Anti-PD-L1 plus chemoradiotherapy for limited-stage small-cell lung cancer: a retrospective cohort evaluating efficacy, safety, T-cell subsets and tumor markers

Anti-PD-L1 plus chemoradiotherapy for limited-stage small-cell lung cancer: a retrospective cohort evaluating efficacy, safety, T-cell subsets and tumor markers | 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 Anti-PD-L1 plus chemoradiotherapy for limited-stage small-cell lung cancer: a retrospective cohort evaluating efficacy, safety, T-cell subsets and tumor markers Shuai Li, Mengting Zhuang, Zhaoxue Lu, Xianjun Lv, Liubing Zhao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7859919/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 Evidence for immune checkpoint blockade with chemoradiotherapy (CRT) in limited-stage small-cell lung cancer (LS-SCLC) remains limited. We evaluated anti-PD-L1 plus CRT versus CRT alone in routine practice. Methods We retrospectively included 42 LS-SCLC patients (June 2020–February 2022). The study group received atezolizumab or durvalumab plus platinum–etoposide CRT; the control group received CRT alone. Primary outcome: progression-free survival (PFS). Secondary outcomes: objective response rate (ORR), disease control rate (DCR), adverse events (AEs), T-cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and serum tumor markers (NSE, Pro-GRP, CYFRA21-1, CEA). Responses followed iRECIST; AEs were graded per CTCAE; Kaplan–Meier/log-rank compared PFS. Results Groups were balanced at baseline. Compared with CRT, anti-PD-L1 + CRT yielded numerically higher ORR (90.0% vs 72.7%) and DCR (95.0% vs 90.9%), with significantly longer PFS (p < 0.05). Post-treatment, the combination group showed greater increases in CD3+, CD4+, CD4+/CD8 + and larger reductions in NSE and Pro-GRP (all p < 0.05). Safety was comparable with no new signals. Median follow-up was 15.3 months. Conclusions Adding anti-PD-L1 to CRT for LS-SCLC was associated with improved PFS, favorable immunologic and biomarker changes, and manageable safety in this retrospective cohort, supporting prospective validation. limited-stage small-cell lung cancer chemoradiotherapy PD-L1 inhibitor iRECIST progression-free survival T-lymphocyte subsets NSE Pro-GRP Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy that exhibits early metastasis and poor clinical prognosis. It constitutes approximately 15% of all lung cancer types, with limited-stage small cell lung cancer (LS-SCLC) ac-counting for about one-third of SCLC cases[ 1 , 2 ]. The limited stage is defined as being restricted to I-III stage or being confined to one side of the chest and treatable with a single radiation therapy field. The standard treatment for LS-SCLC is chemoradio-therapy (CRT), which includes platinum-based chemotherapy, etoposide, and thoracic radiotherapy [ 2 , 3 ]. Despite being responsive to chemoradiotherapy, patients with LS-SCLC are susceptible to drug resistance and disease progression, leading to a poor prognosis. The median survival period is typically 15–30 months, with a 5-year surviv-al rate of only 30%[ 4 ] . Our enhanced comprehension of tumor cells' immune evasion mechanisms has spurred the development of immunotherapy techniques, particularly immune check-point inhibitors (ICIs), which exhibit efficacy against small cell lung cancer (SCLC). Among clinical immunotherapy research, anti-PD-L1 immunotherapy has garnered significant attention. Atezolizumab and Durvalumab, antitumor drugs endorsed for clinical use, obstruct the tumor PD-L1 immune evasion pathway, thus preserving T cell tumor-killing activity to effectuate tumor clearance. In the IMPOWER133 and CAS-PIAN clinical trials, atezolizumab and durvalumab demonstrated favorable clinical efficacy in SCLC treatment relative to chemotherapy alone. Currently, an-ti-programmed death ligand 1 immunotherapy is sanctioned for widespread stage SCLC [ 5 , 6 ]. A phase 1/2 trial by James W[ 7 ] found that Pembrolizumab and concur-rent chemoradiotherapy for LS-SCLC produced favorable safety and efficacy outcomes. However, it is unclear what the clinical efficacy of atezolizumab and durvalumab in combination with radiotherapy is for limited-stage small cell lung cancer, and few overseas trials have been conducted. This study investigates the clinical efficacy and safety of anti-PD-L1 plus CRT in LS-SCLC treatment to offer guidance for clinical treatment of this disease. 2. Materials and Methods 2.1. Baseline Data From June 2020 to February 2022, a total of 42 LS-SCLC patients with a median age of 64 and an average age of 64.26 ± 8.28 years who were treated in Xuzhou Cancer Hospital and the Affiliated Hospital of Xuzhou Medical University were selected for retrospective analysis. According to the different treatment methods, the patients were divided into groups. Patients receiving CRT were selected as the control group( n = 22), and patients receiving anti PD-L1 combined with CRT were selected as the study group( n = 20). All included patients submitted written informed consents. Differences in general clinical data such as gender, age, smoking status, ECOG PS, prophylactic cranial irradiation and CRT sequence between the two groups had no effect on this study ( p > 0.05). Please refer to Table 1 for more details. This study was approved by the Ethics Committee of Xuzhou Cancer Hospital(XYFY2022-KL488-01)and Affiliated Hospital of Xuzhou Medical University(2022-03-054-K01). 2.2. Inclusion and exclusion criteria Inclusion criteria: (1) imaging and pathology examination confirmed clinical LS-SCLC, Measurable lesions were evaluated by imaging. (2) score of 0–2 on the performance status of the Eastern Cooperative Tumor Group (ECOG); (3) patients were not treated with radical surgery and receive chemotherapy and thoracic radiotherapy consisting of platinum plus etoposide, including or excluding anti-PD-L1 (Atezolizumab/Durvalumab); and (4) complete clinical information records, a 3 -month survival time was project. Exclusion criteria: (1) no clear pathological diagnosis information; (2) patients with other tumors at the same time or had other tumors within 5 years; (3) patients who need to take corticosteroids for a long time; (4) patients with systemic immune disease or severe mental disorder. 2.3. Treatment The patients in the control group received concurrent chemoradiotherapy (CRT) consisting of platinum and etoposide intravenous infusions with an infusion time of more than 0.5 hours. Infusions were administered once every three weeks for 4 to 6 cycles (21 days each). Thoracic radiotherapy was administered using three-dimensional conformal radiotherapy technology with a radiation dose of 1.8-2.0 Gy per fraction, once a day, five times a week, for a total dose of 54–60 Gy in 25–30 fractions. This was initiated after the first or second cycle of concurrent chemotherapy and at the end of sequential chemotherapy. Preventive intracranial irradiation (25 Gy in 10 fractions) was administered at the discretion of the treating physician for patients who responded well to the initial treatment. For the study group, the observation group received Atezolizumab/Durvalumab (Atezolizumab (1200 mg/time, intravenous injection on the first day of each cycle) or Durvalumab (concentration of 10 mg/kg, intravenous injection on the first day of each cycle) plus those used in the control group once every 3 weeks. If the patient acquired disease progression, serious adverse reactions (AEs), or drug toxicity, the drug should be discontinued immediately. 2.4. Evaluation of Efficacy, AEs, and Progression free survival Disease-control rate (DCR) and response rate (ORR) were used to determine the treatment efficacy. The short-term efficacy was evaluated according to the solid tumor immunotherapy standard, iRECIST standard. Complete remission (iCR): complete ablation of non-lymph node lesions, short axis of lymph nodes < 10 mm, no new lesions. Partial remission (iPR): tumor load reduction ≥ 30% Disease progression (iUPD): there are new measurable /unmeasurable lesions, or the tumor load increases by ≥ 20% relative to the lowest point. Disease stability (iSD): inconformity with iCR, iPR and iUPD. DCR (%) = iCR (%) + iPR (%) + iSD (%) and ORR (%) = iCR (%) + iPR (%). The target date is defined as the date of starting treatment. The occurrence of adverse reactions in patients in both groups was recorded and. graded according to CTCAE standards. The patient is followed up to the last follow-up date or the study end date. (July. 2022), whichever occurs first. PFS is calculated from the index date to the date of progress, death or final follow-up (whichever comes first). 