Table 4). Safety results Out of the 54 patients, 36 (66.7%) experienced treatment-related adverse events (Table 2). The majority of TRAEs were mild to moderate in severity (grade 1-2), with a 25.9% incidence of Grade 3-4 adverse events. The most common TRAEs included alopecia (57.4%), decreased neutrophil count (53.7%), and decreased white blood cell count (51.9%). Four patients(12.5%) required a dose reduction of cisplatin due to myelosuppression. All TRAEs were manageable, and no patients withdrew from the study due to adverse effects or disease progression. Discussion ICIs have demonstrated notable efficacy in the management of esophageal cancer, progressively transitioning from the adjuvant to the second-line [ 8 – 10 ], the first-line [ 11 – 13 ], and even perioperative settings [ 17 ]. Moreover, treatment paradigms have evolved from monotherapy to combination regimens. The ORIENT-15 study, has achieved its primary research endpoints. In the overall population, the median Overall Survival (OS) reached 16.7 months, resulting in a 37% reduction in the risk of death. Among patients with PD-L1 CPS ≥ 10, the median OS in both groups was 17.2 months versus 13.6 months, representing a approximately 36% reduction in the risk of death. These findings underscore the promising therapeutic efficacy of sintilimab [ 14 ]. Studies concerning whether preoperative immunotherapy in combination with chemotherapy or chemoradiotherapy can yield enhanced therapeutic outcomes are ongoing. The PERFECT study, based on the CROSS study regimen combined with Atezolizumab for five cycles, recently published its results. However, no significant differences were observed in pCR rates (25% vs 20.1%) and median OS (29.7 months vs 34.3 months) [ 18 ]. Additionally, PALACE-1[ 19 ], focusing on esophageal squamous cell carcinoma patients, incorporated Pembrolizumab into the CROSS study regimen, resulting in a postoperative pCR rate of 55.6% [ 1 ]. These clinical studies suggest that immunotherapy may exert a greater effect on esophageal squamous cell carcinoma compared to adenocarcinoma. Given the higher likelihood of complications and mortality following neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy, research into neoadjuvant chemotherapy combined with immunotherapy is also underway. Results from the phase II NICE study, investigating neoadjuvant treatment for locally advanced thoracic esophageal squamous cell carcinoma with multi-station lymph node metastasis, revealed that 55 (91.7%) out of 60 patients received two cycles of neoadjuvant treatment. Among the 47 patients undergoing surgery, 7 (14.9%) experienced TRAEs resulting in delay, while 20 (42.5%) achieved pCR. The incidence rate of Grade 3–5 TRAEs was 53.3% [ 15 ]. Similar ongoing auxiliary studies are investigating Nivolumab [ 20 ], Pembrolizumab [ 16 ], and Toripalimab [ 21 ]. In the previously discussed research, neoadjuvant immunotherapy demonstrated encouraging results, including a notable achievement of a promising pCR rate, along with safety, feasibility, and the absence of operational delays, underscoring its potential efficacy. However, discrepancies in the effectiveness of neoadjuvant immunotherapy when paired with chemoradiotherapy or chemotherapy were observed. In some cases, outcomes did not surpass those achieved with concurrent chemoradiotherapy. This variation could be ascribed to variances in drug selection, timing, and duration of neoadjuvant immunotherapy protocols. In our study, R0 resection was accomplished in 53 patients (98.1%). Among these R0 resection patients , the pCR rate was 40.7%, and TRAEs ≥ Grade 3 were observed in 25.9% of cases. Although the pCR rate was slightly lower compared to the NICE study [ 15 ] and the KEYSTONE-001 study [ 16 ], our results still demonstrated favorable therapeutic efficacy and safety, particularly noteworthy given the advanced disease stage of the enrolled patients, classified as stage III and IV. Considering the distinct mechanisms of action between chemotherapy and immunotherapy, the pathological response and histopathological characteristics may vary. Consequently, meticulous evaluation of treatment response is crucial in the context of ongoing clinical trials involving neoadjuvant immunotherapy. Notably, neoadjuvant pCR has been established as a predictive marker for survival outcomes [ 22 ]. Both imaging and pathological assessments were utilized in our study to comprehensively, thoroughly, and standardly evaluate treatment efficacy. The ORR reached 83.33%, with preoperative CT evaluations largely aligning with final pathological evaluations. Numerous ongoing clinical trials have investigated immunotherapy-related biomarkers, with PD-L1 expression demonstrating promising predictive potential and practical application [ 23 ]. However, accurately discerning the population that benefits most from immunotherapy remains a challenge. Existing research on biomarkers predicting immunotherapy efficacy predominantly stems from advanced esophageal cancer clinical trials. The translatability of validated biomarkers' predictive abilities to perioperative settings is a critical issue warranting exploration. As research into tumor immunology progresses, the body's immune function emerges as a pivotal factor in various tumor developments, particularly concerning lymphocyte subpopulations. Dysregulation in lymphocyte subpopulation levels often signifies immune system dysfunction [ 24 ]. Normally, lymphocyte subpopulation numbers and proportions fall within specific ranges [ 25 ]. Decreases in CD4 + T lymphocyte levels indicate diminished lymphoid factors, while decreases in CD8 + lymphocyte levels suggest inhibited cellular immunity [ 26 ]. Moreover, under physiological conditions, the CD4+/CD8 + ratio maintains dynamic equilibrium, with decreases indicating T lymphocyte imbalances [ 27 ]. In our study, post-treatment frequencies of CD4 + T cells and CD4+/CD8 + ratios were significantly higher than pre-treatment levels, while CD8 + T cell frequencies were notably lower, indicating restored immune function upon tumor control. Additionally, lower CD4+/CD8 + ratios or CD4 + T cell frequencies were significantly associated with higher pCR rates, suggesting that peripheral blood CD4+/CD8 + ratios and CD4 + T cell frequencies could serve as novel indicators for