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.

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).

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.

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.

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.

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 .

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.

The potential benefits of adding immune checkpoint inhibitors (ICIs) to definitive chemoradiotherapy (dCRT) for inoperable esophageal squamous cell carcinoma (ESCC) remain unclear, different timing for immunotherapy intervention during the peri-dCRT period on survival outcomes is worth exploring. Patients with inoperable ESCC receiving dCRT combined with ICIs between April 2018 and April 2022 were recruited from five hospitals in China. A historical control group treated with dCRT alone was used for comparison. Stabilized inverse probability of treatment weights (sIPTW) analyses were conducted to compare survival. The survival outcomes and treatment-related adverse effects were analyzed. A total of 290 patients with inoperable ESCC who received dCRT+ICI treatment were analyzed. The median follow-up was 35.7 months. The 1-year and 2-year overall survival (OS) rates were 86.7% and 66.9%, respectively, and the 1-year and 2-year progression-free survival (PFS) rates were 66.7% and 47.3%, respectively. The median PFS was 22.4 months, and the median OS was not reached. The dCRT+ICI group had significantly longer OS than the historical control group (2-year OS: 66.9% vs. 56.5%, for sIPTW-adjusted data: HR = 0.62, p < .001). After sIPTW, no differences in OS were found among the induction, concurrent, and consolidation groups. The sIPTW-adjusted analysis showed that both the induction and concurrent groups had significantly longer PFS than the consolidation group. Combining immunotherapy with dCRT improved survival outcomes and demonstrated a favorable safety profile in patients with inoperable ESCC. Induction or concurrent immunotherapy may provide superior survival benefits compared to consolidation immunotherapy.Trial registration Trial no. NCT04821778 registered in ClinicalTrials.gov

This study aims to compare the therapeutic efficacy of whole brain radiotherapy (WBRT) versus WBRT plus simultaneous integrated boost (WBRT + SIB) in patients with brain metastases (BMs) from small cell lung cancer (SCLC). A retrospective analysis was conducted on 127 patients with BMs from SCLC who received brain radiotherapy between 2014 and 2023 at the Cancer Hospital of the Chinese Academy of Medical Science. Among them, 71 patients underwent WBRT (25.0–54.0 Gy in 10–21 fractions), while 56 patients received WBRT + SIB (SIB to metastases: 18.0–60.0 Gy in 5–20 fractions). The overall survival (OS), intracranial progression-free survival (iPFS), objective response rate (ORR), and local control rate (LCR) were evaluated to assess the efficacy of the treatments. With a median follow-up of 14.9 months, the median OS was significantly longer in the WBRT + SIB group compared to the WBRT group (18.0 vs. 11.7 months). Similarly, the iPFS was extended in the WBRT + SIB group (12.2 vs. 7.6 months). Kaplan-Meier analysis revealed that WBRT + SIB significantly improved OS in patients with SCLC of BMs (P = 0.009). Subgroup analysis indicated that male patients, age < 60 years old, and multiple intracranial metastases benefited more from WBRT + SIB. Interaction tests suggested that age significantly influence the efficacy of WBRT + SIB, with patients < 60 years old deriving more benefit (P = 0.049). Concurrent WBRT + SIB with anti-angiogenic targeted therapy significantly improved iPFS (P < 0.001). WBRT + SIB can prolong the OS in SCLC patients with BMs, with younger age and those receiving anti-angiogenesis therapy potentially achieving additional survival benefits.

BACKGROUND AND PURPOSE:Magnetic resonance-guided adaptive radiotherapy (MRgART) may improve the efficacy of large brain metastases (BMs)(≥2 cm), whereas the workflow requires optimized. This study develops a two-stage, personalized deep learning auto-segmentation (DLAS) model to assist online delineation of large BMs. MATERIALS AND METHODS:Multi-sequences images from 177 BMs were trained to develop the basic DLAS model. Then, 741 daily online MR images of 20 large BMs from a prospective trial were collected for developing a personalized model. The dice similarity coefficient (DSC) was evaluated across three methods: basic model, rigid registration and personalized model, at intervals of every five fractions. The accuracy and efficiency were compared between manual delineation (MD) and DLAS assistant delineation (DLAS-AD) in 8 patients who underwent contrast T1 re-scan during MRgART. RESULTS:The personalized DLAS model demonstrated significantly better performance compared to the basic model and rigid registration during the last fraction of MRgART (when the tumor volume achieved a significant reduction). The mean DSC for basic model vs. rigid registration vs. personalized model were 0.86 (p = 0.01) vs. 0.88 (p = 0.05) vs. 0.90, respectively. The DLAS-AD significantly improved contouring accuracy compared to MD, with a mean DSC of 0.89 vs. 0.85 (p = 0.001), and reduced contouring time by an average of 53.5 % (193 s vs. 424 s, p < 0.001). CONCLUSION:Personalized DLAS model may increase the accuracy and efficiency of MD to optimize the workflow of MRgART for large BMs.

