Efficacy and safety of radiotherapy following chemoimmunotherapy in extensive-stage small cell lung cancer: a retrospective comparative cohort study of consolidation versus salvage indications

Introduction

Lung cancer ranks among the most common cancers worldwide. Globally, small cell lung cancer (SCLC) accounts for approximately 250,000 new annual diagnoses and 200,000 deaths (1). SCLC has consistently presented a significant clinical challenge, as traditional therapeutic approaches yield limited clinical benefits. Accumulating evidence indicates that SCLC exhibits distinct biological properties compared with other lung cancer subtypes (2), including differences in pathological features (3), molecular profiles, biological behaviors, and clinical manifestations. SCLC notably has a poor prognosis. Clinically, 60–70% of patients already have distant metastases at initial diagnosis (1). For patients with extensive-stage SCLC (ES-SCLC), the 5-year overall survival (OS) rate is generally less than 5%, and fewer than 7% of patients with SCLC achieve 5-year survival (4). Based on results from the IMPOWER133 and CASPIAN clinical trials, the combination of immunomodulators such as atezolizumab and durvalumab with chemotherapy has become the recommended first-line treatment regimen for ES-SCLC (5). Although first-line chemoimmunotherapy (CIT) has improved survival outcomes in ES-SCLC, patients remain at high risk of local recurrence and distant progression (1,4). Increasing preclinical and clinical evidence suggests that radiotherapy (RT) can enhance antitumor immunity and improve the efficacy of immunotherapy, yielding positive outcomes in various lung cancer types (3,6-10). However, whether adding local RT to CIT further improves survival without causing unacceptable toxicity remains unclear.

In the treatment of ES-SCLC, many unknowns remain regarding combined RT approaches, requiring further investigation. High-level evidence from large-scale randomized controlled trials on this combination is still lacking. Current clinical guidelines [e.g., National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO)] do not provide clear recommendations on thoracic RT following CIT (11-13). A 2025 meta-analysis reported that consolidative thoracic RT significantly improved OS (HR =0.57) and PFS (HR =0.53) but increased the incidence of grade ≥3 pneumonitis (3.9%) and esophagitis (1.3%) (14). Therefore, real-world retrospective studies may help address this gap by evaluating potential synergistic effects of RT, optimal timing (consolidation vs. salvage), and risks of increased toxicity such as radiation pneumonitis (RP).

Results from a secondary analysis of the KEYNOTE-001 clinical trial indicated that patients with advanced NSCLC receiving RT before pembrolizumab had longer progression-free survival (PFS) and OS compared with patients who did not receive RT (15). Extensive research has also confirmed the abscopal effect of RT, in which tumor lesions outside the radiation field shrink (14,16-18). Results from the ADRIATIC study suggest that concurrent chemoradiotherapy may initiate tumor response to programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy (19). Studies have also identified potential synergistic effects when combining palliative low-dose thoracic RT with CIT regimens. Many researchers are exploring how RT can achieve optimal synergy while ensuring safety, investigating combinations of two or more modalities (20). The large-scale phase 3 randomized controlled trial CREST recommended thoracic RT for all ES-SCLC patients responsive to chemotherapy (21). Currently, the optimal timing, regimen, safety, and efficacy of thoracic RT for ES-SCLC remain unclear.

Numerous studies have explored the combination of RT and immune checkpoint inhibitors (ICIs) (22,23). Accordingly, we conducted a retrospective analysis of ES-SCLC patients who received first-line chemotherapy and immunotherapy at Xuzhou Medical University Affiliated Hospital. Patients were categorized into RT and non-RT groups to evaluate treatment efficacy and adverse reactions. This study aimed to address specific knowledge gaps by evaluating the efficacy, safety, and timing of RT added to first-line CIT in a real-world cohort. Notably, this is the first study to specifically examine PFS for distant metastases (PFS-DM). Our results showed that the RT group achieved significantly better outcomes than the non-RT group, highlighting the potential value of RT in managing distant metastatic lesions. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0882/rc).

Methods

Study design and participants

This retrospective study included 132 patients with ES-SCLC hospitalized at Xuzhou Medical University Affiliated Hospital from January 1, 2019, to December 31, 2024. All patients received first-line chemotherapy combined with immunotherapy, with or without local RT.

