BACKGROUND:Despite being a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy (nCRT) followed by surgery was frequently associated with toxicities. Body composition was a potential factor influencing both the toxicity and efficacy of nCRT. The aim of this study was therefore to assess, within a large retrospective cohort derived from prospective trials, the associations of body composition measures-including skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) with nCRT-related toxicities and outcomes. MATERIALS AND METHODS:Patients with locally advanced ESCC who underwent standard nCRT between January 2019 and December 2024 were included in this retrospective analysis. Body composition parameters were derived from pre-treatment computed tomography (CT) scans at the third lumbar vertebra (L3). SMD was calculated as the mean radiation attenuation (Hounsfield units) of the muscle area. Based on established criteria, patients were stratified as having low or high SMI according to Martin's BMI-specific thresholds, while SMD and VAT were categorized into tertiles (low, intermediate, high). Hematologic toxicities and dose-limiting toxicities (DLT) were graded using CTCAE v5.0. Associations between body composition and toxicities/efficacy were analyzed using logistic regression. The relationship between body composition and absolute lymphocyte count (ALC) nadir and baseline lymphocyte subsets (CD4+, CD8+, CD3+) was also evaluated. RESULTS:This study included 297 patients (median age 66 years; 85.5% male; 72.4% stage III). Following nCRT, 278 patients underwent surgery, achieving a pathological complete response (pCR) rate of 42.8% and tumor regression grade (TRG) 0-1 of 72.3%. Grade ≥2 hematologic toxicity occurred in 80.5% (n = 239) of patients, and 35.4% (n = 105) experienced DLT. While body composition showed no significant association with pCR or TRG, multivariate analysis revealed that both high SMI (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.26-0.89, P = 0.02) and high VAT (adjusted OR 0.46, 95% CI 0.22-0.94, P = 0.034) were independent protective factors against grade ≥2 hematologic toxicity. Additionally, high SMI was significantly associated with reduced risk of DLT (adjusted OR 0.56, 95% CI 0.34-0.92, P = 0.023). Notably, patients with low VAT had significantly lower median ALC nadir and baseline CD4+ T-cell counts. CONCLUSION:In this cohort, pretreatment high SMI and high VAT were associated with reduced nCRT-related hematologic toxicities (grade ≥2) and DLT in patients with locally advanced ESCC. Pathological response (pCR/TRG 0-1) was not associated with body composition. The protective role of high VAT might be partially mediated by its association with higher lymphocyte nadirs and baseline CD4+ T-cell counts. Future studies should investigate long-term outcomes and assess whether prehabilitation strategies targeting SMI and VAT can mitigate toxicity without compromising treatment efficacy.

BACKGROUND:The current standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) consists of neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery. Recent single-arm trials have demonstrated that incorporating immune checkpoint inhibitors (ICIs) into neoadjuvant regimens improves pathological complete response (pCR) rates. However, the comparative risk of postoperative complications between nCRT and neoadjuvant chemoimmunoradiotherapy (nCIRT) followed by esophagectomy in patients with ESCC remains unclear. MATERIALS AND METHODS:We retrospectively analyzed ESCC patients who underwent neoadjuvant therapy followed by esophagectomy at Ruijin Hospital (April 2019-April 2025). Postoperative complications were defined as adverse events occurring within 90 days after surgery, primarily involving the respiratory, digestive, and cardiovascular systems. Severity was assessed using the Clavien-Dindo classification (CDC), and Grade IIIA or higher levels were considered severe complications. To overcome limitations of CDC in capturing the full morbidity spectrum and burden, we further evaluated complications using the Comprehensive Complication Index (CCI). RESULTS:A total of 271 patients who underwent curative esophagectomy were enrolled, including 169 in the nCRT group and 102 in the nCIRT group. No significant differences were observed in age or gender distribution between the two groups. According to Clavien-Dindo classification, there was no significant difference in overall complication rates between the nCRT and nCIRT groups (p = 0.76). Regarding severe complications (Grade ≥ IIIA), the overall incidence was 35.50% in the nCRT group and 28.43% in the nCIRT group (p = 0.23). The CCI analysis indicated a comparable morbidity burden, with median CCI scores of 22.60 in both nCRT and nCIRT cohorts (p = 0.65). Furthermore, no statistically significant differences were observed in subgroups analyses of patients with cardiac complications, pulmonary complications, anastomotic leakage, chyle leakage and wound infections, especially in severe complications. CONCLUSIONS:In this retrospective analysis of a prospectively maintained cohort, the addition of pembrolizumab to nCRT was not associated with a statistically significant increase in postoperative complications among patients with ESCC. These findings provided preliminary evidence regarding the perioperative safety of this combination. Further studies were warranted to investigate the long-term efficacy of nCIRT for the treatment of ESCC.