BACKGROUND AND PURPOSE:To evaluate the safety and efficacy of consolidative thoracic radiotherapy (cTRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy. MATERIALS AND METHODS:We retrospectively analyzed patients with ES-SCLC who accepted first-line platinum-based chemotherapy plus immunotherapy in our hospital from January 2018 to December 2021. CTRT was recommended for patients who achieved complete response (CR)/ partial response (PR) / stable disease (SD) after first-line systemic therapy. Patients were divided into cTRT and non-cTRT groups based on their receipt of cTRT. Categorical variables were compared using the Chi-squared test or Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method, with comparisons by the log-rank test. Univariate and multivariate analyses were employed to identify prognostic factors for OS using the Cox proportional hazards model. Cumulative incidence of local regional progression (LRP) was calculated using the Fine-Gray competing risks regression model. RESULTS:We finally enrolled 100 patients in our cohort, comprising 48 patients who received cTRT and 52 who did not. The cTRT group exhibited significantly younger age distribution (72.9 % <65 years vs. 50 % in non-cTRT, p = 0.019), limited metastatic sites (≤1 metastatic site: 66.7 % vs. 32.7 %, p < 0.001), and fewer liver metastases (12.5 % vs. 32.7 %, p = 0.017), alongside higher PCI uptake rates (27.1 % vs 0 %, p = 0.001). The cTRT group had significantly longer median OS (26 vs. 17 months, p = 0.006) and PFS (10 vs. 6 months, p = 0.005) compared with the non-cTRT group. Multivariate analysis identified cTRT as the only prognostic factor correlated with improved OS (HR = 0.48, p = 0.04). The LRP at 1 year were 55.4 % and 22.3 % in the non-cTRT and cTRT group, respectively (p < 0.001). 3 (6.3 %) patients had grade 3 radiation esophagitis and 5 (10.4 %) patients developed grade 1-2 radiation pneumonitis in the cTRT group. CONCLUSION:The administration of cTRT is safe and holds potential benefits for ES-SCLC patients responding to first-line chemoimmunotherapy.

Purpose: We constructed a prediction model to predict a 2-year locoregional recurrence based on the clinical features and radiomic features extracted from the machine learning method using computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal cancer. Patients and methods: A total of 264 patients (156 in Beijing, 87 in Tianjin, and 21 in Jiangsu) were included in this study. All those locally advanced esophageal cancer patients received definite radiotherapy and were randomly divided into five subgroups with a similar number and divided into training groups and validation groups by five cross-validations. The esophageal tumor and extratumoral esophagus were segmented to extract radiomic features from the gross tumor volume (GTV) drawn by radiation therapists before radiotherapy, and six clinical features associated with prognosis were added. T stage, N stage, M stage, total TNM stage, GTV, and GTVnd volume were included to construct a prediction model to predict the 2-year locoregional recurrence of patients after definitive radiotherapy. Results: A total of 264 patients were enrolled from August 2012 to April 2018, with a median age of 62 years and 81% were males. The 2-year locoregional recurrence rate was 52.6%, and the 2-year overall survival rate was 45.6%. About 66% of patients received concurrent chemotherapy. In total, we extracted 786 radiomic features from CT images and the Principal Component Analysis (PCA) method was used to screen out the maximum 30 features. Finally, the Support Vector Machine (SVM) method was used to construct the integrated prediction model combining radiomics and clinical features. In the five training groups for predicting locoregional recurrence, the mean value of C-index was 0.9841 (95%CI, 0.9809–0.9873), and in the five validation groups, the mean value was 0.744 (95%CI, 0.7437–0.7443). Conclusions: The integrated radiomics model could predict the 2-year locoregional recurrence after dCRT. The model showed promising results and could help guide treatment decisions by identifying high-risk patients and enabling strategies to prevent early recurrence.

