OBJECTIVE:To determine whether incidental radiation dose to pulmonary vein (PV) substructures---known arrhythmogenic sites---was associated with increased risk of atrial fibrillation (AF) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). METHODS:We conducted a retrospective analysis of 209 ESCC patients treated with nCRT. PV substructures (LSPV, LIPV, RSPV, RIPV) were contoured on radiotherapy planning scans, and dose-volume histogram parameters were extracted. AF events were ascertained through systematic cardiac monitoring. Multivariate competing risk regression was employed to assess associations between PV doses and AF, with adjustment for cardiovascular risk factors, surgical resection as a time-dependent covariate, and mortality as a competing risk. RESULTS:Among 209 patients (84.9% male; median age 66 years), the 2-year cumulative incidence of AF was 8.89%, with a median time to AF of 13 months. Among the 25 AF events, 15 (60%) occurred after esophagectomy, with a median time from surgery to AF of 2.1 months. On univariate analysis, age, hypertension, LIPV-∼Dmax∼, RSPV-∼Dmax∼, and coronary heart disease (CHD) were associated with AF. In the multivariable model, LIPV-∼Dmax remained an independent predictor (adjusted HR = 3.16, 95% CI: 1.19-8.42, p = 0.021) after adjustment for age (HR = 3.66, p = 0.009), CHD (HR = 2.59, p = 0.019), and surgical resection. Patients with LIPV-∼Dmax∼ >28.87 Gy had a significantly higher AF incidence (12.3%) than those below this threshold (p = 0.008). Moreover, AF was associated with inferior 2-year recurrence-free survival (36.9% vs. 78.6%, p = 0.0051) and inferior 2-year overall survival (58.3% vs. 82.1%, p = 0.012). CONCLUSION:Maximum dose to the LIPV was independently associated with increased AF risk and worse survival outcomes in ESCC patients receiving nCRT. These results highlighted the potential value of LIPV-sparing radiotherapy techniques and enhanced AF surveillance in this population. External validation in larger prospective cohorts was needed before firm clinical guidelines can be established.

This study aims to identify the role of tumor immune microenvironment (IME) in ductal carcinoma in situ (DCIS) in predicting benefit of whole breast irradiation (WBI). Different subtypes of tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs) and tertiary lymphoid structures (TLSs) were determined in tumor tissues of DCIS cohort who received breast-conserving surgery (BCS). In total, 165 patients were enrolled with 113 received WBI. After a median follow-up of 73.7 months, 15 ipsilateral breast tumor recurrence (IBTR) events occurred. Nine IBTRs occurred outside of the original quadrant (elsewhere failure event, EFE). After LASSO and multivariate Cox regression analyses, the ER negative status, high ratios of CD4 + /CD8 + , dense CD68 + TAMs, sparse CD8 + T cell and dense TLSs with follicular dendritic cells (F-TLSs) remained independent risk factors of IBTR (all p < 0.05) to develop a nomogram. Points of nomogram were defined as immune microenvironment score (IMS) which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed among these three risk subgroups (5y-rate: 0.0

PURPOSE:Axillary substructures may contribute to the development of breast cancer-related lymphedema (BCRL). This study aimed to compare dose-volume parameters of various substructures to identify high-risk regions associated with BCRL and to evaluate the clinical applicability of these findings. METHODS AND MATERIALS:Cohort-Initial included 336 patients with pT1-3N0-1M0 breast cancer who underwent mastectomy or lumpectomy with axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) between August 2018 and February 2021. The Norman questionnaire was used to assess BCRL. Thirteen dose-volume parameters across 8 axillary substructures were assessed for association with BCRL. Cohort-Recurrence comprised 50 consecutive ALND-treated patients with regional nodal recurrence diagnosed using positron emission tomography/computed tomography, used to evaluate the recurrence risk in the candidate substructures. Cohort-Reoptimization involved 20 patients from the Cohort-Initial who received excessive radiation doses in the candidate substructure. Their treatment plans were reoptimized to assess the feasibility of dose reduction while maintaining target coverage and organ dose. RESULTS:The patient-reported cumulative incidence of BCRL was 33.9% during a median follow-up of 60 months. Significant baseline risk factors included body mass index ≥ 27.18 kg/m2, tumor size ≥ 1.9 cm, premenopausal status, and ≥ 18 lymph nodes removed (all P < .05). The most significant dosimetric parameter was axillary-lateral thoracic vessel juncture (ALTJ)-V35Gy ≥ 79.2%. A predictive nomogram incorporating these clinicopathologic factors and the ALTJ parameter was developed with reasonable accuracy, as confirmed by self-training (area under the curve value, 0.780) and internal validation (area under the curve value, 0.769). None of the 196 fluorodeoxyglucose-avid regional nodes in Cohort-Recurrence were located within the ALTJ. Reoptimization of ALTJ-V35Gy was feasible without compromising the radiation therapy plan quality. CONCLUSIONS:ALTJ-V35Gy < 79.2% may serve as a recommended dose constraint for patients undergoing RNI after ALND. Avoiding excessive radiation to the ALTJ is clinically feasible and safe, potentially mitigating BCRL risk without compromising dose coverage to high-risk nodal regions.

Breast cancer is the most prevalent malignancy among women, posing a significant threat to female health. Radiation therapy serves as a critical component of comprehensive breast cancer treatment, yet its clinical benefit varies substantially across patients with differing recurrence risks. In the era of precision radiation therapy, optimizing the "escalation" or "de-escalation" of radiation therapy regimens based on individualized recurrence risk assessment to maximize net therapeutic benefit for early-stage breast cancer patients has emerged as a key research focus. Previous precision radiation therapy studies for postoperative early-stage pN0 breast cancer primarily centered on treatment de-escalation for low-risk cohorts, while clinical investigations on radiation therapy escalation for high-risk pN0 patients remain scarce. This was a prospective, open-labelled, randomized controlled trial aimed to investigate whether the addition of regional node irradiation (RNI) to whole breast irradiation (WBI)/chest wall irradiation (CWI) could improve disease-free survival in clinical high-risk pN0 breast cancer in comparison to WBI/CWI alone. Clinical high-risk was defined as breast cancer patients presented with two or more high-risk factors [tumor size (>2cm), tumor site (medial and central quadrants), ki-67 level (>14

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.

Acute radiation-induced esophagitis (ARIE) remains a clinically significant toxicity during definitive thoracic radiation therapy (TRT), particularly in patients with close esophagus–planning target volume (PTV) proximity. This study evaluated a risk-adapted, dose-optimized esophagus-sparing (ES) strategy designed to reduce ARIE while maintaining adequate target coverage in high-risk patients. Eighty patients with lung cancer treated with definitive TRT between May 2023 and January 2025 were enrolled. The injury-effective esophagus (IEE) was defined as the local high-risk esophageal segment consisting of the central-IEE and an additional 2-cm superior and inferior cranio-caudal expansion. The central-IEE encompassed all axial levels where PTV–esophagus overlap was present, and the ES region was contoured as the portion of the IEE outside the PTV. Based on the degree of PTV/central-IEE overlap (< 1/3, 1/3–2/3, > 2/3), the ES mean dose was constrained to 1/3, 1/2, and 2/3 of the prescribed dose, respectively. ARIE was graded using Radiation Therapy Oncology Group (RTOG) criteria. Progression-free survival (PFS) was defined from initiation of the TRT to progression or death; overall survival (OS) was also evaluated. Among 80 high-risk patients with the esophagus located within 5 mm of the clinical target volume (CTV), ARIE occurred in 24 patients (30.0

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.