2.5. Observation indexes T lymphocyte subsets: venous blood was taken from patients in both groups one day before treatment and after treatment, and the levels of T lymphocyte subsets (CD3+, CD4+, CD8 + and CD4+/CD8+) were detected using flow cytometry before and after therapy. Tumor markers: the serum levels of NSE, CYFRA21-1, Pro-GRP and CEA levels were determined using ELISA kits before and after treatment. 2.6. Statistical Analysis Statistical analysis and visualization of data were performed using SPSS 26.0 software and R (version 3.6.3). Measurement data were expressed as “mean ± standard.” To analyze the enumeration data, presented as percentage, we used the t-test and χ 2 test. Kaplan-Meier curves and log-rank tests were performed to determine the differences in PFS between the two groups. Statistically significant difference was set at the p < 0.05 level. 3. Results 3.1 General Data Comparison The clinical characteristics of the two patient groups, including gender, average age, smoking status, ECOG PS, and other general data, were analyzed using a chi-squared test. The results indicated no significant differences between the groups (p > 0.05), as presented in Table 1 . Table 1 Characteristics between study and control groups. Characteristic study group ( n = 20) Control group ( n = 22) P value Age(years) 0.952 < 65 12 13 ³65 8 9 Sex 0.716 Male 18 19 Female 2 3 ECOG PS 0.985 0–1 19 21 2 1 1 CRT sequence 0.827 Concurrent 7 7 Sequential 13 15 Prophylactic cranial irradiation 0.976 Yes 9 10 No 11 12 Smoking status 0.662 Ever 14 14 Never 6 8 * Compared with the CRT group p 0.05), as evidenced by statistical analysis of the data. Following treatment, both groups exhibited significant increases in CD3+, CD4+, and CD4+/CD8 + levels compared to pre-treatment levels ( p < 0.05). The study group demonstrated significantly higher increases in these levels compared to the control group, with a statistically significant difference ( p 0.05). Please refer to Table 2 and Fig. 1 for detailed results. Table 2 Comparison of T lymphocyte subsets of patients in two groups (x ± s) Groups CD3+(×106/L) CD4+ (×106/L) CD8+ (×106/L) CD4+/CD8+ Study group (n = 20) Before treatment 1123.35 ± 263.93 569.00 ± 143.92 496.35 ± 145.12 1.19 ± 0.30 After treatment 1645.25 ± 472.59* 848.55 ± 233.74* 527.50 ± 158.79 1.69 ± 0.51* p value 0.001 < 0.001 0.362 < 0.001 Control group (n = 22) Before treatment 1091.14 ± 252.23 551.18 ± 141.71 506.41 ± 164.76 1.15 ± 0.38 After treatment 1320.63 ± 519.18 697.82 ± 231.50 522.14 ± 121.98 1.36 ± 0.41 *Compared with the CRT group p 0.05). However, post-treatment, there were significant reductions in the levels of NSE and Pro-GRP when compared to CYFRA21-1 ( p < 0.05). Notably, only the study group exhibited statistically significant decreases in NSE and Pro-GRP levels compared to the control group ( p < 0.05), as shown in Table 3 and Fig. 2 . Table 3 Comparison of the content of lung cancer related tumor markers between the two groups (x ± s). Groups CYFRA21-1 NSE Pro-GRP CEA Study group ( n = 20) Before treatment 5.07 ± 3.83 33.45 ± 23.44 253.84 ± 125.60 5.74 ± 5.17 After treatment 3.97 ± 3.18 14.78 ± 8.64* 54.32 ± 55.79* 4.63 ± 3.98 p value 0.074 0.004 < 0.001 0.305 Control group ( n = 22) Before treatment 4.49 ± 3.61 41.34 ± 24.90 280.85 ± 166.48 5.13 ± 4.28 After treatment 3.62 ± 2.41 22.06 ± 13.24 104.89 ± 94.78 4.18 ± 4.57 p value 0.04 0.004 0.001 0.101 * Compared with the CRT group p < 0.05. 3.4. Comparison of Clinical Efficacy The short-term efficacy of the two patient groups was compared, and after treatment, the study group exhibited an overall response rate (ORR) of 90.0%, while the control group had an ORR of 72.73%. Additionally, the disease control rate (DCR) in the study group was 95.00%, compared to 90.90% in the control group. However, there was no statistically significant difference observed between the two groups ( p > 0.05), as shown in Table 4 . Table 4 Comparison of short-term efficacy between the two groups of patients. Groups iCR iPR iSD UPD ORR DCR Study group ( n = 20) 2 16 1 1 90.00% 95.00% Control group( n = 22) 1 15 4 2 72.73% 90.90% P value 0.493 0.384 0.188 0.607 0.155 0.607 * Compared with the CRT group p < 0.05. 3.5 Adverse Events (AEs) In both the control and study groups, adverse events (AEs) were predominantly related to the immune system, as well as the blood and gastrointestinal systems. The study group exhibited a tendency towards a higher occurrence of AEs associated with the blood and gastrointestinal systems, but this disparity did not reach statistical significance ( p > 0.05), as demonstrated in Table 5 . Table 5 Comparison of patients' AEs in the two groups. AEs, n (%) Level I - V P value Level III - V P value Study group Control group Study group Control group ( n = 20) ( n = 22) ( n = 20) ( n = 22) Led to discontinuation 3(15.0%) 1(4.5%) 0.333 2(10%) 0(0.0%) 0.221 Anemia 5(25.0%) 6(27.3%) 1 1(5.0%) 1(4.5%) 1 Fatigue 8(40.0%) 9(40.9%) 0.764 2(10%) 2(9.1%) 1 Nausea and vomiting 8(40.0%) 9(40.9%) 1 2(10.0%) 2(9.1%) 0.598 Elevated transaminases 2(10.0%) 1 (4.5%) 1 0(0.0%) 0(0.0%) 1 Decreased white cell count 9(45.0%) 11(50.0%) 0.767 2(10.0%) 2(9.1%) 1 Decreased neutrophil count 10(50.0%) 10(45.5%) 1 2(10%) 2(9.1%) 1 Decreased platelet count 2(10.0%) 3(13.6%) 1 0(0.0%) 1(4.5%) 1 Skin reaction 2(10.0%) 0 (0.0%) 0.221 1(5.0%) 0(0.0%) 0.476 Pneumonitis 5(25.0%) 2(9.1%) 0.229 1(5.0%) 0(0.0%) 0.476 Hypothyroidism 3(15.0%) 1(4.5%) 0.333 1(5.0%) 0(0.0%) 0.476 Total 17 (85.0%) 17 (77.3%) 0.7 8(40.0%) 6(27.3%) 0.515 * Compared with the CRT group p < 0.05. 3.6 Progression free survival (PFS) As of July 1st, 2022, the median follow-up time for the study group and control group were 14.2 months and 15.3 months, respectively, as reported in our study. Disease progression was observed in 40.0% (8 patients) of the study group and 86.36% (19 patients) of the control group, with no significant difference observed ( p > 0.05). Median progression-free survival (PFS) was not reached in the study group, while it was 8.7 months [95% confidence interval (CI), 7.5–10.5 months] in the control group. Our analysis demonstrated that the study group exhibited better PFS compared to the control group, as evidenced by the PFS curve depicted in Fig. 3. 3.7 Ease the depth The study group exhibited a DCR of 95.00%, consisting of a complete response rate of 10%, partial response rate of 80.0%, and a disease stability rate of 5.00%. In comparison, the control group demonstrated a DCR of 90.91%, comprising a complete response rate of 4.55%, partial response rate of 68.18%, and a disease stability rate of 18.19%, as illustrated in Table 4. The study group also displayed an ORR of 90.0%, with a complete response rate of 10.00% and partial response rate of 80.00%, while the control group had an ORR of 72.73%, with a complete response rate of 4.55% and partial response rate of 68.18%, as presented in Table 4. These results indicate that the addition of anti PD-L1 to CRT treatment resulted in a slight enhancement of both ORR and DCR when compared to CRT alone. However, there was no significant difference in ORR and DCR between the two groups ( p > 0.05). The study group experienced a reduction in tumor burden within a few months, with a better depth of tumor remission than the control group, as demonstrated in Figure 4. 4. Discussion The emergence of immunotherapy has brought about a change in the approach to treating SCLC, thanks to the development of ICIs that target the PD-1/PD-L1 pathway. For those with SCLC, the primary options are atezolizumab or durvalumab. Recent studies such as IMPOWER133 and CASPIAN have altered the first-line treatment paradigm for ES-SCLC, revealing that patients receiving atezolizumab or durvalumab with chemotherapy (platinum plus etoposide) have seen significant improvements in their survival rate (OS and PFS) compared to chemotherapy alone [ 5 , 6 ]. However, no new drugs have been approved for LS-SCLC, including immunotherapy. A phase 1/2 trial led by James W. has demonstrated the good safety and efficacy of Pembrolizumab combined with concurrent chemoradiotherapy in the treatment of LS-SCLC [ 7 ]. However, a study by Bilani et al, utilizing a large national database, suggested that immunotherapy as a first-line treatment for LS-SCLC patients did not result in a significant increase in survival rates[ 8 ]. Therefore, the efficacy and safety of immunotherapy in LS-SCLC remains inconclusive. It is worth noting that SCLC is closely linked to smoking and is a neuroendocrine carcinoma with a high tumor mutation burden, indicating that patients may benefit from immunotherapy. In the present study, patients with LS-SCLC were treated with anti PD-L1 plus CRT as the initial therapy and compared with CRT alone. The immune response