Background:The PORT-C trial was the first published phase III randomized clinical trial (RCT) to evaluate the role of postoperative radiotherapy (PORT) using intensity-modulated radiation therapy (IMRT)/three-dimensional conformal radiation therapy (3D-CRT) in patients with resected pIIIA-N2 non-small-cell lung cancer (NSCLC). We aimed to assess the long-term outcomes of this RCT. Methods:Patients with pIIIA-N2 NSCLC treated with complete resection followed by four cycles of platinum-based chemotherapy between January 1, 2009 and December 31, 2017 were randomly assigned in a 1:1 ratio to PORT or observation. Radiotherapy was delivered using a 6 MV-X ray linear accelerator via 3D-CRT or IMRT, with 2 Gy per fraction up to 50 Gy over 5 weeks. The primary endpoint was disease-free survival (DFS), analyzed using modified intent-to-treat (mITT). Secondary endpoints included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and toxic effects. DFS, OS, LRFS, and DMFS rates were estimated using Kaplan-Meier method, compared using log-rank test, and modeled using Cox proportional hazards method. The patterns of first failures were analyzed using competing risk analyses. This trial is registered with ClinicalTrials.gov, NCT00880971. Findings:Overall, 394 patients were randomly allocated to the PORT (n = 184) or observation (n = 180) arms. The median follow-up time was 87.9 months (interquartile range [IQR] 72.2-113.8). In the mITT analyses, DFS showed no significant difference between the PORT and observation arms (hazards ratio [HR], 0.90; 95% CI, 0.70-1.12; p = 0.39). The 5-year DFS rates in the PORT and observation arms were 36% (95% confidence interval [CI], 28.9%-43.1%) and 31.5% (95% CI, 24.6%-38.4%), respectively; the 5-year OS rates were 64.7% (95% CI, 57.6%-71.8%) and 70.4% (95% CI, 63.5%-77.3%), respectively (p = 0.20). In the per-protocol analyses, 140 and 170 patients were included in the PORT and observation arms, respectively. PORT did not significantly improve DFS (HR, 0.80; 95% CI, 0.61-1.05; p = 0.11) or OS (HR, 1.09; 95% CI, 0.77-1.53; p = 0.63). Most patients died of cancer. However, more deaths due to cardiopulmonary disease were observed in the PORT arm than in the observation arm (6/184, 3.3% vs. 2/180, 1.1%). The first failure of locoregional recurrence (LR)-only was significantly lower in the PORT arm than in the observation arm (10.9%, 95% CI, 6.8%-15.9% vs. 18.9%, 95% CI, 14.0%-26.2%, p = 0.031). Only 1 patient (0.5%) in the PORT arm had grade 3 radiation pneumonitis. No radiotherapy-related grade 4 or 5 AEs were observed. Interpretation:The long-term results of the PORT-C trial indicated no DFS benefit from receiving PORT for patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy. Funding:National Key R&D Program of China, National Natural Science Foundation of China, Capital's Funds for Health Improvement and Research, Beijing Hope Run Special Fund of Cancer Foundation of China, and Beijing Xisike Clinical Oncology Research Foundation.

Purpose Simultaneous integrated dose reduction (SDR) radiation therapy (SDR-RT) with a definitive dose to the gross tumor volume (GTV) and a relatively lower dose to the clinical target volume (CTV) might be beneficial in improving normal tissue sparing with low toxicity. We aimed to compare the efficacies of SDR-RT and conventional fractionated radiation therapy (CF-RT) for limited-stage small cell lung cancer (LS-SCLC). Methods and Materials Eligible patients with LS-SCLC were 1:1 randomized to receive CF-RT (60 Gy in 30 once-daily fractions over 6 weeks for both CTV and GTV) or SDR-RT (50 Gy for CTV and 60 Gy for GTV in 28 once-daily fractions over 5.5 weeks) along with 4 to 6 cycles of chemotherapy. The primary endpoint was progression-free survival (PFS) rate in the intention-to-treat population, whereas the secondary endpoints were overall survival rate and adverse event incidence. Results Between February 2017 and March 2023, 336 patients randomly received either SDR-RT (n = 165) or CF-RT (n = 171). Over a median follow-up of 56 months, the 2- and 5-year PFS rates in the intention-to-treat analysis were, respectively, 42.0% and 31.9% with SDR-RT, and 40.7% and 30.5% with CF-RT (P = .015 for noninferiority). The between-group differences in overall survival, locoregional PFS, and locoregional recurrence rates were nonsignificant. Compared with CF-RT, SDR-RT was associated with lower median values of V20 (21.0% vs 22.8%) and Dmean (12.1 vs 13.4 Gy) of the bilateral lungs (both P < .001). Acute grade ≥3 toxicities and radiation pneumonitis incidence were lower with SDR-RT than that with CF-RT (54.5% vs 66.9%, P = .020; 2.4% vs 7.7%, P = .027). Conclusions Compared with CF-RT, SDR-RT led to similar survival and less acute adverse events. SDR-RT may be considered as a more protective approach for LS-SCLC treatment.

8043 Background: Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, parts of patients only receive sequential chemoradiotherapy (sCRT) due to various reasons. This phase II study aimed to improve the outcomes of patients receiving sCRT by combining anti-angiogenesis therapy (anlotinib) during radiotherapy course. Methods: Patients with unresectable LA-NSCLC intolerable to cCRT were prospectively enrolled. Induction chemotherapy with or without immunotherapy were given for 4-6 cycles. Then patients were prescribed oral 12 mg anlotinib up for 3 cycles during radiotherapy. The primary endpoint is 2-year overall survival (OS). Acute adverse events (AEs) were defined as any treatment related events from the start of radiotherapy until 3 months post-radiotherapy. The trial has been registered in ChiCTR.org as ChiCTR2200060712. Results: From October 2020 to January 2024, 41 patients with stage II-III NSCLC were enrolled. 11 (26.8%) patients received induction chemotherapy and 30 (73.2%) patients received induction chemotherapy combined with immunotherapy. The rate of grade 3–4 acute hematological AEs was 29.3% (12 cases). The rates of grade 3 hemoptysis were 2.4% (1 case), with no grade 4 hemoptysis reported. The incidence of grade 3–4 radiation pneumonitis was 9.8% (4/41). No grade 5 AEs occurred in all patients. The median follow-up was 16.8 (range: 7.0–50.7) months. 22 (53.7%) patients experienced recurrence, including 5 patients (12.2%) with primary-site recurrence and 7 patients (17.1%) with regional-node recurrence, 12 patients (29.3%) had distant metastases. The median progression-free survival (PFS) was 18.9 months (95%CI 14.6-23.2 months) and 1-year PFS was 77.2%. 9 patients (22.0%) died, including 3 patients who died of covid-19 pneumonia during the follow-up period, 1 patient who died of hydatid pneumonia due to long-term bed rest after cerebral infarction, and 4 patients who died of tumor-related diseases. The 1-year overall survival was 89.9%. Conclusions: Our data first showed the combination of thoracic radiotherapy and anti-angiogenesis therapy (anlotinib) is of safety, well controlled toxicity, and efficacy for inoperable LA-NSCNC patients who cannot tolerate cCRT. Clinical trial information: ChiCTR2200060712 .

PURPOSE:This prospective study in a real-world setting investigated the feasibility and safety of S-1 plus nimotuzumab (S-1-Nimo) based concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients who failed to neoadjuvant chemotherapy or chemoimmunotherapy. METHODS:LA-ESCC patients who failed to converse to resectable disease after neoadjuvant chemotherapy or chemoimmunotherapy were enrolled to receive the 4-week S-1-Nimo regimen of radiotherapy (40 Gy in 20 fractions, 5 days per week), S-1 chemotherapy, and nimotuzumab. Then, after surgical assessments, patients evaluated as resectable disease received surgery; patients with unresectable disease continued to receive definitive radiotherapy (50-60 Gy in 25-30 fractions, 5 days per week) concurrently with S-1-Nimo. The primary endpoint was event-free survival (EFS). RESULTS:Sixty-four patients were enrolled and evaluated. The median follow-up time was 23.2 months. Median EFS was 9.6 (95% confidence interval [CI], 7.1-14.0) months, with an estimated 2-year EFS rate of 24.2%. The median overall survival (OS) and the estimated OS rate at 2 years were 13.4 (95% CI, 10.3-17.5) months and 31.2%, respectively. Twelve underwent surgery, with a surgical conversion rate of 18.8% and an R0 resection rate of 100.0%. Subgroup analysis identified the significantly prolonged EFS and OS in patients who experienced radical surgery (median EFS, not reached vs. 8.7 months; p = .0117. median OS, 24.9 vs. 10.6 months; p = .0205) as compared to those treated with CCRT. Of 64 patients, grade 3 adverse events mainly included radiation esophagitis (4.7%), anemia (1.6%), and thrombocytopenia (1.6%). CONCLUSION:The study demonstrated the reasonable efficacy and promising safety of the S-1-Nimo-based CCRT in LA-ESCC patients with failure to neoadjuvant chemotherapy or chemoimmunotherapy.

