Whether to omit elective nodal irradiation (ENI) in thoracic radiotherapy for limited-stage small cell lung cancer (LS-SCLC) remains controversial. The purpose of this study was to compare the efficacy and safety of ENI in high-risk lymph node regions compared to involved field radiotherapy (IFRT). We conducted a real-world retrospective study of LS-SCLC who received radical simultaneous dose-reduction radiotherapy (SDR-RT) and chemotherapy with or without immunotherapy from January 2018 to June 2023. Patients were divided into two groups based on the target volume delineation method: the ENI group and the IFRT group. Propensity score matching (PSM) was applied to balance the observable potential confounding factors between the two groups. The primary endpoints were overall survival (OS). A total of 540 eligible patients were enrolled, of whom 196 (36.3

Stage III non-small cell lung cancer (NSCLC) presents marked heterogeneity under evolving therapeutic paradigms. Real-world evidence on current treatment practices and outcomes remains limited. The MOOREA study aimed to evaluate real-world molecular testing, treatment patterns, and clinical outcomes of treatment-naïve Chinese patients with stage III NSCLC. MOOREA is a prospective, multicenter Chinese study enrolling patients with untreated stage III NSCLC (16 July 2019 to 28 February 2022) from 28 hospitals. Patients were consecutively enrolled. The primary endpoint was treatment pattern of cohort 1 (C1; unresectable stage III NSCLC), and the secondary endpoints included molecular testing pattern, progression-free survival (PFS), overall survival (OS) of C1, and treatment pattern of cohort 2 (C2; resectable stage III NSCLC). In total, 486 patients were analyzed (C1: 379; C2: 107). Molecular testing rates were: EGFR (20.0

BackgroundSurvival benefit of thoracic radiotherapy (TRT) in patients with stage IV non-small cell lung cancer (NSCLC) receiving first-line chemo-immunotherapy remains uncertain. This study developed and validated an overall survival (OS) prediction model and assessed whether TRT benefit varied across risk strata.MethodsPatients with stage IV NSCLC treated with first-line chemo-immunotherapy were enrolled. A nomogram was developed using baseline clinical variables to calculate individual risk scores. Patients were classified into high- and low-risk groups according to the median nomogram-derived score. OS was compared between ICI and ICI+TRT groups in the overall cohort and risk subgroups. Treatment-by-risk interaction, 1:1 propensity score matching (PSM), treatment response, TRT pattern, BED10, and metastatic burden subgroup analyses, and safety assessments were performed.ResultsAmong 514 patients, 284 without TRT were assigned to training and internal validation cohorts at a 7:3 ratio, and 84 non-TRT patients formed an external validation cohort. ECOG performance status, alkaline phosphatase, total protein, platelet-to-lymphocyte ratio, and systemic immune-inflammation index were selected as optimal prognostic factors. The nomogram showed good 1- and 2-year OS discrimination, calibration, and clinical utility. Using a median risk score of 103.1, TRT improved OS only in low-risk patients (HR 0.456, 95% CI 0.285–0.730; P = 0.0011), not high-risk patients (HR 0.914, 95% CI 0.556–1.503; P = 0.7239), with consistent findings after PSM. Treatment-by-risk interaction was significant (P = 0.0309). Grade 1–2 pneumonitis was higher with ICI+TRT than ICI alone (28.8% vs. 10.3%; P < 0.001), without significant differences in severe pneumonitis or immune-related adverse events.ConclusionTRT benefit was risk-dependent, improving OS in low-risk but not high-risk patients.

