Consolidative Thoracic Radiotherapy Research Articles

EP.09A.05 Consolidative Thoracic Radiotherapy Induced Lymphopenia in Metastatic NSCLC Is Predicted by EDIC and Associated with Poor Clinical Outcomes

EP.09A.05 Consolidative Thoracic Radiotherapy Induced Lymphopenia in Metastatic NSCLC Is Predicted by EDIC and Associated with Poor Clinical Outcomes

1799P Efficacy and safety of integrating consolidative thoracic radiotherapy with immunochemotherapy in ES-SCLC: A real-world retrospective analysis

1799P Efficacy and safety of integrating consolidative thoracic radiotherapy with immunochemotherapy in ES-SCLC: A real-world retrospective analysis

Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small–cell lung cancer (ES-SCLC): a phase II trial

This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small-cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4-6 cycles of adebrelimab (20mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100mg/m2, D1-3, Q3W and cisplatin, 75mg/m2, D1, Q3W or carboplatin, AUC=5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30Gy in 10 fractions or≥50Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2-not reached months) and 10.1 months (95% CI: 6.9-15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3-82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7-95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P=0.071; ctDNA, P=0.060) and OS (tissue, P=0.032; ctDNA, P=0.031). Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

JCOG2002: A randomized phase III study of thoracic radiotherapy for extensive stage small cell lung cancer.

TPS8132 Background: Consolidative thoracic radiotherapy (cTRT) has shown a marginal improvement in overall survival (OS) and progression-free survival (PFS) for extensive-stage small-cell cancer (ES-SCLC). Consequently, ASTRO and NCCN guidelines conditionally recommend the use of cTRT. Despite the recent establishment of anti-PD-L1 antibody (aPD-L1) combined with platinum-doublet chemotherapy as the standard first-line treatment for ES-SCLC, the impact of cTRT in the era of immunotherapy remains uncertain. Methods: The JCOG2002 study, a randomized, multicenter phase 3 trial, initiated in October 2021 to assess the superiority of additional cTRT in terms of OS for ES-SCLC following induction aPD-L1 plus platinum doublet chemotherapy. Eligibility patients must meet criteria for the first registration including ES-SCLC, no prior radiation or chemotherapy history, age 20 or older, ECOG performance status 0 or 1, and adequate organ function. Induction treatment involves atezolizumab + carboplatin + etoposide or durvalumab + cisplatin / carboplatin + etoposide. Responding patients proceed to the second registration, randomization (1:1 between 30 Gy in 10 fractions of cTRT plus aPD-L1 maintenance therapy and maintenance therapy only). The cTRT targets metastatic lymph nodes in stations #1-7 and ipsilateral stations #10-12 identified at diagnosis. The adjustment factors include response to induction treatment (CR/PR versus SD), presence of brain metastasis (yes versus no), participating institutions, and aPD-L1 type (atezolizumab versus durvalumab). The primary endpoint is OS, with secondary endpoints being PFS and safety. The study aims to enroll 240 randomized patients, with 330 in the first registration, providing 80 % power at a one-sided 5 % significance level to detect a hazard ratio of 0.69 with 3-year accrual period and 1-year follow-up. As of February 6, 2024, 239 patients initiated induction treatment, and 121 have been randomized. This trial is registered at Japan Registry of Clinical Trials as jRCTs031210393 (https://jrct.niph.go.jp/detail/jRCTs031210393). Clinical trial information: jRCTs031210393 .

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.

Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented. A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy. Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027). Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation.

Efficacy of carboplatin–etoposide rechallenge after first-line chemo-immunotherapy in ES-SCLC: an international multicentric analysis

Background and objectives: Second-line treatment for small-cell lung cancer (SCLC) is primarily guided by the time elapsed since the last platinum dose. Rechallenge with carboplatin and etoposide has demonstrated superior outcomes compared to topotecan if the platinum-free interval (PFI) is longer than 90 days and is considered the standard of care. However, these findings predate the chemo-immunotherapy era. This study investigates the effectiveness of the rechallenge strategy after chemo-immunotherapy in a real-world setting. Design and methods: We retrospectively reviewed patients with the extensive stage (ES)-SCLC who received rechallenge with carboplatin and etoposide after first-line chemoimmunotherapy between September 2020 and August 2023 in nine European centres. Demographic and clinical data were collected and analysed. Results: A total of 93 patients were included. Sixty-six (71%) patients had a PFI between 3 and 6 months. Consolidation thoracic radiotherapy and prophylactic cranial irradiation had been administered in 31 (33.3%) patients and 20 (21.5%) patients, respectively. Overall response rate was 59.1%. Median progression-free survival (PFS) was 5 months (95% confidence interval (CI) 4.3–5.7) and median overall survival (OS) was 7 months (95% CI 5.7–8.3). Notably, PFS and OS were not different according to PFI (3–6 m vs &gt; 6 m). Conclusion: Rechallenge with carboplatin and etoposide is a valid second-line option in patients with ES-SCLC whose disease progresses after first-line chemoimmunotherapy. Our analysis shows similar results to previous studies. Furthermore, outcomes were consistent across patients with different PFIs, confirming its efficacy in patients with a PFI longer than 3 months.