is primarily mediated by T lymphocytes, which serve as a crucial indicator for clinical evaluation of immune function[ 9 ]. CD3 + enhances the anti-tumor immune response, while CD4 + plays a more immunomodulatory and paracrine role. Additionally, CD8 + and CD4+/CD8 + reflect the tumor-killing activity [ 10 ]. Therefore, monitoring lymphocyte subsets is essential for evaluating tumor drug efficacy. Malignant tumors can disturb the immune response and reduce the counts of CD3+, CD4+, and CD8 + due to the secretion of specific factors. However, PD-L1 inhibitors can improve the prognosis of patients by reducing the body's immunosuppressive effect and enhancing the anti-tumor effect of the body. Our study found that CD3 + and CD4 + levels, as well as CD4+/CD8 + levels, were significantly higher in the study group after treatment than before treatment, compared to the control group. High expression of CD3 + has been associated with good prognosis in SCLC[ 11 , 12 ]. Moreover, higher expression levels of CD3+, CD4+, CD8+, and FOXP3 were associated with better survival[ 13 ]. Although reduced CD8 + T lymphocytes are typically associated with better prognosis, the expansion of CD8 + observed in our study may be related to the clinical efficacy of anti-PD-L1 inhibitors[ 14 ], which can interfere with PD-L1 signaling and promote early CD8 + proliferation[ 15 ] without affecting PD-L1 efficacy [ 16 ]. Taken together, these findings suggest that PD-L1 mobilizes the patient's own antitumor capacity by activating T lymphocytes with a killing effect after relieving the inhibitory effect of immune checkpoints. Tumor markers are synthesized and secreted by malignant neoplastic tissues and cells [ 17 ]. Their concentration levels are positively correlated with the severity of the patient's condition[ 18 ]. NSE serves as a sensitive biomarker for neuroendocrine tumors, reflecting the onset and progression of the tumors. ProGRP, on the other hand, is a critical biomarker for the evaluation of tumor progression and prognosis. Its expression level is directly associated with disease severity and is thus of great importance for evaluating disease condition and predicting prognosis [ 19 – 21 ]. CYFRA21-1 can be released into the bloodstream when tumor cells undergo necrosis or lysis, which offers a high diagnostic and therapeutic assessment for patients with small cell lung cancer[ 22 ]. Prior to CEA treatment, no significant differences were observed between the two patient groups, which may be attributed to the higher frequency of CEA positivity in lung adenocarcinoma[ 23 ]. Baseline biomarker levels were comparable between the two groups in this study. Following treatment, the serum levels of NSE and ProGRP in the observation group decreased significantly relative to those in the control group, indicating that the treatment protocol was able to lower the serum tumor marker levels. Anti PD-L1 treatment can activate the immune system, attack cancer cells, and form the foundation of tumor immunotherapy, effectively ameliorating the patient's condition and reducing serum factor expression. The data of this study also showed that the incidence of thrombocytopenia, nausea and vomiting, leukopenia, neutropenia, anemia, and pneumonia in the study group were 10.0%, 40.0%, 45.0%, 50.0%, 25.0%, and 25.0%, respectively, compared with 13.6%, 40.9%, 50.0%, 45.5%,27.3%, and 9.1% of the control group, there was no statistically significant difference ( p > 0.05), indicating that adjuvant immunotherapy did not significantly increase adverse reactions and had good safety. The results showed that anti-PD-L1 plus CRT had appropriate safety at least in the short term. Due to the short follow-up period of this study (median 15.3 months), long-term toxic reactions (e.g. pericarditis and esophageal fistula) were not evaluated at the time of this analysis. Also, this paper did not count eosinophils, which are extremely important cells in immune and allergic reactions, releasing granule contents, causing tissue damage and promoting the progression of inflammation. We are cautiously optimistic about the risk of long-term complications. In terms of toxicity and side effects, the incidence of toxicity between the two groups was similar, and there was no new safety signal. In terms of immune adverse reactions such as hypothyroidism and rash, the symptoms were controllable after symptomatic treatment However, foreign studies have also shown that the use of anti-PD-L1 immunotherapy may increase the risk of liver and kidney function and thyroid function damage in patients[ 24 ]. Therefore, attention should be paid to regular monitoring of patients' biochemical indicators during use Patients take 10 mg/kg Durvalumab every 3 weeks instead of ES-SCLC (1500 mg every 4 weeks). Immunotherapy has a wide therapeutic index and unique pharmacokinetic and pharmacodynamic behavior. We predict that this adjustment will not affect the efficacy[ 25 ]. The results of the study demonstrate that the addition of anti-PD-L1 to CRT led to significant improvements in ORR, DCR, PFS, and depth of tumor remission when compared to CRT alone. PFS was notably longer in the study group than in the control group ( p < 0.05), which may be explained by the synergistic effect of CRT and tumor immunotherapy as a means of enhancing antigen presentation, T cell recruitment, and tumor interstitial lymphocyte infiltration while modifying the microenvironment[ 26 ]. In the CONVERT trial, chest radiation combined with synchronous chemotherapy was established as the standard treatment for cancer. This approach, consisting of 30 doses and twice-daily administration of 45 Gy, was found to have similar therapeutic effects and tolerable toxicity features to the approach of 33 doses of daily fractionated radiotherapy and chemotherapy totaling 66 Gy[ 27 ]. Although the ORR and DCR of the study group tended to increase, no significant difference was found between the two groups ( p > 0.05), which may be attributed to the small number of patients and the typical reduction of tumor burden in the study group within a few months. However, the depth of tumor remission in the study group was superior to that in the control group. These findings may have implications for patients of Chinese descent, whose genetic background and tumor characteristics may differ from those of Western patients. This study exhibits several limitations. Firstly, the retrospective nature of the study precludes the detection of anti-PD-L1 expression. Additionally, the study's limited sample size and short follow-up duration restrict the assessment of the efficacy of anti-PD-L1 and the combination of chemoradiotherapy. Furthermore, there exist variations in individual doses of chemoradiotherapy, potentially leading to deviations in both efficacy and side effects. Therefore, further investigation with an expanded sample size is necessary to overcome these limitations. 5. Conclusions In summary, treatment with anti-PD-L1 immunotherapy significantly improved T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+), tumor markers (Pro-GRP, NSE), and curative effects in patients with LS-SCLC compared to pre-treatment levels. The improvement seen with this treatment was greater than that observed with CRT. Therefore, anti-PD-L1 immunotherapy combined with CRT should be considered as the initial treatment option for LS-SCLC patients due to its favorable safety and efficacy profile. This represents an important step towards providing a viable treatment strategy for LS-SCLC patients. Abbreviations CRT Chemoradiotherapy LS-SCLC Limited-stage small-cell lung cancer PD-L1 Programmed death-ligand 1 ORR Objective response rate DCR Disease control rate PFS Progression-free survival AEs Adverse events NSE Neuron-specific enolase Pro-GRP Pro-gastrin-releasing peptide CEA Carcinoembryonic antigen. Declarations Ethics approval and consent to participate This retrospective study was approved by the Ethics Committees of Xuzhou Cancer Hospital (XYFY2022-KL488-01) and the Affiliated Hospital of Xuzhou Medical University (2022-03-054-K01). The study was conducted in accordance with the ethical standards of the institutional and national research committees and with the 1964 Declaration of Helsinki and its later amendments. All participants provided written informed consent before inclusion. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No external funding was received for this study. Authors’ contributions Conceptualization: S.L., X.L., Z.L., M.Z., and J.C.; Methodology: S.L. and J.C.; Investigation: S.L., Z.L., M.Z., and X.L.; Writing—original draft: S.L. and J.C.; Writing—review and editing: Z.L., M.Z., and X.L.; Supervision: J.C.; All authors read and approved the final manuscript. Acknowledgements The authors thank all participating patients and their families, as well as the clinical and research staff who contributed to this work. References Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. 