predicting neoadjuvant immunotherapy efficacy in patients with locally advanced esophageal squamous cell carcinoma [28]. In conclusion, our study demonstrated encouraging efficacy of chemotherapy in combination with sintilimab for locally advanced esophageal squamous cell carcinoma, achieving a pCR rate of 40.7%. TRAEs were manageable, indicating the treatment's tolerability. These promising results warrant further investigation in clinical trials to fully evaluate the effects and safety profile. Additionally, the CD4+/CD8 + ratio and the frequency of CD4 + T cells may serve as pivotal independent biomarkers for identifying suitable candidates for neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma. However, the applicability and reliability of these biomarkers require confirmation through prospective, multicenter randomized controlled studies. Declarations Ethics approval This study was approved by the Medical Ethical Committee of Yuhuangding Hospital Affiliated with Qingdao University. The written informed consent was obtained from each patient. Fundings Not applicable. References Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68: 394-424. Abnet CC, Arnold M and Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology, 2018, 154: 360-373. Miyata H, Yamasaki M, Kurokawa Y, et al. Survival factors in patients with recurrence after curative resection of esophageal squamous cell carcinomas. Ann Surg Oncol, 2011, 18: 3353-3361. Ohashi S, Miyamoto S, Kikuchi O, et al. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology, 2015, 149: 1700-1715. Arnott SJ, Duncan W, Gignoux M, et al. Preoperative radiotherapy for esophageal carcinoma. Cochrane Database Syst Rev. 2005, 4: CD001799. Iizuka T, Ide H, Kakegawa T, et al. Preoperative radioactive therapy for esophageal carcinoma. Randomized evaluation trial in eight institutions. Chest, 1988, 93(5): 1054‐1058. Huang TX, Fu L. The immune landscape of esophageal cancer. Cancer Commun (Lond) 2019, 39(1): 79. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION‐3): a multicentre, randomised, open‐label, phase 3 trial. Lancet Oncol, 2019, 20(11): 1506‐1517. Kojima T, Shah MA, Muro K, et al. Randomized phase Ⅲ KEYNOTE‐181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol, 2020, 38(35): 4138‐4148. Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator′s choice of chemotherapy as second‐line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open‐label, phase 3 study. Lancet Oncol, 2020, 21(6): 832‐842. Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet, 2021, 398(10302): 759-771. Chau I, Doki Y, Ajani JA, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study. J Clin Oncol, 2021, 39(18_suppl): LBA4001-LBA4001. Luo HY, Lu J, Bai YX, et al. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA, 2021, 326(10): 916-925. Lu ZH, Wang JY, Shu YQ, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ, 2022, 377:e068714. Liu J, Li Z, Fu X, et al. 127P A prospective phase II clinical trial exploring neoadjuvant immunotherapy combined with chemotherapy in resectable thoracic esophageal squamous cell cancer(TESCC) with multi-station lymph node metastases (NICE study): preliminary results. Ann Oncol, 2020, 31: S1292. Shang XB, Zhao G, Liang F, et al. Safety and effectiveness of pembrolizumab combined with paclitaxel and cisplatin as neoadjuvant therapy followed by surgery for locally advanced resectable (stage III) esophageal squamous cell carcinoma: a study protocol for a prospective, single-arm, single-center, open-label, phase-II trial (Keystone-001). Ann Transl Med. 2022,10(4): 229. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021, 384(13):1191-1203. van den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT). Clin Cancer Res, 2021, 27(12): 3351-3359. Li CQ, Zhao SG, Zheng YY, et al. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma( PALACE-1)． Eur J Cancer, 2021, 144: 232-241． Yamamoto S，Kato K，Daiko H，et al. Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E). Future Oncol, 2020, 16(19) : 1351-1357． Zheng Y, Liu XB, Sun HB, et al. A phase Ⅲ study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909). Ann Transl Med, 2021, 9(1): 73． Lin JW, HSU CP, YEH HL, et al. The impact of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced squamous cell carcinoma of esophagus. J Chin Med Assoc, 2018, 81(1): 18-24. Qu HX, Zhao LP, Zhan SH, et al. Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis. J Thorac Dis, 2016, 8 (11): 3197-3204． Yan Y, Wang XY, Liu CN, et al. Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.BMC Pulm Med, 2022, 22(1): 166. GUO H, KUANG P, LUO Q, et al. Effects of sodium fluoride on blood cellular and humoral immunity in mice. Oncotarget, 2017, 8(49): 85504-85515. Philip M, Schietinger A. CD8+T cell differentiation and dysfuction in cancer. Nat Rev Immunol, 2022, 22(4): 209-223. Lee PH, Yang TY, Chen KC, et al. Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors. Sci Rep, 2021, 11(1): 9381. Tables Table1 Patient characteristics at baseline Characteristic NO. of Patients(%)(N=54) Age Median 60.6 Range 45-70 Gender Male 48 Female 6 Smoking history Yes 46 NO 8 Drinking history Yes 45 NO 9 Basis disease None 28 Hypertension 15 Heart disease 8 Diabetes 7 ECOG 0 12 1 42 Tumour location Proximal third 3 Middle third 31 Distal third 20 Clinical T stage cT1 0 cT2 5 cT3 42 cT4a 7 Clinical N stage N0 0 N1 34 N2 15 N3 5 PD-L1（CPS） ≥10 24 <10 26 Not available 4 ECOG, eastern cooperative oncology group Table 2 Adverse events Adverse Event Grade1-2 No. of patients (%) Grade3-4 No. of patients (%) All Grade No. of patients (%) Anaemia 25(46.3) 6(11.1) 31(57.4) White blood cell count decreased 23(42.6) 5(9.3) 28(51.9) Neutrophil count decreased 23(42.6) 6(11.1) 29(53.7) Nausea 17(31.5) 0 17(31.5) Fatigue 13(24.1) 0 13(24.1) Vomiting 11(20.4) 0 11(20.4) Alopecia 11(20.4) 0 11(20.4) Decreased appetite 9(16.7) 0 9(16.7) Rash 7(13.0) 1(1.9) 8(14.8) Platelet count decreased 6(11.1) 0 6(11.1) Hypothyroisdism 6(11.1) 0 6(11.1) Diarrhea 5(9.3) 0 5(9.3) Liver dysfunction 5(9.3) 1(1.9) 6(11.1) Neurotoxic effects 4(7.4) 0 4(7.4) Table 3 Tumor response evaluated by a computed tomography (CT) scan before surgery Response N CR 23 PR 22 SD 9 PD 0 ORR 45(83.33%) DCR 54(100%) CR, Complete Response; PR, Partial Response; SD, Stable Disease; PD, Progressive Disease; ORR, objective