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Article

Benefit of Consolidation Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer Patients Treated with Immunotherapy: Data from Slovenian Cohort

by
Marina Čakš
1,
Urška Janžič
2,3,
Tjaša Rutar
1,
Mojca Unk
3,4,
Ana Demšar
1,
Katja Mohorčič
2,
Nina Turnšek
3,4,
Erika Matos
3,4 and
Jasna But-Hadžić
3,5,*
1
Department of Oncology, University Medical Centre Maribor, 2000 Maribor, Slovenia
2
Medical Oncology Unit, University Clinic Golnik, 4204 Golnik, Slovenia
3
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
4
Department of Medical Oncology, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
5
Department of Radiotherapy, Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(8), 3631; https://doi.org/10.3390/ijms26083631
Submission received: 20 February 2025 / Revised: 29 March 2025 / Accepted: 10 April 2025 / Published: 11 April 2025
(This article belongs to the Special Issue Challenges and Future Perspectives in Treatment for Lung Cancer)
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Abstract

:
Chemoimmunotherapy (CT/IO) with immune checkpoint inhibitors has recently become the standard of care for extensive-stage small cell lung cancer (ES-SCLC). Given the uncertain role of consolidation thoracic radiotherapy (cTRT) in this setting, we conducted a real-world study to evaluate the efficacy and safety of cTRT in ES-SCLC patients receiving first-line CT/IO. We performed a retrospective analysis of ES-SCLC patients treated with first-line CT/IO in Slovenia from December 2019 to June 2024. Patient characteristics, treatment patterns, survival outcomes, and adverse events were analyzed, with subgroup comparisons based on cTRT administration. Among 208 patients (median age: 66 years), median overall survival was 12.1 months (95% CI: 10.6–13.7). cTRT was administered to 46 patients (22.1%), who had fewer metastases. cTRT was associated with improved OS (17.0 vs. 10.8 months; p < 0.001) and was an independent OS predictor (HR = 0.58, p = 0.035). Grade ≥ 3 adverse events were similar (26.1% vs. 21.3%), though pneumonitis occurred more frequently with cTRT (6.5% vs. 0%, p = 0.001). cTRT may improve survival in ES-SCLC patients treated with CT/IO, with no significant increase in toxicity apart from pneumonitis. Further prospective studies are needed.

1. Introduction

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma that occurs predominantly in current or former smokers and has an extremely poor prognosis. It represents roughly 15% of all lung cancer cases [1,2] and is traditionally divided into extensive (ES) and limited stage (LS), depending on whether the cancer can be encompassed within a single radiation field. Over 70% of SCLC cases are diagnosed at ES [2,3,4].
For more than 30 years, platinum-based chemotherapy, with or without prophylactic cranial irradiation (PCI), remained the standard of care for extensive-stage small-cell lung cancer (ES-SCLC) [5,6,7]. While this approach often achieved high initial objective response rates (ORR), median overall survival (mOS) was limited to around 10 months [8,9]. Consolidation thoracic radiotherapy (cTRT) has been shown in prior meta-analyses and prospective studies to improve both local control (LC) and overall survival (OS) in patients who achieve a response to chemotherapy [10,11,12].
The addition of immunotherapy (IO) with immune checkpoint inhibitors (ICIs) has recently become a new therapeutic option for ES-SCLC. The IMpower133 and CASPIAN randomized trials confirmed that chemoimmunotherapy (CT/IO), a combination of IO with anti-programmed death-ligand 1 (anti-PD-L1) antibodies atezolizumab or durvalumab and four cycles of chemotherapy with platinum/etoposide, resulted in a significant increase in mOS compared to chemotherapy alone, without significantly increasing the incidence of adverse events (AEs) [13,14]. Atezolizumab and durvalumab have received global approval and are now incorporated into the standard first-line treatment for ES-SCLC [15,16]. In Slovenia, both atezolizumab and durvalumab were launched for ES-SCLC at the end of 2019.
cTRT after CT/IO could further improve LC and survival outcomes in selected patients, offering promising potential in the era of IO. However, the feasibility and safety of this approach remain uncertain, as it was not included in the two aforementioned prospective clinical trials [13,14], and only limited data from early-phase clinical trials and retrospective studies are available in the literature [17,18,19,20,21,22,23,24,25,26].
Here, we report the findings of a real-world observational study evaluating the treatment outcomes of patients with ES-SCLC treated with first-line CT/IO in Slovenia. Specifically, we aim to evaluate the efficacy and safety of combining cTRT with CT/IO.