Differential Effect of Consolidative Thoracic Radiation Therapy in Extensive-Stage Small Cell Lung Cancer Based on Sex

BackgroundThe landmark CREST trial demonstrated that consolidative thoracic radiotherapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer (ES-SCLC), with potentially increased benefit in women compared to men. It is unknown whether similar findings would apply after chemoimmunotherapy (chemo-IO) became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. MethodsWe included patients from a nationwide de-identified electronic health record-derived database diagnosed with stage IV SCLC (2014-2021) who completed 4-6 cycles of first-line systemic therapy (platinum-doublet chemo or chemo-IO). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. ResultsA total of 1,227 patients were included (850 chemo, 377 chemo-IO). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio (HR) 0.67; 95% confidence interval [CI] 0.52-0.87) and PFS (HR 0.63; 95% CI 0.49-0.82) compared to those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men [(OS HR 1.03; 95% CI 0.80-1.31; PFS HR 1.12; 95% CI 0.85-1.47)]. Findings were similar in weighted analyses. ConclusionThe survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. While the underpinnings of this association need to be elucidated, stratification by sex should be considered for RCTs studying cTRT in ES-SCLC.

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy.

This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

2001P Consolidative thoracic radiotherapy of extensive-stage small cell lung cancer in the era of chemoimmunotherapy: A retrospective analysis concerning patients from southern Italy

2001P Consolidative thoracic radiotherapy of extensive-stage small cell lung cancer in the era of chemoimmunotherapy: A retrospective analysis concerning patients from southern Italy

Safety and efficacy of thoracic radiotherapy combined with chemo-immunotherapy in patients with extensive-stage small cell lung cancer: a multicenter retrospective analysis.

Immunotherapy has greatly increased the survival time of patients with extensive-stage small cell lung cancer (ES-SCLC), and is now a standard first-line treatment for these patients. Increasing evidence suggests a possible synergistic effect between immunotherapy and radiotherapy, yet there is a paucity of evidence regarding the efficacy and safety of thoracic radiotherapy (TRT) combined with chemo-immunotherapy for ES-SCLC. The medical records of 78 consecutive patients with ES-SCLC who received TRT in combination with chemo-immunotherapy at Jinling Hospital and Jiangsu Cancer Hospital from January 2019 to January 2023 were retrospectively reviewed. The median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, and the incidence of adverse events (AEs) was used to evaluate safety. The median follow-up time was 31.9 months, the objective response rate (ORR) was 59%, and the disease control rate (DCR) was 89.8%. The mOS time was 20.0 months, and the 6-month OS rate was 95%. The mPFS time was 9.2 months, and the 6-month PFS rate was 78%. There were no treatment-related deaths. The incidence of pneumonitis was 23.1%, the incidence of radiation esophagitis was 5.1%, and 2 patients experienced high-grade pneumonitis. Primary liver metastasis was a predictor of poor OS and PFS. Patients who received consolidative TRT after chemo-immunotherapy experienced more benefit than those who received TRT as palliative or salvage treatment for superior vena cava syndrome or disease progression. TRT is a feasible treatment for patients who receive chemo-immunotherapy for the management of ES-SCLC in consideration of its considerable efficacy and tolerable safety risk. This treatment is especially useful for patients without primary liver metastasis and who receive consolidative TRT after chemo-immunotherapy. Large-scale prospective studies are needed to confirm the efficacy and safety of this treatment modality.

Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Center

Most small cell lung cancer cases present as Stage IV (M1) or extensive stage (ES-SCLC), which are defined as tumor extending outside the hemithorax without a tolerable radiation portal. The CREST trial demonstrated improved local control with a modest overall survival (OS) benefit at the 2-year secondary endpoint of 14% survival with consolidative thoracic radiotherapy (CTRT) compared to 3% without CTRT. Low toxicity rates were also observed. This study reports our institutional ES-SCLC experience for patients treated with CTRT. A retrospective review was conducted on ES-SCLC patients treated with CTRT at our institution between 2014 and 2019. CTRT was defined as ≥30 Gy of thoracic radiotherapy. OS and tolerability of treatment were assessed in this population. Chemotherapy details were also captured. OS rate was determined using the Kaplan-Meier method and the time from start of CTRT to last date of follow-up or death. CTRT tolerability was determined using incidence and grade of esophagitis and radiation pneumonitis as per CTCAE v5. We identified 100 ES-SCLC patients treated with any thoracic RT at our institute, of which 45 received thoracic RT for palliative intent or with <30 Gy. The remaining 55 patients received ≥30 Gy CTRT and were included for analysis. The median age was 65.1 years (range 46.6-86.9) and 36 (65%) were male. The median follow-up for this sample was 0.8 (range 0.03-4.2) years. Median chemotherapy cycles were 6 (range 1-6), most receiving ≥4 cycles (87%) and completing chemotherapy prior to CTRT initiation (91%) with a minority concurrently receiving chemotherapy and CTRT (9%). Platinum chemotherapy was the most common (96%) with 2 patients receiving etoposide alone (4%). The most common CTRT regimens were 30 Gy in 10 fractions (80%) followed by 40 Gy in 15 fractions (9%) and 45 Gy in 30 twice-daily fractions (7%). Most patients (67%) were treated with IMRT/VMAT technique, while the remaining (33%) patients were treated with 3DCRT. The median survival time was 1.3 years with 1- and 2-year OS of 57.2% (CI 44.0 - 74.3%) and 26.1% (CI 12.9 - 52.7%), respectively. CTRT was well tolerated with no grade 4+ toxicities. The most common toxicity was esophagitis with 21 patients (39%), of which 15 were G1 (28%) and 6 were G2 (11%). Radiation pneumonitis was present in 5 patients (9.2%) with 1 G1 (2%), 3 G2 (6%), and 1 G3 (2%) cases. Consolidative TRT for ES-SCLC in this institutional series was at least as good as the reported CREST outcome with modest acute toxicities in this cohort. Disease burden at diagnosis, chemotherapy response, patterns of failure, and subsequent therapies will be further investigated.

Survival Outcomes for Oligometastatic vs. Polymetastatic Extensive-Stage Small Cell Lung Cancer Following Consolidative Thoracic Radiotherapy

For patients with limited metastatic burden, metastasis-directed radiotherapy has been shown to be associated with improved OS for certain types of cancer. However, these prior trials did not include patients with ES-SCLC. It is not yet clear if patients with oligometastatic ES-SCLC have improved outcomes over polymetastatic ES-SCLC after cTRT. We identified patients treated with cTRT for ES-SCLC in 2013-2020 at a single institution. Oligometastatic disease was defined at the time of diagnosis as three or fewer organs with distant disease, and with each organ having three or fewer metastatic lesions. All other patients were considered polymetastatic. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare OS, progression-free survival (PFS), local recurrence-free survival (LRFS), and new metastasis-free survival (NMFS) between oligometastatic and polymetastatic ES-SCLC patients undergoing cTRT. Among 70 included patients, 36 were defined as oligometastatic. All patients received platinum-doublet chemotherapy and cT. Immunotherapy was given in 7 (19.4%) oligometastatic patients and 5 (14.7%) polymetastatic patients (p = 0.56). Median follow-up time was 38.2 months. Multivariable Cox regression analysis showed that oligometastatic disease (vs. polymetastatic disease) at diagnosis was associated with improved OS (hazard ratio [HR] 0.44, 95% CI 0.25-0.78, p = 0.005, 1-year OS 86.1% vs. 46.9%, 2-year OS 47.1% vs. 15.1%). PFS, LRFS, and NMFS were not significantly different between the cohorts. Among oligometastatic patients, pleural involvement (HR 2.44, 95% CI 1.02-5.83, p = 0.046) and lung involvement (HR 4.93, 95% CI 1.02-23.9, p = 0.047) were associated with inferior OS. Among the 26 of 36 (72.2%) oligometastatic patients with neither pleural nor bilateral lung involvement, 1-year OS was 88.5% and 2-year OS was 58.3%. We observed that oligometastatic ES-SCLC patients treated with cTRT (especially those without pleural or bilateral lung involvement) have superior OS than those with polymetastatic disease. We encourage enrollment on the NRG LU007/RAPTOR randomized trial to determine the impact of complete or incomplete consolidative RT to up to 5 sites in ES-SCLC, especially in those with oligometastatic disease.