response rate; DCR, disease control rate Table 4 Comparison of T lymphocyte subpopulation counts before and after neoadjuvant therapy Time CD4 + % CD8 + % CD4 + /CD8 + Before treatment 37.35±7.81 25.079±8.62 1.76±0.19 After treatment 38.67±7.23 23.45±8.11 2.12±1.31 t -3.176 7.285 -4.231 P 0.004 < 0.001 < 0.001 Table 5 Association between patients with different treatment effects and clinicopathological characteristics N PCR nPR P1 Age 54 60.82 60.44 0.81(3) Gender 1.00(2) Male 48 20 28 Female 6 2 4 Smoking history 1.00(2) Yes 46 19 27 NO 8 3 5 Drinking history 1.00(2) Yes 46 19 27 NO 8 3 5 Course 0.17(1) 2 18 5 13 ＞2 36 17 19 Tumour location 0.74(2) Proximal third 3 1 2 Middle third 31 14 17 Distal third 20 7 13 Staging 0.94(1) III 42 17 25 IVa 12 5 7 PD-L1（CPS） 0.16(1) ≥10 24 12 12 <10 26 8 18 Not available 4 2 2 frequency of CD4 + T cell 32.74±6.17 38.6±7.58 0.01(3) frequency of CD8 + T cell 28.64±6.53 24.41±8.91 0.09(3) CD4 + /CD8 + 1.14±0.26 1.58±0.68 0.01(3) pCR, complete pathological response; (1): P value is calculated by t-test; (2): P value is calculated by Fisher exact test; (3): P value is calculated byindependent samples t-test Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4580244","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":320453944,"identity":"b76af9d0-3ab6-4a44-84e3-a5ab05724fe8","order_by":0,"name":"Congcong Wang","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Congcong","middleName":"","lastName":"Wang","suffix":""},{"id":320453945,"identity":"2997b755-9d82-4655-8f7d-ae5ced0d3d9e","order_by":1,"name":"Lulu XU","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Lulu","middleName":"","lastName":"XU","suffix":""},{"id":320453946,"identity":"19045c53-ec28-40fa-ba7f-66f75479520a","order_by":2,"name":"Zeyu LIU","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Zeyu","middleName":"","lastName":"LIU","suffix":""},{"id":320453947,"identity":"27d70a15-b9f2-4e55-a9c9-b06af0e7bd37","order_by":3,"name":"Fenge JIANG","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Fenge","middleName":"","lastName":"JIANG","suffix":""},{"id":320453948,"identity":"70d8849a-a4e1-4286-9302-77d51b10645e","order_by":4,"name":"Jiannan LIU","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Jiannan","middleName":"","lastName":"LIU","suffix":""},{"id":320453949,"identity":"8cca0ba1-ca11-4d31-a22c-0daeedec47df","order_by":5,"name":"Ping SUN","email":"","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"SUN","suffix":""},{"id":320453950,"identity":"bb1b61dd-6325-4f9c-ba73-1ca0909c13c0","order_by":6,"name":"Aina LIU","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYLACiR8ScvwMjA0kaLHssTCWbCBJSwVbReKGA8SqNmc/e/DDDR4Jxs3nD7c9+MFgJ6dLyDLLnrxkyRkWEsxmNxLbDXsYko3NCFlncCDHQFqCR4LN7AZjmwQPw4HEbQS1nH9j/PsPmwSPcf/BNsk/RGm5kWMmIcEmIWHAkNgmTZwtN96YWUj2SBhI3ABqkTEgxi/nc4xvSPyoq+/vP/5M8k2FnRxBLegmkKZ8FIyCUTAKRgEOAAARSj6e9vdToAAAAABJRU5ErkJggg==","orcid":"","institution":"The Affiliated Yantai Yuhuangding Hospital of Qingdao University","correspondingAuthor":true,"prefix":"","firstName":"Aina","middleName":"","lastName":"LIU","suffix":""}],"badges":[],"createdAt":"2024-06-14 07:26:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4580244/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4580244/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60366303,"identity":"1c7e3388-1378-4115-b7a2-1750757b0a75","added_by":"auto","created_at":"2024-07-16 03:46:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":565039,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4580244/v1/98389daf-7765-431f-9359-1197c7445a47.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neoadjuvant Sintilimab Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophageal cancer ranks as the seventh most common malignancy worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This disease is primarily categorized into two histologic subtypes: esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC). ESCC is the predominant subtype in Eastern Asia and Sub-Saharan Africa, representing over 90% of cases in these regions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. At diagnosis, the majority of patients present with locally advanced disease, and the five-year survival rates for those treated with surgery alone at stages II-III range from only 20.6\u0026ndash;34% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The pressing need to enhance resection rates and improve long-term survival has led to increased emphasis on a multidisciplinary approach, integrating neoadjuvant therapy with surgical management.\u003c/p\u003e \u003cp\u003eCurrently, there is no consensus on a standard protocol for neoadjuvant therapy in ESCC, and the choice between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy remains a subject of debate [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Immunotherapy, particularly with immune checkpoint inhibitors (ICIs), has shown significant promise in the treatment of advanced or metastatic ESCC and is now broadly implemented in clinical practice [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Key studies such as KEYNOTE-181[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], ATTRACTION-3[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and ESCORT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] have demonstrated the superiority of ICIs over chemotherapy in the second-line treatment setting. Further pivotal trials, including KEYNOTE-590[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], CheckMate-648[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], ESCORT 1st [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and ORIENT-15[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], have positioned immunotherapy at the forefront of the treatment paradigm for advanced ESCC. Ongoing investigations into neoadjuvant immunotherapy for locally advanced ESCC, such as the NICE [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and KEYSTONE-001[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] studies, have reported favorable outcomes in terms of efficacy and safety, alongside high rates of pathological response and R0 resection rates.