2. Results

2.1. Overall Study Population (Baseline Characteristics & Overall Survival Analysis)

From December 2019 to June 2024 there were 208 patients with ES-SCLC treated with CT/IO in Slovenia. Baseline characteristics are shown in Table 1. The median age was 66 years (range 41–79 years), 55.3% of patients were 65 years or older and 55.8% of patients were male. The majority of patients were smokers (98.6%). Most patients (74%) were in a good PS of 0–1. Brain metastases were present in 19.7%, liver metastases in 43.8%, and bone metastases in 34.1% at the time of diagnosis and 34.6% of patients had 3 or more metastatic sites involved.
Durvalumab and atezolizumab were administered to 142 (68.3%) and 66 (31.7%) patients, respectively. In the induction phase, patients received platinum-based chemotherapy concurrently with IO, the median number of induction cycles was 4 (range 1–6). The induction phase was followed by the maintenance phase with IO only; the median number of maintenance cycles was 3 (range 0–38).
Consolidation radiotherapy was performed in 46 (22.1%) patients. In all patients, the primary tumor and the affected regional lymph nodes were included in the treatment field. In 7 patients, metastatic sites were also irradiated (suprarenal gland, kidney, and lymph nodes). The median interval between chemoimmunotherapy and cTRT was 42 days (range 14–111), and in more than 90% of patients, cTRT was started within 60 days after the last CT/IO cycle. Radiotherapy (RT) doses ranged from 20 Gy to 60 Gy, with 80.4% (37/46) of patients receiving 30 Gy in 10 once-daily fractions. Other fractionations used were 5 × 4 Gy (1 patient), 13 × 3 Gy (3 patients), 18 × 2.5 Gy (1 patient) and 30 × 2 Gy (4 patients). Prophylactic cranial irradiation (PCI) was delivered at the discretion of the treating physician. Only 3 patients (1.4%) received PCI.
The ORR was 84.9%, with 5.5% and 79.4% of patients achieving a complete response (CR) and partial response (PR), respectively. Progressive disease was observed in 6.5% of patients.
With a median follow-up time of 25.9 months, the mPFS was 7.1 months (95% CI 6.4–7.8; Figure 1) and mOS was 12.1 months (95% CI 10.6–13.7; Figure 2). The estimated 12-month PFS rate was 20%, estimated 12 and 24-month OS rates were 51% and 19%, respectively.
In the univariate Cox regression analysis, several factors were significantly associated with OS. Female sex, median number of CT/IO cycles, PR or CR at evaluation (vs. stable disease), and cTRT were associated with better survival. Conversely, poor ECOG PS (≥2 vs. 0–1), liver metastases, bone metastases, involvement of ≥3 metastatic sites, M1c stage, and high LDH levels at presentation were associated with worse survival (Table 2). Age (≥65 vs. <65), brain metastases (yes vs. no), T stage (Tx-T2 vs. T3-T4), N stage (N0-N2 vs. N3), M1a, M1b stage and type of ICI (durvalumab or atezolizumab) had no influence on OS.
In the multivariate Cox regression analysis, female sex, PR or CR at evaluation, and cTRT remained independently associated with improved survival. Poor ECOG PS (≥2 vs. 0–1) and involvement of ≥3 metastatic sites remained significant predictors of worse OS (Table 2). Liver metastases, bone metastases, M1c stage, high LDH levels, and a median number of CT/IO cycles lost statistical significance after adjustment, suggesting their effects were confounded by other variables.

2.2. cTRT vs. Non-cTRT Subgroup Analysis

At diagnosis, there were significant differences in terms of disease burden and treatment parameters between the cTRT group (n = 46) and the non-cTRT group (n = 162) (Table 3). Patients in the cTRT group had more T3-T4 stage, but were less likely to have liver metastases, bone metastases, more than three metastatic sites involved, and M1c stage. In addition, the median LDH level was lower in the cTRT group.
In terms of treatment exposure, patients in the cTRT group received a higher median number of CT/IO cycles (median 5, range 4–5) compared to the non-cTRT group (median 4, range 4–4). In addition, they received more cycles of maintenance IO (median 5.5, range 2–9 vs. median 2, range 1–4, respectively).
At first progression, the proportion of patients with intrathoracic progression with or without systemic progression was significantly lower in the cTRT group (35.5% vs. 65.9%, respectively). There was no difference in systemic sites of progression between the groups.
Median PFS was 9.7 months in the cTRT group and 6.1 months in the non-cTRT group (HR = 0.44, 95% CI 0.30–0.65, p < 0.001; Figure 3) and the estimated 12-month PFS rate was 37% in the cTRT group and 15% in non-cTRT group. Median OS was 17.0 months in the cTRT group and 10.8 months in the non-cTRT group (HR = 0.58, 95% CI 0.35–0.96, p = 0.035; Figure 4). The estimated 12 and 24-month OS rates were 79% and 32% in the cTRT group compared with 43% and 16% in the non-cTRT group.

2.3. Safety

Out of 208 patients, 47 (22.6%) experienced grade 3 or 4 CTCAE adverse events, the majority of which were related to systemic treatment. Grade 3 or 4 hematological toxicities occurred in 19 patients (9.0%), while 20 patients (9.6%) experienced immune-related adverse events (irAEs) grade 3 or 4. Hepatitis was the most common, occurring in four patients.
No significant differences in the incidence of grade 3 or 4 AEs or irAEs between the cTRT and non-cTRT groups (26.1% vs. 21.3% and 8.7% vs. 9%, respectively) were observed. Pneumonitis grade 3 or 4 was reported in three (1.4%) patients, all of whom had received thoracic RT during systemic treatment. The difference in pneumonitis in cTRT vs. non-cTRT group was significant (6.5% vs. 0%, respectively; p = 0.001) (Table 4). No cases of grade 5 pneumonitis were reported.

3. Patients and Methods

The study included treatment-naïve consecutive patients with pathologically confirmed ES-SCLC treated with first-line CT/IO between December 2019 and June 2024 in routine clinical practice at three academic institutions in Slovenia: the Institute of Oncology Ljubljana, University Clinic Golnik, and University Clinical Center Maribor, in which all lung cancer patients in the country are treated. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee and Review Board of the Institute of Oncology Ljubljana (No. ERIDNPVO-0076/2024). Individual patient consent was waived based on the retrospective design of the study, the minimal risk to participants, and the fact that the institution’s standard treatment consent forms already included permission for the use of patient data, biological materials, and test results for research purposes.
Patients received at least one cycle of CT/IO with the anti-PD-L1 antibody atezolizumab or durvalumab, followed by maintenance therapy of the anti-PD-L1 antibody until disease progression or unacceptable toxicity. Patients treated for LS-SCLC and those not receiving IO were excluded. Consolidation of thoracic radiotherapy after CT/IO and PCI was allowed and decided by the multidisciplinary tumor board. Only patients without progressive disease after CT/IO were eligible for cTRT.
Patients’ clinical characteristics were taken from the medical records by the treating oncologists. The data collected included age, sex, smoking status, Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, tumor stage, laboratory results at diagnosis, and treatment patterns. Response to treatment was evaluated by computer tomography (CT) scan, according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1. Adverse events were assessed and graded based on the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 [27].
Statistical analyses were conducted using SPSS (version 26.0; IBM Corp., Armonk, NY, USA). Descriptive statistics were used to describe patient characteristics and AEs. OS was defined as the time from diagnosis until death from any cause or the last follow-up visit. Progression-free survival (PFS) was defined as the time from diagnosis until the time of disease progression, death from any cause, or last follow-up visit. Survival analysis was performed using the Kaplan–Meier method. Differences in survival between the cTRT and non-cTRT groups were analyzed using the log-rank test and the Cox proportional hazards regression model. A p-value of less than 0.05 was considered statistically significant. The chi-square test and non-parametric tests were used to compare variables between the cTRT and non-cTRT groups.