Differential Impact of Consolidative Thoracic Radiotherapy in Extensive-Stage Small Cell Lung Cancer Based on Systemic Therapy Type and Sex

Consolidative thoracic radiotherapy (cTRT) has been shown in phase III RCTs to improve overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer (ES-SCLC). This benefit was particularly pronounced in women compared to men in the 2015 CREST trial (hazard ratio [HR] 0.68 vs. 1.01, respectively). However, it is unknown whether similar findings would apply after chemoimmunotherapy (chemo-IO) became standard of care first-line treatment in 2018. In this analysis, we report national practice patterns and survival outcomes of cTRT versus no cTRT following chemo or chemo-IO, stratified by sex. Patients from the nationwide Flatiron Health de-identified electronic health record-derived database were included if they completed 4-6 cycles of first-line systemic therapy (platinum-doublet chemo or chemo-IO) for stage IV SCLC diagnosed between 2014 and 2021. Patients who progressed or started cTRT within 14 days or died within 90 days of completing systemic therapy were excluded to account for immortal time bias. We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent covariate and last date of chemo as index date. As a sensitivity analysis to address potential selection bias, we weighted the models by the inverse probability of receiving cTRT. All OS and PFS analyses were stratified by systemic therapy type and sex. A total of 1,227 patients were included (850 chemo, 377 chemo-IO). The proportion of patients who received cTRT increased from 11.7% in 2014 to 20.7% in 2017, and then decreased to 16.4% in 2021. There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. In adjusted analyses among women receiving chemo, cTRT was associated with superior OS (HR 0.68; 95% confidence interval [CI] 0.51-0.91) and PFS (HR 0.64; 95% CI 0.47-0.86) [Table 1]. There was a non-statistically significant trend towards improved OS (HR 0.57; 95% CI 0.32-1.02) and PFS (HR 0.59; 95% CI 0.34-1.02) among women receiving chemo-IO. No OS or PFS benefit with cTRT was observed in men receiving either chemo or chemo-IO. Findings were similar in weighted analyses. The survival impact of cTRT may be differentially impacted by sex, with female patients appearing more likely to benefit than male patients regardless of systemic therapy type. While the underpinnings of this association need to be elucidated, stratification by sex should be considered for RCTs studying cTRT in ES-SCLC.

30 Gy vs. 45 Gy Consolidative Thoracic Radiation (cTRT) for Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Multicenter, Randomized, Phase 3 Trial

Consolidative thoracic radiotherapy (cTRT) showed potential benefit to extensive stage small cell lung cancer (ES-SCLC). However, the optimum dose of cTRT is unknown. The purpose of this randomized trial was to compare the effect of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. This phase III, randomized trial was conducted in 12 public hospitals in China. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions or 45 Gy in 15 fractions cTRT. The primary outcome was 2-year overall survival (OS). Secondary outcomes included 2-year progression-free survival (PFS), 2-year local control (LC) and radiation treatment related toxicity. The primary objective was to detect an OS improvement in 45 Gy cTRT group at 2 years from 13% to 26% assuming a two-sided a = 0.05 and power of 85%, with a planned sample size of 186 patients. This trial was registered with Clinical Trials.gov, number NCT02675088. Between January 15, 2016, and September 20, 2022, 90 patients were randomly assigned either 30 Gy in 10 fractions (n = 50) or 45 Gy in 15 fractions (n = 40) cTRT group. Recruitment to the trial closed early due to slow accrual since first-line chemoimmunotherapy has become the new standard of care for ES-SCLC. The median age of patients was 58 years, 87.8% were male, 76.7% had a smoking history, 95.6% received IMRT, and 58.9% received prophylactic cranial irradiation. At a median follow-up of 39.9 months (IQR 27.2-59.2), there was no significant difference in the 2-year OS between the 45 Gy group and the 30 Gy group, at 43.4% (95% CI 29.3%-64.3%) and 40.0% (95% CI 27.9%-59.1%), respectively (log-rank p = 0.62; HR 1.13 [95% CI 0.69-1.84]). The 2-year PFS was 12.1% (95% CI 4.3%-33.8%) in the 45 Gy group and 9.0% (95% CI 3.2%-25.2%) in the 30 Gy group (log-rank p = 0.25, HR 0.76(95% CI [0.478-1.22]). There were also no significant differences in locoregional recurrence free survival (log-rank p = 0.75; HR 0.888 [95% CI 0.423-1.863]) and distant metastasis free survival (log-rank p = 0.95; HR 1.015 [95% CI 0.624-1.651]) between two groups. No grade 5 toxicity was observed in both groups. Patients treated with higher cTRT dose presented with increased incidence of grade 3+ radiation pneumonitis (10% vs 2%) and hematological toxicity (20% vs 12.5%). This randomized trial did not find a higher probability of survival improvement in patients with ES-SCLC receiving cTRT of 45 Gy in 15 fractions compared with 30 Gy in 10 fractions. In contrast, there was an increase in toxicity, especially radiation pneumonitis. Additional randomized studies investigating the role of cTRT in ES-SCLC after a response to chemoimmunotherapy are warranted.

