Despite the lack of predictive biomarkers and a prognostic stratification strategy, immune checkpoint inhibitor (ICI) has shown promise in improving outcomes for patients with limited-stage small cell lung cancer (LS-SCLC). We evaluated the potential of circulating tumor DNA (ctDNA) to dynamically predict outcomes in patients with LS-SCLC receiving concurrent chemoradiotherapy (CCRT) with or without consolidation ICI. We analyzed 490 serial samples collected from 144 LS-SCLC patients at baseline (t0), post-induction chemotherapy and pre-thoracic radiotherapy (t1), post-radiotherapy (t2), and progressive disease (t3). For 44 patients receiving consolidation ICI with serplulimab, an investigational PD-1 inhibitor, ctDNA dynamics during consolidation ICI were also assessed at multiple time points. Patients with undetectable ctDNA after CCRT had good outcomes with or without consolidation ICI, whereas ctDNA-positive patients at t2, indicating poor response to CCRT, derived survival benefit from consolidation ICI. Notably, ctDNA status at t1 appeared more predictive than at t2. A three-level risk stratification strategy integrating t1 ctDNA status with radiological tumor shrinkage identified a high-risk subgroup of patients who achieved significantly improved progression-free survival (PFS) (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.08-0.75; p = 0.014) and overall survival (OS) (HR, 0.06; 95% CI, 0.00-0.42; p = 0.001) from consolidation ICI, prioritizing CCRT plus consolidation ICI. Furthermore, maintaining ctDNA negativity during consolidation ICI was associated with favorable outcomes. These data provide valuable insights into the individualized management of LS-SCLC in the era of immunotherapy.

ABSTRACT Objectives To evaluate the prognosis of patients with nonsmall cell lung cancer (NSCLC) who did not undergo surgery after neoadjuvant chemotherapy combined with immunotherapy (NACI). Patients were grouped according to subsequent treatment: radiotherapy (RT) or nonradiotherapy (non‐RT), and the prognostic importance of positron emission tomography/computed tomography (PET/CT) was further assessed. Materials and Methods This retrospective study included NSCLC patients who received NACI between November 2020 and September 2024 at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Not all patients underwent surgery and subsequently received either RT or non‐RT treatment. Patients were stratified by whether PET/CT was performed and by their SUV‐max values before RT or non‐RT. Progression‐free survival (PFS) and overall survival (OS) were calculated from the start of neoadjuvant therapy using the Kaplan–Meier method. Results A total of 73 eligible patients were enrolled: 21 (28.8%) in the non‐RT group (nRTG) and 52 (71.2%) in the RT group (RTG). The median follow‐up time for all patients in the group was 18 months. The results show no significant difference in PFS (p = 0.653) or OS (p = 0.742) between RTG and nRTG. Among the patients who did not undergo PET/CT examination, the results showed a significant difference in PFS (p = 0.022), but no difference in OS (p = 0.320). Among the patients undergoing PET/CT examinations, in terms of PFS, compared to nRTG + SUV‐max ≤ 4 g/mL, there is no significant difference in RTG + SUV‐max ≤ 4 g/mL (p = 0.584), and RTG + SUV‐max > 4, < 8 g/mL (p = 0.156). However, RTG + SUV‐max ≥ 8 shows a statistical difference (p = 0.005). Conclusion Among NSCLC patients who did not undergo surgery following NACI, no significant differences in OS or PFS were observed between the RTG and nRTG groups. For patients who did not receive PET/CT evaluation, radiotherapy remains a key therapeutic option. In patients with a PET/CT SUVmax ≤ 4, radiotherapy may be safely omitted. In comparison, patients with a PET/CT SUVmax > 4 should be managed with a comprehensive treatment strategy that includes radiotherapy as the main component. PET/CT plays a critical role in guiding subsequent treatment selection.