Background: To report the early toxicity and quality assurance of the HARVEST study which was to investigate whether hypofractionated radiotherapy (HF-RT) with regional nodal irradiation (RNI, including internal mammary nodes) is non-inferior to conventional fractionated radiotherapy (CF-RT) for breast cancer. Methods: Breast cancer patients after breast surgery were randomized into the HF-RT group (40.05 Gy/15Fx) or CF-RT group (50 Gy/25Fx). Acute toxicity was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) V.3.0 scale. Cosmetic outcome was assessed using the Harvard scale. Findings: There were 400 and 401 patients enrolled in HF-RT and CF-RT group, respectively. No significant differences were observed in clinical pathological factors between two groups. Protocol compliances were above 90% for targets coverage and OARs constraints in both groups. No significant difference between the two groups in proportion of ≥ grade 2 any acute toxicity (p=0.34). Dermatitis was the most common acute toxicity with a significantly higher incidence in the CF-RT group than the HF-RT group (≥ grade 2: 6.7% vs. 3.3%, p=0.02). There were no significant differences in the incidence of other acute toxicities, including radiation-induced fatigue, radiation pneumonitis, breast pain, dysphagia and breast edema, and the proportion of good or excellent cosmesis in breast conservative patients between the two groups. Interpretation: This early analysis demonstrated that HF-RT with RNI is associated with comparable acute toxicities and cosmesis results compared with CF-RT. Additional follow-up is needed to assess the long-term safety and efficacy.

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.

This multicohort, single-center, phase II trial explored the efficacy and safety of a biomarker-driven total neoadjuvant therapy (TNT) regimen in high-risk locally advanced rectal cancer (LARC) patients. The regimen included induction chemotherapy (4 cycles of mFOLFOX6) with targeted agents (bevacizumab for cohort B and cetuximab for cohort C), followed by short-course radiotherapy (25 Gy/5Fx) and consolidation chemotherapy (2 cycles of mFOLFOX6, with cetuximab in cohort C). The primary endpoint was complete response (CR; sustained clinical CR [cCR] + pathological CR [pCR]). Secondary endpoints included compliance, safety, pathological outcomes, and survival. Between April 2021 and October 2024, 90 of 96 patients completed the prescribed treatment. CR was achieved in 36 (18 in cohort B and 18 in cohort C) patients (40%). No grade IV-V toxicity was observed, although three and 41 patients experienced targeted agent-related adverse effects in cohort B and C, respectively. In the two cohorts, 43 and 38 patients underwent curative surgery with sphincter preservation in 39 (90.7%) and 34 (89.5%) patients, respectively. Postoperative complications occurred in seven (16.3%) and five (13.2%) patients, of whom one (2.6%) patient in cohort C received reoperation. This intensified TNT regimen with targeted agents for high-risk LARC patients achieved a satisfactory CR rate with acceptable toxicities and complications.

This study aimed to analyze the clinical characteristics of metachronous breast cancer bone metastasis (BCBM) and construct a graded prognostic assessment (GPA) model. A retrospective analysis was conducted on the clinical data of newly diagnosed breast cancer patients with bone metastasis (BM). Data collected included initial involvement of bone substructures and metastatic burden other than BM. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA) were used to evaluate the efficacy of the Cox regression model, and a GPA model for overall survival (bmOS) after BM was constructed. The DeLong test was used to compare the area under the curve (AUC) of the training and validation sets to validate the model efficacy. A total of 2103 BMs were detected in 308 patients with metachronous BCBM. The most common sites were the thoracic spine (24.8%), lumbar spine (16.7%), ribs (11.9%), and iliac bone (10.2%); 80.1% of the lesions were osteolytic. Independent prognostic risk factors for bmOS included in the GPA model included initial stage, molecular subtype, time to BM (TTBM), BM numbers, and extraosseous visceral metastases (EVM). The model showed no statistically significant difference in AUC between the training and validation sets (DeLong test, P > 0.05). Patients were divided into three risk strata based on GPA scores (0-8.5), with significant differences in median survival: 60.3, 40.0, and 32.6 months in the training set (P < 0.001), and 64.0, 41.6, and 25.3 months in the validation set (P < 0.001). Initial treatment failure was predominantly due to bone progression (39.3%) and visceral progression (28.2%). In conclusion, the prognosis of patients with metachronous BCBM exhibits significant heterogeneity. The GPA model developed in this study can serve as a practical prognostic assessment tool and provide a reference for individualized treatment planning.