Safety and Efficacy Analysis of Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Treated with SHR-1316 Plus Chemotherapy and Sequential Chest Radiotherapy as First-Line Therapy from a Phase II Trial

CAPSTONE-1, a phase 3 trial, showed that SHR-1316 (PD-L1 antibody) combined with standard first-line chemotherapy could prolong overall survival (OS) in patients (pts) with ES-SCLC. The CREST trial reported consolidative thoracic radiotherapy (TRT) of 30 Gy in 10 fractions provided a 10% 2-year OS benefit and more intensive TRT should be investigated in ES-SCLC. In the era of immunotherapy, the role of TRT also needs further exploration. Therefore, we designed this clinical trial to investigate the efficacy and safety of SHR-1316 plus first-line chemotherapy followed by TRT combined with SHR-1316. Key inclusion criteria were pts aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC, and an ECOG performance status of 0-1. Eligible pts would receive 4∼6 cycles of SHR-1316 (20mg/kg, D1, q3w) combined with EP/EC (etoposide, 100mg/m2, D1-5, q3w and cisplatin, 75mg/m², D1-3, q3w or carboplatin, AUC = 5, D1, q3w), followed by SHR-1316 combined with TRT (≥3 Gy*10 f or ≥2 Gy*25 f, involved-field irradiation), and then the maintenance therapy with SHR-1316 until disease progression or intolerable adverse events (AEs). The main endpoints included ORR, PFS and safety. From October 2020 to January 2023, 33 pts received SHR-1316 and sequential consolidative TRT. Among them, 19 pts received high-dose TRT (>3 Gy*10 f or ≥2 Gy*25 f) and 14 pts received low-dose TRT (≤3 Gy*10 f or<2 Gy*25 f). The median age was 62 (range: 38-73). Most pts were male (28, 84.8%), former smokers (22, 66.7%) with an ECOG performance status 1 (32, 97%). Ten (30.3%) pts were diagnosed with brain metastasis and 10 (30.3%) pts had liver metastasis at baseline. At the data cutoff date, 9 pts remained on treatment, the average number of treatment cycles was 9.2. 33 pts had at least one 1 post-treatment tumor assessment. The confirmed ORR and DCR were 90.9% (30/33) and 100% (33/33) in all pts, were 89.5% (17/19) and 100% (19/19) in high-dose TRT group, and were 92.9% (13/14) and 100% (14/14) in low-dose TRT group. The median PFS was 10.2(CI: 5.8∼14.7) months in all pts, was 7 (CI: 3.8∼10.2) months in high-dose TRT group and 10.4 (CI: 8.4∼12.3) months in low-dose TRT group. AEs occurred in 27 (81.8%) pts and grade 3 or 4 AEs occurred in 20 (60.6%) pts. The most common grade 3 or 4 AEs included neutropenia (15, 45.5%), leukopenia (8, 24.2%), lymphocytopenia (5, 15.2%), pneumonia (3, 9.1%), anemia (3, 9.1%) and thrombocytopenia (2, 6.1%). SHR-1316 plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. There is no significant difference between high-dose and low-dose TRT groups in terms of safety and efficacy according to current data.

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre

215 Survival Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated with Consolidative Thoracic Radiotherapy at a Tertiary Cancer Centre

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Efficacy and safety of thoracic radiotherapy for extensive stage small cell lung cancer after immunotherapy in real world.

The immunotherapy combined chemotherapy has been the standard treatment strategy for extensive-stage small lung cancer (ES-SCLC). The CREST trial reported consolidative thoracic radiotherapy (cTRT) improved overall survival (OS) for ES-SCLC with intrathoracic residual after chemotherapy. In this study, patients with ES-SCLC who received immunotherapy were assigned to receive either TRT or no TRT. TRT significantly improved progression-free survival (PFS), local recurrence-free survival (LRFS) and OS with well tolerated toxicity. Further sub-cohort analysis, TRT significantly improved LRFS in patients with oligo-metastasis and without liver metastasis.

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Progress in radiotherapy for small‐cell lung cancer

AbstractSmall‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC.