International Journal Of Radiation Oncology, Biology, Physics[JOURNAL]
Sun
200 papers
Long-Term Outcomes After Proton Therapy Versus Intensity Modulated Photon Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: Post Hoc Analysis of a Prospective Randomized Trial.
Su T, Xu T, Chen M … +24 more , Chen X, Nguyen QN, Chun SG, Lin SH, Chang JY, Heymach JV, Tsao A, Deswal A, Koutroumpakis E, Qian D, Bronk J, Ning M, Chen A, O'Reilly M, Gandhi S, Fossella FV, Blumenschein GR, Vaporciyan AA, Swisher SG, Lu CS, Mohan R, Zhang X, Lee JJ, Liao Z
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42173326 · Publisher ↗
PURPOSE: To report long-term toxicity and disease outcomes from a randomized trial comparing passive scattering proton therapy (PSPT) and intensity modulated photon radiation therapy (IMRT), both with concurrent chemothe...
PURPOSE: To report long-term toxicity and disease outcomes from a randomized trial comparing passive scattering proton therapy (PSPT) and intensity modulated photon radiation therapy (IMRT), both with concurrent chemotherapy, for non-small cell lung cancer. METHODS AND MATERIALS: One hundred forty-nine patients with locally advanced non-small cell lung cancer were randomly assigned to IMRT or PSPT; 147 completed the assigned treatment. Local failure, radiation pneumonitis (RP), major adverse cardiac events (MACEs), long-term esophageal toxicity, and survival were estimated and compared between IMRT and PSPT. Risk factors for each endpoint were analyzed using Cox proportional hazards regression or competing-risks regression. RESULTS: The median follow-up time was 28.5 months (29.7 months IMRT, 26.2 months PSPT); 7 patients were lost to follow-up. Grade ≥3 RP was experienced by 10 patients in the IMRT group (10.9%) and 6 in the PSPT group (10.5%; P = .98); 2 patients treated with IMRT and no patients treated with PSPT had grade 5 RP. Pre-existing pulmonary disease and mean lung dose were found to be associated with grade ≥3 RP. Esophageal toxicity rates did not differ between groups and consisted of 7 grade 3 strictures and 1 secondary cancer. Of the 10 definitely/possibly radiation-related MACEs, 1 was in PSPT, and 9 were in IMRT; doses to coronary arteries may have been associated with MACE. No differences were found in local failure or progression-free survival. Tumor volume and radiation dose influenced survival outcomes. CONCLUSIONS: When both IMRT and PSPT plans met dose-volume constraints for the lung, no differences were found in lung toxicity or local failure after IMRT versus PSPT, consistent with our original findings. PSPT led to fewer cases of radiation-related MACE, presumably from reduced radiation dose to the coronary arteries. Survival outcomes were comparable to those of Radiation Therapy Oncology Group 0617, a phase 3 trial that included only patients with stage IIB to IIIA disease and good performance status.
Radiation Therapy De-escalation in Breast Cancer Patients With Pathologic Complete Response: An Integrated Analysis Using Real-World and Simulated Data.
Wang J, Ning J, Shaitelman SF … +3 more , Lin HY, Bedrosian I, Shen Y
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42173325 · Full text
PURPOSE: Advances in neoadjuvant chemotherapy (NAC) have markedly increased pathologic complete response (pCR) rates in breast cancer, prompting re-evaluation of the need for adjuvant radiation therapy (RT) in patients w...