4. Discussion

The present study provides results from an observational study evaluating the real-world efficacy of first-line CT/IO in patients with ES-SCLC. The median OS of patients in our cohort (12.1 months) was comparable to those observed in the pivotal trials (12.3 months in Impower 133, 13.0 months in CASPIAN) [13,14], despite the fact that our study included a more heterogeneous real-world population with a higher proportion of patients with worse PS, more advanced age and involvement of brain metastases, which are known poor prognostic factors in patients with ES-SCLC. Similar conclusions were made in other published real-world prospective and retrospective studies [28,29,30,31,32,33,34].
Our subgroup analysis suggests that the addition of cTRT to CT/IO may improve survival. The role of cTRT in ES-SCLC was established long before the introduction of IO. In 1999, Jeremic et al. first demonstrated that the addition of cTRT to platinum-based CT significantly improved OS [11]. The CREST trial in 2015 further validated its efficacy by enrolling 495 patients with ES-SCLC who had shown response to CT. The patients in the cTRT group were treated with thoracic irradiation of 30 Gy in 10 fractions. The 1-year and 2-year OS rates were higher in the cTRT group compared to the control group (33% vs. 28%, p = 0.066; and 13% vs. 3%, p = 0.004, respectively) [12]. The RTOG 0937 study reported delayed progression with cTRT but did not show a significant improvement in 1-year OS. However, no difference in survival was observed between early and late cTRT administration [35]. A meta-analysis later confirmed that the addition of cTRT to first-line platinum-based CT reduced disease progression and improved OS [10]. Findings from this meta-analysis led to the incorporation of cTRT into the standard of care for patients with ES-SCLC in response to the first-line CT, though practices globally varied as there was no clear consensus on the application of cTRT [36,37].
With the introduction of CT/IO as the new standard of care, the role of cTRT has been further debated. The IMpower133 and CASPIAN trials did not include cTRT, as there was limited safety data on combining thoracic RT with IO [13,14]. However, the benefit of the addition of IO to CT remains modest, and the most common site of progression after first-line CT/IO is locoregional [38]. In addition, preclinical and clinical studies suggest a potential synergy between radiotherapy and immunotherapy, supporting the rationale for further investigation the putative beneficial role of cTRT in the CT/IO era [39,40,41].
Welsh et al. confirmed the safety and promising efficacy of combining pembrolizumab with TRT after induction CT in a phase 1 trial, providing a rationale for this synergistic therapeutic approach [17]. Subsequently, several retrospective studies have demonstrated improved OS in patients receiving both CT/IO and cTRT [18,19,20,21,22,23,25,26]. A recent meta-analysis, which included 12 retrospective and 3 prospective studies, suggested that integrating cTRT with CT/IO improves survival outcomes [24]. Ongoing randomized clinical trials are currently evaluating the efficacy and safety of such an approach (NCT05223647, NCT04462276, and NCT04402788).
In our analysis, patients who received cTRT had a significantly longer mOS compared to those who did not receive cTRT (17.0 months vs. 10.8 months, p < 0.001). After adjustment for confounders, cTRT remained an independent predictor of improved survival (HR = 0.58, 95% CI 0.35–0.96, p = 0.035). However, the possibility of selection bias should be considered, as the cTRT group had a more favorable prognosis, including fewer liver and bone metastases and a lower overall metastatic burden, and additionally, patients in this group also received more cycles of systemic therapy. These imbalances suggest that the observed survival benefit may be partially influenced by baseline differences rather than cTRT alone. However, at least three retrospective studies (Xie et al., Peng et al., and Yao et al. [19,21,25]) evaluated cTRT in combination with CT/IO with a similar or greater number of patients (45, 57, and 99, respectively). In these studies, the cTRT and non-cTRT groups were better balanced, with Peng et al. and Yao et al. utilizing propensity score matching to minimize selection bias. Notably, all studies included more patients with liver metastases in the cTRT groups (31% in Xie et al., 25% in Peng et al., and 24% in Yao et al.). Nevertheless, all studies reported improved progression-free survival (PFS) and OS with cTRT, suggesting that the survival benefit observed in our study is unlikely to be solely due to group imbalances [19,21,25]. Still, our survival benefit observed in the cTRT group must be interpreted with caution due to group imbalance.
The ideal cTRT dose in the context of immunotherapy remains uncertain due to the absence of prospective studies. Additionally, the sequencing of cTRT and IO maintenance therapy has not been well-defined.
In our cohort, 80.4% of patients received radiotherapy with 30 Gy in 10 once-daily fractions. cTRT was initiated after the completion of CT/IO, during the IO maintenance phase. The majority of patients began cTRT within 60 days following their last cycle of CT/IO.
A retrospective study found no significant difference in outcomes between early cTRT (administered within ≤3 cycles of chemotherapy) and late cTRT (administered after >3 cycles of chemotherapy) [42]. Han et al. suggested that initiating cTRT within 6 cycles of chemotherapy may improve local control [43]. In a study by Peng et al., patients with ES-SCLC received cTRT primarily during IO maintenance, while 15 patients (26.3%) underwent synchronous cTRT within the first two cycles of systemic therapy [21]. However, safety and efficacy data were not reported. Several prospective trials are currently investigating the role of cTRT, with most studies administering cTRT during maintenance IO. Until these results are available, the American Society of Clinical Oncology (ASCO) guidelines recommend that cTRT should be administered within 6–8 weeks after CT/IO and before the start of IO maintenance with 30 Gy delivered in 10 fractions [37]. This regimen was employed in both the CREST trial and a phase 1/2 study evaluating ipilimumab and nivolumab in ES-SCLC, with no significant toxicity reported in either study [12,44]. Higher doses (45 Gy in 15 fractions) have been tested in RTOG 0937 and a phase 1 trial of pembrolizumab [17,35]. Several retrospective studies have employed different cTRT protocols, but no direct comparisons between them have been made. However, evidence suggests that high-dose cTRT may improve LC and OS in ES-SCLC while potentially leading to an increased risk of pulmonary toxicity [18,45].
In our analysis, the treatment regimen was well tolerated, with a manageable incidence of grade 3 or higher AEs. Overall, there were no significant differences between the cTRT and non-cTRT groups. All cases of pneumonitis occurred in the cTRT group; however, the incidence was low, and all cases were effectively managed.
IO combined concurrently or sequentially with TRT, may increase pulmonary toxicity. Following chemoradiotherapy, the rate of grade 2 or higher pneumonitis was reported in up to 30% [46]. The incidence of immune-related pneumonitis after IO ranges from 3 to 5% [47,48]. Treatment with IO after conventional TRT resulted in up to 62% of any grade and 1–9% of grade 3 pneumonitis [49]. Safety data for the combination of IO and TRT in ES-SCLC patients have also been published. In a phase 1 study with 38 patients, concurrent thoracic radiotherapy and pembrolizumab was well tolerated. No grade 4 or 5 toxicities were observed, and grade 3 toxicity occurred in only 6% of patients [17]. In real-world studies, the incidence of grade 3 pulmonary toxicity was approximately 0–9% [18,19,20]. In addition, a meta-analysis confirmed a manageable incidence of grade 3 AEs and radiation pneumonitis [24]. Our safety results are consistent with published data and overall, the toxicity of combining TRT with immunotherapy appears to be manageable.
This study provides valuable insights into the efficacy of CT/IO in ES-SCLC patients in a real-world setting, where the patient population differs from that in clinical trials. It also offers real-world data on the efficacy and safety of cTRT in the immunotherapy era, an area where prospective data are lacking. Additionally, most retrospective studies have been conducted in Asian and North American populations, with only limited data available from European countries. As patient characteristics, healthcare systems, access to drugs, and healthcare facilities may differ between regions, findings from North America and Asia may not be fully generalizable to the Central European population. We acknowledge the limitations of this study. As a retrospective analysis of a real-world population, it is prone to selection bias. The cTRT group was relatively small, and the observed OS benefit may partly reflect a more favorable prognosis of selected patients. Due to the small cohort size, propensity score matching to minimize selection bias was not performed. In addition, we could only report grade ≥ 3 toxicities due to the retrospective study design. Furthermore, there is a tendency of the underreporting AE in real-world clinical settings [31]. Additionally, the distinction between irAE pneumonitis and radiation pneumonitis is challenging, as their clinical presentations overlap, and their management strategies are similar. We acknowledge the low proportion of patients receiving PCI in our cohort. As our focus was on cTRT with CT/IO, PCI was not explored in detail. Its limited use reflects current practice in Slovenia, influenced by emerging evidence, uncertainties in the IO era, and routine CNS imaging.

5. Conclusions

This analysis suggests that the addition of cTRT to first-line CT/IO may be associated with prolonged OS and a manageable safety profile. However, prospective clinical studies are needed to confirm these findings. Furthermore, determining the optimal type, dose, and timing of TRT in combination with IO is crucial for improving patient outcomes, underscoring the need for further research.

Author Contributions

Conceptualization, J.B.-H. and M.Č.; methodology, J.B.-H. and M.Č.; software, M.Č.; validation, J.B.-H. and M.Č.; formal analysis, M.Č.; investigation, J.B.-H., M.Č., T.R., A.D. and U.J.; resources, J.B.-H., M.Č., T.R., A.D., U.J., K.M., M.U. and N.T.; data curation, J.B.-H., M.Č. and E.M.; writing—original draft preparation, M.Č.; writing—review and editing, J.B.-H., M.Č., U.J., K.M., M.U., N.T. and E.M.; visualization, M.Č.; supervision, J.B.-H.; project administration, J.B.-H. and M.Č. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee and Review Board of the Institute of Oncology Ljubljana (No. ERIDNPVO-0076/2024).

Informed Consent Statement

Individual patient consent was waived based on the retrospective design of the study, the minimal risk to participants, and the fact that the institution’s standard treatment consent forms already included permission for the use of patient data, biological materials, and test results for research purposes.

Data Availability Statement

The data presented in this study are available on request to the corresponding author due to ethical reasons.

Acknowledgments

The study was supported by Slovenian research programe for comprehensive cancer control SLORApro (P3-0429).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Rudin, C.M.; Brambilla, E.; Faivre-Finn, C.; Sage, J. Small-cell lung cancer. Nat. Rev. Dis. Primers 2021, 7, 3. [Google Scholar] [CrossRef]
  2. Matera, R.; Chiang, A. What Is New in Small Cell Lung Cancer. Hematol. Oncol. Clin. N. Am. 2023, 37, 595–607. [Google Scholar] [CrossRef]
  3. Micke, P.; Faldum, A.; Metz, T.; Beeh, K.-M.; Bittinger, F.; Hengstler, J.-G.; Buhl, R. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—What limits limited disease? Lung Cancer 2002, 37, 271–276. [Google Scholar] [CrossRef]
  4. Goldstraw, P.; Chansky, K.; Crowley, J.; Rami-Porta, R.; Asamura, H.; Eberhardt, W.E.E.; Nicholson, A.G.; Groome, P.; Mitchell, A.; Bolejack, V.; et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J. Thorac. Oncol. 2016, 11, 39–51. [Google Scholar] [CrossRef]
  5. Slotman, B.; Faivre-Finn, C.; Kramer, G.; Rankin, E.; Snee, M.; Hatton, M.; Postmus, P.; Collette, L.; Musat, E.; Senan, S. Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer. N. Engl. J. Med. 2007, 357, 664–672. [Google Scholar] [CrossRef]
  6. Green, R.A.; Humphrey, E.; Close, H.; Patno, M.E. Alkylating agents in bronchogenic carcinoma. Am. J. Med. 1969, 46, 516–525. [Google Scholar] [CrossRef]
  7. Pietanza, M.C.; Byers, L.A.; Minna, J.D.; Rudin, C.M. Small Cell Lung Cancer: Will Recent Progress Lead to Improved Outcomes? Clin. Cancer Res. 2015, 21, 2244–2255. [Google Scholar] [CrossRef]
  8. Socinski, M.A.; Smit, E.F.; Lorigan, P.; Konduri, K.; Reck, M.; Szczesna, A.; Blakely, J.; Serwatowski, P.; Karaseva, N.A.; Ciuleanu, T.; et al. Phase III Study of Pemetrexed Plus Carboplatin Compared with Etoposide Plus Carboplatin in Chemotherapy-Naive Patients with Extensive-Stage Small-Cell Lung Cancer. J. Clin. Oncol. 2009, 27, 4787–4792. [Google Scholar] [CrossRef]
  9. Lara, P.N.; Natale, R.; Crowley, J.; Lenz, H.J.; Redman, M.W.; Carleton, J.E.; Jett, J.; Langer, C.J.; Kuebler, J.P.; Dakhil, S.R.; et al. Phase III Trial of Irinotecan/Cisplatin Compared with Etoposide/Cisplatin in Extensive-Stage Small-Cell Lung Cancer: Clinical and Pharmacogenomic Results From SWOG S0124. J. Clin. Oncol. 2009, 27, 2530–2535. [Google Scholar] [CrossRef]
  10. Palma, D.A.; Warner, A.; Louie, A.V.; Senan, S.; Slotman, B.; Rodrigues, G.B. Thoracic Radiotherapy for Extensive Stage Small-Cell Lung Cancer: A Meta-Analysis. Clin. Lung Cancer 2016, 17, 239–244. [Google Scholar] [CrossRef]
  11. Jeremic, B.; Shibamoto, Y.; Nikolic, N.; Milicic, B.; Milisavljevic, S.; Dagovic, A.; Aleksandrovic, J.; Radosavljevic-Asic, G. Role of Radiation Therapy in the Combined-Modality Treatment of Patients with Extensive Disease Small-Cell Lung Cancer: A Randomized Study. J. Clin. Oncol. 1999, 17, 2092. [Google Scholar] [CrossRef] [PubMed]
  12. Slotman, B.J.; Van Tinteren, H.; Praag, J.O.; Knegjens, J.L.; El Sharouni, S.Y.; Hatton, M.; Keijser, A.; Faivre-Finn, C.; Senan, S. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: A phase 3 randomised controlled trial. Lancet 2015, 385, 36–42. [Google Scholar] [CrossRef]
  13. Horn, L.; Mansfield, A.S.; Szczęsna, A.; Havel, L.; Krzakowski, M.; Hochmair, M.J.; Huemer, F.; Losonczy, G.; Johnson, M.L.; Nishio, M.; et al. First-Line Atezolizumab Plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 379, 2220–2229. [Google Scholar] [CrossRef]
  14. Paz-Ares, L.; Dvorkin, M.; Chen, Y.; Reinmuth, N.; Hotta, K.; Trukhin, D.; Statsenko, G.; Hochmair, M.J.; Özgüroğlu, M.; Ji, J.H.; 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, 1929–1939. [Google Scholar] [CrossRef] [PubMed]
  15. Dingemans, A.-M.C.; Früh, M.; Ardizzoni, A.; Besse, B.; Faivre-Finn, C.; Hendriks, L.E.; Lantuejoul, S.; Peters, S.; Reguart, N.; Rudin, C.M.; et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2021, 32, 839–853. [Google Scholar] [CrossRef]
  16. Ganti, A.K.P.; Loo, B.W.; Bassetti, M.; Blakely, C.; Chiang, A.; D’Amico, T.A.; D’Avella, C.; Dowlati, A.; Downey, R.J.; Edelman, M.; et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2021, 19, 1441–1464. [Google Scholar] [CrossRef] [PubMed]
  17. Welsh, J.W.; Heymach, J.V.; Chen, D.; Verma, V.; Cushman, T.R.; Hess, K.R.; Shroff, G.; Tang, C.; Skoulidis, F.; Jeter, M.; et al. Phase I Trial of Pembrolizumab and Radiation Therapy After Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. J. Thorac. Oncol. 2020, 15, 266–273. [Google Scholar] [CrossRef]
  18. Li, L.; Yang, D.; Min, Y.; Liao, A.; Zhao, J.; Jiang, L.; Dong, X.; Deng, W.; Yu, H.; Yu, R.; et al. First-line atezolizumab/durvalumab plus platinum–etoposide combined with radiotherapy in extensive-stage small-cell lung cancer. BMC Cancer 2023, 23, 318. [Google Scholar] [CrossRef]
  19. Xie, Z.; Liu, J.; Wu, M.; Wang, X.; Lu, Y.; Han, C.; Cong, L.; Li, J.; Meng, X. Real-World Efficacy and Safety of Thoracic Radiotherapy After First-Line Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer. J. Clin. Med. 2023, 12, 3828. [Google Scholar] [CrossRef]