\u003c/p\u003e \u003cp\u003eDespite these advancements, responses to neoadjuvant therapy among esophageal cancer patients are highly variable. Currently, there are no universally accepted treatment regimens or biomarkers for assessing efficacy in the predominant patient population. Peripheral blood lymphocyte subpopulations, crucial components of the immune response, have been identified as potential biomarkers. Emerging research emphasizes the importance of maintaining a dynamic equilibrium among these subpopulations for effective immune function. This study aims to assess the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy for treating locally advanced ESCC in a real-world context, while also exploring the potential of peripheral blood lymphocyte subpopulations as biomarkers for predicting therapy responses.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study enrolled 54 patients from November 2019 to March 2023 who met the following inclusion criteria: histologically confirmed, potentially curable ESCC staged as cT1N1-3M0 or cT2-4aN0-3M0 according to the Union for International Cancer Control TNM Classification, 8th Edition; aged 18\u0026ndash;75 years; an ECOG performance status of 0 or 1; at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1; suitability for curative resection; adequate pulmonary and cardiac function; and normal organ function. Patients were excluded if they had a history of autoimmune disease, infectious disease, or other serious medical conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatments and assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients received 2-4 cycles of neoadjuvant therapy consisting of sintilimab (200 mg every three weeks) combined with chemotherapy, which included albumin-bound paclitaxel (100 mg/m\u0026sup2;\u0026nbsp;on days 1 and 8) and cisplatin (75 mg/m\u0026sup2;\u0026nbsp;on day 1). The patients were closely monitored for toxic effects using the National Cancer Institute\u0026apos;s Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Complete pathological response (pCR) was defined as the absence of tumor cells in the resected tissue specimen. Tumor response was evaluated via computed tomography (CT) scan, using RECIST version 1.1 criteria. The overall response rate (ORR) was defined as the proportion of patients achieving either a complete response (CR) or a partial response (PR). The disease control rate (DCR) was determined as the proportion of patients with CR, PR, or stable disease (SD). Clinicopathologic data collected included age, sex, underlying diseases, tumor stage and location, lymphocyte subpopulation counts (frequency of CD4+ T cells, frequency of CD8+ T cells, and CD4+/CD8+ ratio), and PD-L1 expression. Peripheral blood was sampled to analyze lymphocyte subpopulation counts before and after neoadjuvant therapy, specifically assessing the frequency of CD4+T cells (CD3+ CD4+ T cells), frequency of CD8+T cells (CD3+ CD8+ T cells), and the CD4+/CD8+ ratio. PD-L1 expression was detected using immunohistochemistry and quantified based on the Combined Positive Score (CPS). PD-L1 expression levels were categorized as negative (CPS \u0026lt; 10) and positive (CPS\u0026nbsp;\u0026ge;\u0026nbsp;10).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT-test was utilized for continuous variables and the Fisher exact test for categorical variables, to evaluate the correlation between pCR rates and variables such as age, smoking status, alcohol consumption history, clinical stage, and PD-L1 expression. Data conforming to a normal distribution were presented as mean \u0026plusmn; standard deviation and analyzed using independent samples t-tests. P-values reported are two-sided, with a significance threshold set at 0.05. Statistical analyses were performed using SPSS version 23.0.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween November 1, 2019, and March 31, 2023, a total of 54 ESCC patients were included for the final analysis. The cohort consisted predominantly of males (n=48) with a median age of 60.6 years (range 45–70 years) (Table 1). The majority were smokers (n=46), drinkers (n=45), and 28 patients had no underlying diseases. Most tumors were located in the middle (57.4%) and distal third (37.0%) of the esophagus, with 42 patients (77.8%) at stage III and 12 (22.2%) at stage IVA. All patients completed at least two cycles of neoadjuvant therapy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEfficacy results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eR0 resection was successfully achieved in 53 of the 54 patients (98.1%). Among those who achieved R0 resection, 22 (40.7%) attained a pCR as shown in Table 3. Out of the 54 patients, 23 attained a CR, 22 saw a PR, and 9 maintained SD. This resulted in an ORR of 83.33% (45 out of 54 patients), with a DCR of 100% across all 54 patients.\u003c/p\u003e\n\u003cp\u003eIn addition, association between treatment outcomes and clinicopathological characteristics was examined (Table 5). Peripheral blood lymphocyte subpopulation counts of 48 patients were assessed prior to neoadjuvant therapy. No significant associations were observed regarding gender, smoking history, alcohol consumption, treatment duration, tumor location, clinical stage, or PD-L1 expression. Among these patients, 20 achieved a pCR. Significantly, the CD4+/CD8+ ratio and CD4+ T cell frequency was associated with pCR (p = 0.01 for both).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiomarker analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 24 patients who underwent peripheral blood lymphocyte subpopulation analysis before and after neoadjuvant therapy, post-treatment assessments revealed notable increases in the frequencies of CD4+ T cells and CD4+/CD8+ ratios, accompanied by a decrease in CD8+ T cell frequency. These alterations were statistically significant (P \u0026lt; 0.05) (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the 54 patients, 36 (66.7%) experienced treatment-related adverse events (Table 2). The majority of TRAEs were mild to moderate in severity (grade 1-2), with a 25.9% incidence of Grade 3-4 adverse events. The most common TRAEs included alopecia (57.4%), decreased neutrophil count (53.7%), and decreased white blood cell count (51.9%). Four patients(12.5%) required a dose reduction of cisplatin due to myelosuppression. All TRAEs were manageable, and no patients withdrew from the study due to adverse effects or disease progression.