ABSTRACT Purpose This study aimed to assess the efficacy and safety of intensity‐modulated radiotherapy (IMRT) combined with regorafenib with or without immune checkpoint inhibitors (ICIs) as a second‐ or later‐line treatment for advanced hepatocellular carcinoma (HCC). Materials and Methods Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus ICIs after failures of at least one line of systemic treatment in a single center from April 2018 to August 2022 were retrospectively reviewed. Progression‐free survival (PFS) was the primary endpoint, while overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints. Results Fifty patients were included, with 44 (88.0%) in BCLC stage C, 37 (74.0%) having portal vein tumor thrombosis (PVTT), and 12 (24.0%) with extrahepatic metastasis. Thirty‐eight patients received conventional fractionated RT (56.4Gy/22–28f), while 12 received hyperfractionated RT (50Gy/5–10f). Twenty‐six were treated concurrently with regorafenib and 24 sequentially. ICIs were applied in 34 patients. For the entire cohort, when measured from the start of RT initiation, the median PFS and OS were 10.9 months and not reached. The corresponding 2‐year PFS and OS rates were 25.3% and 53.5%, respectively. When assessed from regorafenib initiation, the median PFS and OS were 5.9 months and not reached, with 2‐year PFS and OS rates of 22.8% and 54.9%, respectively. For tumors in the RT field, the ORR was 74.0% (RECIST) and 92.0% (mRECIST). The most common grade 3 toxicities were hand‐foot syndrome (16.0%), thrombocytopenia (8.0%), dermatitis (8.0%), and transaminase elevation (6.0%). Conclusion IMRT concurrently or sequentially combined with regorafenib with or without ICIs is an effective, well‐tolerated, and promising regimen as second‐line or further‐line treatment in patients with advanced HCC.

BACKGROUND:Segmentation is the most effort-consuming step for magnetic resonance imaging guided adaptive radiotherapy (MRIgART). Although the segment anything model (SAM) exhibits impressive capabilities, its application in medical imaging necessitates clicks, bounding boxes, or providing mask prompts on each target image, which would still require complex human interactions. PURPOSE:This study introduces SAM-ART, a large vision model that integrates personalized information to enhance the segmentation accuracy of MRIgART. METHODS:This study utilized planning computed tomography (pCT), approved contours, and daily MRI (dMRI) from 38 patients with prostate cancer and 10 patients with rectal cancer. SAM-ART comprises an image encoder, a prompt encoder, and a mask decoder. Using mask and box prompts, SAM-ART propagates contours from pCT to dMRI using deformable image registration (DIR) and employs them as mask prompts, providing patient-specific information. The box prompts are used in slices prone to false negative (FN) predictions. A 5-fold cross-validation was then conducted, comparing SAM-ART with DIR, traditional deep learning (tDL), and SAM-ART using other manual prompts (point or box). RESULTS:The proposed SAM-ART exhibited a mean dice similarity coefficient of 0.934 ± 0.023 for the regions of interest, surpassing DIR (0.873 ± 0.063) and tDL (0.887 ± 0.056). Moreover, the proposed mask/box prompts also outperformed the other modes (point: 0.910 ± 0.027, and box: 0.921 ± 0.025). Mask/box prompts effectively mitigated FN predictions with minimal manual intervention. The ratio of acceptable slices (using the criteria of dice ≥ 0.85, 95th percentile of Hausdorff distance ≤ 5 mm, and mean distance to agreement ≤ 1.5 mm) was 89.38% with the proposed method, which means that the segmentations on about 90% of the slices did not require manual modification. CONCLUSIONS:This study proposed a novel method that integrates personalized information and manual prompts into a SAM-based segmentation model. It outperformed the baseline methods, with only a few contours needing to be revised for clinical use.

Accurate motion tracking in magnetic resonance imaging-guided radiotherapy (MRIgRT) is essential for effective treatment delivery. This study aimed to enhance motion tracking precision in MRIgRT through an automatic real-time markerless tracking method using an enhanced Tracking-Learning-Detection (ETLD) framework combined with automatic segmentation, eliminating the need for pre-training. We developed a novel motion tracking and segmentation method by integrating the ETLD framework with an improved Chan-Vese (ICV) model, termed ETLD + ICV. The ETLD framework was upgraded for real-time MRIgRT, including search process optimization, an enhanced median-flow tracker, and dynamic detection region adjustments. It receives 3.5D MRI data as input and outputs the location prediction of the target volume for each frame. Based on this, ICV was used for precise target volume coverage, refining the segmented region frame by frame using tracking results, with optimized key parameters. The method requires no pre-training and was tested on 3.5D MRI scans from 10 patients with liver metastases. No-reference image quality assessment and manual verification were used to filter out low-quality image data. Comprehensive statistical analyses were performed to assess the statistical significance of differences between experimental outcomes (p < 0.05). In addition, comparative experiments based on an external benchmark dataset were conducted to further evaluate the performance of the proposed method. Evaluation across 106,000 frames from 77 treatment fractions demonstrated sub-millimeter tracking errors of less than 0.8 mm, with over 99

Accurately predicting axillary pathological complete response (ypN0) after neoadjuvant chemotherapy (NACT) is of vital importance for making decisions regarding the axillary treatment plan for breast cancer patients. This study aimed to identify factors influencing ypN0 and to develop a predictive nomogram to evaluate the probability of ypN0 in NACT-treated patients with breast cancer. Overall, 1559 patients with cT1-4N1-2M0 breast cancer who received NACT and mastectomy between 2000 and 2014 in 12 institutions in China were analyzed retrospectively. Patients treated in three cancer hospitals (training set, n = 1072) were used to construct a nomogram based on multivariate logistic regression analyses. The nomogram was validated by determining the area under the receiver operating characteristic curve (AUC) and calibration curve values in patients from nine other general hospitals (validation set, n = 487). In the training and validation sets, 26.8

Objective.Current automatic segmentation models in radiotherapy, which are predominantly unimodal and image-based, have limited generalizability due to boundary ambiguity and the lack of guideline integration. This study proposes a text-guided segmentation network, termed (TG-SegNet), for the automatic delineation of clinical target volumes (CTVs) in rectal cancer radiotherapy.Approach.Data from 567 preoperative patients with rectal cancer were retrospectively collected. Text prompts contained (i) patient case information (age, sex, tumor stage, tumor location, position) and (ii) guideline-derived descriptions indicating which CTV subsites should be included. TG-SegNet integrates computed tomography-derived visual features with structured clinical text prompts encoded by PubMedBERT, fused via cross-attention and fine-grained fusion. The model was trained on 452 patients and tested on 115. Its performance was compared with that of nnU-Net and two ablated variants (TG-SegNet without text prompts and TG-SegNet with simplified fusion). The evaluation comprised quantitative metrics, including dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), mean surface distance (MSD), surface DSC (S-DSC), and average path length (APL), along with blinded expert scoring and an efficiency analysis. In additional analyses, we conducted text-prompt and module ablations.Main results.TG-SegNet achieved the best performance across all quantitative metrics: DSC 0.927 ± 0.022, HD95 7.01 ± 6.05 mm, MSD 1.94 ± 1.08 mm, S-DSC 0.799 ± 0.074, and APL 7372 ± 4452 (allp< 0.01). In clinical evaluation, TG-SegNet significantly improved target coverage, guideline adherence, and overall clinical acceptability compared with nnU-Net and ablations (p< 0.05), with boundary appropriateness comparable to nnU-Net. TG-SegNet had the shortest correction time (3.39 ± 1.10 min), corresponding to 82.1% time savings versus manual delineation. Text-prompt ablations suggested that the CTV-subsite prompt component contributed more to performance. Module ablations showed that both cross-attention and fine-grained fusion were beneficial.Significance.By integrating clinical semantics with imaging, TG-SegNet demonstrated superior accuracy, efficiency, and clinical acceptability over nnU-Net and ablated models, highlighting its potential for clinical translation.