  20. Hoffmann, E.; De-Colle, C.; Potkrajcic, V.; Baumann, D.; Spengler, W.; Gani, C.; Utz, D. Is consolidative thoracic radiotherapy of extensive-stage small cell lung cancer still beneficial in the era of immunotherapy? A retrospective analysis. Strahlenther. Onkol. 2023, 199, 668–675. [Google Scholar] [CrossRef]
  21. Peng, J.; Zhang, L.; Wang, L.; Feng, H.; Yao, D.; Meng, R.; Liu, X.; Li, X.; Liu, N.; Tan, B.; et al. Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer. Radiat. Oncol. 2023, 18, 111. [Google Scholar] [CrossRef] [PubMed]
  22. Gross, A.J.; Sheikh, S.; Kharouta, M.; Chaung, K.; Choi, S.; Margevicius, S.; Fu, P.; Machtay, M.; Bruno, D.S.; Dowlati, A.; et al. The Impact of Prophylactic Cranial Irradiation and Consolidative Thoracic Radiation Therapy for Extensive Stage Small-Cell Lung Cancer in the Transition to the Chemo-Immunotherapy Era: A Single Institution Series. Clin. Lung Cancer 2023, 24, 696–705. [Google Scholar] [CrossRef]
  23. Longo, V.; Della Corte, C.M.; Russo, A.; Spinnato, F.; Ambrosio, F.; Ronga, R.; Marchese, A.; Del Giudice, T.; Sergi, C.; Casaluce, F.; et al. Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: Preclinical data and a retrospective study in Southern Italy. Front. Immunol. 2024, 14, 1289434. [Google Scholar] [CrossRef] [PubMed]
  24. Feng, B.; Zheng, Y.; Zhang, J.; Tang, M.; Na, F. Chemoimmunotherapy combined with consolidative thoracic radiotherapy for extensive-stage small cell lung cancer: A systematic review and meta-analysis. Radiother. Oncol. 2024, 190, 110014. [Google Scholar] [CrossRef] [PubMed]
  25. Yao, Y.; Li, B.; Song, R.; Yang, L.; Zou, B.; Wang, L. Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy: A propensity score matched multicentre retrospective analysis. Radiat. Oncol. 2024, 19, 25. [Google Scholar] [CrossRef]
  26. Varlotto, J.; Voland, R.; DeCamp, M.; Khatri, J.; Shweihat, Y.; Nwanwene, K.; Tirona, M.; Wright, T.; Pacioles, T.; Jamil, M.; et al. Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era. Radiother. Oncol. 2025, 202, 110619. [Google Scholar] [CrossRef]
  27. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; National Cancer Institute: Bethesda, MD, USA, 2017. Available online: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm (accessed on 22 January 2025).
  28. Bria, E.; Morgillo, F.; Garassino, M.C.; Ciardiello, F.; Ardizzoni, A.; Stefani, A.; Verderame, F.; Morabito, A.; Chella, A.; Tonini, G.; et al. Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial. Oncologist 2024, 29, e690–e698. [Google Scholar] [CrossRef]
  29. Garcia Campelo, M.; Domine Gomez, M.; De Castro Carpeno, J.; Moreno Vega, A.; Ponce Aix, S.; Arriola, S.; Carcereny Costa, E.; Majem Tarruella, M.; Huidobro Vence, G.; Esteban Gonzalez, E.; et al. 1531P Primary results from IMfirst, a phase IIIb open-label safety study of atezolizumab (ATZ) + carboplatin (CB)/cisplatin (CP) + etoposide (ET) in an interventional real-world (RW) clinical setting of extensive-stage small cell lung cancer (ES-SCLC) in Spain. Ann. Oncol. 2022, 33 (Suppl. S7), S1246–S1247. [Google Scholar]
  30. Reinmuth, N.; Özgüroğlu, M.; Leighl, N.B.; Galetta, D.; Hacibekiroglu, I.; Roubec, J.; Sendur, M.A.N.; Bria, E.; Cicin, I.; Grohé, C.; et al. LBA2 First-line (1L) durvalumab (D) + platinum-etoposide (EP) for patients (pts) with extensive-stage SCLC (ES-SCLC): Primary results from the phase IIIb LUMINANCE study. Immuno-Oncol. Technol. 2023, 20, 100692. [Google Scholar] [CrossRef]
  31. Elegbede, A.A.; Gibson, A.J.; Fung, A.S.; Cheung, W.Y.; Dean, M.L.; Bebb, D.G.; Pabani, A. A Real-World Evaluation of Atezolizumab Plus Platinum-Etoposide Chemotherapy in Patients with Extensive-Stage SCLC in Canada. JTO Clin. Res. Rep. 2021, 2, 100249. [Google Scholar] [CrossRef]
  32. Falchero, L.; Guisier, F.; Darrason, M.; Boyer, A.; Dayen, C.; Cousin, S.; Merle, P.; Lamy, R.; Madroszyk, A.; Otto, J.; et al. Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Lung Cancer 2023, 185, 107379. [Google Scholar] [CrossRef] [PubMed]
  33. Ezzedine, R.; Canellas, A.; Naltet, C.; Wislez, M.; Azarian, R.; Seferian, A.; Giroux Leprieur, E. Evaluation of Real-Life Chemoimmunotherapy Combination in Patients with Metastatic Small Cell Lung Carcinoma (SCLC): A Multicentric Case–Control Study. Cancers 2023, 15, 4593. [Google Scholar] [CrossRef]
  34. Lee, S.; Shim, H.S.; Ahn, B.-C.; Lim, S.M.; Kim, H.R.; Cho, B.C.; Hong, M.H. Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: A single-center experience. Cancer Immunol. Immunother. 2022, 71, 1093–1101. [Google Scholar] [CrossRef] [PubMed]
  35. Gore, E.M.; Hu, C.; Sun, A.Y.; Grimm, D.F.; Ramalingam, S.S.; Dunlap, N.E.; Higgins, K.A.; Werner-Wasik, M.; Allen, A.M.; Iyengar, P.; et al. Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937. J. Thorac. Oncol. 2017, 12, 1561–1570. [Google Scholar] [CrossRef]
  36. Simone, C.B.; Bogart, J.A.; Cabrera, A.R.; Daly, M.E.; DeNunzio, N.J.; Detterbeck, F.; Faivre-Finn, C.; Gatschet, N.; Gore, E.; Jabbour, S.K.; et al. Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline. Pract. Radiat. Oncol. 2020, 10, 158–173. [Google Scholar] [CrossRef] [PubMed]