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Miao K, Zhang X, Wang H, Si X, Ni J, Zhong W, Zhao J, Xu Y, Chen M, Pan R, et al. Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer. Front Immunol. 2022;13:912180. 10.3389/fimmu.2022.912180 . Chen Z, Liu X, Shang X, Qi K, Zhang S. The diagnostic value of the combination of carcinoembryonic antigen, squamous cell carcinoma-related antigen, CYFRA 21 – 1, neuron-specific enolase, tissue polypeptide antigen, and progastrin-releasing peptide in small cell lung cancer discrimination. Int J Biol Markers. 2021;36:36–44. 10.1177/17246008211049446 . Li LL, Zhang ZB, Hu Y. Neuron-specific enolase predicts the prognosis in advanced small cell lung cancer patients treated with first-line PD-1/PD-L1 inhibitors. Medicine. 2021;100. 10.1097/MD.0000000000027029 . Barchiesi V, Simeon V, Sandomenico C, Cantile M, Cerasuolo D, Chiodini P, Morabito A, Cavalcanti E. Circulating progastrin-releasing peptide in the diagnosis of Small Cell Lung Cancer (SCLC) and in therapeutic monitoring. J Circ Biomark. 2021;10:9–13. 10.33393/jcb.2021.2212 . Wang L, Wang D, Zheng G, Yang Y, Du L, Dong Z, Zhang X, Wang C. Clinical evaluation and therapeutic monitoring value of serum tumor markers in lung cancer. Int J Biol Markers. 2016;31:e80–87. 10.5301/jbm.5000177 . Petrovic M, Bukumiric Z, Zdravkovic V, Mitrovic S, Atkinson HD, Jurisic V. The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer. Med Oncol. 2014;31:823. 10.1007/s12032-013-0823-1 . Wang L, Lei X, Wang X. Efficacy and Safety of PD-1/PD-L1 Inhibitor Chemotherapy Combined with Lung Cancer Fang No. 1 in Relapsed and Refractory SCLC: A Retrospective Observational Study. Comput Math Methods Med 2022, 2022 , 2848220. 10.1155/2022/2848220 Gao J, Zhang L, Peng K, Sun H. [Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types]. Nan Fang Yi Ke Da Xue Xue Bao. 2022;42:886–91. 10.12122/j.issn.1673-4254.2022.06.12 . Mathew M, Enzler T, Shu CA, Rizvi NA. Combining chemotherapy with PD-1 blockade in NSCLC. Pharmacol Therapeut. 2018;186:130–7. 10.1016/j.pharmthera.2018.01.003 . Sheng J, Srivastava S, Sanghavi K, Lu Z, Schmidt BJ, Bello A, Gupta M. Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors. J Clin Pharmacol. 2017;57(Suppl 10):S26–42. 10.1002/jcph.990 . Yu WD, Sun G, Li J, Xu J, Wang X. Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy. Cancer Lett. 2019;452:66–70. 10.1016/j.canlet.2019.02.048 . Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18:1116–25. 10.1016/S1470-2045(17)30318-2 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7859919","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542059869,"identity":"1b98c663-3d90-4620-9be9-b7ed48e4beea","order_by":0,"name":"Shuai Li","email":"","orcid":"","institution":"Affiliated Hospital of Jiangnan University","correspondingAuthor":false,"prefix":"","firstName":"Shuai","middleName":"","lastName":"Li","suffix":""},{"id":542059873,"identity":"55a7e508-98a2-4f5e-b770-7e906e184644","order_by":1,"name":"Mengting Zhuang","email":"","orcid":"","institution":"Nanjing Mingji 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16:18:42","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":121918,"visible":true,"origin":"","legend":"","description":"","filename":"f132d97e634f4d3db274e06eebb53cf31structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/f6b5deb1f74b578850ce9cea.xml"},{"id":95566438,"identity":"e4c05d27-0cac-44bd-8547-df2ceae343b5","added_by":"auto","created_at":"2025-11-10 16:18:42","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":131674,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/738164882242ea711b4087d5.html"},{"id":95566432,"identity":"2ad6bbc6-762d-451a-a238-bd1785e5ab78","added_by":"auto","created_at":"2025-11-10 16:18:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7590,"visible":true,"origin":"","legend":"\u003cp\u003eAbsolute counts of T lymphocyte subsets in peripheral blood between study and control group according to CD3+ (a), CD4+ (b), CD8+ (c) T cells and CD4+/CD8+ (d) ratio, respectively.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/fe56f8494f11a654a3f62812.png"},{"id":95655475,"identity":"eb38794b-8145-4cf2-a468-c2560b44b433","added_by":"auto","created_at":"2025-11-11 16:16:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20706,"visible":true,"origin":"","legend":"\u003cp\u003eTumor marker levels comparing in peripheral blood between study and control group according to NSE (a), pro-GFR (b), CYFRA21-1 (c) and CEA (d), respectively.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/609eb10e2902cbdefff9d953.png"},{"id":95655164,"identity":"f2b2d59e-3fef-4735-a324-01d2b48466f4","added_by":"auto","created_at":"2025-11-11 16:14:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":9022,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves comparing progression free survival for patients between study and control group.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/bdebe847d64896d2fc7f13bf.png"},{"id":95654803,"identity":"65fec965-7250-4c65-ad3d-c2dc7947939d","added_by":"auto","created_at":"2025-11-11 16:13:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":7790,"visible":true,"origin":"","legend":"\u003cp\u003eMaximum percentage change from baseline in the sum of longest target lesion diameters in patients.\u003c/p\u003e","description":"","filename":"Onlinefloatimage43.png","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/5139446c65b11fa164c30186.png"},{"id":98421120,"identity":"e7518f48-08e7-4544-b3d8-50f563a17d84","added_by":"auto","created_at":"2025-12-17 16:23:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1003991,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7859919/v1/6214bc8e-8f61-46e9-bffe-e0829b843275.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anti-PD-L1 plus chemoradiotherapy for limited-stage small-cell lung cancer: a retrospective cohort evaluating efficacy, safety, T-cell subsets and tumor markers","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eSmall cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy that exhibits early metastasis and poor clinical prognosis. It constitutes approximately 15% of all lung cancer types, with limited-stage small cell lung cancer (LS-SCLC) ac-counting for about one-third of SCLC cases[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The limited stage is defined as being restricted to I-III stage or being confined to one side of the chest and treatable with a single radiation therapy field. The standard treatment for LS-SCLC is chemoradio-therapy (CRT), which includes platinum-based chemotherapy, etoposide, and thoracic radiotherapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Despite being responsive to chemoradiotherapy, patients with LS-SCLC are susceptible to drug resistance and disease progression, leading to a poor prognosis. The median survival period is typically 15\u0026ndash;30 months, with a 5-year surviv-al rate of only 30%[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] .\u003c/p\u003e\u003cp\u003eOur enhanced comprehension of tumor cells' immune evasion mechanisms has spurred the development of immunotherapy techniques, particularly immune check-point inhibitors (ICIs), which exhibit efficacy against small cell lung cancer (SCLC). Among clinical immunotherapy research, anti-PD-L1 immunotherapy has garnered significant attention. Atezolizumab and Durvalumab, antitumor drugs endorsed for clinical use, obstruct the tumor PD-L1 immune evasion pathway, thus preserving T cell tumor-killing activity to effectuate tumor clearance. In the IMPOWER133 and CAS-PIAN clinical trials, atezolizumab and durvalumab demonstrated favorable clinical efficacy in SCLC treatment relative to chemotherapy alone. Currently, an-ti-programmed death ligand 1 immunotherapy is sanctioned for widespread stage SCLC [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A phase 1/2 trial by James W[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] found that Pembrolizumab and concur-rent chemoradiotherapy for LS-SCLC produced favorable safety and efficacy outcomes. However, it is unclear what the clinical efficacy of atezolizumab and durvalumab in combination with radiotherapy is for limited-stage small cell lung cancer, and few overseas trials have been conducted. This study investigates the clinical efficacy and safety of anti-PD-L1 plus CRT in LS-SCLC treatment to offer guidance for clinical treatment of this disease.