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eICIs have demonstrated notable efficacy in the management of esophageal cancer, progressively transitioning from the adjuvant to the second-line [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], the first-line [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and even perioperative settings [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Moreover, treatment paradigms have evolved from monotherapy to combination regimens. The ORIENT-15 study, has achieved its primary research endpoints. In the overall population, the median Overall Survival (OS) reached 16.7 months, resulting in a 37% reduction in the risk of death. Among patients with PD-L1 CPS\u0026thinsp;\u0026ge;\u0026thinsp;10, the median OS in both groups was 17.2 months versus 13.6 months, representing a approximately 36% reduction in the risk of death. These findings underscore the promising therapeutic efficacy of sintilimab [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies concerning whether preoperative immunotherapy in combination with chemotherapy or chemoradiotherapy can yield enhanced therapeutic outcomes are ongoing. The PERFECT study, based on the CROSS study regimen combined with Atezolizumab for five cycles, recently published its results. However, no significant differences were observed in pCR rates (25% vs 20.1%) and median OS (29.7 months vs 34.3 months) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Additionally, PALACE-1[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], focusing on esophageal squamous cell carcinoma patients, incorporated Pembrolizumab into the CROSS study regimen, resulting in a postoperative pCR rate of 55.6% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These clinical studies suggest that immunotherapy may exert a greater effect on esophageal squamous cell carcinoma compared to adenocarcinoma.\u003c/p\u003e \u003cp\u003eGiven the higher likelihood of complications and mortality following neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy, research into neoadjuvant chemotherapy combined with immunotherapy is also underway. Results from the phase II NICE study, investigating neoadjuvant treatment for locally advanced thoracic esophageal squamous cell carcinoma with multi-station lymph node metastasis, revealed that 55 (91.7%) out of 60 patients received two cycles of neoadjuvant treatment. Among the 47 patients undergoing surgery, 7 (14.9%) experienced TRAEs resulting in delay, while 20 (42.5%) achieved pCR. The incidence rate of Grade 3\u0026ndash;5 TRAEs was 53.3% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similar ongoing auxiliary studies are investigating Nivolumab [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], Pembrolizumab [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and Toripalimab [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the previously discussed research, neoadjuvant immunotherapy demonstrated encouraging results, including a notable achievement of a promising pCR rate, along with safety, feasibility, and the absence of operational delays, underscoring its potential efficacy. However, discrepancies in the effectiveness of neoadjuvant immunotherapy when paired with chemoradiotherapy or chemotherapy were observed. In some cases, outcomes did not surpass those achieved with concurrent chemoradiotherapy. This variation could be ascribed to variances in drug selection, timing, and duration of neoadjuvant immunotherapy protocols. In our study, R0 resection was accomplished in 53 patients (98.1%). Among these R0 resection \u003cspan refid=\"Sec3\" class=\"InternalRef\"\u003epatients\u003c/span\u003e, the pCR rate was 40.7%, and TRAEs\u0026thinsp;\u0026ge;\u0026thinsp;Grade 3 were observed in 25.9% of cases. Although the pCR rate was slightly lower compared to the NICE study [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and the KEYSTONE-001 study [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], our results still demonstrated favorable therapeutic efficacy and safety, particularly noteworthy given the advanced disease stage of the enrolled patients, classified as stage III and IV.\u003c/p\u003e \u003cp\u003eConsidering the distinct mechanisms of action between chemotherapy and immunotherapy, the pathological response and histopathological characteristics may vary. Consequently, meticulous evaluation of treatment response is crucial in the context of ongoing clinical trials involving neoadjuvant immunotherapy. Notably, neoadjuvant pCR has been established as a predictive marker for survival outcomes [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Both imaging and pathological assessments were utilized in our study to comprehensively, thoroughly, and standardly evaluate treatment efficacy. The ORR reached 83.33%, with preoperative CT evaluations largely aligning with final pathological evaluations.\u003c/p\u003e \u003cp\u003eNumerous ongoing clinical trials have investigated immunotherapy-related biomarkers, with PD-L1 expression demonstrating promising predictive potential and practical application [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, accurately discerning the population that benefits most from immunotherapy remains a challenge. Existing research on biomarkers predicting immunotherapy efficacy predominantly stems from advanced esophageal cancer clinical trials. The translatability of validated biomarkers' predictive abilities to perioperative settings is a critical issue warranting exploration. As research into tumor immunology progresses, the body's immune function emerges as a pivotal factor in various tumor developments, particularly concerning lymphocyte subpopulations. Dysregulation in lymphocyte subpopulation levels often signifies immune system dysfunction [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Normally, lymphocyte subpopulation numbers and proportions fall within specific ranges [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Decreases in CD4\u0026thinsp;+\u0026thinsp;T lymphocyte levels indicate diminished lymphoid factors, while decreases in CD8\u0026thinsp;+\u0026thinsp;lymphocyte levels suggest inhibited cellular immunity [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Moreover, under physiological conditions, the CD4+/CD8\u0026thinsp;+\u0026thinsp;ratio maintains dynamic equilibrium, with decreases indicating T lymphocyte imbalances [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In our study, post-treatment frequencies of CD4\u0026thinsp;+\u0026thinsp;T cells and CD4+/CD8\u0026thinsp;+\u0026thinsp;ratios were significantly higher than pre-treatment levels, while CD8\u0026thinsp;+\u0026thinsp;T cell frequencies were notably lower, indicating restored immune function upon tumor control. Additionally, lower CD4+/CD8\u0026thinsp;+\u0026thinsp;ratios or CD4\u0026thinsp;+\u0026thinsp;T cell frequencies were significantly associated with higher pCR rates, suggesting that peripheral blood CD4+/CD8\u0026thinsp;+\u0026thinsp;ratios and CD4\u0026thinsp;+\u0026thinsp;T cell frequencies could serve as novel indicators for predicting neoadjuvant immunotherapy efficacy in patients with locally advanced esophageal squamous cell carcinoma [28].