Introduction: At the first interim analysis of the phase 3 ADRIATIC trial, durvalumab consolidation significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with limited-stage SCLC (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT). We report a prespecified subgroup analysis of patients enrolled in China. Methods: Patients with stage I to III LS-SCLC were randomized to durvalumab, durvalumab plus tremelimumab (arm remained blinded), or placebo for up to 24 months. The dual primary end points were OS and PFS by blinded independent central review for durvalumab versus placebo. Results: Of the global population, 95 of 530 patients (17.9%) were randomized in China; 49 of 264 versus 46 of 266 received durvalumab versus placebo. For prior cCRT, 69.4% versus 69.6% of the China subgroup received cisplatin-etoposide, and 53.1% versus 69.6% had once-daily radiotherapy; post-cCRT, 55.1% versus 67.4% received prophylactic cranial irradiation. The hazard ratio for OS (durvalumab versus placebo; median follow-up 35.5 mo) was 0.71 (95% confidence interval: 0.37–1.37). Median OS was not reached in either arm (36-mo OS: 63.7% versus 55.4%). The hazard ratio for PFS (median follow-up 27.7 mo) was 0.67 (95% confidence interval: 0.39–1.14); median PFS was 22.9 versus 14.3 months (24-mo PFS: 45.8% versus 37.6%). With durvalumab versus placebo, 16.3% versus 17.4% of patients had maximum grade 3 or 4 adverse events (AEs), 42.9% versus 21.7% had serious AEs, and 10.2% versus 13.0% discontinued treatment due to AEs; 55.1% versus 63.0% had pneumonitis/radiation pneumonitis (grade 3 or 4: 4.1% versus 4.3%). Conclusion: Consolidation durvalumab demonstrated a favorable benefit to risk profile in patients with LS-SCLC without progression after cCRT who were enrolled in China.

PurposeThe purpose of this study was to evaluate the effect of consolidation immunotherapy on patients with stage III non-small cell lung cancer (NSCLC) who received induction chemoimmunotherapy before chemoradiotherapy (CRT).Materials and methodsPatients with stage III NSCLC who received induction chemoimmunotherapy before CRT with or without consolidation immunotherapy at 4 hospitals between February 2018 and December 2022 were retrospectively analyzed. The patients were divided into two groups on the basis of whether they received consolidation immunotherapy (Ind+Con group) or not (Ind group). Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and were estimated using the Kaplan–Meier method. One-to-one propensity score matching (PSM) was used to further minimize confounding effects.ResultsA total of 196 eligible patients were enrolled, with 124 (63.3%) in the Ind group and 72 (36.7%) in the Ind+Con group. The median follow-up was 24.6 months, and the median PFS and OS for the whole cohort were 24.8 months and 46.0 months, respectively. The median PFS was 25.5 months in the Ind group vs. 24.0 months in the Ind+Con group, with 2-year PFS rates of 52.2% vs. 47.7% (P = 0.472). The median OS was 46.0 months in the Ind group vs. not reached (NR) in the Ind+Con group, with 2-year OS rates of 78.0% vs. 83.8% (P = 0.578). After 1:1 PSM, the median PFS was 30.2 months vs. 24.0 months, with 2-year PFS rates of 55.4% vs. 47.7% (P = 0.261). The median OS was 46.0 months vs. NR, with 2-year OS rates of 80.8% vs. 83.8% (P = 0.960).ConclusionThe effect of consolidation immunotherapy on patients with stage III NSCLC who receive induction chemoimmunotherapy before CRT needs to be further studied.

Background: While first-line systemic therapy is the standard of care for extensive-stage small-cell lung cancer (ES-SCLC), therapeutic failure remains nearly universal, with survival heavily dictated by progression patterns. Extracranial oligoprogression represents a distinct treatment failure phenotype lacking standardized management. Objectives: To evaluate the efficacy and survival impact of salvage radiotherapy (RT) in ES-SCLC patients experiencing extracranial oligoprogression after first-line therapy. Design: A multicenter retrospective cohort study. Methods: We retrospectively enrolled patients with ES-SCLC developing extracranial oligoprogression after first-line therapy from three cancer centers in China between January 2020 and March 2025. Patients were stratified into RT and non-RT groups based on the administration of radiotherapy post-progression. Propensity score matching (PSM) was employed to balance baseline characteristics. Primary endpoints included second-line overall survival (OS2) and progression-free survival (PFS2), estimated via Kaplan–Meier analysis and compared using log-rank tests. Results: A total of 232 Chinese patients experienced extracranial oligoprogression, with a median time to progression of 6.1 months (range: 1.0–37.8 months). In the matched cohort, RT significantly prolonged median PFS2 (6.1 vs 3.3 months; p = 0.007) and OS2 (13.4 vs 8.4 months; p = 0.029). Subgroup analyses revealed more pronounced survival benefits in patients characterized by prior immunotherapy, progression of existing lesions, intrathoracic progression, and delayed progression (PFS1 >6 months). Furthermore, among patients who received RT, continuation of first-line systemic therapy was associated with superior PFS2 (9.6 vs 5.4 months; p = 0.017) and OS2 (14.4 vs 13.4 months; p = 0.030) compared with switching to an alternative systemic therapy. Conclusion: This multicenter study is one of the first to indicate that radiotherapy is associated with a survival benefit in patients with ES-SCLC and extracranial oligoprogression. Notably, combining radiotherapy with continuation of first-line systemic therapy offered greater clinical utility than switching to an alternative systemic therapy.