PURPOSE:The multicenter, single-arm, phase 2 SHIFT trial evaluated an ultra-hypofractionated radiation therapy regimen that completes both whole breast irradiation and a sequential tumor bed boost within 1.5 weeks, with the primary endpoint of acute toxicity. METHODS AND MATERIALS:Patients at 4 tertiary hospitals in China aged 18 years or above with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ after BCS were eligible. All enrolled patients underwent whole breast irradiation of 26 Gy in 5 fractions over 5 days. A sequential tumor bed boost of 10.4 Gy in 2 fractions over 2 days was at the discretion of the radiation oncologist. The primary endpoint was the incidence of grade ≥2 acute radiation-induced toxicity within 6 months after RT, including fatigue, dermatitis, and breast pain. This trial is registered at ClinicalTrials.gov (NCT04926766). RESULTS:Between January 2021 and July 2023, recruitment of 217 patients has been completed, of whom 209 received tumor bed boost. Within 6 months after RT, 157 (72.4%) patients experienced G1 acute toxicity only, 16 (7.4%) patients experienced G2 acute toxicity, with no G3 events observed. No toxicity event was reported in 44 (20.3%) patients. At a median follow-up of 28.3 months, no severe toxicities were found in any patient at any time during follow-up. No locoregional recurrence, distant metastasis, or death occurred. Dosimetric analysis demonstrated high protocol compliance across all centers. CONCLUSIONS:The integrated ultra-hypofractionated radiation therapy regimen is well-tolerated, with acute toxicity profiles confirming its favorable safety profile. Long-term follow-up is ongoing to assess late effects and efficacy.

Background Sentinel lymph node biopsy (SLNB) has been the standard treatment procedure for clinically node-negative (cN0) breast cancer (BC). Three randomized trials (Z0011, AMAROS and SENOMAC) have shown that patients with low-burden sentinel lymph node metastasis can be safely omitted axillary lymph node dissection who receive adjuvant radiotherapy. However, these published studies have been insufficient to accurately assess the recurrence risk in this patient population, leading to variability in adjuvant radiotherapy volume across different studies. Objective This study evaluates whether an integrated axillary management strategy combining SLNB with individualized regional nodal irradiation (RNI) based on recurrence risk reduces 2-year lymphedema compared to ALND followed by comprehensive RNI. Materials and Methods This trial is a single institute, open-labeled, non-randomized cohort trial. Participants are stratified into two cohorts based on the extent of axillary surgery after enrollment. For SLNB cohort, patients are divided into three groups according to clinical and genomic risk assessment. Clinically high-risk patients are defined as having at least two factors (tumor size≥2cm, percent of positive SLNs>30%, LVI positive and SLN macro-metastases), who have a predicted risk of n-SLN involvement greater than 30%. Clinically high-risk n-SLN involvement patients are further detected by using RecurIndex test. For pathological node positive (pN+) after ALND cohort, patients are treated with WBI/chest wall irradiation combined with comprehensive RNI excluding the dissected axillary region; A total of 205 patients will be enrolled, with 68 patients in SLNB cohort and 137 patients in ALND cohort with a 1:2 ratio assignment. The RNI precision trial uses a clinical-genomic model to accurately stratify the recurrence risk and provides the individualized RNI volume for early-stage BC with low-burden sentinel lymph node metastasis, and we anticipate that our study will provide high-quality data to potentially support individualized RNI in this patient population.