Inclusion criteria: (I) age ≥18 years; (II) availability of complete medical records, including baseline demographics, histopathological reports, imaging findings, treatment details (chemotherapy regimens, immunotherapy agents, RT parameters), and regular follow-up data; (III) histologically or cytologically confirmed ES-SCLC according to the Veterans Administration Lung Study Group staging system; (IV) at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; (V) Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0–2; (VI) at least two cycles of chemotherapy and two cycles of ICI therapy; and (VII) for the immunochemotherapy combined with RT (ICRT) group, RT administered following first-line systemic therapy; for the immunochemotherapy-only (ICT) group, no RT administered during first-line systemic therapy.

Exclusion criteria: (I) pregnancy or lactation; (II) loss to follow-up or insufficient clinical data; (III) concurrent other malignancies; (IV) severe contraindications to RT, chemotherapy, or immunotherapy, such as severe bone marrow suppression, coagulation disorders, hepatic or renal insufficiency, or severe cardiopulmonary impairment; and (V) loss to follow-up due to unexpected death.

The patient selection process is illustrated in Figure 1. Baseline staging included contrast-enhanced computed tomography (CT), with brain magnetic resonance imaging (MRI) or positron emission tomography (PET)-CT performed when available. Response evaluation imaging was conducted every 2–3 cycles, with baseline defined as the start of treatment.

Figure 1 Flowchart of patient selection. Among 186 screened patients, 54 were excluded because of inadequate treatment or failure to meet eligibility criteria (n=16), medical contraindications or comorbidities (n=23), or incomplete data/loss to follow-up (n=15). A total of 132 patients were included in the final analysis. The ICT group (n=59) and ICRT group (n=73) are shown in parallel; within the ICRT group, 54 patients received sequential consolidation radiotherapy and 19 received salvage radiotherapy. ICT group: immunochemotherapy-only; ICRT group: immunochemotherapy combined with RT. RT, radiotherapy.

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and the International Council for Harmonization Good Clinical Practice. The study was approved by the Ethics Review Committee of Xuzhou Medical University Affiliated Hospital (No. XYFY2025-KL669-01). The requirement for written informed consent was waived by the ethics committee because of the retrospective nature of the study.

Treatment

Chemotherapy and immunotherapy

All patients received at least two cycles of first-line chemotherapy. Chemotherapy regimens consisted of etoposide (100 mg/m², days 1–3) combined with cisplatin (75 mg/m², day 1) or carboplatin (AUC =5), repeated every 3 weeks for 4–6 cycles. Alternative platinum-based regimens included lobaplatin (30 mg/m², day 1) or nedaplatin (80 mg/m², Day 1), each combined with etoposide (100 mg/m², days 1–3) every 3 weeks. All patients received immunotherapy either concurrently or sequentially with chemotherapy. Immunotherapy agents included serplulimab (300 mg), adebrelimab (1,200 mg), atezolizumab (1,200 mg), or durvalumab (1,500 mg), administered every 3 weeks.

RT

Patients in the combined RT group underwent intensity-modulated radiation therapy (IMRT) following first-line systemic treatment for ES-SCLC. Patients receiving RT were categorized into consolidation RT or salvage RT subgroups. RT followed the involved-field RT (IFRT) approach, targeting only the primary lung lesions and radiographically visible metastatic lymph nodes. The prescribed dose ensured that at least 95% of the planning target volume (PTV) received the prescribed dose, with 100% of the PTV receiving at least 95% of the dose. The RT dose ranged from 30.0 to 60.0 Gy, administered in fractions of 1.5 to 3.0 Gy. Individual doses depended on tumor volume, location, and patient condition. The median interval between the last immunotherapy session and RT initiation was 1.8 months (range, 0–5.2 months). Consolidation RT was defined as thoracic RT or prophylactic cranial irradiation for patients achieving complete response (CR), partial response (PR), or stable disease (SD) after 4–6 cycles of first-line chemotherapy and immunotherapy. Salvage RT was palliative RT for local recurrence or isolated distant metastases occurring after initial treatment. A multidisciplinary tumor board decided on RT based on patient performance status, tumor response to initial CIT, and absence of rapid progression. All patients in the RT group had at least SD following 4–6 cycles of first-line CIT before initiating RT.