\u003c/p\u003e \u003cp\u003eIn conclusion, our study demonstrated encouraging efficacy of chemotherapy in combination with sintilimab for locally advanced esophageal squamous cell carcinoma, achieving a pCR rate of 40.7%. TRAEs were manageable, indicating the treatment's tolerability. These promising results warrant further investigation in clinical trials to fully evaluate the effects and safety profile. Additionally, the CD4+/CD8\u0026thinsp;+\u0026thinsp;ratio and the frequency of CD4\u0026thinsp;+\u0026thinsp;T cells may serve as pivotal independent biomarkers for identifying suitable candidates for neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma. However, the applicability and reliability of these biomarkers require confirmation through prospective, multicenter randomized controlled studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Ethical Committee of Yuhuangding Hospital Affiliated with Qingdao University.\u0026nbsp;The written informed consent was obtained from each patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68: 394-424.\u003c/li\u003e\n \u003cli\u003eAbnet CC, Arnold M and Wei WQ. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology, 2018, 154: 360-373.\u003c/li\u003e\n \u003cli\u003eMiyata H, Yamasaki M, Kurokawa Y, et al. Survival factors in patients with recurrence after curative resection of esophageal squamous cell carcinomas. Ann Surg Oncol, 2011, 18: 3353-3361.\u003c/li\u003e\n \u003cli\u003eOhashi S, Miyamoto S, Kikuchi O, et al. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology, 2015, 149: 1700-1715.\u003c/li\u003e\n \u003cli\u003eArnott SJ, Duncan W, Gignoux M, et al. Preoperative\u0026ensp;radiotherapy\u0026ensp;for\u0026ensp; esophageal\u0026ensp;carcinoma. Cochrane Database Syst Rev. 2005, 4: CD001799.\u003c/li\u003e\n \u003cli\u003eIizuka T, Ide H, Kakegawa T, et al. Preoperative radioactive therapy for esophageal carcinoma. Randomized evaluation trial in eight institutions. Chest, 1988, 93(5): 1054‐1058.\u003c/li\u003e\n \u003cli\u003eHuang TX, Fu L. The immune landscape of esophageal cancer. Cancer Commun (Lond) 2019, 39(1): 79.\u003c/li\u003e\n \u003cli\u003eKato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION‐3): a multicentre, randomised, open‐label, phase 3 trial. Lancet Oncol, 2019, 20(11): 1506‐1517.\u003c/li\u003e\n \u003cli\u003eKojima T, Shah MA, Muro K, et al. Randomized phase Ⅲ KEYNOTE‐181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol, 2020, 38(35): 4138‐4148.\u003c/li\u003e\n \u003cli\u003eHuang J, Xu J, Chen Y, et al. Camrelizumab versus investigator\u0026prime;s choice of chemotherapy as second‐line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open‐label, phase 3 study. Lancet Oncol, 2020, 21(6): 832‐842.\u003c/li\u003e\n \u003cli\u003eSun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet, 2021, 398(10302): 759-771.\u003c/li\u003e\n \u003cli\u003eChau I, Doki Y, Ajani JA, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study. J Clin Oncol, 2021, 39(18_suppl): LBA4001-LBA4001.\u003c/li\u003e\n \u003cli\u003eLuo HY, Lu J, Bai YX, et al. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA, 2021, 326(10): 916-925.\u003c/li\u003e\n \u003cli\u003eLu ZH, Wang JY, Shu YQ, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ, 2022, 377:e068714.\u003c/li\u003e\n \u003cli\u003eLiu J, Li Z, Fu X, et al. 127P A prospective phase II clinical trial exploring neoadjuvant immunotherapy combined with chemotherapy in resectable thoracic esophageal squamous cell cancer(TESCC) with multi-station lymph node metastases (NICE study): preliminary results. Ann Oncol, 2020, 31: S1292.\u003c/li\u003e\n \u003cli\u003eShang XB, Zhao G, Liang F, et al. Safety and effectiveness of pembrolizumab combined with paclitaxel and cisplatin as neoadjuvant therapy followed by surgery for locally advanced resectable (stage III) esophageal squamous cell carcinoma: a study protocol for a prospective, single-arm, single-center, open-label, phase-II trial (Keystone-001). Ann Transl Med. 2022,10(4): 229.\u003c/li\u003e\n \u003cli\u003eKelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021, 384(13):1191-1203.\u003c/li\u003e\n \u003cli\u003evan den Ende T, de Clercq NC, van Berge Henegouwen MI, et al. Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single-arm Phase II Feasibility Trial (PERFECT). Clin Cancer Res, 2021, 27(12): 3351-3359.\u003c/li\u003e\n \u003cli\u003eLi CQ, Zhao SG, Zheng YY, et al. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma( PALACE-1)． Eur J Cancer, 2021, 144: 232-241．\u003c/li\u003e\n \u003cli\u003eYamamoto S，Kato K，Daiko H，et al. Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER (JCOG1804E). Future Oncol, 2020, 16(19) : 1351-1357．\u003c/li\u003e\n \u003cli\u003eZheng Y, Liu XB, Sun HB, et al. A phase Ⅲ study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909). Ann Transl Med, 2021, 9(1): 73．\u003c/li\u003e\n \u003cli\u003eLin JW, HSU CP, YEH HL, et al. The impact of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced squamous cell carcinoma of esophagus. J Chin Med Assoc, 2018, 81(1): 18-24.\u003c/li\u003e\n \u003cli\u003eQu HX, Zhao LP, Zhan SH, et al. Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis. J Thorac Dis, 2016, 8 (11): 3197-3204．\u003c/li\u003e\n \u003cli\u003eYan Y, Wang XY, Liu CN, et al. Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study.BMC Pulm Med, 2022, 22(1): 166.