PURPOSE:To compare the safety and efficacy of preoperative simultaneous integrated boost chemoradiation therapy (SIB-CRT) versus standard chemoradiation therapy (CRT) for locally advanced rectal cancer. METHODS AND MATERIALS:This prospective, randomized phase II trial (NCT02195141) enrolled patients with stage II/III rectal adenocarcinoma. Patients were randomly assigned (1:1) to CRT (50 Gy/25 fx to the pelvis) or SIB-CRT (50 Gy/25 fx to the pelvis with a simultaneous integrated boost of 56 Gy to PGTV and 60 Gy to lateral metastatic nodes if present). Radical surgery was planned 6-8 weeks after CRT. The primary endpoint was pathologic complete response (pCR) rate; secondary endpoints were disease-free survival (DFS), overall survival, metastasis-free survival, local control, cancer-specific survival, and toxicity. RESULTS:From August 2013 to February 2015, 106 patients were enrolled: 55 in the SIB-CRT group and 51 in the CRT group. Acute grade 3 toxicity occurred in 14.5% (SIB-CRT) and 19.6% (CRT) of patients, primarily manifested as radiation dermatitis. Curative treatment (radical surgery or watch-and-wait) was achieved in 89.1% (49/55) of SIB-CRT patients and 78.4% (40/51) of CRT patients (P = .135). After a median follow-up of 116.6 months, the SIB-CRT group showed superior 9-year outcomes in the intention-to-treat population: DFS (70.8% vs 47.4%; hazard ratio [HR], 0.46; P = .013), overall survival (74.3% vs 48.9%; HR, 0.43; P = .008), metastasis-free survival (70.8% vs 47.2%; HR, 0.48; P = .017), local control (87.1% vs 70.1%; HR, 0.40; P = .038) and cancer-specific survival (77.4% vs 57.2%, P = .027). Similar benefits were observed in the curative treatment cohort. The pCR rates were comparable (15.2% vs 18.4%, P = .695). Exploratory subgroup analysis showed that the survival benefit of SIB-CRT was statistically significant in patients who did not receive perioperative chemotherapy (9-year DFS, 70.8%; HR, 0.343; P = .014), whereas no additional benefit was observed in those receiving chemotherapy. CONCLUSIONS:Dose escalation through simultaneous integrated boost during neoadjuvant CRT translates into superior long-term survival outcomes. Despite comparable pCR rates, the intensified control of both local disease and micrometastases by SIB-CRT, coupled with its significant superiority within the chemotherapy-naive subgroup, likely contributed to these robust results. These findings establish dose escalation as a potent strategy for optimizing long-term cure in the modern management of locally advanced rectal cancer, particularly in chemotherapy-ineligible patients.

Purpose:Deep inspiration breath-hold (DIBH) is widely used in breast cancer radiation therapy to reduce cardiac radiation exposure. However, not all patients benefit from it. This study evaluated the performance of a convolutional neural network (CNN) model to predict cardiac doses under free-breathing (FB) and DIBH conditions for left-sided breast cancer radiation therapy, aiming to identify patients most likely to benefit from DIBH based on cardiac dosimetry. Methods and Materials:A total of 265 left-sided breast cancer patients undergoing whole-breast irradiation were included, with 200 retrospectively assigned to the training set and 65 prospectively assigned to the test set. The CNN model incorporated anatomic data, including organ structures and distance-to-target volume maps, to predict 3-dimensional dose distributions. Predicted dosimetric parameters were compared with clinical data to assess accuracy, and agreement between model-based and clinical classifications of DIBH benefit was evaluated using kappa statistics. Results:The CNN model demonstrated high accuracy in predicting cardiac dosimetric parameters, with correlation coefficients ranging from 0.84 to 0.99 for mean dose (Dmean) and D2% in the heart, left anterior descending coronary artery, and ventricles under both FB and DIBH conditions. The model also accurately predicted dose-volume histograms for these structures, with no significant differences between clinical and predicted values. Using a classification approach based on heart Dmean in FB and its reduction via DIBH, the model correctly identified 90.8% of patients as DIBH beneficiaries (kappa value, 0.876). When applying a threshold of ΔHeart Dmean ≥1 Gy, the model identified significant DIBH benefits in 63.1% of patients, with 96.9% agreement between predicted and clinical classifications. Conclusions:The CNN-based model provides an efficient and accurate framework for predicting cardiac dose and identifying patients most likely to benefit from DIBH. Future studies should explore its applicability across broader radiation therapy scenarios and evaluate its long-term impact on cardiac outcomes.

The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial. This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression. Group 4 achieved the highest 5-year OS (82.1

The incidence of Prostate cancer (PC) has risen steadily in China, and hypofractionated radiotherapy offers a biologically advantageous and time-efficient treatment strategy. However, long-term data in Chinese populations are limited. This study evaluated the 10-year outcomes of hypofractionated radiotherapy regimen (45 Gy in 9 fractions) for localized PC. A propensity score–matched comparison was conducted to contextualize its effectiveness and toxicity relative to a moderately hypofractionated regimen. From October 2011 to April 2017, thirty patients with localized PC who received hypofractionated radiotherapy (45 Gy in 9 fractions) were enrolled in this prospective trial. Ninety-five patients treated with a moderately hypofractionated regimen at the same center between February 2009 and October 2019 were selected. The propensity score matching (PSM) was applied to balance the potential confounding bias. Survival outcomes were analyzed using the Kaplan–Meier method. Genitourinary (GU) and gastrointestinal (GI) toxicities (grade ≥ 2) were assessed using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 3.0) and Radiation Therapy Oncology Group late morbidity criteria. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), biochemical recurrence-free survival (bRFS), PC-specific survival (PCSS), and GU and GI toxicities. After a median follow-up of 10.3 years, patients treated with the 45 Gy in 9 fractions regimen achieved favorable long-term outcomes, with the 10-year PFS, bRFS, and OS rates of 78.1

Intensity-modulated radiation therapy (IMRT) may reduce mortality in patients with squamous cell carcinoma of the anus (SCCA), but there are limited data in long-term outcomes. This study reported 5-year outcomes in SCCA patients treated with IMRT-based definitive chemoradiation. Sixty-five consecutive patients with T1-4N0-3M0 SCCA treated with IMRT-based concurrent chemoradiation (CCRT) from Jan 1, 2010, were retrospectively reviewed. Treatment outcomes included overall survival (OS), disease-free survival (DFS), anal cancer-specific mortality (ACSM), local-regional failure (LRF), distant metastasis (DM) and colostomy failure (CF), late toxicity and anorectal function. The patients had a median age of 52 years; 70.8

BACKGROUND:Accurate delineation of target volumes and organs-at-risk (OARs) is a critical yet labor-intensive component of rectal cancer radiotherapy. While deep learning (DL)-based automatic contouring systems are increasingly used to address inter-observer variability and improve efficiency, artificial intelligence models require rigorous quality assurance and updates to reflect current technology. However, high-level evidence regarding the longitudinal real-world impact of implementing and iteratively updating these systems in clinical workflows is currently lacking. PURPOSE:This study aimed to evaluate the real-world clinical impact of implementing and updating a DL-based automatic contouring system in rectal cancer radiotherapy to generate high-quality evidence of iterative updates. METHODS:This longitudinal retrospective analysis included 150 patients divided into three cohorts: pre-implementation (n1 = 50), post-implementation (n2 = 50), and post-update (n3 = 50). Geometric similarities between unedited-automatic and final treatment contours were compared across cohorts. Failure rates were systematically analyzed. Six oncologists contoured 21 additional cases through manual, first-generation (Auto1), and second-generation (Auto2) system-assisted methods to evaluate contouring time, inter-observer consistency, and accuracy. Additionally, a 5-point Likert scale was used by two blinded senior oncologists to assess the clinical acceptability of the generated contours. RESULTS:The mean Dice similarity coefficient (DSC) values of clinical target volume (CTV) before and after implementing the automatic contouring system were 0.87 ± 0.04 and 0.88 ± 0.04 (P = 0.067), while those of OARs were 0.80 ± 0.06 and 0.88 ± 0.05 (P < 0.001), respectively. Following the system update, they improved from 0.88 ± 0.04 to 0.93 ± 0.04 for CTV (P < 0.001) and from 0.88 ± 0.05 to 0.95 ± 0.02 for OARs (P < 0.001). The system update achieved an approximately 80.6% reduction in the mean failure rate. Auto2-assisted method decreased the total time by approximately 58.8% compared with the manual method, and 21.9% compared with the Auto1-assisted method. This method also demonstrated optimal inter-observer consistency (0.95 ± 0.03) and accuracy (0.94 ± 0.03) for CTV. In the blinded clinical evaluation, 99.2% (125/126) of the oncologist-revised final contours received a Likert score of ≥ 4, and Auto2-generated unedited contours showed significantly higher clinical acceptability than Auto1 (4.02 ± 0.25 vs. 3.26 ± 0.49, P < 0.001) CONCLUSIONS: Implementing an automatic contouring system provided crucial guidance for clinical practice. Its iterative update significantly reduced workload and inter-observer variation while enhancing contouring efficiency and quality.

Background: The aim of the study was to determine the interactive effect of age on overall survival (OS) and relative survival (RS) benefits of radiotherapy (RT) in early-stage diffuse large B-cell lymphoma (DLBCL). Methods: Data for 10,841 adults with early-stage DLBCL from the Surveillance, Epidemiology, and End Results database between 2002 and 2015 were retrospectively analyzed. Primary therapy was classified as combined-modality treatment (CMT; n = 3,631) and chemotherapy alone (n = 7,210). Inverse probability of treatment weighting was used to balance covariate distribution between the treatment groups. Survival was estimated and compared using the Kaplan-Mei er method and log-rank test, respectively. Age-RT interactive effect on survival was examined through Cox regression multiplicative interaction analysis. Results: Using age of 60 years as the reference, older age was an independent predictor of shorter OS in the multivariable Cox model (hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.06-1.07; P < 0.001). After controlling for background mortality, older age was not an independent predictor of RS (HR, 1.00; 95% CI, 0.99-1.00; P = 0.842). Across all age groups, patients treated with CMT had better OS and RS than those who received chemotherapy alone. A significant interaction between age and RT was identified for both OS (Pinteraction = 0.020) and RS (Pinteraction = 0.038), indicating greater RT benefit in young patients. A linear correlation existed between RS and OS at the treatment arm level. Conclusions: RT was associated with improved net survival across all ages, particularly for young adults. RS was a valid alternative endpoint for prognostication and benefit evaluation.

In adult patients with early-stage follicular lymphoma (FL), age-related differences in the risk of non-lymphoma-related death (LRD) during the follow-up period after treatment are unclear. We aimed to investigate the interactive effects of age and primary treatment on the risk of non-LRD and survival. We retrospectively analyzed the data of 6030 adult patients with early-stage FL from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2020). Primary therapy involved observation (n = 2509), chemotherapy (CT) alone (n = 1844), radiotherapy alone (RT, n = 1191) or RT and CT (RT + CT, n = 486). The groups were balanced by inverse probability of treatment weighting (IPTW). Comparisons of the cumulative incidence of non-LRD were performed using competing-risk analysis and transformed Cox regression analysis. The median patient age was 64 years (RT, 62 years; RT + CT, 60 years; CT, 63 years; observation, 66 years). Over a median follow-up period of 132 months, 830 patients (13.8