Follow-up

Imaging assessments were performed every 2–3 cycles after initiation of immunotherapy. Treatment efficacy was evaluated according to the RECIST version 1.1, including CR, PR, SD, and progressive disease (PD). The objective response rate (ORR) was defined as the proportion of patients achieving CR or PR. The disease control rate (DCR) was defined as the proportion of patients achieving CR, PR, or SD.

All survival endpoints were measured from treatment initiation to the occurrence of the specified event. OS was defined as the time to death from any cause. PFS was defined as the time to first disease progression (recurrence or metastasis) or death. Primary tumor PFS (PFS-PT) was defined as the time to primary tumor progression or death. PFS-DM was defined as the time to progression of existing distant metastases or death. Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

The primary endpoint of this study was OS. Secondary endpoints included PFS, PFS-PT, and PFS-DM. Although PFS-DM is not a conventional endpoint, it was included for two reasons. First, distant metastasis is the predominant failure pattern in ES-SCLC. In a recent real-world analysis (n=2,788) of first-line CIT, new distant metastases represented the most common progression event (37.7%) (24). Second, exploration of PFS-DM may help identify potential abscopal effects. A 2025 meta-analysis reported that consolidative thoracic RT significantly improved brain metastasis-free survival [hazard ratio (HR) =0.46] (25), supporting the hypothesis that local RT may influence distant disease control. This hypothesis-generating endpoint may provide evidence for future prospective trial design.

Tumor response included ORR, DCR, and treatment-related AEs. The effects of RT-related variables, including RT timing, on survival outcomes in the ICRT subgroup were also analyzed. All imaging assessments were independently reviewed by two radiologists blinded to group assignment. PFS-DM was assessed according to RECIST version 1.1 criteria. Distant metastasis was defined as any new lesion outside the thorax or progression of pre-existing distant lesions.

Statistical analysis

Statistical analyses were performed using Statistical Product and Service Solutions (SPSS) software (version 24.0; IBM Corp., Armonk, NY, USA). Clinical characteristics were compared using the Chi-squared test for categorical variables. Survival analyses were conducted using the Kaplan-Meier method, and differences between groups were compared using the log-rank test. Univariate and multivariate analyses of PFS and OS were performed using the Cox proportional hazards model. To reduce potential model overfitting and evaluate the stability of independent prognostic factors, internal validation of the Cox proportional hazards models was conducted using the bootstrap method with 200 resamples. All statistical tests were two-sided, and P<0.05 was considered statistically significant.

Results

Patient characteristics

A total of 132 patients with ES-SCLC were enrolled and categorized into the ICRT group (n=73) and the ICT group (n=59). Baseline characteristics were generally balanced between the two groups, except for a significantly higher incidence of baseline brain and adrenal metastases in the ICRT group (Table 1). Among the 73 patients in the RT group, RT sites included the thoracic cavity (n=51), salvage cranial irradiation (n=21), prophylactic cranial irradiation (n=10), and bone (n=8). These categories were not mutually exclusive.

Treatment and outcomes

All eligible patients were evaluated according to RECIST version 1.1. Detailed tumor responses are shown in Figure 2. No patients achieved a CR in either group. However, RT significantly improved the ORR (83.6% vs. 49.2%, P<0.001) and DCR (90.4% vs. 62.7%, P<0.001) compared to the ICT group.

Figure 2 Tumor response. (A) Objective response rate in the RT and non-RT groups. (B) Disease control rate in the RT and non-RT groups. Non-RT, chemoimmunotherapy-only group; NR, disease progression; R, partial response and stable disease; RT, chemoimmunotherapy plus radiotherapy group.

With a median follow-up of 21.0 months (95% CI: 18.4–25.5) for the entire cohort, median OS and PFS were 17.1 months (95% CI: 15.6–20.0) and 8.2 months (95% CI: 7.3–9.6), respectively (Figure 3A,3B). Median PFS for the PFS-PT and PFS-DM was 10.0 months (Figure 3C,3D).

Figure 3 Kaplan-Meier curves for all 132 patients. (A) Overall survival; (B) progression-free survival; (C) local progression-free survival; (D) distant metastasis progression-free survival.