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Baseline Data\u003c/h2\u003e\u003cp\u003eFrom June 2020 to February 2022, a total of 42 LS-SCLC patients with a median age of 64 and an average age of 64.26\u0026thinsp;\u0026plusmn;\u0026thinsp;8.28 years who were treated in Xuzhou Cancer Hospital and the Affiliated Hospital of Xuzhou Medical University were selected for retrospective analysis. According to the different treatment methods, the patients were divided into groups. Patients receiving CRT were selected as the control group(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22), and patients receiving anti PD-L1 combined with CRT were selected as the study group(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20). All included patients submitted written informed consents. Differences in general clinical data such as gender, age, smoking status, ECOG PS, prophylactic cranial irradiation and CRT sequence between the two groups had no effect on this study (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Please refer to Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for more details. This study was approved by the Ethics Committee of Xuzhou Cancer Hospital(XYFY2022-KL488-01)and Affiliated Hospital of Xuzhou Medical University(2022-03-054-K01).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Inclusion and exclusion criteria\u003c/h2\u003e\u003cp\u003eInclusion criteria: (1) imaging and pathology examination confirmed clinical LS-SCLC, Measurable lesions were evaluated by imaging. (2) score of 0\u0026ndash;2 on the performance status of the Eastern Cooperative Tumor Group (ECOG); (3) patients were not treated with radical surgery and receive chemotherapy and thoracic radiotherapy consisting of platinum plus etoposide, including or excluding anti-PD-L1 (Atezolizumab/Durvalumab); and (4) complete clinical information records, a 3 -month survival time was project.\u003c/p\u003e\u003cp\u003eExclusion criteria: (1) no clear pathological diagnosis information; (2) patients with other tumors at the same time or had other tumors within 5 years; (3) patients who need to take corticosteroids for a long time; (4) patients with systemic immune disease or severe mental disorder.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Treatment\u003c/h2\u003e\u003cp\u003eThe patients in the control group received concurrent chemoradiotherapy (CRT) consisting of platinum and etoposide intravenous infusions with an infusion time of more than 0.5 hours. Infusions were administered once every three weeks for 4 to 6 cycles (21 days each). Thoracic radiotherapy was administered using three-dimensional conformal radiotherapy technology with a radiation dose of 1.8-2.0 Gy per fraction, once a day, five times a week, for a total dose of 54\u0026ndash;60 Gy in 25\u0026ndash;30 fractions. This was initiated after the first or second cycle of concurrent chemotherapy and at the end of sequential chemotherapy. Preventive intracranial irradiation (25 Gy in 10 fractions) was administered at the discretion of the treating physician for patients who responded well to the initial treatment.\u003c/p\u003e\u003cp\u003eFor the study group, the observation group received Atezolizumab/Durvalumab (Atezolizumab (1200 mg/time, intravenous injection on the first day of each cycle) or Durvalumab (concentration of 10 mg/kg, intravenous injection on the first day of each cycle) plus those used in the control group once every 3 weeks. If the patient acquired disease progression, serious adverse reactions (AEs), or drug toxicity, the drug should be discontinued immediately.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Evaluation of Efficacy, AEs, and Progression free survival\u003c/h2\u003e\u003cp\u003eDisease-control rate (DCR) and response rate (ORR) were used to determine the treatment efficacy. The short-term efficacy was evaluated according to the solid tumor immunotherapy standard, iRECIST standard. Complete remission (iCR): complete ablation of non-lymph node lesions, short axis of lymph nodes\u0026thinsp;\u0026lt;\u0026thinsp;10 mm, no new lesions. Partial remission (iPR): tumor load reduction\u0026thinsp;\u0026ge;\u0026thinsp;30% Disease progression (iUPD): there are new measurable /unmeasurable lesions, or the tumor load increases by \u0026ge;\u0026thinsp;20% relative to the lowest point. Disease stability (iSD): inconformity with iCR, iPR and iUPD. DCR (%)\u0026thinsp;=\u0026thinsp;iCR (%)\u0026thinsp;+\u0026thinsp;iPR (%)\u0026thinsp;+\u0026thinsp;iSD (%) and ORR (%)\u0026thinsp;=\u0026thinsp;iCR (%)\u0026thinsp;+\u0026thinsp;iPR (%). The target date is defined as the date of starting treatment.\u003c/p\u003e\u003cp\u003eThe occurrence of adverse reactions in patients in both groups was recorded and. graded according to CTCAE standards.\u003c/p\u003e\u003cp\u003eThe patient is followed up to the last follow-up date or the study end date. (July. 2022), whichever occurs first. PFS is calculated from the index date to the date of progress, death or final follow-up (whichever comes first).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Observation indexes\u003c/h2\u003e\u003cp\u003eT lymphocyte subsets: venous blood was taken from patients in both groups one day before treatment and after treatment, and the levels of T lymphocyte subsets (CD3+, CD4+, CD8\u0026thinsp;+\u0026thinsp;and CD4+/CD8+) were detected using flow cytometry before and after therapy. Tumor markers: the serum levels of NSE, CYFRA21-1, Pro-GRP and CEA levels were determined using ELISA kits before and after treatment.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. Statistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis and visualization of data were performed using SPSS 26.0 software and R (version 3.6.3). Measurement data were expressed as \u0026ldquo;mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard.\u0026rdquo; To analyze the enumeration data, presented as percentage, we used the t-test and χ\u003csup\u003e2\u003c/sup\u003e test. Kaplan-Meier curves and log-rank tests were performed to determine the differences in PFS between the two groups. Statistically significant difference was set at the p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 level.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1 General Data Comparison\u003c/h2\u003e\u003cp\u003eThe clinical characteristics of the two patient groups, including gender, average age, smoking status, ECOG PS, and other general data, were analyzed using a chi-squared test. The results indicated no significant differences between the groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics between study and control groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003estudy group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eControl group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge(years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u0026sup3;65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.716\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eECOG PS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.985\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e0\u0026ndash;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCRT sequence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.827\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eConcurrent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSequential\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eProphylactic cranial irradiation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.976\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSmoking status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e0.662\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eEver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c9\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e* Compared with the CRT group p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Immune Level Comparison\u003c/h2\u003e\u003cp\u003eThere were no significant differences in T lymphocyte subsets, including CD3\u0026thinsp;+\u0026thinsp;CD4+, CD8+, and CD4+/CD8+, between the two groups prior to treatment (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as evidenced by statistical analysis of the data. Following treatment, both groups exhibited significant increases in CD3+, CD4+, and CD4+/CD8\u0026thinsp;+\u0026thinsp;levels compared to pre-treatment levels (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The study group demonstrated significantly higher increases in these levels compared to the control group, with a statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, the count of CD8\u0026thinsp;+\u0026thinsp;and the ratio of CD4+/CD8\u0026thinsp;+\u0026thinsp;in the control group did not change significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Please refer to Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for detailed results.