PURPOSE: Advances in neoadjuvant chemotherapy (NAC) have markedly increased pathologic complete response (pCR) rates in breast cancer, prompting re-evaluation of the need for adjuvant radiation therapy (RT) in patients with excellent treatment response. The NSABP B-51 trial showed no survival benefit from regional nodal irradiation in patients achieving nodal pCR after NAC; whole-breast RT was still routinely delivered irrespective of breast response. Thus, the potential to safely omit RT in patients achieving breast pCR remains uncertain. METHODS AND MATERIALS: We conducted an integrated analysis combining real-world evidence, clinical trial data, and simulated extensions to evaluate long-term overall survival (OS) with versus without adjuvant RT in patients achieving pCR (defined as ypT0 ypN0) after NAC and breast-conserving surgery. Model inputs were derived from published trials, observational cohorts, and cancer registry data. We assessed OS across a range of local-regional recurrence (LRR) risks and time-to-recurrence distributions reflective of contemporary clinical practice. RESULTS: RT was associated with small OS gains across stages. For stage I disease, 5-year LRR rates of 3.0% with RT versus 7.5% without RT corresponded to 20-year OS of 85.6% and 84.0%, respectively (absolute difference 1.6%), requiring >12,000 patients for 80% power. For stage II to III disease (5-year LRR 3.0% vs 10.5%), 20-year OS was 81.6% vs 78.3%, respectively (difference 3.3%), requiring ∼3800 patients for adequate power. Treatment effects on OS were consistent across age groups (≥65 years) and in the triple-negative subtype. CONCLUSIONS: Among patients achieving pCR after NAC, the projected OS benefit from adjuvant RT appears small. This supports efforts toward more selective RT use and suggests that RT de-escalation warrants further investigation in subgroups with favorable biology and excellent treatment response. These findings reinforce the need for response-adapted decision frameworks and the incorporation of pCR into future RT guidelines. As treatment becomes increasingly personalized, integrating pathologic response into RT decision-making may reduce treatment burden without compromising outcomes. Prospective randomized trials are needed to validate these findings.
External Beam Radiotherapy (EBRT) & Immunotherapy (IO) in the Management of Hepatobiliary Malignancies: A Meta-analysis of Treatment Response Rates.
Whaley JJJV, Peters ML, Abrams MJ
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42173324 · Publisher ↗
PURPOSE: To evaluate in a meta-analysis the efficacy of external beam radiotherapy (EBRT) with immunotherapy (IO) in hepatobiliary malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and...
PURPOSE: To evaluate in a meta-analysis the efficacy of external beam radiotherapy (EBRT) with immunotherapy (IO) in hepatobiliary malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and identify factors associated with improved treatment response. METHODS AND MATERIALS: Observational studies or clinical trials reporting objective response rates (ORR) and disease control rates (DCR) for patients with advanced or unresectable HCC or CCA treated with EBRT plus at least one IO agent were included. PubMed, Web of Science, and Cochrane were searched through February 2025. Pooled ORR and DCR were calculated using random-effects models with inverse variance weighting and double-arcsine transformation. Subgroup analyses were performed by study design (retrospective studies vs clinical trials), radiation target (primary vs primary + metastasis), radiation dose (high vs low BED), and IO regimen. Meta-regression was performed to study the associated between BED and response rates. RESULTS: Twenty-two HCC studies (971 patients) and three CCA studies (136 patients met inclusion criteria). Pooled ORR was 58% (95%CI, 50-65%) and DCR was 79% (95%CI, 71-85%) for HCC, with no difference between study design. Radiation target, and dose were not associated with improved response in subgroup analysis. However, meta-regression showed an improved ORR for higher BED (1.14% increase per Gy) on clinical trials (p = 0.021). No differences were found in response rates between anti-PD1 and anti-PDL1 agents or combination therapy with or without VEGF inhibitors. For CCA, pooled ORR was 32% and DCR 70%. Subgroup analysis was unable to be performed due to sample size limitations. CONCLUSIONS: EBRT in combination with IO shows favorable response rates in advanced hepatobiliary malignancies, particularly in HCC. Higher BED appears to enhance tumor response; however, it requires further prospective studies with current standard of care systemic therapies.
Radiation-Induced Vaginal Stenosis in Patients With Cervical Cancer in Low- and Middle-Income Countries: A Scoping Review.
Myagmarsuren D, Alani A, Olatunji E … +6 more , Ndassi DK, Rohani N, Seppo S, Oboh E, Mallum A, Incrocci L
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42167703 · Publisher ↗
PURPOSE: Radiation-induced vaginal stenosis (RIVS) is a common late toxicity of cervical cancer radiation therapy, yet its incidence, assessment, and reporting in low- and middle-income countries (LMICs) are poorly chara...