Background:Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for locally advanced non-small-cell lung cancer (LA-NSCLC), whereas responses to anti-programmed cell death-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) are heterogeneous. Though consolidation ICI following concurrent chemoradiotherapy (cCRT) improves survival of NSCLC, this regimen is challenging for patients with bulky tumors due to excessive target volumes and radiation-resistant hypoxia during upfront cCRT, leading to higher risk of pneumonitis and inferior local-regional control. Recent trials have demonstrated neoadjuvant ICI brought greater benefit to stage III than stage I-II NSCLC. Our previous study also supported the therapeutic advantage of 2-cycle induction ICI for patients with bulky unresectable stage III NSCLC. In the context of induction immunotherapy, radiotherapy is more likely to exert immune synergistic effects, reverse anti-PD-1 resistance, and activate abscopal immune responses. Prospective trials to determine the efficacy and safety of induction ICI for bulky LA-NSCLC are necessary. Methods:This randomized, open-label, two-arm phase II study aims to explore whether 2 cycles of induction anti-PD-1 toripalimab plus chemotherapy can improve progression-free survival (PFS) in bulky LA-NSCLC. Bulky tumors are defined as primary lesion ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter. A total of 50 patients with bulky unresectable stage III NSCLC will be recruited and 1:1 randomized into the experimental arm: 2-cycle induction PD-1 inhibitor toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab; or control arm: 2-cycle induction chemotherapy followed by cCRT and consolidation toripalimab. Patients are stratified by pathology (squamous versus non-squamous). The primary endpoint is PFS. Secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and incidence of adverse events. Exploratory analyses include PD-L1 expression and liquid biopsy-based biomarker testing, tumor microenvironment profiling at single-cell levels, and quality-of-life assessments. Discussion:The InTRist study is the first randomized phase II trial to investigate the feasibility of induction anti-PD-1 toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab in bulky LA-NSCLC, providing novel evidence for the synergistic strategy combining anti-PD-1 blockade with radiotherapy to prolong immunotherapy benefits, overcome resistance, and enhance abscopal immune response. Clinical trial registration:ClinicalTrials.gov, identifier NCT05888402.

Purpose/Objective(s) We aim to evaluate dynamic survival of limited-stage small cell lung cancer (LS-SCLC) treated with intensity-modulate radiation therapy (IMRT) in the first-line chemoradiotherapy (CRT) era. Materials/Methods This retrospective cohort study reviewed 821 LS-SCLC patients who underwent chemoradiotherapy with IMRT. Conditional survival and annual hazard rates were used to evaluate the dynamic survival. The clinical prognostic factors were estimated by Cox regression proportional analysis. The corresponding conditional survival of each factor was calculated, with IPTW used to balance other confounding factors. The differences of conditional survival were evaluated by standardized differences (D value). Sensitivity analysis was also conducted. Results The median follow-up of the entire cohort was 66 months (95% CI：62.20-69.80). 3-year survival rates raised from 45.47% (95% CI: 42.1%-48.9%) at diagnosis to 93.01% (95% CI: 88.4%-97.7%) at year five for conditional overall survival and from 30.31% (95% CI: 27.2%-33.5%) to 90.71% (95% CI: 83.9%-97.5%) at year five for conditional progression-free survival. The annual hazard rates for patients reach the highest point between year 1 to year 2 for death and drop continuously for progression. Supraclavicular metastasis, smoking history, sequence of chemoradiotherapy were clinical prognostic factors at diagnosis, while the difference remained or disappeared in the follow-up for OS and PFS. Results in subgroup of patients achieved CR and PR was consistent. Conclusion In the first-line chemoradiotherapy era, the survival probability for LS-SCLC increased and progression probability decreased over time. The influence of prognostic factors at initial diagnosis may change in the long-term follow-up.