Purpose Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, reliable biomarkers for predicting response to immunotherapy remain limited. Among circulating immune cells, PD-1⁺CD8⁺ T cells represent an activated subset that directly responds to PD-1 blockade. Profiling the T-cell receptor (TCR) repertoire within this population may reflect antitumor immune activity and holds promise as noninvasive, blood-based biomarker. Methods and Materials We prospectively enrolled 63 patients with unresectable LA-NSCLC who underwent chemoradiation therapy. Peripheral blood PD-1⁺CD8⁺ T cells were isolated from peripheral blood mononuclear cells obtained by density gradient centrifugation at 3 time points: before radiation therapy, during radiation therapy (on-RT, approximately at the 20th fraction), and after radiation therapy (post-RT), yielding a total of 141 blood samples. TCR sequencing was performed to assess repertoire diversity. Dynamic changes in TCR diversity metrics across time points were analyzed and correlated with progression-free survival (PFS). Results A higher D50 index on-RT was significantly associated with improved median PFS (not reached vs 21.95 months; P = .0246), regardless of the timing of immunotherapy. Patients with more stable TCR diversity and clonality on-RT experienced significantly longer PFS. Specifically, patients with low D50 index variation between on-RT and post-RT had a median PFS that was not reached (95% CI, 30.72-NA), compared with 21.95 months (95% CI, 17.84-NA; P = .018) in the high-variation group. Similarly, patients with low clonality variation demonstrated longer PFS from pre-RT to on-RT (30.72 vs 21.95 months; P = .0425) and from on-RT to post-RT (not reached vs 22.21 months; P = .0331). Clonal tracking analyses revealed that patients with short-PFS exhibited a higher proportion of markedly decreased TCR clones, particularly among high-frequency clones, suggesting impaired antitumor immune responses. Conclusions Peripheral PD-1⁺CD8⁺ TCR diversity and its dynamic changes on-RT are associated with PFS in patients with LA-NSCLC. These findings suggest that TCR repertoire profiling of circulating PD-1⁺CD8⁺ T cells may serve as a noninvasive biomarker to identify patients less likely to benefit from consolidation immunotherapy. Further validation in larger, prospective cohorts is warranted.

Despite the predictive impact of circulating tumor DNA (ctDNA) minimal residual disease (MRD), accurate prediction of failure risk after curative-intent treatments for early-stage or localized non-small cell lung cancer (NSCLC) patients to guide personalized therapy remains challenging. This study aimed to develop and validate an interpretable artificial intelligence-assisted model using global data resources. Liquid biopsy data, blood-based genomic alterations, clinicopathological features, and survival outcomes of stage I–III NSCLC patients who underwent surgery or definitive chemoradiotherapy were collected from 6 cohorts. PRIME (Progression Risk prediction by Interpretable Machine learning on ctDNA-MRD, Mutations, and clinical-therapeutic features) was trained by 6 machine learning algorithms across 4 cohorts and validated in 2 independent cohorts. Model performance was evaluated by the area under the curve (AUC) and interpreted by SHapley Additive exPlanations (SHAP). Whole-exome sequencing (WES) or whole-genome sequencing (WGS) of tumor tissue from 430 stage II–III NSCLC patients and RNA-sequencing (RNA-seq) data from 1149 subjects, sourced from The Cancer Genome Atlas, were used to validate the prognostic effect of mutations identified in peripheral blood and investigate the underlying mechanisms. A global dataset encompassing 781 blood samples from 493 patients was analyzed. Clinical stage, pre-treatment ctDNA, post-treatment MRD, blood-based Kelch-like ECH-associated protein 1 (KEAP1), serine/threonine kinase 11 (STK11), and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations, and treatment modality were significantly associated with the risk of disease progression and were thereby included in the model training. WES/WGS and RNA-seq confirmed the poor prognostic effect of KEAP1, STK11, and CDKN2A mutations, which were characterized by the suppressive tumor microenvironment and attenuated humoral immunity. The neural network (NN) model exhibited optimal prediction of treatment failure risk in the training (AUC = 0.85, 95

To systematically evaluate the efficacy differences between stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) in treating brain metastases from small cell lung cancer (SCLC), and to analyze key factors affecting patient prognosis, providing evidence-based support for developing individualized clinical treatment plans. Strictly following PRISMA guidelines and registered on the PROSPERO platform (CRD420251147208), we systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant literature from their inception to August 2025. Meta-analysis was performed using R software. The stability of results and publication bias were assessed through sensitivity analysis and funnel plots. 10 retrospective studies were included, involving 41,240 patients. Compared with WBRT, SRS significantly prolonged overall survival (HR = 0.74). Prognostic factor analysis showed that ECOG score 0–1 (HR = 0.61), female gender (HR = 0.89), receiving chemotherapy (HR = 0.37) or immunotherapy (HR = 0.69) were associated with better survival, while > 4 brain metastases (HR = 1.78), extracranial metastases (HR = 1.46), and age > 65 years (HR = 1.34) were poor prognostic factors. Sensitivity analysis indicated robust results, and funnel plot indicated no significant publishing bias. In patients with SCLC brain metastases, SRS was associated with improved overall survival compared with WBRT, with particularly notable advantages in younger patients with good physical condition, limited intracranial lesions, and well-controlled systemic disease.

Background:Individuals with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) who receive complete concurrent chemoradiotherapy (cCRT) can benefit from long-term survival. Although neoadjuvant chemoimmunotherapy (NACIT) have achieved breakthroughs in treating unresectable stage Ⅲ NSCLC, patients who have received induction chemoimmunotherapy are considered poor candidates for cCRT due to concerns about tolerability. Oral vinorelbine chemotherapy is widely used in clinical settings because of its safety, even for frail patients. The objective of this trial was to assess the efficacy and safety of oral vinorelbine plus concurrent radiotherapy (RT) for individuals with unresectable stage Ⅲ NSCLC following NACIT who were not candidates for concurrent intravenous chemotherapy. Methods:This was a single-arm, phase 2 trial. The primary endpoint was the objective response rate (ORR), while the secondary endpoints consisted of the disease control rate (DCR), safety, overall survival (OS), as well as progression-free survival (PFS). Results:Between March 10, 2023 and April 24, 2025, 46 individuals with unresectable stage Ⅲ NSCLC were administered oral vinorelbine plus thoracic RT. Patients were treated with oral vinorelbine (60 mg/m2 once a week for 2 weeks as induction therapy before thoracic RT) and 30 mg/m2 per week with concurrent RT (59.4-60.2 Gy) over 5.5 weeks. The median age of the patients was 62.5 years, with 42 being male (91.3 %). The ORR was 52.1 % (95 % confidence interval [CI], 35.1 %-65.9 %), with 24 partial responders. A 95.7 % DCR (85.5 %-98.8 %) was observed, and 20 patients had stable disease. The median follow-up was 22.5 months; the median PFS was 18.0 months and the median OS was not reached. The most commonly observed adverse events (AEs) included leukopenia (grade 1, 26.1 %), anemia (grade 1, 17.4 %), neutropenia (grade 1, 10.9 %), acute esophagitis (grade 2, 17.4 %), and treatment-related pneumonitis (grade 1-2, 60.9 %). No grade 3 or 4 treatment-related AEs were recorded. Conclusion:In individuals with unresectable stage Ⅲ NSCLC who had received NACIT and were not candidates for concurrent intravenous chemotherapy with RT, the oral vinorelbine plus concurrent RT demonstrated promising antitumor efficacy with acceptable toxicity profiles. Trial registration:ClinicalTrials.gov (NCT06540950).

Radiotherapy is a crucial part of cancer treatment that applies to over 50 % of cancer patients. However, its administration could inadvertently damage healthy tissues, such as radiation-induced heart damage (RIHD), when thoracic radiation is implemented. Myocardial fibrosis is a key feature of RIHD that is characterized by excessive extracellular matrix (ECM) protein accumulation, resulting in cardiac stiffness and dysfunction. Macrophage pyroptosis, which is triggered by radiation, leads to the release of inflammatory mediators IL-1 beta and IL-18, which are crucial in inflammatory response and fibrosis. In this study, apoptosis-associated speck-like protein containing a CARD domain (ASC)-overexpressing RAW264.7 cells were exposed to 2 Gy, 4 Gy, and 8 Gy radiation to assess macrophage pyroptosis. Both IL-1 beta and IL-18 levels increased dose-dependently, peaking at 8 Gy. Similarly, LDH activity, which is a pyroptosis indicator, increases dose-dependently. Higher radiation dosages increased ASC specks. NLRP3, cleaved-caspase1 (P20), and GSDMD-N protein levels increased considerably in irradiation groups. Since macrophage pyroptosis promotes inflammation, it was investigated whether irradiated macrophages could cause cardiac fibroblast fibrosis. In co-culture with irradiated macrophages, cardiac fibroblasts showed dose-dependent elevation of fibrotic markers alpha-SMA and Collagen I. Blocking NLRP3-mediated pyroptosis by MCC950 in macrophages and found significant decreases in pyroptotic indicators, fibrosis markers, and Hh pathway activation in co-cultured fibroblasts. The activation of Hedgehog signaling in fibroblasts with Jervine successfully reverses fibrotic alterations caused by macrophage pyroptosis, as evidenced by decreased alpha-SMA, Collagen I, Shh, Smo, and Gli1 levels. These findings emphasize macrophage pyroptosis in radiation-induced cardiac fibrosis and identify NLRP3 and Hh pathway therapeutic targets. Collectively, targeting macrophage pyroptosis and the Hh pathway could offer new therapeutic avenues for preventing myocardial fibrosis in RIHD.

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 .

Introduction With the inspiring results of the PACIFIC trial in non-small-cell lung cancer (NSCLC), and the CAPIAN and IMpower133 trials in extensive-stage small-cell lung cancer (SCLC), immunotherapy has increasingly gained attention. Serplulimab, a PD-1 inhibitor, showed great antitumour activity in the ASTRUM-005 trial and has been recommended as first-line therapy in extensive-stage SCLC. Whether serplulimab following hypofractionation radiotherapy and chemotherapy could bring better outcomes in limited-stage SCLC remains to be answered.Methods and analysis We designed a prospective multicentre single-arm phase II clinical trial to evaluate both the efficacy and safety of chemoradiotherapy and consolidation by serplulimab in limited-stage SCLC. Eligible patients will receive standard chemotherapy for four cycles and concurrent thoracic radiotherapy with a total dose of 45 Gy in 3 weeks and a 3 Gy dose per fraction. Prophylactic cranial irradiation is recommended for responding patients. Serplulimab will be delivered afterwards every 3 weeks for up to 1 year. Based on sample size estimation, 55 patients will be enrolled in total.Ethics and dissemination Ethics approval was obtained from the Independent Ethics Committee of National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (22/236-3438).Trial registration number NCT05443646.

To establish prediction models to predict 2-year overall survival (OS) and stratify patients with different risks based on radiomics features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Patients with locally advanced ESCC were recruited. We extracted 547 radiomics features from MRI and CT images. The least absolute shrinkage and selection operator (LASSO) for COX algorithm was used to obtain features highly correlated with survival outcomes in the training cohort. Based on MRI, CT, and the hybrid image data, three prediction models were built. The predictive performance of the radiomics models was evaluated in the training cohort and verified in the validation cohort using AUC values. A total of 192 patients were included and randomized into the training and validation cohorts. In predicting 2-year OS, the AUCs of the CT-based model were 0.733 and 0.654 for the training and validation sets. The MRI radiomics-based model was observed with similar AUCs of 0.750 and 0.686 in the training and validation sets. The AUC values of hybrid model combining MRI and CT radiomics features in predicting 2-year OS were 0.792 and 0.715 in the training and validation cohorts. It showed significant differences in 2-year OS in the high-risk and low-risk groups divided by the best cutoff value in the hybrid radiomics-based model. The hybrid radiomics-based model demontrated the best performance of predicting 2-year OS and can differentiate the high-risk and low-risk patients.

PURPOSE:This study reports the long-term outcomes of simultaneous integrated boost radiotherapy (SIB-RT) combined with oral S-1 chemotherapy (CRTCT) in inoperable patients aged ≥ 70 years with inoperable esophageal squamous cell carcinoma (ESCC). METHODS:In this multicenter, phase III randomized trial, patients with inoperable, locally advanced stage II-IV ESCC were randomized to receive either CRTCT or RT alone. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), restricted mean survival time (RMST), and patterns of failure. RESULTS:After a median follow-up of 75 months, patients in the CRTCT group had longer OS than those in the RT group (hazard ratio (HR), 0.74; 95 % confidence interval (CI), 0.57-0.95; P = 0.02), with better 5-year OS rates (34.1 % vs. 23.6 %,P = 0.02), PFS (31.1 % vs. 20.9 %,P = 0.02), and RMST (33.0 vs. 27.0 months,P = 0.02). CRTCT's effect on OS stabilized over 5 years. Locoregional failure was lower in the CRTCT group (HR, 0.64; 95 % CI, 0.45-0.92; P = 0.02), with similar distant and mixed failure risks. CONCLUSIONS:SIB-RT combined with oral S-1 chemotherapy significantly improved long-term survival and therefore might be considered a standard of care for elderly patients with inoperable ESCC. TRIAL REGISTRATION Clinical Trials.gov Identifier: NCT0297969.

ABSTRACT Background Currently, neoadjuvant chemoradiotherapy combined with immunotherapy (NCRI) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is attracting attention. The purpose of this study was to compare the surgical outcomes and survival between patients receiving NCRI and neoadjuvant chemoradiotherapy (NCRT) followed by surgery. Methods This study retrospectively included patients with locally advanced ESCC and treated with NCRI or NCRT followed by esophagectomy. Two groups were compared for pathologic complete response (pCR) rate, R0 resection rate, and 3‐year recurrence‐free survival (RFS). Surgery time, the number of lymph nodes removed, postoperative complications, and 30‐day mortality were also compared. Propensity score matching (PSM) was performed to minimize the potential impact of confounding factors. Results After PSM, patients in the NCRI group showed a significantly higher pCR rate compared with those in the NCRT group (54.2% vs. 27.1%, p = 0.046). R0 resection rate (100% vs. 89.6%, p = 0.251), surgery time (p = 0.614), the number of lymph nodes removed (p = 0.526), the incidence of total postoperative complications (46.4% vs. 37.9%, p = 0.564) and 30‐day mortality (3.6% vs. 1.1%, p = 0.983) were comparable between the two groups. The NCRI group exhibited a significantly higher 3‐year RFS rate compared to the NCRT group (79.2% vs. 62.5%, p = 0.032). Conclusion For patients with locally advanced ESCC, NCRI showed a significantly higher pCR rate than conventional NCRT, without increased operative risk. NCRI followed by surgery exhibited a superior RFS compared to NCRT followed by surgery. Prospective studies are needed in the future.

Esophageal cancer is one of the most common malignant tumors, with China accounting for 50

Predicting the effect of consolidation immunotherapy after chemoradiotherapy (CRT) for unresectable locally advanced non‐small‐cell lung cancer (LA‐NSCLC) patients remains a challenge, given the restricted sensitivity of single circulating tumor DNA (ctDNA) molecular residual disease (MRD) detection. In this study, 384 longitudinal blood samples from 160 patients with LA‐NSCLC undergoing CRT ± consolidation immunotherapy, tumor tissue whole‐genome or whole‐exome sequencing (WGS/WES) from 421 LA‐NSCLC patients treated with radiotherapy, and RNA‐sequencing data from 1149 subjects are analyzed. Pretreatment ctDNA‐based STK11(LKB1)/KEAP1 mutations are associated with poor prognosis and resistance to CRT but suggest benefits from consolidation immunotherapy after CRT. WGS/WES data confirm that STK11/KEAP1 ‐mutated tumors are radiotherapy‐resistant. RNA‐sequencing reveals an immunosuppressive tumor microenvironment for STK11/KEAP1 ‐mutated patients, characterized by strikingly decreased Th17 cells through the IL‐17 signaling downregulation, which could cause impaired response to upfront CRT but improved immunotherapy response after radiotherapy‐activated immunity. Predictive performance with individual ctDNA‐MRD detection is limited, while combining baseline STK11/KEAP1 mutations with ctDNA‐MRD effectively enhances prediction sensitivity, particularly in MRD‐negative patients. Integrating genomics with liquid biopsies could inform personalized and risk‐adaptive therapeutic decisions on consolidation immunotherapy.

Background:Thrombocytopenia is a common hematological toxicity in esophageal cancer (EC) patients receiving radiation therapy. Objectives:The purpose of this study was to construct and validate a nomogram for predicting the incidence of thrombocytopenia in EC patients receiving radiotherapy. Design:A retrospective study. Methods:All data were collected from 435 EC patients who received radiation therapy from a real-world cohort study from 2016 to 2021. Thrombocytopenia was assessed according to the toxicity criteria of the Radiation Therapy Oncology Group (RTOG). Univariate and multivariate logistic regression analyses were used to identify significant risk factors for thrombocytopenia. The result was presented in the form of a nomogram. The performance of the model was evaluated by the receiver operating characteristic (ROC) curves and calibration curves. External validation was conducted using an independent cohort of 149 EC patients from another cancer center. Propensity score matching was utilized to balance the covariates between the 1:1 matched two groups. Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test. Results:A total of 104(23.91%) patients developed thrombocytopenia. Univariate and multivariate logistic regression analysis showed that age, body mass index, planning target volume, tumor location, tumor-node-metastasis stage, platelet count before radiotherapy, history of liver cirrhosis, cycles of induction chemotherapy, and concurrent chemotherapy regimen were the independent predictors of chemoradiotherapy-associated thrombocytopenia and were finally incorporated into our nomogram. The results of the ROC curve showed that the nomogram had high prediction accuracy. The sensitivity of the external validation set was 0.852 (95% CI: 0.663-0.958), and the specificity was 0.820 (95% CI: 0.740-0.883). The calibration curve presented good concordance (Hosmer-Lemeshow test, p = 0.825). An online nomogram-based prediction tool was developed to facilitate clinical implementation. No significant difference was observed in overall survival between patients who experienced severe thrombocytopenia and not (log-rank test, p = 0.390). Conclusion:This nomogram provides a prediction tool of chemoradiotherapy-associated thrombocytopenia in EC patients receiving radiotherapy, which may facilitate the potential candidate's selection of high-risk EC patients for thrombocytopenia.

8012 Background: Unresectable stage III NSCLC patients with large tumor volumes remain challenging. Our previous retrospective study has showed promising results of induction chemoimmunotherapy before definitive chemoradiotherapy (CRT) for these patients. Here we report preliminary results of the randomized phase II study on this regimen. Methods: This InTRist study is a randomized, single-center, phase 2 trial, enrolling patients with unresectable stage III NSCLC with bulky diseases, and without EGFR/ALK alterations. Bulky diseases were defined as primary tumor ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter. Eligible patients were 1:1 randomly assigned to receive induction toripalimab (240 mg every 3 weeks) plus platinum-based doublet chemotherapy for 2 cycles (toripalimab group) versus induction chemotherapy alone for 2 cycles (chemo group) followed by concurrent CRT (60 Gy radiotherapy plus concurrent platinum-based chemotherapy). All patients without disease progression or grade ≥2 pneumonitis after CRT received consolidation toripalimab (240 mg every 3 weeks) for up to 12 months. Randomization was stratified according to histologic type. The primary endpoint was progression-free survival (PFS) from randomization. This trial is registered with ClinicalTrials.gov, NCT05888402. Results: BetweenJanuary 20th, 2023 and October 8th, 2024, 52 patients were randomized to induction toripalimab (n = 27) or chemo (n = 25) groups. By the data cutoff date (January 15th, 2025), the median follow-up was 13.1 months. Induction toripalimab plus chemotherapy exhibited significantly longer PFS compared to chemotherapy alone (median not reached [NR] vs NR; hazard ratio 0.25 [95% CI, 0.07-0.90], P =0.034). The 12-month PFS rate was 89.4% (95% CI, 76.0%-100%) in the toripalimab group and 57.8% (95% CI, 40.7%-81.9%) in the chemo group. Objective response rate after induction therapy was 77.8% (21/27) for the toripalimab group and 40.0% (10/25) for the chemo group (median tumor reduction 32% vs 21%). Grade 2 pneumonitis occurred in 26.9% (14/52) of all patients, with 18.5% (5/27) in the toripalimab group and 36.0% (9/25) in the chemo group. Grade 3 pneumonitis occurred in 7.7% (4/52) of all patients, with 11.1% (3/27) in the toripalimab group compared to 4.0% (1/25) in the chemo group. No grade 4-5 pneumonitis. Conclusions: Induction toripalimab plus chemotherapy, followed by concurrent CRT and consolidation toripalimab, demonstrated potentially improved short-term efficacy and manageable toxicity for patients with bulky unresectable stage III NSCLC. Further follow-up is necessary to confirm these results. Clinical trial information: NCT05888402 .

e16116 Background: Previous large phase III trials of preoperative concurrent chemoradiotherapy and definitive chemoradiotherapy (Dt 40-60Gy) in esophageal cancer have shown rates of platelet inhibition (grade 1-4) of 25-54%. The aim of the trial is to reduce acute thrombocytopenia in patients in thoracic esophageal cancer (EC) patients treated with concurrent chemoradiotherapy (CRT) by sparing the hematopoietical active bone marrow (BM) indentified by magnetic resonance (MR) and prophylactic recombinant human thrombopoietin (rhTPO). (registered in Clinical Trials.gov as NCT05944809). Methods: Thoracic EC patients staged I-IVa (AJCC 7 th ) were prospectively enrolled. The MR images of thoracic vertebra were fused with the simulating CT images. Active BM indentified by MR was contoured as an organ at risk in the treatment plan. The treatment regimen consisted of BM-sparing intensity modulated radiotherapy (BMS-IMRT) (≥45Gy) and concurrent chemotherapy (five cycles of weekly intravenous paclitaxel [50 mg/m²] and cisplatin/nedaplatin [25 mg/m²], or two cycles of intravenous paclitaxel [135-175 mg/m²] and cisplatin [80 mg/m²]), and rhTPO (15000U ih. qw during the radiotherapy). The dose limits for active BM are: volume received more than 5 Gy (V5) < 95%,V10 < 85%,V20 < 60%，V30 < 40%. The primary endpoint is any grade of thrombocytopenia during the radiotherapy and 1 month after the radiotherapy. In order to lower the incidence of thrombocytopenia to ≤ 15% by BMS-IMRT plus prophylactic rhTPO, 23 patients are needed with 80% power to declare 25% absolute reduction compared with that of historical report at a 1-sided significance level of 0.05. Results: From July 20 2023 to June 30 2024, a total of 32 patients met the inclusion criteria for this study. One patient failed to finish MR, three patients had grade 1(G1) thrombocytopenia and one patient had disease progressed during screening phase. Finally, 27 patients were enrolled. Our patient population was predominantly male (92.6% men vs. 7.4% women), with a median age of 59 years (range, 38–75 years). A majority of patients presented with stage II-IVa (70.4%). Before concurrent CRT, seven patients received inductive chemotherapy combined with or without immunotherapy. All patients finished the treatment plan with median radiation dose of 49.45Gy (range 42.8 - 66.66Gy). Concurrent chemotherapy was administered with a median cycle of 5 cycles (range 1-5 cycles). Four patients (14.8%) developed thrombocytopenia (1 pts with G1 and 3 pts with G3). 11 patients experienced leukopenia (2 pts with G1, 7 pts with G2 and 2 pts with G3). Only one patient happened anemia (G2). Conclusions: Techniques to limit low dose radiation to active BM and prophylactic rhTPO could reduce thrombocytopenia in thoracic EC patients treated with CRT. Clinical trial information: NCT05944809 .

PURPOSE:To compare the efficacy of dCRT versus dCRT plus consolidation ICIs (dCRT + cICIs) in LA-ESCC and to evaluate the safety of dCRT + cICIs. METHODS:Patients with LA-ESCC who received dCRT or dCRT + cICIs were included. sIPTW adjusted for sex, age, clinical TNM stage, smoking, and alcohol consumption between the two groups. The study analyzed overall survival (OS) and progression-free survival (PFS) between the two groups, and evaluated immune-related adverse events (irAEs) within the dCRT + cICIs cohort. RESULTS:We retrospectively identified 176 ESCC patients, with 123 in the dCRT group and 53 in the dCRT + cICIs group. Pre-sIPTW analysis showed significantly improved OS in the dCRT + cICIs group (median, 46.4 vs. 20.9 months; P = 0.02). The dCRT + cICIs group had a better PFS than the dCRT group (median, 27.4 vs. 12.9 months; P = 0.02). After sIPTW, the OS was numerically better in the dCRT + cICIs group than in the dCRT group (median, 42.9 vs. 21.6 months; P = 0.1), with improvement in 1- and 2-year OS rates. There was no significant difference in PFS between dCRT + cICIs group and dCRT group (median, 23.0 vs. 13.0 months; P = 0.2), with numerically better 1- and 2-year PFS in the dCRT + cICIs group. In the dCRT + cICIs group, approximately 43.4 % of patients experienced irAEs, and grade 3-4 irAEs occurred in 13.2 % of patients. The most common was hypothyroidism in 11.3 % of patients. CONCLUSIONS:Our preliminary findings suggested that consolidation immunotherapy following dCRT might trend toward prolonged OS and PFS in patients with LA-ESCC, and that irAEs are generally tolerated.

BACKGROUND:Radiation-induced lung injury is a major dose-limiting toxicity in thoracic radiotherapy. Pirfenidone, an oral antifibrotic drug that is often used to treat idiopathic pulmonary fibrosis, could offer therapeutic benefits for patients with radiation-induced lung injury. We evaluated the efficacy and safety of pirfenidone in patients with grade 2 or grade 3 radiation-induced lung injury. METHODS:This multicentre, open-label, randomised, phase 2 clinical trial enrolled patients with grade 2 or grade 3 radiation-induced lung injury diagnosed according to Common Terminology Criteria for Adverse Events version 5.0 from ten medical centres across China. Eligible patients were aged 18-75 years with an Eastern Cooperative Oncology Group performance status of 0-2 and had grade 2 or grade 3 radiation-induced lung injury. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either pirfenidone plus glucocorticoids or glucocorticoids alone. Pirfenidone was given orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3-24. Glucocorticoids were administered concurrently at the equivalent dose of prednisone 40 mg/day, divided into two oral doses, and maintained for 2 weeks, followed by a tapering schedule of 10 mg every 2 weeks over a period of 6 to 8 weeks. The control group received glucocorticoids only. The primary endpoint, evaluated in the modified intention-to-treat population, was the change in the percentage of carbon monoxide diffusing capacity (DLCO%) from baseline to week 24. Safety was assessed in all participants who received at least one dose of treatment. The trial is registered with ClinicalTrials.gov, NCT03902509, and has completed enrolment. FINDINGS:Between Nov 29, 2021, and Dec 4, 2023, 134 patients were enrolled and randomly assigned, with 67 patients in each group study group. 105 (78%) of 134 patients were male and 29 (22%) were female. The median follow-up was 9·2 months (IQR 6·3-16·0). At week 24, the pirfenidone group showed an 8·0% improvement from baseline in DLCO%, whereas the control group showed a 2·4% reduction (least squares mean difference 10·4%, 95% CI 4·3-16·5; p=0·0010). The most common grade 3 or worse adverse events included pneumonia (four [6%] of 67 patients in the pirfenidone group vs eight [12%] of 67 patients in the control group), and rash (two [3%] of 67 patients in the pirfenidone group vs none in the control group). Serious adverse events occurred in 12 (18%) of 67 patients in the pirfenidone group and 11 (16%) of 67 patients in the control group. There were no treatment related deaths. INTERPRETATION:Pirfenidone in combination with glucocorticoids provides a potential therapeutic strategy for grade 2 or grade 3 radiation-induced lung injury, addressing the unmet clinical need for effective antifibrotic therapy in patients receiving thoracic radiotherapy. Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here. FUNDING:Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, National Natural Science Foundation of China, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.

This multicenter, randomized phase III clinical trial assesses the efficacy and toxicity of SIB-RT with/without concurrent chemotherapy in patients with inoperable esophageal squamous cell carcinoma (ESCC) in the era of intensity-modulated RT and was conducted between December 2017 and November 2020. Patients with inoperable clinical stage II-III diseases or clinical stage IV disease with metastatic lymph nodes in supraclavicular/celiac trunk area were enrolled and randomized to receive SIB-RT concurrent with chemotherapy (SIB-RT + CT arm, N = 82) or SIB-RT alone (SIB-RT arm, N = 82). Planning gross tumor volume and planning target volume were administered with 59.92 and 50.4 Gy of radiation, respectively, in 28 fractions. The concurrent chemotherapy regimen comprised weekly doses of paclitaxel and nedaplatin for 5 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were treatment response, progression-free survival (PFS), quality of life (QoL), and toxicity profiles. The SIB-RT + CT arm exhibited a superior treatment response to that in SIB-RT arm (69.5% vs. 53.7%, p = .04). The 5-year OS in SIB-RT arm and SIB-RT + CT arm was 23.9% vs. 28.8% (p = .33). The 5-year PFS in SIB-RT arm and SIB-RT + CT arm was 23.9% vs. 27.4% (p = .22). The improvement of EORTC QLQ-OES18 dysphagia subscale score was higher in SIB-RT + CT arm compared with SIB-RT arm (p = .02). The incidences of grade 3 or higher leukopenia and nausea were higher in SIB-RT + CT arm (p < .01 and p = .01). SIB-RT should be realized as the essential treatment modality for inoperable ESCC. SIB-RT + CT should be the preferred treatment option, as it affords a superior treatment response and greater dysphagia relief.