ABSTRACT Background Dose exposure to supraventricular cardiac conduction system doses has been reported to be associated with distinct arrhythmia classes after thoracic radiotherapy, but its impact in esophageal squamous cell carcinoma (ESCC) remains unknown. Materials and Methods Locally advanced ESCC treated with neoadjuvant chemoradiotherapy (nCRT) were included. The primary endpoint was grade ≥ 3 adverse cardiac arrhythmia events. Prediction performance was evaluated through time‐dependent receiver operating characteristic curves, and competing risk frameworks were implemented to quantify the cumulative incidence of distinct cardiac arrhythmia. Results Of 358 patients, 84.9% were men, with a median age of 66 years (range: 39–79 years). A total of 60 (16.8%) patients experienced at least 1 grade ≥ 3 arrhythmia, with a median time to first arrhythmia of 13 months (95% CI: 12–15 months). The 2‐year cumulative incidences of distinct cardiac arrhythmia were 8.89% for AF, 2.96% for atrial flutter, and 5.12% for other SVT. Baseline coronary heart disease was a risk factor for all types of arrhythmia (p < 0.05). After adjusting for baseline cardiovascular risk factors, Heart Dmax (sHR 3.69, p = 0.0024) was associated with AF, Heart volume receiving 5 Gy with atrial flutter (sHR: 9.35, p = 0.0077), and Heart volume receiving 40 Gy (sHR 5.72, p = 0.00078) with other SVT. Conclusion Grade ≥ 3 cardiac arrhythmia associated with thoracic radiation occurs in 16.7% of ESCC patients undergoing nCRT within a median time of 13 months. The radiation dose exposure of the supraventricular cardiac conduction system is not associated with increased cardiac arrhythmia. Specific arrhythmia subtypes exhibited differential associations with distinct dose‐volume parameters of whole heart irradiation.

BackgroundThe appropriateness of concurrent chemoradiotherapy (cCRT) for older or clinically vulnerable stage III unresectable non-small-cell lung cancer (NSCLC) patients remains contentious. Furthermore, the survival implications of de-escalating thoracic radiotherapy (RT) intensity in this population have not been conclusively elucidated.Methods and findingsWe conducted a phase II randomized, open-label, two-cohort (non-comparative) trial at a tertiary hospital in China (NCT05557552). Between September 30, 2022 and April 30, 2024, we enrolled 56 older and/or frail patients with stage III NSCLC who were ineligible for cCRT. The primary endpoint was the 1-year progression-free survival (PFS) rate estimated using the Kaplan-Meier method. Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. In the intention-to-treat (ITT) set, which included all 56 randomized patients who received at least one dose of study treatment, the 1-year PFS was 84.3% (95% confidence interval [CI] [70.3%, 98.3%]) in the standard RT group and 70.7% (95% CI [54.3%, 87.1%]) in the reduced RT group. In the per-protocol set (53 patients), the 1-year PFS was 82.9% (95% CI [68.9%, 98.8%]) in the standard RT group and 73.4% (95% CI [58.3%, 92.4%]), with a median follow-up of 24 months. Among 56 patients in the safety analysis set, 71.4% of patients experienced grade 3/4 adverse events (AEs) in the standard RT group and 53.6% in the reduced RT group. One patient (3.6%) in the reduced RT and three patients (10.7%) in the standardized RT experienced grade 5 AEs. The main limitations are the non-comparative design, small sample size, and lack of power to establish non-inferiority or superiority.ConclusionThe current study suggested that reduced RT combined with sequential chemo-immunotherapy might be feasible for older/frail patients intolerant to cCRT, showing numerically similar survival outcomes. These exploratory findings warrant confirmation in larger, adequately powered randomized trials.Trial registrationThe trial had been registered on ClinicalTrials.gov on Sep 30, 2022. ClinicalTrials.gov NCT05557552.