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of T lymphocyte subsets of patients in two groups (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCD3+(\u0026times;106/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCD4+ (\u0026times;106/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCD8+ (\u0026times;106/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCD4+/CD8+\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy group (n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1123.35\u0026thinsp;\u0026plusmn;\u0026thinsp;263.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e569.00\u0026thinsp;\u0026plusmn;\u0026thinsp;143.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e496.35\u0026thinsp;\u0026plusmn;\u0026thinsp;145.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1645.25\u0026thinsp;\u0026plusmn;\u0026thinsp;472.59*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e848.55\u0026thinsp;\u0026plusmn;\u0026thinsp;233.74*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e527.50\u0026thinsp;\u0026plusmn;\u0026thinsp;158.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.362\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1091.14\u0026thinsp;\u0026plusmn;\u0026thinsp;252.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e551.18\u0026thinsp;\u0026plusmn;\u0026thinsp;141.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e506.41\u0026thinsp;\u0026plusmn;\u0026thinsp;164.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1320.63\u0026thinsp;\u0026plusmn;\u0026thinsp;519.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e697.82\u0026thinsp;\u0026plusmn;\u0026thinsp;231.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e522.14\u0026thinsp;\u0026plusmn;\u0026thinsp;121.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Compared with the CRT group \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Comparison of Tumor Marker Levels\u003c/h2\u003e\u003cp\u003eThe levels of tumor markers did not differ significantly between the two groups prior to treatment (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, post-treatment, there were significant reductions in the levels of NSE and Pro-GRP when compared to CYFRA21-1 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Notably, only the study group exhibited statistically significant decreases in NSE and Pro-GRP levels compared to the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the content of lung cancer related tumor markers between the two groups (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCYFRA21-1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePro-GRP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCEA\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;3.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.45\u0026thinsp;\u0026plusmn;\u0026thinsp;23.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e253.84\u0026thinsp;\u0026plusmn;\u0026thinsp;125.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.74\u0026thinsp;\u0026plusmn;\u0026thinsp;5.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.78\u0026thinsp;\u0026plusmn;\u0026thinsp;8.64*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54.32\u0026thinsp;\u0026plusmn;\u0026thinsp;55.79*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;3.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.305\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.49\u0026thinsp;\u0026plusmn;\u0026thinsp;3.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.34\u0026thinsp;\u0026plusmn;\u0026thinsp;24.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e280.85\u0026thinsp;\u0026plusmn;\u0026thinsp;166.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;4.28\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.06\u0026thinsp;\u0026plusmn;\u0026thinsp;13.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e104.89\u0026thinsp;\u0026plusmn;\u0026thinsp;94.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.101\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e* Compared with the CRT group \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Comparison of Clinical Efficacy\u003c/h2\u003e\u003cp\u003eThe short-term efficacy of the two patient groups was compared, and after treatment, the study group exhibited an overall response rate (ORR) of 90.0%, while the control group had an ORR of 72.73%. Additionally, the disease control rate (DCR) in the study group was 95.00%, compared to 90.90% in the control group. However, there was no statistically significant difference observed between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of short-term efficacy between the two groups of patients.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eiCR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eiPR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eiSD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eUPD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eORR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDCR\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e90.00%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95.00%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eControl group(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e72.73%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e90.90%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.493\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.384\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.188\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.607\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.607\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e* Compared with the CRT group \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Adverse Events (AEs)\u003c/h2\u003e\u003cp\u003eIn both the control and study groups, adverse events (AEs) were predominantly related to the immune system, as well as the blood and gastrointestinal systems. The study group exhibited a tendency towards a higher occurrence of AEs associated with the blood and gastrointestinal systems, but this disparity did not reach statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of patients' AEs in the two groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eAEs, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eLevel I - V\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eLevel III - V\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eControl group\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLed to discontinuation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.221\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6(27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(40.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.764\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea and vomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(40.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.598\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated transaminases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDecreased white cell count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(45.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11(50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.767\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDecreased neutrophil count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10(45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDecreased platelet count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(13.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSkin reaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.221\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.476\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePneumonitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.476\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypothyroidism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1(5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.476\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (85.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (77.