  37. Daly, M.E.; Ismaila, N.; Decker, R.H.; Higgins, K.; Owen, D.; Saxena, A.; Franklin, G.E.; Donaldson, D.; Schneider, B.J. Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline. J. Clin. Oncol. 2021, 39, 931–939. [Google Scholar] [CrossRef]
  38. Liu, L.; Liu, T.; Wang, X.; Wang, J.; Wang, J.; Yuan, M.; Yang, Y.; Zhang, Y.; Wang, H.; Hu, P.; et al. Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment. Transl. Oncol. 2023, 33, 101687. [Google Scholar] [CrossRef]
  39. Demaria, S.; Ng, B.; Devitt, M.L.; Babb, J.S.; Kawashima, N.; Liebes, L.; Formenti, S.C. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int. J. Radiat. Oncol. Biol. Phys. 2004, 58, 862–870. [Google Scholar] [CrossRef]
  40. Deng, L.; Liang, H.; Burnette, B.; Beckett, M.; Darga, T.; Weichselbaum, R.R.; Fu, Y.-X. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice. J. Clin. Investig. 2014, 124, 687–695. [Google Scholar] [CrossRef]
  41. Hanna, G.G.; Illidge, T. Radiotherapy and Immunotherapy Combinations in Non-small Cell Lung Cancer: A Promising Future? Clin. Oncol. 2016, 28, 726–731. [Google Scholar] [CrossRef]
  42. Luo, J.; Xu, L.; Zhao, L.; Cao, Y.; Pang, Q.; Wang, J.; Yuan, Z.; Wang, P. Timing of thoracic radiotherapy in the treatment of extensive-stage small-cell lung cancer: Important or not? Radiat. Oncol. 2017, 12, 42. [Google Scholar] [CrossRef] [PubMed]
  43. Han, J.; Fu, C.; Li, B. Clinical outcomes of extensive-stage small cell lung cancer patients treated with thoracic radiotherapy at different times and fractionations. Radiat. Oncol. 2021, 16, 47. [Google Scholar] [CrossRef] [PubMed]
  44. Perez, B.A.; Kim, S.; Wang, M.; Karimi, A.M.; Powell, C.; Li, J.; Dilling, T.J.; Chiappori, A.; Latifi, K.; Rose, T.; et al. Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab with Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2021, 109, 425–435. [Google Scholar] [CrossRef]
  45. Stanic, K.; Vrankar, M.; But-Hadzic, J. Consolidation radiotherapy for patients with extended disease small cell lung cancer in a single tertiary institution: Impact of dose and perspectives in the era of immunotherapy. Radiol. Oncol. 2020, 54, 353–363. [Google Scholar] [CrossRef]
  46. Palma, D.A.; Senan, S.; Tsujino, K.; Barriger, R.B.; Rengan, R.; Moreno, M.; Bradley, J.D.; Kim, T.H.; Ramella, S.; Marks, L.B.; et al. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis. Int. J. Radiat. Oncol. Biol. Phys. 2013, 85, 444–450. [Google Scholar] [CrossRef]
  47. Khunger, M.; Rakshit, S.; Pasupuleti, V.; Hernandez, A.V.; Mazzone, P.; Stevenson, J.; Pennell, N.A.; Velcheti, V. Incidence of Pneumonitis with Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer. Chest 2017, 152, 271–281. [Google Scholar] [CrossRef] [PubMed]
  48. De Velasco, G.; Je, Y.; Bossé, D.; Awad, M.M.; Ott, P.A.; Moreira, R.B.; Schutz, F.; Bellmunt, J.; Sonpavde, G.P.; Hodi, F.S.; et al. Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. Cancer Immunol. Res. 2017, 5, 312–318. [Google Scholar] [CrossRef]
  49. Lu, X.; Wang, J.; Zhang, T.; Zhou, Z.; Deng, L.; Wang, X.; Wang, W.; Liu, W.; Tang, W.; Wang, Z.; et al. Comprehensive Pneumonitis Profile of Thoracic Radiotherapy Followed by Immune Checkpoint Inhibitor and Risk Factors for Radiation Recall Pneumonitis in Lung Cancer. Front. Immunol. 2022, 13, 918787. [Google Scholar] [CrossRef]
Ijms 26 03631 g001
Figure 1. Kaplan–Meier curve showing progression-free survival for all 208 enrolled patients with ES-SCLC.
Figure 1. Kaplan–Meier curve showing progression-free survival for all 208 enrolled patients with ES-SCLC.
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Figure 2. Kaplan–Meier curve showing overall survival for all 208 enrolled patients with ES-SCLC.
Figure 2. Kaplan–Meier curve showing overall survival for all 208 enrolled patients with ES-SCLC.
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Figure 3. Kaplan–Meier curves showing progression–free survival for ES–SCLC patients in two treatment groups.
Figure 3. Kaplan–Meier curves showing progression–free survival for ES–SCLC patients in two treatment groups.
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Figure 4. Kaplan–Meier survival curves of overall survival of ES–SCLC patients in two treatment groups.
Figure 4. Kaplan–Meier survival curves of overall survival of ES–SCLC patients in two treatment groups.
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Table 1. Patients and disease characteristics of 208 included patients.
Table 1. Patients and disease characteristics of 208 included patients.
Characteristics at DiagnosisAll Included Patients (N = 208)
Median Age (years) 66 (range 41–79)
Age ≥ 65 y (%)55.3
Male Patients (%)55.8
Smokers (former/current) (%)98.6
ECOG PS 0–1 (%)74
Brain Metastasis (%)19.7
Liver Metastasis (%)43.8
Bone Metastasis (%)34.1
Patients with ≥3 Metastatic Sites (%)34.6
T stage
Tx–T2 (%)
T3–T4 (%)
26.4
73.6
N stage
N0–N2 (%)
N3 (%)
39.9
60.1
M stage
M1a (%)
M1b (%)
M1c (%)
9.6
9.6
78.4
Median LDH4.29 (95% CI 3.98; 4.79)
Patients with Elevated LDH (%)53.4