Background:Recent research suggests that the emerging neutrophil-albumin ratio (NAR) has a significant correlation with the survival outcomes across a range of tumors, yet its predictive significance for nasopharyngeal carcinoma (NPC) remains insufficiently investigated. This study aimed to evaluate the relationship between the neutrophil-to-albumin ratio (NAR) and overall survival (OS) in patients with NPC, as well as to develop a corresponding prognostic model. Methods:This retrospective analysis included 861 NPC patients treated with concurrent chemoradiotherapy (CCRT), who were randomly divided into a training group (n = 605) and a validation group (n = 256). To identify factors associated with OS and construct a prognostic nomogram, both univariate and multivariate Cox regression analyses were performed. The nomogram's prognostic accuracy was evaluated and independently validated. Results:The NAR score successfully segregated NPC patients into two categories with significantly different OS (HR = 0.536; 95 % CI: 0.296-0.972, P = 0.040). Through multivariate analysis, factors such as age, T stage, N stage, and NAR score were identified as independent predictors of OS, leading to the creation of a prognostic nomogram. This nomogram demonstrated superior predictive capability for OS [C-index = 0.702 (95 % CI: 0.636-0.768)], surpassing that of the conventional staging system [C-index = 0.651 (95 % CI: 0.549-0.752)]. The findings underwent internal validation within an independent cohort. Conclusions:The NAR, an emergent biomarker combining nutritional and inflammatory status, offers a practical, low-cost, and non-invasive prognostic measure for NPC patients treated with CCRT. Additionally, the prognostic nomogram derived from NAR surpasses traditional staging systems in predictive accuracy.

Abstract Background Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.

BackgroundRecent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. MethodsA total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. ResultsThe LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. ConclusionThe pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

Background Recent studies have shown that ovarian aging is strongly associated with the risk of breast cancer, however, its prognostic impact on breast cancer is not yet fully understood. In this study, we performed a multicohort genetic analysis to explore its prognostic value and biological features in breast cancer. Methods The gene expression and clinicopathological data of 3366 patients from the The Cancer Genome Atlas (TCGA) cohort, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian aging-related genes (OARGs) were included in the establishment of the prognostic model. Furthermore, functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated using bioinformatic methods. Results An eight OARG-based signature was established and validated using independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram with good predictive performance was developed by integrating the OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair, immune cell signaling pathways, and immunomodulatory functions. The patients in the low-risk subgroup were found to be sensitive to traditional chemotherapeutic, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel targeted drugs (sunitinib, pazopanib, etc.). Moreover, patients in the low-risk subgroup may be more susceptible to immune escape and therefore respond less effectively to immunotherapy. Conclusions In this study, we proposed a comprehensive analytical method for breast cancer assessment based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity of breast cancer patients.

BACKGROUND:Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel albumin-related nutrition marker called "lymphocyte × albumin (LA)" and disease-free survival (DFS) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).METHODS:In total, 711 non-metastatic breast cancer patients who underwent NAC at two medical centers were retrospectively analyzed. We performed least absolute shrinkage and selection operator (LASSO) Cox regression analysis as well as multivariate Cox regression analyses to identify the variables associated with DFS and to establish a predictive nomogram.RESULTS:The nomogram incorporated four variables based on the multivariate analysis of DFS in the training cohort: LA, ypN stage, ypT stage, and hormone receptor status. In comparison with the traditional TNM staging system, the nomogram demonstrated superior discrimination, calibration ability, and clinical usefulness in both the training set and internal and external validation sets. Furthermore, patients stratified into different risk groups resulted in significant differences in DFS.CONCLUSIONS:LA is an independent prognostic biomarker, and LA-based prognostic nomogram offers a more precise assessment of DFS for breast cancer patients treated with NAC, potentially serving as a valuable tool for personalized prognostic predictions.

Purpose To determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs). Methods Continuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR. Results A total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11–20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079–4.881) and RFS (HR = 2.126, 95% CI 1.038–4.356) compared with the TTR of 10–20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10–20 weeks. Conclusion There exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.

放射性心脏疾病已成为胸部放射治疗患者非恶性肿瘤死亡的主要原因之一.心血管内皮细胞损伤是放射性心脏损伤的初始靶点,因此研究心血管内皮细胞放射性损伤机制对于改善放射治疗患者预后具有重要的临床价值.现综述放射相关内皮细胞可能的损伤机制及潜在的保护策略,以期为临床预防或干预放射性心脏疾病提供新思路.