Prognostic factors

Univariate Cox analyses were performed to identify prognostic factors for OS and PFS. Variables with P<0.05 were included in multivariate analysis to identify independent prognostic factors. Univariate analysis showed combined RT, chemotherapy cycles exceeding six, and immunotherapy cycles exceeding six as protective factors for OS. Conversely, male gender, metastases involving more than three sites, ECOG performance status of 2, and elevated lactate dehydrogenase (LDH) levels were risk factors for OS (Table 2). Multivariate analysis confirmed RT and immunotherapy cycles exceeding six as independent protective factors, while metastases involving more than three sites represented an independent risk factor for OS (Table 2). For PFS, univariate analysis indicated combined RT as a protective factor, whereas PD-L1 inhibitor use was identified as a risk factor (Table 3). Multivariate analysis confirmed RT as an independent protective factor for PFS (Table 3). These results suggest RT is an independent favorable prognostic factor for both OS and PFS in ES-SCLC.

Survival analysis

Kaplan-Meier analyses compared survival outcomes between patients receiving CIT with and without RT, evaluating OS, PFS, PFS-PT, and PFS-DM.

The ICRT group showed significantly longer median OS (21.0 vs. 13.0 months, HR =0.514, P=0.003) and median PFS (9.5 vs. 6.0 months, HR =0.552, P=0.001) compared to the ICT group, along with improvements in 1-year and 2-year survival rates (Figure 4A,4B). RT also provided significant benefits in local and distant disease control, extending median PFS-PT (11.8 vs. 8.0 months, P<0.001) and PFS-DM (11.8 vs. 7.1 months, P=0.01) (Figure 4C,4D).

Figure 4 Kaplan-Meier survival curves comparing the RT and non-RT groups. (A) Overall survival; (B) progression-free survival; (C) primary tumor progression-free survival; (D) distant metastasis progression-free survival. HR, hazard ratio; non-RT, chemoimmunotherapy-only group; PFS-DM, progression-free survival of distant metastases; PFS-PT, progression-free survival of primary tumor; RT, chemoimmunotherapy plus radiotherapy group.

Among the 73 RT patients, 54 received consolidation RT, and 19 received salvage RT. OS and PFS were compared to assess the impact of RT timing on prognosis. Patients receiving salvage RT had significantly worse OS and PFS compared to those receiving consolidation RT (Log-rank P=0.002 and 0.001; HR 2.714, 95% CI: 1.386–5.312 and HR 2.456, 95% CI: 1.404–4.298) (Figure 5).

Figure 5 Kaplan-Meier survival curves stratified by radiotherapy timing among patients receiving radiotherapy. (A) Overall survival for consolidation versus salvage radiotherapy; (B) progression-free survival for consolidation versus salvage radiotherapy. HR, hazard ratio.

To confirm robustness and mitigate potential immortal time bias, a landmark analysis was performed as a sensitivity analysis. The landmark was set at 4.1 months (median interval from CIT initiation to RT start). Patients experiencing disease progression or death before this landmark were excluded, and survival outcomes were re-evaluated in this subgroup (n=79) (Figure S1).

Adverse reactions

Treatment-related AEs were compared between the RT plus CIT (ICRT) group and the CIT-only (ICT) group. Most AEs were mild and predominantly self-limiting or tolerable, consisting mainly of Grade I–II events. No treatment-related deaths occurred in either group. The incidence of Grade I–II and Grade III–IV AEs was compared between groups. No significant differences were observed in the incidence of either Grade I–II or Grade III–IV AEs between the two groups (Tables 4,5).

The ICRT (n=73) and ICT (n=59) groups demonstrated different AE profiles. The incidence of bone marrow suppression was slightly higher in the ICRT group than in the ICT group (17.8% vs. 11.9%). Immune-related myocarditis occurred in two patients (3.39%) in the ICT group but was not observed in the ICRT group. Pneumonia cases were further analyzed. Among the 73 patients in the RT group, 3 (4.0%) developed immune-mediated pneumonitis, and 11 (15.0%) experienced Grade 1–2 RP. In comparison, 5 of 59 patients (8.5%) in the ICT group developed immune-mediated pneumonitis. Among the 11 patients with RP, most (8/11) had tumors with a maximum diameter ≥5 cm, whereas the remaining three had tumors <5 cm. Radiation doses in these patients were distributed as follows: 30 Gy (1 case), 42 Gy (1 case), 45 Gy (3 cases), 50 Gy (3 cases), and 60 Gy (3 cases). Of these patients, 8 were male and 3 were female. Elevated LDH levels during treatment were observed in 10 of the 11 patients.