BackgroundNeoadjuvant chemoradiotherapy (nCRT) is recommended as the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). Adding immunotherapy to nCRT (nICRT) has gained attention in clinical practice. We evaluated the differences in clinicopathologic outcomes and the patterns of lymph node metastasis in patients receiving nCRT and nICRT for locally advanced ESCC.MethodsA total of 208 ESCC patients who completed transthoracic esophagectomy after neoadjuvant treatment were enrolled. Clinicopathologic parameters and the rates of lymph node metastasis in each station classified using both the eighth edition of the American Joint Committee on Cancer (AJCC) esophageal cancer staging system and the 11th edition of the Japanese Classification of Esophageal Cancer (JCEC) standard were recorded and evaluated.ResultsThe rates of pathological complete response (pCR) and major pathological response (MPR) were 44.9% in nICRT vs. 37.0% in nCRT (p = 0.263) and 79.5% in nICRT vs. 65.4% in nCRT (p = 0.024), respectively. The common sites of lymph node metastasis after neoadjuvant treatment were station 112pulL (8.3%), followed by station 104L (4.9%), station 7 (4.5%), and station 3a (4.3%), according to the 11th JCEC standard. Compared with nCRT, nICRT can significantly reduce the rates of lymph node metastasis in station 2R (0.8% vs. 4.6%, p = 0.039) classified using the AJCC system, and those in station 106recR (0.8% vs. 4.6%, p = 0.042) and station 20 (0 vs. 12.5%, p = 0.030) classified using the JCEC standard.ConclusionnICRT followed by surgery may lead to a promising pathological response. For patients with lymph node metastasis in certain regions, nICRT should be considered as a better preoperative treatment option.

Purpose:Intensity-modulated proton therapy (IMPT) significantly reduces mean heart dose (MHD), but data on cardiac substructure dose and toxicity compared to intensity-modulated radiation therapy (IMRT) are limited. This study evaluated dose reduction in cardiac substructures between IMPT and IMRT and assessed cardiac toxicity risks using 2 normal tissue complication probability models. Materials and methods:A retrospective analysis was conducted on 30 breast cancer patients from a randomized trial with the highest MHD receiving IMRT. IMPT plans were created for a prescribed dose of 4005 cGy(RBE) in 15 fractions. Normal tissue complication probability models were used to compare individual acute coronary events (ACEs) risk between IMPT and IMRT. Results:Intensity-modulated proton therapy reduced cardiac substructure doses by 63.34% to 100%, with greater absolute reductions in left-sided and relative reductions in right-sided patients. For left-sided internal mammary node irradiation (IMNI), IMPT achieved an 82.25% reduction for left anterior descending coronary artery (P = .009), 79.45% for RV (P < .001), and over 90% for other substructures. Right-sided patients had near-zero mean doses in most substructures. The Darby model indicates IMPT reduces individual ACE risk by 1.58% to 5.16% for left-sided IMNI (P = .001) and 0.59% to 1.05% for right-sided IMNI (P = .063). The Bogaard model shows a 0.19% to 2.75% reduction in individual 9-year ACE risk-based MHD for left-sided IMNI (P = .0015). Risk reduction variations are influenced by dose reduction and other risk factors. Conclusion:Intensity-modulated proton therapy provides excellent cardiac protection, particularly for left-sided IMNI and high-risk patients.

PURPOSE:To evaluate survival outcomes and prognostic factors in breast cancer patients with clinically positive internal mammary lymph nodes (cIMN+) after combined-modality therapy, and to identify indicators for internal mammary nodal boost irradiation. METHOD:Consecutive cIMN + patients between January 2010 and April 2023 were retrospectively reviewed. According to nodal response to neoadjuvant therapy (NAT), patients were divided into three groups: no IMN clinical complete response (cCR) (Group A), IMN cCR without ALN pathological complete response (pCR) (Group B), both IMN cCR and ALN pCR (Group C). RESULTS:Among 141 eligible patients (median follow-up 49.5 months), the 5-year rates for overall survival (OS) and recurrence-free survival (RFS) were 85.7 % and 76.7 %, respectively. Multivariable analysis confirmed ALN pCR and IMN cCR as independent favorable prognostic factors. Patients in group C exhibited superior 5-year OS (97.4 % vs. 88.9 % vs. 71.0 %, p = 0.007) and RFS (93.9 % vs. 71.8 % vs. 61.4 %, p < 0.001), along with the lowest rate of distant metastasis (5.8 % vs. 22.7 % vs. 33.3 %, p = 0.003) compared to Groups B and A. In Group A patients, higher cumulative radiation dose (≥60 Gy) to IMN significantly improved both 5-year OS (71.0 % vs. 93.5 %, p = 0.009) and 5-year RFS (33.3 % vs. 69.3 %, p = 0.031). CONCLUSION:The dual achievement of IMN cCR and ALN pCR after NAT predicts exceptional outcomes. For patients with persistent IMN involvement after NAT, IMN dose escalation to ≥60 Gy significantly improved OS and RFS. These findings support individualized radiotherapy strategies based on nodal response.