PURPOSE:The optimal second-line strategy for patients with extensive-stage small cell lung cancer (ES-SCLC) developing brain-only progression (BOP) after first-line therapy remains undefined. We aimed to evaluate the efficacy of continuing the original systemic therapy versus switching strategies. METHODS:This multicenter cohort study screened 889 patients with ES-SCLC. A total of 203 patients developing BOP were assigned to 3 second-line strategies: continuation of original systemic therapy plus brain radiotherapy (OTP + BRT), substitution therapy plus BRT (ST + BRT), or substitution therapy alone (ST). Inverse probability of treatment weighting was used to balance baseline characteristics. The primary end point was overall survival from second-line initiation (OS2). RESULTS:In the inverse probability of treatment weighting-weighted analysis of 203 BOP patients, OTP + BRT demonstrated significantly superior median OS2 (14.7 months) compared with ST (10.2 months; hazard ratio [HR], 1.68; P = .028) and ST + BRT (9.8 months; HR, 1.67; P = .023). OTP + BRT also yielded improved median second-line progression-free survival (PFS) (8.0 months) versus ST (4.0 months; P = .024). Multivariable analysis confirmed OTP + BRT as an independent prognostic factor for improved survival. The benefit was most pronounced in patients with prior immunotherapy and longer initial PFS (≥7.5 months). No significant survival differences were observed among radiotherapy modalities (whole-brain radiotherapy v stereotactic radiosurgery). CONCLUSION:For ES-SCLC patients with BOP, continuing the original systemic regimen plus BRT yields superior survival compared with switching systemic therapy. This supports a site-of-progression-directed strategy, effectively controlling the CNS sanctuary while maintaining an effective systemic backbone.

Background : Chemotherapy combined with immunotherapy (CIT) has reshaped the first-line treatment landscape for locally advanced and advanced non-small cell lung cancer (NSCLC). However, the optimal radiotherapy (RT) fractionation regimen for patients who remain inoperable after neoadjuvant therapy has yet to be defined. This study aimed to systematically compare survival outcomes and toxicity between hypofractionated radiotherapy (HFRT) and conventionally fractionated radiotherapy (CFRT) following induction CIT. Methods : In this retrospective analysis, 201 patients with locally advanced/advanced NSCLC receiving RT after CIT were divided into HFRT (45–54 Gy/15–18 fractions, n=69) and CFRT (60 Gy/30 fractions, n=132) groups. Overall survival (OS) was the primary endpoint; secondary endpoints included progression‑free survival (PFS), locoregional PFS (LPFS), and toxicity. Multivariable Cox regression and propensity score matching adjusted for confounders. A novel endpoint—LPFS based on conventional PTV—directly compared “gross‑tumor‑only” versus elective‑nodal irradiation. Results : After a median follow‑up of 26.2 months, adjusted analyses showed no significant differences in OS (HR=1.29, P=0.340), PFS, or LPFS between HFRT and CFRT. Exploratory analyses suggested trends favoring HFRT for PFS with consolidative immunotherapy (HR=0.58) and for OS/PFS in patients with high tumor burden (GTV ≥100 cm³; HR=0.85 and 0.88). HFRT was associated with significantly lower rates of acute radiation pneumonitis, key hematologic toxicities, and grade ≥2 pulmonary fibrosis (17.19% vs. 32.81%, P=0.041). The “PGTV‑only” strategy achieved locoregional control comparable to elective nodal irradiation (HR=1.063, P=0.765). All out‑of‑field nodal recurrences occurred with or after distant metastasis. Conclusion : HFRT provides survival outcomes equivalent to CFRT after CIT, with a more favorable safety profile, supporting a “precision intensification” paradigm of target‑volume de‑escalation combined with hypofractionation.