Sensitivity analysis

In the landmark cohort (n=79), the OS benefit remained stable compared with the full cohort, with an HR of 0.500 (95% CI: 0.270–0.927, P=0.02; Figure S1A). Similarly, RT continued to demonstrate a significant benefit in primary tumor control (PFS-PT, P=0.043; Figure S1D). However, differences in overall PFS (P=0.51) and PFS-DM (P=0.90) were no longer statistically significant in this restricted cohort. Nevertheless, the consistent OS benefit supports the prognostic value of RT.

Discussion

To our knowledge, this is the first study to specifically evaluate PFS-DM in this setting. Although PFS-DM is not a validated surrogate endpoint, it was included to explore potential RT-induced systemic antitumor effects, such as the abscopal effect. Although hypothesis-generating, the prolonged PFS-DM observed in the ICRT group (11.8 vs. 7.1 months, P=0.01) provides a novel perspective on distant disease control. These findings are generally consistent with benchmark results from the IMpower133 study (23,26), suggesting that the addition of RT does not compromise the established efficacy of first-line CIT.

Importantly, baseline analysis demonstrated that the ICRT group had significantly higher rates of brain (P=0.004) and adrenal metastases (P=0.01), both recognized as poor prognostic factors in ES-SCLC. Despite this unfavorable baseline profile, reflecting more aggressive disease, the ICRT group still achieved significantly improved OS and PFS-PT. These findings suggest that the addition of thoracic RT may provide survival benefits even in patients with high-risk baseline characteristics, such as brain and adrenal metastases. However, further prospective validation is required.

The key finding of this study is that adding local RT to CHT + ICIs significantly improved median PFS from 6.0 to 9.5 months, extended median OS from 13.0 to 21.0 months, and increased the 1-year OS rate from 52.8% to 79.6%. This survival benefit surpasses historical benchmarks. For example, the landmark CREST study showed consolidation thoracic RT (cTRT) after chemotherapy increased the 2-year OS rate only from 3% to 13% (21). While cross-trial comparisons require caution, these findings suggest that RT may enhance the effects of immunotherapy, possibly through mechanisms such as immunogenic cell death, tumor antigen release, and tumor microenvironment remodeling (20,22,27,28).

Initial analysis showed that RT improved PFS at both the primary tumor site (PFS-PT) and distant metastatic sites (PFS-DM). However, the significance of PFS-DM disappeared in the landmark sensitivity analysis (P=0.90), indicating the initial distant control benefit in the full cohort likely resulted from immortal time bias. Thus, while local RT reliably stabilizes primary disease, its systemic impact on distant metastases remains speculative and requires cautious interpretation in future prospective trials (14,16,17,29).

Notably, subgroup analysis showed consolidation RT, administered before disease progression, was associated with better survival outcomes than salvage RT. However, as mentioned in the Methods section, this comparison is confounded by indication bias, as consolidation RT was limited to patients who achieved initial disease control. Therefore, the apparent advantage of consolidation RT may partly reflect patient selection rather than a true timing effect.

Regarding safety, no unexpected AEs occurred in the combined RT group. RP was the main concern, with incidence correlated to larger tumor volumes (maximum diameter ≥5 cm) and higher RT doses (≥45 Gy). Elevated pretreatment LDH levels may also indicate increased RP risk, serving as a potential predictive biomarker. Compared to the CHT + ICIs-alone group, the combination group showed increased Grade 3–4 hematologic toxicity but no significant rise in immune-related AEs such as pneumonia or myocarditis. The overall safety profile remained manageable (30,31). These findings contrast some exploratory reports suggesting safety concerns (32) but align with a pooled analysis of US Food and Drug Administration (FDA) data concluding concurrent RT does not substantially increase immunotherapy-associated AE risk (30).