Purpose:To evaluate the influence of Lipiodol area on radiotherapy dose distribution in the photon-beam treatment planning system (TPS) and develop a new simulation model of Lipiodol deposition in patients with hepatocellular carcinoma (HCC). Patients and Materials:We developed a Lipiodol deposition simulation model (LDSM) using a Lipiodol-porcine liver mixture to simulate the Lipiodol area after transcatheter arterial chemoembolization (TACE). The dose calculated by the TPS (DTPS) and the detected dose (DDET) using 6 MV X-ray irradiation using different fractional doses (1-10 Gy/f) delivered by flattening-filter (FF) or flattening-filter-free (FFF) beams were compared. The computed tomography (CT) images of 60 patients with HCC who had undergone TACE were retrospectively reviewed and subjected to relative electron density (RED) correction and dosimetric evaluation. The dose deviation was evaluated across different TPS platforms and calculation algorithms. Results:In the Pinnacle3 TPS with the collapsed cone convolution algorithm, the LDSM revealed a dose underestimation due to Lipiodol area in the photon-beam TPS, with the dose deviation factor (δ) increasing with increasing Lipiodol concentration (p < 0.001). The effects of FF and FFF beams ranged from 0.3% to 4.3% and 0.5% to 5.7%, respectively, but dose deviation was not correlated with fractional dose. In patients' re-evaluated radiotherapy plans, the prescription dose coverage of gross tumor volume improved by a mean of 3.42% ± 0.92% (range, 2.00-4.99%). The 50% prescription dose coverage of normal liver increased by 0.72% ± 0.36% (range, 0-1.3%), and the maximum dose (DMAX) to gastrointestinal tissue increased by 183.22 ± 138.80 cGy (range, 2.00-453.00 cGy). The shortest distance between the tumor and the gastrointestinal tissue was an independent predictor of gastrointestinal dosimetric deviation. Conclusion:After TACE, Lipiodol area has a clinically significant dosimetric effect leading to the TPS underestimating the gastrointestinal DMAX delivered by the photon-beam. The dosimetric deviations should be corrected, especially in the TPS with the convolution algorithm.

Background and Purpose:The optimal management of early-stage follicular lymphoma (FL) remains an active research area, particularly in China. This retrospective cohort study examined long-term survival outcomes, recurrence patterns, and potential prognostic factors in patients with early-stage FL. Materials and Methods:We retrospectively analyzed 107 patients diagnosed with early-stage FL between 2000 and 2020 at the National Cancer Center in China. Treatment modalities included radiotherapy with or without chemoimmunotherapy or chemotherapy, chemoimmunotherapy or chemotherapy, and observation. Overall survival, progression-free survival, and lymphoma-specific survival were assessed using the Kaplan-Meier method and Cox regression models. We evaluated failure patterns, including locoregional and systemic failures, using cumulative incidence analysis with competing risks. Exploratory LASSO regression and machine learning-based approaches were applied to identify potential prognostic factors. Results:The median age was 53 years, and the median follow-up was 86 months. In this 20-year real-world cohort from the National Cancer Center of China (n = 107), long-term outcomes were favorable, with 5- and 10-year rates of 88.7% and 68.8% for OS, 93.3% and 89.9% for LSS, and 76.0% and 57.2% for PFS. No statistically significant differences in survival or cumulative failure were observed across initial management strategies, including radiotherapy with or without systemic therapy, systemic therapy alone, and observation. Recurrence occurred in 21 patients (19.6%), predominantly locoregional (14 locoregional only vs. 6 systemic only; 1 both). The 5- and 10-year cumulative incidences were 16.3% and 19.5% for overall failure, 14.5% and 16.2% for locoregional failure, and 3.1% and 4.8% for systemic failure. POD24 occurred in 6.5% of patients and was associated with inferior OS, although event numbers were limited. Low neutrophil-to-lymphocyte ratio (NLR <1.8) was associated with poorer survival in exploratory analyses. Conclusion:Patients with early-stage FL in this 20-year real-world Chinese cohort demonstrated an overall favorable long-term prognosis across diverse initial management strategies. No treatment modality showed a clear survival advantage in this limited-size cohort, while relapse was uncommon and more frequently locoregional than systemic. POD24 identified a small subset of patients with inferior survival, highlighting the need for individualized, risk-adapted management and long-term follow-up.