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6(27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.515\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e* Compared with the CRT group p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e3.6 Progression free survival (PFS)\u003c/h2\u003e\u003cp\u003eAs of July 1st, 2022, the median follow-up time for the study group and control group were 14.2 months and 15.3 months, respectively, as reported in our study. Disease progression was observed in 40.0% (8 patients) of the study group and 86.36% (19 patients) of the control group, with no significant difference observed (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Median progression-free survival (PFS) was not reached in the study group, while it was 8.7 months [95% confidence interval (CI), 7.5\u0026ndash;10.5 months] in the control group. Our analysis demonstrated that the study group exhibited better PFS compared to the control group, as evidenced by the PFS curve depicted in Fig.\u0026nbsp;3.\u003c/p\u003e\u003cp\u003e\u003cem\u003e3.7\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Ease the depth\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study group exhibited a DCR of 95.00%, consisting of a complete response rate of 10%, partial response rate of 80.0%, and a disease stability rate of 5.00%. In comparison, the control group demonstrated a DCR of 90.91%, comprising a complete response rate of 4.55%, partial response rate of 68.18%, and a disease stability rate of 18.19%, as illustrated in Table 4. The study group also displayed an ORR of 90.0%, with a complete response rate of 10.00% and partial response rate of 80.00%, while the control group had an ORR of 72.73%, with a complete response rate of 4.55% and partial response rate of 68.18%, as presented in Table 4. These results indicate that the addition of anti PD-L1 to CRT treatment resulted in a slight enhancement of both ORR and DCR when compared to CRT alone. However, there was no significant difference in ORR and DCR between the two groups (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05). The study group experienced a reduction in tumor burden within a few months, with a better depth of tumor remission than the control group, as demonstrated in Figure 4.\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe emergence of immunotherapy has brought about a change in the approach to treating SCLC, thanks to the development of ICIs that target the PD-1/PD-L1 pathway. For those with SCLC, the primary options are atezolizumab or durvalumab. Recent studies such as IMPOWER133 and CASPIAN have altered the first-line treatment paradigm for ES-SCLC, revealing that patients receiving atezolizumab or durvalumab with chemotherapy (platinum plus etoposide) have seen significant improvements in their survival rate (OS and PFS) compared to chemotherapy alone [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, no new drugs have been approved for LS-SCLC, including immunotherapy. A phase 1/2 trial led by James W. has demonstrated the good safety and efficacy of Pembrolizumab combined with concurrent chemoradiotherapy in the treatment of LS-SCLC [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, a study by Bilani et al, utilizing a large national database, suggested that immunotherapy as a first-line treatment for LS-SCLC patients did not result in a significant increase in survival rates[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, the efficacy and safety of immunotherapy in LS-SCLC remains inconclusive. It is worth noting that SCLC is closely linked to smoking and is a neuroendocrine carcinoma with a high tumor mutation burden, indicating that patients may benefit from immunotherapy.\u003c/p\u003e\u003cp\u003eIn the present study, patients with LS-SCLC were treated with anti PD-L1 plus CRT as the initial therapy and compared with CRT alone. The immune response is primarily mediated by T lymphocytes, which serve as a crucial indicator for clinical evaluation of immune function[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. CD3\u0026thinsp;+\u0026thinsp;enhances the anti-tumor immune response, while CD4\u0026thinsp;+\u0026thinsp;plays a more immunomodulatory and paracrine role. Additionally, CD8\u0026thinsp;+\u0026thinsp;and CD4+/CD8\u0026thinsp;+\u0026thinsp;reflect the tumor-killing activity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, monitoring lymphocyte subsets is essential for evaluating tumor drug efficacy. Malignant tumors can disturb the immune response and reduce the counts of CD3+, CD4+, and CD8\u0026thinsp;+\u0026thinsp;due to the secretion of specific factors. However, PD-L1 inhibitors can improve the prognosis of patients by reducing the body's immunosuppressive effect and enhancing the anti-tumor effect of the body. Our study found that CD3\u0026thinsp;+\u0026thinsp;and CD4\u0026thinsp;+\u0026thinsp;levels, as well as CD4+/CD8\u0026thinsp;+\u0026thinsp;levels, were significantly higher in the study group after treatment than before treatment, compared to the control group. High expression of CD3\u0026thinsp;+\u0026thinsp;has been associated with good prognosis in SCLC[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, higher expression levels of CD3+, CD4+, CD8+, and FOXP3 were associated with better survival[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although reduced CD8\u0026thinsp;+\u0026thinsp;T lymphocytes are typically associated with better prognosis, the expansion of CD8\u0026thinsp;+\u0026thinsp;observed in our study may be related to the clinical efficacy of anti-PD-L1 inhibitors[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], which can interfere with PD-L1 signaling and promote early CD8\u0026thinsp;+\u0026thinsp;proliferation[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] without affecting PD-L1 efficacy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Taken together, these findings suggest that PD-L1 mobilizes the patient's own antitumor capacity by activating T lymphocytes with a killing effect after relieving the inhibitory effect of immune checkpoints.\u003c/p\u003e\u003cp\u003eTumor markers are synthesized and secreted by malignant neoplastic tissues and cells [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Their concentration levels are positively correlated with the severity of the patient's condition[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. NSE serves as a sensitive biomarker for neuroendocrine tumors, reflecting the onset and progression of the tumors. ProGRP, on the other hand, is a critical biomarker for the evaluation of tumor progression and prognosis. Its expression level is directly associated with disease severity and is thus of great importance for evaluating disease condition and predicting prognosis [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. CYFRA21-1 can be released into the bloodstream when tumor cells undergo necrosis or lysis, which offers a high diagnostic and therapeutic assessment for patients with small cell lung cancer[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Prior to CEA treatment, no significant differences were observed between the two patient groups, which may be attributed to the higher frequency of CEA positivity in lung adenocarcinoma[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Baseline biomarker levels were comparable between the two groups in this study. Following treatment, the serum levels of NSE and ProGRP in the observation group decreased significantly relative to those in the control group, indicating that the treatment protocol was able to lower the serum tumor marker levels. Anti PD-L1 treatment can activate the immune system, attack cancer cells, and form the foundation of tumor immunotherapy, effectively ameliorating the patient's condition and reducing serum factor expression.