Multivariate Cox regression identified RT as independently associated with improved OS (HR: 0.39, 95% CI: 0.22–0.69) and PFS (HR: 0.49, 95% CI: 0.30–0.81) after adjusting for covariates. While these results suggest RT as an independent favorable prognostic factor, residual confounding remains possible given the observational study design. Additionally, metastasis involving more than three sites emerged as an independent risk factor for OS, reflecting ES-SCLC’s aggressive nature (33). Early consolidation RT correlated with superior survival compared to late salvage RT, aligning with the established paradigm in limited-stage disease and highlighting timely local therapy integration in ES-SCLC management (34).

This study has several limitations. As a single-center retrospective analysis, it is vulnerable to inherent selection bias and has limited statistical power due to a small sample size. Specifically, the RT group included only patients who achieved SD or better after first-line CIT, possibly introducing immortal time bias favoring the RT group. Differential synergistic effects among various ICIs (e.g., PD-1 vs. PD-L1 inhibitors) combined with RT were not systematically assessed; future large-scale studies should address these efficacy distinctions (10,35). The loss of statistical significance for PFS and PFS-DM in the landmark analysis reflects successful elimination of immortal time bias. Meanwhile, OS and PFS-PT remained significant in both analyses, strengthening the evidence that thoracic RT primarily stabilizes local disease, reducing early local-related mortality, and significantly improving OS. Optimal RT parameters, such as timing, dose, and target volume, still require clarification through prospective trials.

In summary, these results offer initial guidance for integrating RT into CIT for ES-SCLC. However, small sample size and retrospective design limit statistical power and introduce selection and information biases, reducing reliability and generalizability. Future prospective research with larger sample sizes is necessary to provide more accurate efficacy and safety data. Additionally, PFS-DM as an endpoint remains unvalidated externally; therefore, our findings regarding distant metastasis control must be confirmed in future prospective studies with standardized definitions.

Conclusions

In conclusion, this retrospective cohort study indicates that adding local RT to first-line CIT significantly improves OS and PFS in ES-SCLC patients. RT effectively stabilizes primary disease, though its impact on distant metastasis control appears limited after adjusting for survival bias. Consolidation RT timing was associated with superior outcomes compared to salvage RT. No significant increase in treatment-related AEs occurred. These hypothesis-generating results suggest integrating RT into first-line CIT is a promising strategy requiring prospective validation.