Background With the growing adoption of 5-fraction ultra-hypofractionated radiotherapy (uHFRT) following breast-conserving surgery (BCS), in-treatment breast edema has been increasingly observed. Marked edema may impair target dose coverage and even necessitate radiotherapy interruption. This study aimed to investigate the incidence, evolution and risk factors of this acute adverse event. Methods Patients treated with BCS were enrolled in a prospective phase II trial of uHFRT. Patients received whole-breast irradiation (WBI) at 26 Gy in 5 fractions, with or without simultaneous integrated tumor-bed boost (SIB) of 30 Gy, delivered daily or on alternate days. Cone-beam CT (CBCT) was acquired prior to each fraction. Acute breast edema was defined as outward expansion of the breast contour exceeding 1 mm relative to the planning CT. Clinical and target volume parameters were analyzed to identify risk factors. Results Among 221 patients (224 breasts), edema occurred in 83 breasts (37.1%), with 96.4% developing after the first fraction. The prevalence of edema was 35.7%, 36.6%, 37.1%, and 35.3% at the 2nd to 5th pretreatment CBCT scans, respectively. Edema peaked after the first fraction in 42 swelling breasts (50.6%). Contour expansion was >3–5 mm in 19.6%, >5–8 mm in 7.1%, >8–10 mm in 1.8%, and > 10 mm in 0.9% of all breasts. Multivariate analysis indentified younger age and greater breast thickness as significant factors associated with the occurrence of in-treatment breast edema. Furthermore, breast thickness was positively associated with edema severity. Conclusions The incidence of acute in-treatment breast edema during uHFRT after BCS was 37.1%, with onset immediately after the first fraction in 96.4% of affected cases. Contour expansion >5 mm was observed in 9.8% of the entire cohort. Given the short treatment course and high single-fraction dose, early-onset edema may impair treatment efficacy. Close surveillance and timely intervention are warranted for high-risk patients.

This updated analysis of the STELLAR trial reports 5-year outcomes comparing short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy [TNT]) with standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients with distal or middle-third LARC were randomly assigned to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) was 62.0% in the TNT group and 58.7% in the CRT group, with a hazard ratio (HR) for DFS of 0.849 (95% CI, 0.662 to 1.089). Five-year overall survival (OS) was significantly higher with TNT (78.1% v 69.7%; HR, 0.739 [95% CI, 0.550 to 0.993]). Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the two groups. In high-risk patients (per European Society for Medical Oncology criteria), TNT was associated with improved OS (HR, 0.663 [95% CI, 0.469 to 0.937]) and showed a nonsignificant trend toward improved DFS (HR, 0.765 [95% CI, 0.568 to 1.032]). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR, 0.691 [95% CI, 0.497 to 0.961]) and postrecurrence survival (HR, 0.698 [95% CI, 0.490 to 0.994]). These results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to CRT, especially in patients with high-risk disease.