ECOG = Eastern Cooperative Oncology Group; PS = performance status; LDH = lactate dehydrogenase.
Table 2. Univariate and multivariate Cox regression analyses of overall survival (n = 208).
Table 2. Univariate and multivariate Cox regression analyses of overall survival (n = 208).
VariableUnivariate HR (95% CI)p-ValueMultivariate HR (95% CI)p-Value
Sex (female vs. male)0.67 (0.49–0.93)0.0170.59 (0.40–0.86)0.007
ECOG PS (≥2 vs. 0–1)1.76 (1.23–2.52)0.0022.24 (1.43–3.50)<0.001
Liver Metastasis (yes vs. no)1.68 (1.22–2.32)0.0011.20 (0.79–1.80)0.393
Bone Metastasis (yes vs. no)1.55 (1.12–2.16)0.0090.98 (0.64–1.49)0.916
Metastatic sites (≥3 vs. 0–2)2.09 (1.50–2.92)<0.0011.97 (1.28–3.03)0.002
M stage
M1a vs. M1c
M1b vs. M1c
0.64 (0.037–1.11)
0.42 (0.21–0.83)		0.018
0.116
0.013
1.29 (0.68–2.49)
0.57 (0.24–1.36)		0.281
0.447
0.202
LDH (high vs. normal)1.76 (1.27–2.44)0.0011.41 (0.94–2.09)0.095
Response evaluation (CR/PR vs. SD)0.49 (0.27–0.87)0.0140.37 (0.20–0.71)0.003
CT/IO Cycles (median)0.79 (0.64–0.97)0.0260.99 (0.80–1.23)0.936
cTRT (yes vs. no)0.44 (0.28–0.68)<0.0010.58 (0.35–0.96)0.035
ECOG = Eastern Cooperative Oncology Group; PS = performance status; LDH = lactate dehydrogenase; CR = complete response; PR = partial response; SD = stable disease; CT/IO = chemoimmunotherapy, cTRT = consolidation thoracic radiotherapy; HR = hazard ratio; CI = confidence interval. Values in bold indicate statistical significance in the multivariate analyses (p < 0.05).
Table 3. Patient and treatment characteristics: Chemoimmunotherapy with or without consolidation radiotherapy.
Table 3. Patient and treatment characteristics: Chemoimmunotherapy with or without consolidation radiotherapy.
Characteristics at
Diagnosis		cTRT Group
(n = 46)		Non-cTRT Group
(n = 162)		p-Value
Median age (years)66 (range 61–70)66 (range 61–69)0.834
Age ≥ 65 years (%)56.554.90.849
Male Sex (%)56.555.60.907
ECOG PS 0–1 (%)80.472.80.459
Brain Metastasis (%)19.619.80.977
Liver Metastasis (%)13.052.5<0.001
Bone Metastasis (%)21.737.70.045
Patients with ≥3
Metastatic sites (%)		19.638.90.015
T stage
Tx–T2 (%)
T3–T4 (%)
6.5
95.3
32.1
67.9		0.001
N stage
N0–N2 (%)
N3 (%)
37.0
63.0
40.7
59.3		0.644
M stage
M1a (%)
M1b (%)
M1c (%)
21.7
17.4
56.5
6.2
7.4
84.6		<0.001
Median LDH3.81
(95%CI 3.50;4.29)		4.67
(95%CI 4.12;5.37)		0.005
Patients with elevated
LDH (%)		41.356.80.063
Median No. Of CT/IO
Cycles (n)		5 (range 4–5)4 (range 4–4)0.049
Type of ICI
Durvalumab (%)
Atezolizumab (%)
56.5
43.5
71.6
28.4		0.052
Response before cTRT
CR/PR
SD
93.5
6.5
82.4
9.2		0.478
Median No. Of
Maintenance IO cycles (n)		5.5 (range 2–9)2 (range 1–4)<0.001
Intrathoracic +/− systemic
Progression (%)		35.565.90.002
cTRT = consolidation thoracic radiotherapy; ECOG = Eastern Cooperative Oncology Group; PS = performance status; No. = number, CT/IO = chemoimmunotherapy; IO = immunotherapy; ICI = immune checkpoint inhibitor; CR = complete response, PR = partial response; SD = stable disease. Values in bold indicate statistically significant differences between the cTRT and non-cTRT groups (p < 0.05).
Table 4. Grade 3 and 4 adverse events in two treatment groups of ES-SCLC patients.
Table 4. Grade 3 and 4 adverse events in two treatment groups of ES-SCLC patients.
Adverse Event G3/4cTRT Group (n = 46)Non-cTRT Group (n = 160)
All12 (26.1%)34 (21.3%)
Neutropenia2 (4.3%)10 (6.3%)
Anemia1 (2.2%)5 (3.1%)
Thrombocytopenia1 (2.2%)4 (2.5%)
irAE4 (8.7%)15 (9.0%)
Pneumonitis3 (6.5%)0 (0%)
Esophagitis1 (2.2%)0 (0%)
cTRT = consolidation thoracic radiotherapy; irAE = immune-related adverse event.
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Čakš, M.; Janžič, U.; Rutar, T.; Unk, M.; Demšar, A.; Mohorčič, K.; Turnšek, N.; Matos, E.; But-Hadžić, J. Benefit of Consolidation Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer Patients Treated with Immunotherapy: Data from Slovenian Cohort. Int. J. Mol. Sci. 2025, 26, 3631. https://doi.org/10.3390/ijms26083631

AMA Style

Čakš M, Janžič U, Rutar T, Unk M, Demšar A, Mohorčič K, Turnšek N, Matos E, But-Hadžić J. Benefit of Consolidation Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer Patients Treated with Immunotherapy: Data from Slovenian Cohort. International Journal of Molecular Sciences. 2025; 26(8):3631. https://doi.org/10.3390/ijms26083631

Chicago/Turabian Style

Čakš, Marina, Urška Janžič, Tjaša Rutar, Mojca Unk, Ana Demšar, Katja Mohorčič, Nina Turnšek, Erika Matos, and Jasna But-Hadžić. 2025. "Benefit of Consolidation Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer Patients Treated with Immunotherapy: Data from Slovenian Cohort" International Journal of Molecular Sciences 26, no. 8: 3631. https://doi.org/10.3390/ijms26083631

APA Style

Čakš, M., Janžič, U., Rutar, T., Unk, M., Demšar, A., Mohorčič, K., Turnšek, N., Matos, E., & But-Hadžić, J. (2025). Benefit of Consolidation Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer Patients Treated with Immunotherapy: Data from Slovenian Cohort. International Journal of Molecular Sciences, 26(8), 3631. https://doi.org/10.3390/ijms26083631

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