Acknowledgments

We thank all the investigators, nurses, patients, and their family members who participated in this study. The authors declare that generative artificial intelligence (AI) and AI-assisted technologies were not used in the writing process or any other process during the preparation of this manuscript.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0882/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0882/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0882/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0882/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and the International Council for Harmonization Good Clinical Practice. The study was approved by the Ethics Review Committee of Xuzhou Medical University Affiliated Hospital (No. XYFY2025-KL669-01). The requirement for written informed consent was waived by the ethics committee because of the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Kalemkerian GP. Small Cell Lung Cancer. Semin Respir Crit Care Med 2016;37:783-96. [Crossref] [PubMed]
2. Pacheco JM. Immunotherapy for extensive stage small cell lung cancer. J Thorac Dis 2020;12:6212-24. [Crossref] [PubMed]
3. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 2019;394:1929-39. [Crossref] [PubMed]
4. Früh M, De Ruysscher D, Popat S, et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24.
5. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007;357:664-72. [Crossref] [PubMed]
6. Horn L, Mansfield AS, Szczęsna A, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 2018;379:2220-9. [Crossref] [PubMed]
7. Patel RB, Hernandez R, Carlson P, et al. Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade. Sci Transl Med 2021;13:eabb3631. [Crossref] [PubMed]
8. Wang Y, Zou S, Zhao Z, et al. New insights into small-cell lung cancer development and therapy. Cell Biol Int 2020;44:1564-76. [Crossref] [PubMed]
9. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol 2021;39:619-30. [Crossref] [PubMed]
10. Cheng Y, Han L, Wu L, et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA 2022;328:1223-32. [Crossref] [PubMed]
11. Li H, Zhao Y, Ma T, et al. Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era. Front Immunol 2023;14:1132482. [Crossref] [PubMed]
12. Ganti AKP, Loo BW Jr, Badiyan S, et al. NCCN Guidelines® Insights: Small Cell Lung Cancer, Version 2.2026. J Natl Compr Canc Netw 2026;24:e260002. [Crossref] [PubMed]
13. Chinese Society of Clinical Oncology Small Cell Lung Cancer Expert Committee, Chinese Medical Doctor Association Multidisciplinary Tumor Diagnosis and Treatment Committee. Expert Consensus on Immunotherapy for Small Cell Lung Cancer (2025 edition). Chinese Journal of Oncology 2025;47:65-75.
14. Ngwa W, Irabor OC, Schoenfeld JD, et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018;18:313-22. [Crossref] [PubMed]
15. Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 2017;18:895-903. [Crossref] [PubMed]
16. Rodriguez-Ruiz ME, Rodriguez I, Leaman O, et al. Immune mechanisms mediating abscopal effects in radioimmunotherapy. Pharmacol Ther 2019;196:195-203. [Crossref] [PubMed]
17. Fiorica F, Tebano U, Gabbani M, et al. Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer. Cancers (Basel) 2021;13:2352. [Crossref] [PubMed]
18. Rodríguez-Ruiz ME, Vanpouille-Box C, Melero I, et al. Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect. Trends Immunol 2018;39:644-55. [Crossref] [PubMed]
19. Senan S, Okamoto I, Lee GW, et al. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer 2020;21:e84-8. [Crossref] [PubMed]
20. Jhawar SR, Wang SJ, Thandoni A, et al. Combination oncolytic virus, radiation therapy, and immune checkpoint inhibitor treatment in anti-PD-1-refractory cancer. J Immunother Cancer 2023;11:e006780. [Crossref] [PubMed]
21. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet 2015;385:36-42. [Crossref] [PubMed]
22. Wang Y, Liu ZG, Yuan H, et al. The Reciprocity between Radiotherapy and Cancer Immunotherapy. Clin Cancer Res 2019;25:1709-17. [Crossref] [PubMed]
23. Mansfield AS, Każarnowicz A, Karaseva N, et al. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol 2020;31:310-7. [Crossref] [PubMed]
24. Le X, Serra E, Easson K, et al. Brief Report: Treatment Patterns and Outcomes in a Large Real-World Cohort of Patients With ES-SCLC Treated With First-Line Chemoimmunotherapy in the United States. Clin Lung Cancer 2026;27:41-46.e3. [Crossref] [PubMed]
25. Wróbel D, Wojewoda B, Ziółek W, et al. Consolidative thoracic radiotherapy in the immunotherapy era for extensive-stage small cell lung cancer: a systematic review and meta-analysis with emphasis on brain and liver metastases. Radiother Oncol 2026;216:111328. [Crossref] [PubMed]
26. Nishio M, Sugawara S, Atagi S, et al. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer 2019;20:469-476.
27. Murray N, Livingston RB, Shepherd FA, et al. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol 1999;17:2300-8. [Crossref] [PubMed]
28. Menon H, Ramapriyan R, Cushman TR, et al. Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment. Front Immunol 2019;10:193. [Crossref] [PubMed]
29. Golden EB, Chhabra A, Chachoua A, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 2015;16:795-803. [Crossref] [PubMed]
30. Anscher MS, Arora S, Weinstock C, et al. Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database. JAMA Oncol 2022;8:232-40. [Crossref] [PubMed]
31. Xuan L, Bai C, Ju Z, et al. Radiation-targeted immunotherapy: A new perspective in cancer radiotherapy. Cytokine Growth Factor Rev 2024;75:1-11. [Crossref] [PubMed]
32. Liu C, Zeng L, Deng C, et al. Hypofractionated radiotherapy with immunochemotherapy for extensive-stage small-cell lung cancer. Front Immunol 2023;14:1175960. [Crossref] [PubMed]
33. Fukui T, Itabashi M, Ishihara M, et al. Prognostic factors affecting the risk of thoracic progression in extensive-stage small cell lung cancer. BMC Cancer 2016;16:197. [Crossref] [PubMed]
34. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004;22:4837-45. [Crossref] [PubMed]
35. Sun M, Ji H, Deng F, et al. Clinical outcomes and synergistic effect between radiotherapy and immunotherapy in patients with extensive-stage small cell lung cancer: a real-world study. BMC Cancer 2024;24:1206. [Crossref] [PubMed]