BACKGROUND:To investigate the prognostic and treatment values of maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) in early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). METHODS:MTV and SUVmax of the primary tumor in 122 patients with early-stage ENKTCL were measured. The prognostic capacity of MTV and SUVmax and their implications for treatment selection were evaluated. Potential mechanisms of MTV and SUVmax were evaluated through transcriptome analysis of tumors in 16 patients. RESULTS:Patients with high-SUVmax or large-MTV were more likely to have adverse clinical factors. Both SUVmax and MTV were associated with overall survival (OS) in univariate analysis (P = 0.029 and 0.001, respectively). MTV was independently associated with OS (P = 0.027), and mediation analysis suggested that distant metastasis statistically accounted for 98.2% of this association. In the intermediate- and high-risk early-stage subgroup, patients with MTV < 50 mL had significantly better OS and progression-free survival (PFS) (both P = 0.002) than those with MTV ≥ 50 mL, but showed survival outcomes comparable to low-risk early-stage patients. Furthermore, radiotherapy and combined-modality therapy (CMT) yielded comparable PFS (P = 0.268) and OS (P = 0.570) in patients with MTV < 50 mL. In contrast, for patients with MTV ≥ 50 mL, CMT resulted in better PFS and OS (both P < 0.001) compared to RT alone. CONCLUSION:MTV is an independent metabolic predictor of survival and may identify patients who are more likely to benefit from CMT in early-stage ENKTCL. Further prospective validation is warranted.

Optimal neoadjuvant strategies for locally advanced gastric cancer (LAGC) remain contentious. The purpose of this study was to compare the survival prognosis and safety of LAGC receiving three different neoadjuvant modalities. In this multicenter retrospective cohort, 670 patients with LAGC (Jan 2012 - Dec 2022) receiving neoadjuvant therapy followed by curative-intent gastrectomy were analyzed. Three cohorts were compared: neoadjuvant chemotherapy alone (NAC, n = 339), neoadjuvant chemoimmunotherapy (NACI, n = 233), and neoadjuvant chemoradiotherapy (NACRT, n = 98). Primary endpoints were overall survival (OS) and disease-free survival (DFS); secondary endpoints included local-regional control (LC), distant metastasis-free survival (DMFS), pathological complete response (pCR) and toxicity (CTCAE v5.0). Survival analyses used Kaplan-Meier/log-rank tests; Cox regression assessed hazard ratios (HRs); the categorical endpoints were analyzed by Chi-square or Fisher’s exact tests based on expected frequencies; significance was P < 0.05. The NACRT group achieved significantly higher pCR rates (26.5

PURPOSE:To characterize the long-term endoscopic natural history of chronic radiation proctitis (CRP) and identify predictors of severe lesions in patients with locally advanced rectal cancer from the STELLAR study (NCT02533271) . METHODS AND MATERIALS:This secondary analysis included 74 patients with locally advanced rectal cancer undergoing anal-preserving surgery after neoadjuvant therapy (39: short-course radiation therapy/total neoadjuvant therapy [TNT] and 35: long-course chemoradiation therapy [CRT]). Systematic endoscopic follow-up (>2 years) was performed, with mucosal damage graded by the Vienna Rectoscopy Score (VRS). Multivariate analyses identified factors for severe (VRS ≥3) and persistent severe CRP. RESULTS:The incidence of VRS ≥3 CRP was 33.3% (TNT) versus 20.0% (CRT) (P = .197). Endoscopic severity peaked at 2 years after radiation. A distinct recovery trend was observed in the TNT group, but not in the CRT group. Diabetes mellitus was an independent risk factor for both severe CRP (hazard ratio [HR], 5.46; 95% CI, 1.25-23.89; P = .024) and persistent severe CRP (HR, 6.09; 95% CI, 1.23-30.23; P = .027). Eastern Cooperative Oncology Group performance status 1 predicted persistent severe CRP (HR, 8.81; 95% CI, 1.50-51.68; P = .016). DISCUSSION:Hypofractionated radiation therapy (TNT) did not increase severe CRP risk and showed a favorable recovery pattern. Diabetes and reduced performance status are strong, independent predictors of severe and persistent endoscopic injury, enabling risk-stratified patient management. These findings support tailored surveillance and preventive strategies for high-risk individuals.