INTRODUCTION:Oesophageal squamous cell carcinoma (ESCC) ranks among the most aggressive malignancies and carries a poor prognosis. Lymphocytes play a key role in combating infections and suppressing tumourigenesis. Many studies have established a close association between lymphocyte depletion and adverse therapeutic outcomes in oesophageal cancer. Nevertheless, high-quality data validating the clinical efficacy and safety of lymphocyte-sparing thoracic radiotherapy regimens for ESCC remain scarce. MATERIALS AND METHODS:This prospective, open-label, randomised controlled trial aims to determine whether lympho-nTRT-ESO reduces the incidence of acute grade 3-4 lymphopaenia in patients with ESCC undergoing neoadjuvant chemoradiotherapy (nCRT), compared with conventional thoracic radiotherapy (RT). A total of 212 participants will be enrolled and randomly allocated in a 1:1 ratio to either the lymphocyte-sparing RT (RT) group or the conventional RT group. All patients will receive standardised nCRT, which will deliver a total dose of 41.4 Gy in 23 fractions. For the lymphocyte-sparing RT group, RT planning prioritises the planning target volume (PTV) coverage and conventional organ-at-risk (OAR) constraints while applying dose constraints to lymphocyte-related OARs (LOARs). These LOARs include the T1-T12 vertebral bodies, ribs, spleen and major cardiovascular structures (heart and large blood vessels), with optimisation performed only after PTV coverage and standard OAR constraints are satisfied. ETHICS AND DISSEMINATION:This trial was approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (RJ 2024-210) on 11 July 2024 and registered on ClinicalTrials.gov (NCT06596954) before participant recruitment. All participants should provide written informed consent to be eligible. We planed to publish the primary and secondary results of this study in scientific peer-reviewed journals and present at radiation oncology conferences. TRIAL REGISTRATION NUMBER:NCT06596954.

Background:Leptomeningeal metastasis (LM) in non-small cell lung cancer (NSCLC) is a highly aggressive malignancy associated with poor prognosis and limited therapeutic efficacy. Currently, effective treatment options remain scarce. Although immunotherapy has revolutionised the treatment of NSCLC, its role in LM remains underexplored, and its efficacy as monotherapy is suboptimal. Preclinical and clinical studies suggest that combining programmed cell death protein 1 (PD-1) inhibitors with radiotherapy or granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance antitumor immunity. The combination therapy of stereotactic radiotherapy (SRT), PD-1 inhibitor and GM-CSF is an emerging treatment strategy currently under investigation in various advanced solid tumors, with a growing number of evidence demonstrating promising efficacy and tolerability. This case report offers novel insights and a potential therapeutic strategy for patients with NSCLC and LMs, highlighting the possibility of achieving remarkable and durable response through this combined approach. Case Description:We present the case of a 56-year-old male diagnosed with epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative NSCLC with concurrent brain parenchymal and LMs. After disease progression on first-line chemotherapy, he received second-line therapy consisting of SRT targeting dominant brain metastases, combined with a PD-1 inhibitor and GM-CSF. Remarkably, all lesions including the LMs, achieved complete resolution, with a progression-free survival (PFS) of 69 months to date. Conclusions:Patients with NSCLC and LMs historically face a devastating prognosis, with median survival often limited to weeks. In this case, however, the patient achieved a remarkable PFS of over 4 years following a multimodal regimen combining SRT, PD-1 inhibition, and GM-CSF. This tri-modality strategy emerges as a promising therapeutic paradigm for NSCLC-associated LM.