PURPOSE: Radiation-induced vaginal stenosis (RIVS) is a common late toxicity of cervical cancer radiation therapy, yet its incidence, assessment, and reporting in low- and middle-income countries (LMICs) are poorly characterized. This scoping review synthesizes existing evidence on the incidence, assessment methods, and management of RIVS in LMIC settings. METHODS AND MATERIALS: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. PubMed, Scopus, and Web of Science were searched for available literature through December 2024 for studies reporting RIVS among women with cervical cancer treated with radiation therapy in LMICs. Data were extracted on study characteristics, incidence, assessment methods, and management. Nonparametric tests and Spearman correlations were used to explore associations between reported incidence and study-level variables. RESULTS: Twenty-four studies met the inclusion criteria, representing nine LMICs as defined by the World Bank; no studies originated from low-income countries. The median publication year was 2020, and half of the studies were retrospective. Among studies reporting extractable incidence data, the median (IQR) overall incidence of RIVS was 48.8% (33.5-75.9). Studies that identified RIVS as a primary outcome reported significantly higher incidence than those in which it was not a primary focus (P < .001). Incidence was also higher in studies published after 2014 (P = .02). No significant differences were observed across countries, regions, or income groups. Reporting of management strategies was limited, with only 6 studies describing toxicity management. CONCLUSIONS: RIVS is common among patients with cervical cancer treated in LMICs, yet assessment and reporting remain inconsistent, and management practices are poorly described. The absence of data from low-income countries and the limited use of standardized toxicity assessment hinder accurate estimation of survivorship burden. Improved documentation, standardized assessment, and culturally informed interventions are needed to address late vaginal morbidity in LMICs.
Measure What Matters: Rethinking Surrogate Metrics of Success in Radiation Oncology.
Satish L, Asper J, Bonnen M … +6 more , Tuli R, Corwin T, Wagner T, Delapo N, Mesa R, Dalwadi SM
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42167702 · Publisher ↗
PURPOSE: Census-based surrogates such as patients on treatment, fractions delivered, and course length have traditionally been used to assess radiation oncology departmental performance. These measures may no longer capt...
PURPOSE: Census-based surrogates such as patients on treatment, fractions delivered, and course length have traditionally been used to assess radiation oncology departmental performance. These measures may no longer capture the complexities of modern radiotherapy, given the increased adoption of hypofractionation and stereotactic techniques. This study analyzes longitudinal trends in clinical operations, including treatment modalities, fractionation patterns, and financial performance, to identify value-based departmental performance metrics. METHODS/MATERIALS: A retrospective analysis was conducted at an NCI-designated cancer center spanning a ten-year period (FY15-24). Operational and financial data were extracted from EMR and billing systems, including consultations, treatment starts, total fractions, fractions per patient, and annual collections. Descriptive statistics were used to assess associations between respective operational surrogates and financial outcome. RESULTS: Consultations increased by 77.8%, treatment starts by 43.6%, and average fractions per patient decreased by 12.0%. Utilization of advanced modalities (IMRT, SBRT, SRS) grew substantially, with stereotactic courses rising from 39 courses in FY15 (4%) to 291 courses by FY24 (22%). Mean IMRT course length decreased from 24.6 to 13.8 fractions. Conversion rate from consultations to new treatment starts dropped from 92% to 71%. Fractions per patient (r = -0.42) and other census based surrogates demonstrated weak or inverse associations with collections. Collections were strongly correlated with consultations (r = 0.97) but demonstrated a comparatively weaker regression slope ($7,238/consult) compared with new treatment starts (r = 0.90, R = 0.82, 15,500/start). Professional work RVUs also demonstrated strong correlations with collections but showed heterogenous alignment with clinical activity, reflecting sensitivity to coding structure rather than discrete care delivery. CONCLUSION: Legacy tabulation-based metrics no longer reflect operational and financial value in the contemporary era. New treatment starts represent the most reliable surrogate, capturing clinical throughput, financial performance, and physician workload. Benchmarking based on new treatment initiation may improve performance assessment and appropriate resource allocation in alignment with value-based care.
Noninvasive Reversible Software-Based Electron FLASH Irradiation Configuration of a Linear Accelerator in Clinical Use.
Melemenidis S, Chen D, Jensen C … +11 more , Schulz JB, Surucu M, Yu AS, Graves EE, Shi M, Reilly M, Maxim PG, Currell A, Loo BW, Skinner L, Ashraf MR
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42155735 · Full text
BACKGROUND: Configuring clinical linear accelerators (linacs) for ultra-high-dose-rate (UHDR) electron experiments typically requires invasive hardware manipulation and/or irreversible modifications, limiting broader imp...
BACKGROUND: Configuring clinical linear accelerators (linacs) for ultra-high-dose-rate (UHDR) electron experiments typically requires invasive hardware manipulation and/or irreversible modifications, limiting broader implementation. This work reports a reversible and noninvasive UHDR electron configuration of a clinical TrueBeam linac that enables switching between preclinical UHDR and conventional (CONV) clinical treatment modes through software settings, without accessing the linac interior. METHODS AND MATERIALS: Built-in service mode software was used to configure the UHDR mode with settings typical of a standard megavoltage photon beam. Using service mode, the photon target and monitor chambers were retracted. An unused low-energy electron scattering foil was loaded. An external AC current transformer for beam control and monitoring was mounted on the accessory tray, with an ionization chamber placed downstream in solid water to monitor exit dose. Dose profiles were measured for UHDR and CONV beams with radiochromic films for open field, in vivo, and in vitro setups. Dose per pulse was varied by adjusting the gun voltage and quantified. Day-to-day output variation was assessed to evaluate dose reproducibility. RESULTS: Percent depth-dose measurements confirmed similar energy between UHDR (9.2 and 12.6 MeV) and CONV electron beams (8.4 and 11.7 MeV), with matching profiles throughout the typical thickness of a mouse or cell culture media. Maximum dose per pulse reached 1.5 Gy/pulse and 0.7 Gy/pulse for in vivo and in vitro setups at 64 and 82 cm source-to-surface distances, respectively. Field flatness and symmetry were maintained between UHDR and CONV, supporting organ-specific in vivo irradiation and a maximum of 5 × 5-cm field for in vitro irradiation. Day-to-day output variation remained small, with both inter- and intra-animal coefficients of variation averaging <3% for FLASH and <1% for CONV. CONCLUSION: Accurate and reproducible UHDR electron delivery was demonstrated without invasive hardware manipulation, enabling preclinical FLASH research on a clinical linac.
Technical Considerations on Proton Therapy in NRG's Multi-Institutional Clinical Trials.
Liang X, Taylor PA, Li H … +15 more , Paganetti H, Pankuch M, Beltan CJ, Flampouri S, Hoppe BS, Kooy H, Lin H, Lin L, Liu W, Sahoo N, Simone CB, Teo BK, Xiao Y, Zhou J, Buchsbaum JC
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42150707 · Full text
PURPOSE: Proton therapy is increasingly incorporated into clinical trials. However, its evolving technology and distinct physical and biological properties pose challenges for protocol design, treatment consistency, data...
PURPOSE: Proton therapy is increasingly incorporated into clinical trials. However, its evolving technology and distinct physical and biological properties pose challenges for protocol design, treatment consistency, data collection and interpretation. This work outlines key technical considerations for implementing proton therapy in multi-institutional clinical trials and provides guidance to promote harmonized trial conduct and reliable data collection for outcome assessment. METHODS AND MATERIALS: This technical guideline was developed under the leadership of NRG Oncology. We reviewed NRG Oncology protocols that permit or randomize proton therapy to understand current trial designs, patterns of use, and challenges specific to multi institutional proton therapy clinical trials. Technical challenges specific to proton therapy were examined, including setup and range uncertainties, motion and interplay effects, interfractional anatomical changes, uncertainties in relative biological effectiveness, and limitations in plan evaluation and reporting. Recommendations were developed based on current clinical practice and multi-institutional clinical trial experience. RESULTS: Multiple sources of variability were identified that may affect treatment consistency and outcome interpretation in multi-institutional proton therapy trials, particularly those with long accrual periods and evolving technology. Existing protocols differ in proton therapy stratification, randomization, and technical requirements. Additional, robustness evaluation and reporting practices remain inconsistent across institutions. Practical recommendations are provided to improve protocol clarity, enhance robustness assessment, and standardize data collection and reporting to enable meaningful cross-institutional comparison and retrospective analyses. CONCLUSIONS: As proton therapy becomes more widely integrated into cooperative group clinical trials, clear and consistent technical guidance is essential to ensure data quality, protocol adherence, and interpretability of clinical outcomes. This work provides a technical framework for harmonizing proton therapy implementation in NRG multi institutional clinical trials and supports future investigation of biological dose-response relationships. Considerations for emerging technologies, including proton arc therapy, upright treatment systems, FLASH therapy, and carbon ion therapy, are also discussed.
Long-Term Outcomes of Reduced-Dose Radiotherapy in Patients with Epstein-Barr Virus DNA-Selected Stage III Nasopharyngeal Carcinoma: A 5-Year Follow-Up Secondary Analysis of a Phase II Trial.
Xiao YX, Yang JH, Sun XS … +12 more , Liu LZ, Liu LT, Liu SL, Li XY, Li JB, Liu Q, He JR, Guo HB, Chen QY, Tang LQ, Mai HQ, Guo SS
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42150706 · Publisher ↗
BACKGROUND: We previously reported that reduced-dose (60 Gy) radiation was associated with favorable survival outcomes and limited toxicities in patients with low-risk stage III nasopharyngeal carcinoma (NPC) sensitive t...
BACKGROUND: We previously reported that reduced-dose (60 Gy) radiation was associated with favorable survival outcomes and limited toxicities in patients with low-risk stage III nasopharyngeal carcinoma (NPC) sensitive to induction chemotherapy (IC). However, the consistency of long-term outcomes remains unclear. METHODS: This 5-year follow-up secondary analysis of a single-arm phase II trial enrolled patients with nonkeratinizing stage III NPC with pretreatment Epstein-Barr virus (EBV) DNA <4000 copies/mL. All 215 eligible patients received two cycles of IC. After IC, 116 patients achieved complete response/ partial response (CR/PR) and undetectable EBV DNA, and they were assigned to receive intensity-modulated radiotherapy (IMRT) at 60 Gy in 30 fractions. The remaining 99 patients were assigned to receive standard IMRT at 70 Gy in 33 fractions. The primary endpoint was progression-free survival (PFS). RESULTS: At a median follow-up of 68·1 months, the 5-year PFS was 90·5% (95% confidence interval [CI], 85·3%-96·0%) in the 60 Gy cohort and 79·8% (72·3%-88·1%) in the 70 Gy cohort, while the 5-year overall survival was 96·6% (93·3%-99·9%) and 94·9% (90·7%-99·4%), respectively. The 5-year locoregional relapse-free survival was 93·1% in the 60 Gy cohort and 82·8% in the 70 Gy cohort; the 5-year distant metastasis-free survival was 93·1% in the 60 Gy cohort and 89·9% in the 70 Gy cohort. No grade 3-4 late toxicity was observed in the 60 Gy group. In the 70 Gy cohort, 10·1% of patients experienced grade 3-4 late toxicities, with dry mouth and deafness/otitis being the most frequently reported. CONCLUSIONS: Long-term analysis showed that in patients with low-risk stage III NPC selected by EBV DNA and IC response, reduced-dose IMRT (60 Gy) achieved favorable survival outcomes with limited late toxicities.
MedNext-Insight Model for Automated Metabolic Tumor Volume Delineation on Computed Tomography and Prognostic Value in Nasopharyngeal Carcinoma.
Hao MY, Xiong YX, Li Y … +12 more , Mo ZJ, Feng CY, Hu J, Zhang SM, Yang YX, Jia LC, Li H, He YD, Sun XQ, Xu S, Zhou GQ, Sun Y
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42144163 · Publisher ↗
PURPOSES: To develop a deep learning model for automated metabolic tumor volume (MTV) delineation on routine computed tomography (CT) without positron emission tomography (PET) and to validate its prognostic value in nas...
PURPOSES: To develop a deep learning model for automated metabolic tumor volume (MTV) delineation on routine computed tomography (CT) without positron emission tomography (PET) and to validate its prognostic value in nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A retrospective cohort of 392 patients with NPC undergoing pre-radiotherapy 2-deoxy-2-[fluorine-18]fluoro-D-glucose PET/CT in 2021 was enrolled and randomly divided into training (n = 314, including 63 for validation) and test (n = 78) cohorts. Ground-truth MTV (GT_MTV) was generated from PET-registered CT using standardized uptake value SUV > 2.5 within the primary gross tumor volume. A 7-layer MedNext-Insight model with dual-window CT inputs and Dice-Focal loss was trained to predict MTV using CT alone. Segmentation performance was compared with no-new-U-Net version 2 (nnUNetV2), Conditional Generative Adversarial Network for Image-to-Image Translation (Pix2Pix), and three-dimensional Cycle-Consistent Generative Adversarial Network (3D-CycleGAN) p rimarily using Dice Similarity Coefficient and sensitivity. Radiomic features were extracted from predicted MTV (Pred_MTV) and GT_MTV to construct Cox proportional hazards models for event-free survival, evaluated by concordance index (C-index). Robustness was further assessed in an internal temporal validation cohort from 2022 with different scanners (n = 135) using planning CT as the sole input. RESULTS: MedNext-Insight achieved the highest MTV delineation Dice Similarity Coefficient (Mean ± SD, 0.808 ± 0.110 vs 0.740-0.782; all P < .05) with improved sensitivity. After excluding 12 patients with baseline distant metastasis from event-free survival analysis, Pred_MTV-derived radiomics showed strong reproducibility (median intraclass correlation coefficient, 0.816) and comparable prognostic performance to GT_MTV (C-index [95% CI], 0.712 [0.516-0.899] vs 0.744 [0.601-0.884]; P = .730). MTV-based radiomics outperformed primary gross tumor volume-derived features, particularly when combined with clinical variables (C-index, 0.809 [0.678-0.919]). In the internal temporal validation cohort, CT-only Pred_MTV maintained stable segmentation accuracy and prognostic discrimination (log-rank test, P < .05). CONCLUSION: MedNext-Insight enables accurate PET-free MTV delineation on routine CT with prognostic value, supporting a resource-efficient approach for risk stratification and informing potential future biology-guided adaptive radiation therapy in NPC.