\u003c/p\u003e\u003cp\u003eThe data of this study also showed that the incidence of thrombocytopenia, nausea and vomiting, leukopenia, neutropenia, anemia, and pneumonia in the study group were 10.0%, 40.0%, 45.0%, 50.0%, 25.0%, and 25.0%, respectively, compared with 13.6%, 40.9%, 50.0%, 45.5%,27.3%, and 9.1% of the control group, there was no statistically significant difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating that adjuvant immunotherapy did not significantly increase adverse reactions and had good safety. The results showed that anti-PD-L1 plus CRT had appropriate safety at least in the short term. Due to the short follow-up period of this study (median 15.3 months), long-term toxic reactions (e.g. pericarditis and esophageal fistula) were not evaluated at the time of this analysis. Also, this paper did not count eosinophils, which are extremely important cells in immune and allergic reactions, releasing granule contents, causing tissue damage and promoting the progression of inflammation. We are cautiously optimistic about the risk of long-term complications. In terms of toxicity and side effects, the incidence of toxicity between the two groups was similar, and there was no new safety signal. In terms of immune adverse reactions such as hypothyroidism and rash, the symptoms were controllable after symptomatic treatment However, foreign studies have also shown that the use of anti-PD-L1 immunotherapy may increase the risk of liver and kidney function and thyroid function damage in patients[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, attention should be paid to regular monitoring of patients' biochemical indicators during use Patients take 10 mg/kg Durvalumab every 3 weeks instead of ES-SCLC (1500 mg every 4 weeks). Immunotherapy has a wide therapeutic index and unique pharmacokinetic and pharmacodynamic behavior. We predict that this adjustment will not affect the efficacy[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe results of the study demonstrate that the addition of anti-PD-L1 to CRT led to significant improvements in ORR, DCR, PFS, and depth of tumor remission when compared to CRT alone. PFS was notably longer in the study group than in the control group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), which may be explained by the synergistic effect of CRT and tumor immunotherapy as a means of enhancing antigen presentation, T cell recruitment, and tumor interstitial lymphocyte infiltration while modifying the microenvironment[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In the CONVERT trial, chest radiation combined with synchronous chemotherapy was established as the standard treatment for cancer. This approach, consisting of 30 doses and twice-daily administration of 45 Gy, was found to have similar therapeutic effects and tolerable toxicity features to the approach of 33 doses of daily fractionated radiotherapy and chemotherapy totaling 66 Gy[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Although the ORR and DCR of the study group tended to increase, no significant difference was found between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), which may be attributed to the small number of patients and the typical reduction of tumor burden in the study group within a few months. However, the depth of tumor remission in the study group was superior to that in the control group. These findings may have implications for patients of Chinese descent, whose genetic background and tumor characteristics may differ from those of Western patients.\u003c/p\u003e\u003cp\u003eThis study exhibits several limitations. Firstly, the retrospective nature of the study precludes the detection of anti-PD-L1 expression. Additionally, the study's limited sample size and short follow-up duration restrict the assessment of the efficacy of anti-PD-L1 and the combination of chemoradiotherapy. Furthermore, there exist variations in individual doses of chemoradiotherapy, potentially leading to deviations in both efficacy and side effects. Therefore, further investigation with an expanded sample size is necessary to overcome these limitations.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn summary, treatment with anti-PD-L1 immunotherapy significantly improved T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+), tumor markers (Pro-GRP, NSE), and curative effects in patients with LS-SCLC compared to pre-treatment levels. The improvement seen with this treatment was greater than that observed with CRT. Therefore, anti-PD-L1 immunotherapy combined with CRT should be considered as the initial treatment option for LS-SCLC patients due to its favorable safety and efficacy profile. This represents an important step towards providing a viable treatment strategy for LS-SCLC patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eChemoradiotherapy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLS-SCLC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLimited-stage small-cell lung cancer\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePD-L1\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProgrammed death-ligand 1\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eORR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eObjective response rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDCR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDisease control rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProgression-free survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAEs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAdverse events\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNeuron-specific enolase\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePro-GRP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePro-gastrin-releasing peptide\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCEA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCarcinoembryonic antigen.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003eThis retrospective study was approved by the Ethics Committees of Xuzhou Cancer Hospital (XYFY2022-KL488-01) and the Affiliated Hospital of Xuzhou Medical University (2022-03-054-K01). The study was conducted in accordance with the ethical standards of the institutional and national research committees and with the 1964 Declaration of Helsinki and its later amendments. All participants provided written informed consent before inclusion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003cbr\u003eConceptualization: S.L., X.L., Z.L., M.Z., and J.C.; Methodology: S.L. and J.C.; Investigation: S.L., Z.L., M.Z., and X.L.; Writing\u0026mdash;original draft: S.L. and J.C.; Writing\u0026mdash;review and editing: Z.L., M.Z., and X.L.; Supervision: J.C.; All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003eThe authors thank all participating patients and their families, as well as the clinical and research staff who contributed to this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, et al. 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Lancet Oncol. 2017;18:1116\u0026ndash;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1470-2045(17)30318-2\u003c/span\u003e\u003cspan address=\"10.1016/S1470-2045(17)30318-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"limited-stage small-cell lung cancer, chemoradiotherapy, PD-L1 inhibitor, iRECIST, progression-free survival, T-lymphocyte subsets, NSE, Pro-GRP","lastPublishedDoi":"10.21203/rs.3.rs-7859919/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7859919/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEvidence for immune checkpoint blockade with chemoradiotherapy (CRT) in limited-stage small-cell lung cancer (LS-SCLC) remains limited. We evaluated anti-PD-L1 plus CRT versus CRT alone in routine practice.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe retrospectively included 42 LS-SCLC patients (June 2020\u0026ndash;February 2022). The study group received atezolizumab or durvalumab plus platinum\u0026ndash;etoposide CRT; the control group received CRT alone. Primary outcome: progression-free survival (PFS). Secondary outcomes: objective response rate (ORR), disease control rate (DCR), adverse events (AEs), T-cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and serum tumor markers (NSE, Pro-GRP, CYFRA21-1, CEA). Responses followed iRECIST; AEs were graded per CTCAE; Kaplan\u0026ndash;Meier/log-rank compared PFS.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eGroups were balanced at baseline. Compared with CRT, anti-PD-L1\u0026thinsp;+\u0026thinsp;CRT yielded numerically higher ORR (90.0% vs 72.7%) and DCR (95.0% vs 90.9%), with significantly longer PFS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Post-treatment, the combination group showed greater increases in CD3+, CD4+, CD4+/CD8\u0026thinsp;+\u0026thinsp;and larger reductions in NSE and Pro-GRP (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Safety was comparable with no new signals. Median follow-up was 15.3 months.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eAdding anti-PD-L1 to CRT for LS-SCLC was associated with improved PFS, favorable immunologic and biomarker changes, and manageable safety in this retrospective cohort, supporting prospective validation.\u003c/p\u003e","manuscriptTitle":"Anti-PD-L1 plus chemoradiotherapy for limited-stage small-cell lung cancer: a retrospective cohort evaluating efficacy, safety, T-cell subsets and tumor markers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 16:18:38","doi":"10.21203/rs.3.rs-7859919/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":"01dbf217-1e82-4a88-887b-e8636802466a","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T10:02:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 16:18:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7859919","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7859919","identity":"rs-7859919","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}