Background: Previous studies have demonstrated that thoracic radiotherapy (TRT) following first-line chemoimmunotherapy improves survival in extensive-stage small cell lung cancer (ES-SCLC). However, its efficacy and safety in elderly patients remain unclear. Objectives: To evaluate the efficacy and safety of consolidative TRT in elderly patients with ES-SCLC following first-line chemoimmunotherapy. Design: A multicenter retrospective cohort study. Methods: Elderly (⩾70 years old) ES-SCLC patients from three large-scale cancer centers who received chemoimmunotherapy in the first line were included, they were divided into two groups according to whether they received TRT. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Results: A total of 240 patients who completed four to six of first-line chemoimmunotherapy without progression were included, 83 of whom received consolidative TRT. In the analysis with time zero set at chemoimmunotherapy initiation, TRT was associated with longer median PFS (10.56 vs 8.30 months; hazard ratio (HR), 0.71, p = 0.034) and median OS (18.43 vs 14.39 months; HR, 0.64, p = 0.008). Using time-dependent Cox models with time zero reset to cycle 4 completion to address guarantee-time bias, TRT remained significantly associated with improved OS (14.59 vs 10.92 months; HR, 0.64, p = 0.007) and PFS (7.80 vs 5.12 months; HR, 0.72, p = 0.047). The presence of baseline liver metastasis emerged as an independent adverse prognostic factor. No significant increase in grade ⩾3 adverse events was observed in patients receiving TRT. Conclusion: In elderly ES-SCLC patients undergoing first-line chemoimmunotherapy, the addition of TRT is associated with a survival benefit and an acceptable safety profile. These results hold significant implications for current clinical practice and may help inform treatment strategies for elderly patients with ES-SCLC.

Objectives:Several clinical trials have demonstrated promising outcomes with thoracic radiotherapy (TRT) in patients with advanced lung adenocarcinoma (LUAD). However, a subset of patients derives no significant survival benefit from TRT. This study aimed to develop a risk model integrating biomarkers and clinical factors to identify patients most likely to benefit from TRT. Methods:Prognostic proteins associated with LUAD survival were identified using data from The Cancer Proteome Atlas. Immunohistochemical analysis was performed to evaluate protein expression in patients with advanced LUAD treated at our institution between 2015 and 2019. Univariate and multivariate Cox regression analyses were conducted to determine clinical factors influencing prognosis. A risk model combining biomarkers and clinical variables was constructed to generate individualized risk scores. Results:Four proteins, PAI-1, KU80, FOXO3A_pS318S321, and CKIT, were selected for further analysis. A total of 272 patients were divided into training (n = 181) and validation (n = 91) cohorts. Six prognostic factors including N-stage, presence of sensitive mutations, brain metastasis, adrenal metastasis, leukocyte count, and expression levels of PAI-1 and KU80 were incorporated into the risk model. Patients were stratified into low- and high-risk groups based on calculated risk scores. TRT significantly improved median survival time (69.0 vs. 39.3 months, p = 0.003) and overall survival (67.4 vs. 33.0 months, p = 0.035) in low-risk patients, but not in high-risk patients (median survival time: 19.8 vs. 18.2 months, p = 0.186; overall survival: 19.4 vs. 19.9 months, p = 0.607) for two cohorts. Conclusion:Multiple biomarkers and clinical variables are associated with prognosis in LUAD. The risk model developed herein indicates that TRT confers a survival benefit exclusively in patients classified as low risk.

PURPOSE:Accurate prediction of symptomatic radiation pneumonitis (RP) is critical for radiation therapy, however, the generalization of deep learning models is hindered by restricted access to multicenter data. Although federated learning (FL) bypasses data sharing restrictions, standard FL algorithms underperform on highly heterogeneous clinical data across institutions. Therefore, this study aims to evaluate the clinical feasibility of a center-specific FL approach. METHODS AND MATERIALS:We evaluated the Federated Cross-Center Adaptive Alternating Model (FCAAM), a tailored framework designed to decouple globally transferable representations from the center-specific adaptations. The framework uses a dynamic weighting mechanism to handle data heterogeneity and uses differential privacy for enhanced security. The proposed FCAAM was evaluated for the prediction of RP using planning computed tomography and dose images on a diverse cohort of 1238 patients from 4 data sets representing real-world temporal and spatial shifts. Its performance was compared with single-center model, centralized model, and standard federated average model. RESULTS:FCAAM demonstrated improved cross-center performance and consistent robustness compared to baseline. It achieved a stable area under the curve across all 4 data set test sets (0.71-0.77), outperforming the single-center models (all area under the curves < 0.70) and federated averaging. FCAAM's performance was comparable to the centralized model and showed a relative improvement in sensitivity to small-sized data sets. Interpretability analysis confirmed that FCAAM learned clinically relevant features, and a web platform demonstrated the practical feasibility of applying FCAAM for multicenter collaboration. CONCLUSIONS:FCAAM provides a privacy-preserving, robust and interpretable solution for multicenter RP prediction. This center-specific strategy shows potential to enhance clinical decision-making and reduce cross-center performance gaps, supporting safer personalized radiation therapy.