\u003c/li\u003e\n \u003cli\u003eGUO H, KUANG P, LUO Q, et al. Effects of sodium fluoride on blood cellular and humoral immunity in mice. Oncotarget, 2017, 8(49): 85504-85515.\u003c/li\u003e\n \u003cli\u003ePhilip M, Schietinger A. CD8+T cell differentiation and dysfuction in cancer. Nat Rev Immunol, 2022, 22(4): 209-223.\u003c/li\u003e\n \u003cli\u003eLee PH, Yang TY, Chen KC, et al. Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors. Sci Rep, 2021, 11(1): 9381.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable1 Patient characteristics at baseline\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"379\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eNO. of \u0026nbsp;Patients(%)(N=54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e60.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e45-70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eYes \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eNO \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eDrinking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; NO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eBasis disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; None\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eECOG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eTumour location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eProximal third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Middle third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Distal third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eClinical T stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; cT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; cT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; cT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; cT4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eClinical N stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; N0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003ePD-L1（CPS）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026ge;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eECOG, eastern cooperative oncology group\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Adverse events\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"530\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eAdverse Event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003eGrade1-2\u003c/p\u003e\n \u003cp\u003eNo. of patients (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003eGrade3-4\u003c/p\u003e\n \u003cp\u003eNo. of patients (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003eAll Grade\u003c/p\u003e\n \u003cp\u003eNo. of patients (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eAnaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e25(46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e31(57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eWhite blood cell count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e23(42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e5(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e28(51.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eNeutrophil count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e23(42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e29(53.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e17(31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e17(31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e13(24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e13(24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e11(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e11(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eAlopecia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e11(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e11(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eDecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e9(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e9(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e7(13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e8(14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet count\u0026nbsp;decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eHypothyroisdism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e5(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e5(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eLiver dysfunction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e5(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e1(1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e6(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.41509433962264%\" valign=\"top\"\u003e\n \u003cp\u003eNeurotoxic effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.943396226415093%\" valign=\"top\"\u003e\n \u003cp\u003e4(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.754716981132077%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.88679245283019%\" valign=\"top\"\u003e\n \u003cp\u003e4(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Tumor response\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eevaluated by a computed tomography (CT) scan before surgery\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"453\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e\u0026nbsp;Response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003eORR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e45(83.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003eDCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.01769911504425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.442477876106196%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.76991150442478%\"\u003e\n \u003cp\u003e54(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCR, Complete Response; PR, Partial Response; SD, Stable Disease; PD, Progressive Disease; \u0026nbsp;ORR, objective response rate; DCR, disease control rate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Comparison of T lymphocyte subpopulation\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;counts\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;before and after neoadjuvant therapy\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"453\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;Time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCD8\u003csup\u003e+\u003c/sup\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003e/CD8\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBefore treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e37.35\u0026plusmn;7.