The purpose of this study is to evaluate the efficacy and safety of induction immunochemotherapy before definitive chemoradiotherapy (CRT) in patients with limited-stage small-cell lung cancer (LS-SCLC). This multicenter retrospective study included patients with LS-SCLC treated with definitive CRT, with or without induction immunochemotherapy from January 2021 to July 2024. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) was applied to control potential confounders. Survival was analyzed with Kaplan-Meier method and log-rank tests, and Cox regression was employed for prognostic analysis. Overall, 372 patients were included: 275 received definitive CRT alone (CRT group) and 97 received induction immunochemotherapy followed by definitive CRT (I-CRT group). Before PSM, the median OS was 30.3 months in the CRT group vs. not reached (NR) in the I-CRT group, with a 2-year OS of 59.4

ObjectiveConventional freehand three-dimensional interstitial brachytherapy (F-3DIB) for locally advanced cervical cancer (LACC) is limited by suboptimal dose distribution and operator dependency. This study aimed to evaluate the long-term survival and safety benefits of 3D-printed template-guided interstitial brachytherapy (3D-PTIB).MethodsThis retrospective single-center cohort study included 300 patients with FIGO IIB-IVA LACC who underwent brachytherapy between January 2021 and June 2022. The median follow-up time was 36.2 months (range: 34-41). Follow-up data were collected between January 2024 and June 2025, ensuring adequate follow-up for survival assessment. Patients were divided into 3D-PTIB and F-3DIB groups. Propensity score matching was used to balance baseline characteristics, resulting in a matched cohort of 240 patients. The outcomes assessed included 3-year overall survival (OS), progression-free survival (PFS), local control (LC), dosimetric parameters, and late toxicities.ResultsThe 3D-PTIB group exhibited significantly better 3-year OS (76.7% vs. 66.2%, HR = 0.69, p = 0.02) and LC (90.0% vs. 78.3%, HR = 0.47, p = 0.01) than the F-3DIB group. A trend toward improved 3-year PFS was also observed (70.8% vs. 62.3%, HR = 0.73, p = 0.05). Notably, the 3D-PTIB group achieved an 11.7% absolute improvement in local control (90.0% vs. 78.3%). A post hoc power analysis indicated that the study had approximately 80% power (α = 0.05, two-sided) to detect the observed hazard ratio of 0.69 for OS in the matched cohort. Dosimetric advantages included a significantly greater HR-CTV D90 (87.5 ± 3.2 Gy vs. 82.1 ± 4.8 Gy, p < 0.001) and reduced rectal D2 cc (64.5 ± 5.1 Gy vs. 72.3 ± 6.7 Gy, p < 0.001). Clinically, the incidence of ≥ grade 3 radiation proctitis was significantly lower in the 3D-PTIB group (4.2% vs. 11.7%, p = 0.008).Conclusion3D-printed template-guided interstitial brachytherapy significantly improves intermediate- to long-term survival and reduces late toxicity in LACC patients, particularly high-risk patients with a tumor diameter > 4 cm or parametrial invasion, highlighting its potential as a superior alternative to conventional freehand interstitial brachytherapy.