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.079\u0026plusmn;8.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.76\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAfter treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e38.67\u0026plusmn;7.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.45\u0026plusmn;8.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; 2.12\u0026plusmn;1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-4.231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAssociation between patients with different treatment effects and clinicopathological characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"74%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003ePCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003enPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003eP1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e60.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e60.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.81(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e1.00(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e1.00(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eYes \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eNO \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eDrinking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e1.00(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp; NO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eCourse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.17(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e＞2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eTumour location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.74(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eProximal third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp; Middle third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026nbsp; Distal third\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eStaging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.94(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eIVa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003ePD-L1（CPS）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.16(1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026ge;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003e\u0026lt;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003efrequency of\u0026nbsp;CD4\u003csup\u003e+\u003c/sup\u003e T cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e32.74\u0026plusmn;6.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e38.6\u0026plusmn;7.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.01(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003efrequency of\u0026nbsp;CD8\u003csup\u003e+\u003c/sup\u003e T cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e28.64\u0026plusmn;6.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e24.41\u0026plusmn;8.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.09(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.53061224489796%\"\u003e\n \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003e/CD8\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\"\u003e\n \u003cp\u003e1.14\u0026plusmn;0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1.58\u0026plusmn;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3265306122449%\"\u003e\n \u003cp\u003e0.01(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;pCR, complete pathological response;\u003c/p\u003e\n\u003cp\u003e(1): P value is calculated by t-test; (2): P value is calculated by Fisher exact test; (3): P value is calculated byindependent samples t-test\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neoadjuvant immunochemotherapy, Sintilimab, Lymphocyte subpopulation, Pathological complete response, locally advanced ESCC","lastPublishedDoi":"10.21203/rs.3.rs-4580244/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4580244/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Immunotherapy has demonstrated promise in treating advanced esophageal cancer, yet evidence on neoadjuvant immunotherapy for locally advanced cases remains limited. This study aimed to assess the efficacy and safety of immunotherapy combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA retrospective review of 54 patients undergoing radical esophageal cancer surgery following neoadjuvant immunotherapy combined with chemotherapy was conducted. The treatment regimen consisted of sintilimab (200mg) with albumin paclitaxel (100 mg/m2 on days 1 and 8) and cisplatin (75 mg/m2 on day 1) every 3 weeks. Efficacy and safety were evaluated, alongside peripheral blood lymphocyte subpopulation counts and clinicopathological characteristics to identify predictive factors of neoadjuvant efficacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAll 54 patients underwent surgery, with 53(98.1%) achieving R0 resection. Pathological complete response (pCR) was observed in 22(40.7%) patients. The overall response rate (ORR) was 83.3% (45/54) and the DCR was 100.00% (54/54). A significant association between pCR and CD4+/CD8+ ratio and frequency of CD4+ T cell (p = 0.01, p = 0.01) was identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Neoadjuvant immunochemotherapy combining sintilimab with chemotherapy resulted in favorable clinical outcomes in locally advanced ESCC, accompanied by well tolerability. Peripheral blood CD4+/CD8+ ratio and frequency of CD4+ T cell emerged as promising predictive biomarkers for treatment efficacy.\u003c/p\u003e","manuscriptTitle":"Neoadjuvant Sintilimab Plus Chemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-04 08:51:38","doi":"10.21203/rs.3.rs-4580244/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bd7063fd-9a46-4548-8171-0be0df802132","owner":[],"postedDate":"July 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-16T03:38:34+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-04 08:51:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4580244","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4580244","identity":"rs-4580244","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}