Bulky solid tumors present significant therapeutic challenges. Spatially fractionated radiotherapy (SFRT), a technique delivering alternating high- and low-dose subvolumes, alters the tumor microenvironment while minimizing toxicity. This phase II trial assesses the efficacy and safety of SFRT combined with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in advanced malignancies. This prospective phase II trial enrolled 34 patients with bulky solid tumors between October 2024 and July 2025. All patients underwent SFRT using GRID, LATTICE, or Stereotactic central/core ablative radiation therapy techniques. Multimodal therapy, incorporating pre-radiotherapy administration of granulocyte-macrophage colony-stimulating factor and thymalfasin, as well as concurrent ICIs and anti-angiogenic agents during SFRT, was administered according to clinical recommendations and patient preferences. The endpoints were treatment-related adverse events and the objective response rate (ORR). In addition, a prognostic analysis was performed to identify factors associated with clinical outcomes. Among the 37 treatment courses in 34 patients, 4 patients did not complete the planned therapy, and 1 was lost to follow-up. The median follow-up duration was 6.0 months. Of the 32 evaluable lesions from patients who completed the study, the ORR was 65.63

Dose reduction during concurrent chemoradiotherapy (cCRT) is frequently required in patients with limited-stage small-cell lung cancer (LS-SCLC) because of treatment-related toxicities or poor tolerance. However, the impact of chemotherapy dose reduction on long-term outcomes in LS-SCLC remains unclear. We aimed to evaluate whether chemotherapy dose reduction compromises survival in patients with LS-SCLC receiving definitive cCRT. We retrospectively analyzed patients with LS-SCLC treated with definitive cCRT across multiple centers. Patients were categorized into a dose-maintained group and a dose-reduced group according to whether chemotherapy dose reduction occurred during cCRT. To minimize baseline imbalances, inverse probability of treatment weighting (IPTW) based on propensity scores was applied using clinical covariates including age, sex, T stage, N stage, ECOG performance status, smoking status, weight loss, gross tumor volume, and chemotherapy regimens. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier analysis and Cox proportional hazards models in both unweighted and IPTW-weighted cohorts. Exploratory analyses were additionally performed within the dose-reduced group according to the timing of first dose reduction and the magnitude of dose reduction. A total of 1,013 patients were included, comprising 627 patients in the dose-maintained group and 386 patients in the dose-reduced group. After IPTW adjustment, baseline characteristics were well balanced between groups. For OS, the median OS after IPTW adjustment was 57.8 months (95

Widespread clinical implementation of rapidly evolving auto-segmentation tools remains constrained by a scarcity of high-quality prospective evidence. Here we show the results of a prospective, multicenter, observational trial (NCT05787522) evaluating the clinical performance of a deep learning model (iCurveE) for artificial intelligence (AI)-assisted delineation of organs at risk (OARs) in thoracic and breast cancer radiotherapy. Computed tomography images from 500 patients across five centers are annotated by 37 physicians using manual, AI-generated, and AI-assisted methods. Eleven thoracic OARs are evaluated based on the primary endpoints of volumetric Dice similarity coefficient (vDSC) and contouring time, alongside secondary metrics including 95% Hausdorff Distance (HD95). We prospectively annotate 2,483 OAR sets (27,043 OARs): 993 manual, 497 AI-generated, and 993 AI-assisted. AI-assisted delineation achieves significantly better vDSC (mean, 0.902) and HD95 (mean, 5.20 mm) than manual delineation (mean vDSC, 0.857; mean HD95, 8.01 mm; p < 0.0001) while improving time efficiency by 81.63% (median: 10.0 vs. 55.0 min; p < 0.0001). AI-assisted delineation reduces performance variability across centers and physicians with varying expertise. This study validates the clinical applicability of AI-assisted delineation in improving delineation performance and promoting healthcare equity.

BACKGROUND Thoracic radiation therapy (TRT) is known to enhance the prognosis of patients with advanced stage small-cell lung cancer (AS-SCLC) following chemotherapy. This retrospective study aimed to compare outcomes of patients with AS-SCLC treated with chemotherapy and immunotherapy, with and without TRT. MATERIAL AND METHODS We included AS-SCLC cases at our institute confirmed by histopathology and receiving chemoimmunotherapy. Among them, 60 patients received TRT, while 112 did not. The primary study endpoints were progression-free survival and overall survival. We minimized selection bias by using propensity score matching, which was performed using a 1: 1 ratio with a caliper of 0.02, incorporating variables including sex, bone metastases, and total stage. Kaplan-Meier analysis and the log-rank test were applied to assess survival. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the independent prognostic factors. Subgroup analyses were conducted to identify the potential factors on TRT. RESULTS The median follow-up duration was 20.1 months. Patients who underwent TRT, compared with those that did not, had longer overall survival (24.2 vs 15.9 months, P=0.006) and progression-free survival (11.3 vs 6.6 months, P<0.001). Multivariate Cox regression analysis identified TRT as a favorable prognostic factor for overall survival and progression-free survival (P=0.005 and P<0.001). Subgroup analyses revealed patients without brain or bone metastasis can benefit from TRT (P<0.001). CONCLUSIONS TRT was associated with improved overall and progression-free survival in patients with AS-SCLC receiving chemoimmunotherapy. Prospective randomized trials are warranted to validate these findings.

8048 Background: The LAURA trial established concurrent chemoradiotherapy (cCRT) followed by consolidation targeted therapy as the standard for unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC). The phase III ADVANCE trial (ChiCTR2000040590) evaluated induction aumolertinib followed by aumolertinib and concurrent RT versus cCRT. Methods: Eligible patients (pts) aged 18-75 with unresectable stage III non-squamous NSCLC and centrally confirmed EGFR exon 19 deletion or L858R mutation were randomized 1:1 to receive aumolertinib+RT (experimental) or cCRT (control). The primary endpoint was progression-free survival (PFS), assessed by investigator. The accrual target was 98 pts, aiming for a hazard ratio (HR) of 0.5 (80% power, one-sided α =0.025). A real-world database (RWD; NCT04304638) from 6 trial sites was developed to validate long-term survival outcomes for pts treated with RT and third-generation EGFR TKIs. Results: Between March 2021 and March 2024, 43 eligible pts were randomized (24 to experimental, 19 to control) following early termination due to feasibility issues. At a median follow-up of 25.5 months (mo), the experimental group showed significantly longer PFS (34.0 vs. 7.8 mo; HR 0.15, 95% CI 0.06–0.24). Median overall survival (OS) was not reached in the experimental group but was 30.5 mo in the control (p = 0.17). The control group reported more neutropenia (52.6% vs. 16.7%, p = 0.01) and nausea (26.3% vs. 0.0%, p = 0.03), while quality of life was better in the experimental group. Among 18 experimental and 16 control pts completing RT without progression, the experimental group had significantly longer PFS (not reached vs. 12.8 mo; HR 0.05, 95% CI 0.01–0.16) and OS (HR 0.09, 95% CI 0.01–0.68). From 2012 to 2024, 125 consecutive pts were included in the RWD cohort: 31 in RT + TKI, 33 in CRT + TKI, and 61 in CRT. At a median follow-up of 32.7 mo, PFS and OS were significantly longer in RT + TKI and CRT + TKI compared to CRT (PFS: not reached vs. 36.7 vs. 9.8 mo; OS: not reached vs. not reached vs. 48.9 mo; p < 0.001). No significant differences in PFS and OS were observed between RT + TKI and CRT + TKI (p=0.59 and 0.80, respectively). Conclusions: The ADVANCE trial and RWD demonstrate that induction EGRF TKI followed by TKIs and RT delays progression and improves survival in unresectable stage III EGFR-mutated NSCLC. Clinical trial information: ChiCTR2000040590 .

BACKGROUND AND PURPOSE:To evaluate the value of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) at different risks of brain metastasis (BM). MATERIALS AND METHODS:A retrospective study included 498 LS-SCLC patients from three centers who achieved complete or partial response (CR/PR) after radical chemoradiotherapy. A nomogram was developed using significant factors associated with BM, identified through univariate and multivariate analyses. Patients were stratified into high- and low-risk groups based on risk scores. The incidence of BM was compared between patients with and without PCI in different risk-stratified populations using the log-rank test. RESULTS:The nomogram included age, start of treatment to the end of radiotherapy (SER), hemoglobin, prognostic nutritional index (PNI), ProGRP, and NSE. The area under the receiver operating characteristics (AUC) of the nomogram for predicting the 2-year probability of intracranial progression-free survival (IPFS) were 0.738, 0.811, and 0.726 in the training, internal validation, and external validation cohorts, respectively. In the low-risk group, no significant differences were observed in BM incidence (p = 0.220), OS (p = 0.679), or PFS (p = 0.616) between PCI and non-PCI groups. In the high-risk group, PCI significantly reduced BM incidence (p < 0.0001) and improved PFS (p = 0.032), while no significant differences were found in OS (p = 0.778). Propensity score-matching analysis showed similar results. CONCLUSION:PCI did not improve OS in patients regardless of high or low risk of BM. However, PCI did significantly reduce the incidence of BM and prolong PFS in patients at a high risk of BM.