Diabetes and Performance Status Predict Severe, Persistent Radiation Proctitis: Long-Term Endoscopic Findings From STELLAR Trial.
Wang N, Xu T, Li H … +16 more , Shuai J, Ma H, Fang H, Song Y, Chen B, Lu N, Jing H, Liu X, Qi S, Zhang W, Liu Y, Li Y, Wang S, Dou L, Jin J, Tang Y
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42142768 · Publisher ↗
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 (NCT...
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.
Automated Analysis of Radiation Oncology Incident Reports Using Large Language Models: A Multi-Institutional Technical Validation Study.
Dobranski N, Viscariello NN, Pitcher GM … +12 more , Stam AM, Belliveau JG, Kirby K, Solis DE, Ashford J, Spears H, Dalton A, Sullivan SX, Stephens J, Daniel S, Stathakis S, Alexandrian A
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42142767 · Publisher ↗
PURPOSE: Patient safety incident reporting in radiation oncology requires expert analysis that is time-intensive and subject to variability. This study evaluates the technical feasibility of large language model (LLM) au...
PURPOSE: Patient safety incident reporting in radiation oncology requires expert analysis that is time-intensive and subject to variability. This study evaluates the technical feasibility of large language model (LLM) automation for incident report analysis across multiple cancer centers. METHODS AND MATERIALS: A locally deployed LLM system was developed for automated incident report summarization and taxonomy assignment. The system processed Radiation Oncology Incident Learning System reports from 2 anonymized cancer centers with 600 total expert evaluations. Round 1 established baseline performance with 495 evaluations (institution 1, n = 257; institution 2, n = 238) using Mistral 7B and Mixtral 8x7B models. Round 2 incorporated enhanced prompt engineering, retrieval-augmented generation, and advanced models (Gemma3 27B, DeepSeek R1 70B, Llama3.1 70B) with 105 evaluations (institution 1, n = 60; institution 2, n = 45). Clinical experts evaluated outputs using 5-point ordinal scales (1 = nonsensical to 5 = excellent), with mixed-effects statistical analysis. RESULTS: Multirater analysis demonstrated statistically significant performance improvements between rounds across both institutions. Institution 1 achieved substantial improvements: summary scores (3.34 ± 1.17 → 4.20 ± 0.84; d = 0.78; P < .001) and tag scores (3.28 ± 0.98 → 4.32 ± 0.70; d = 1.11; P < .001). Institution 2 showed improvements: summary scores (3.61 ± 1.24 → 4.02 ± 0.97; d = 0.34; P = .055) and tag scores (3.79 ± 1.10 → 4.40 ± 0.81; d = 0.58; P < .001). Round 2 high-performance thresholds (≥4): institution 1 achieved 80.0% for summaries, and 86.7% for tags; institution 2 achieved 68.9% and 84.4%, respectively. Processing time increased 3-fold (5.6 → 19.2 seconds per report) with substantial performance gains. CONCLUSIONS: This study shows feasibility of automated radiation oncology incident analysis using locally deployed LLMs, with effect sizes ranging from small to large (d = 0.34-1.11) across institutions. Performance improvements establish technical feasibility for further development, while institutional variation suggests that site-specific factors may influence system effectiveness, which warrants further investigation.
Does Radiation Boost Dose Affect Organ Preservation Rates? A Secondary Analysis of the Organ Preservation in Patients With Rectal Adenocarcinoma Trial.
Yariv O, Williams H, Goodman KA … +8 more , Verheij FS, Omer DM, Lin ST, Qin LX, Gollub MJ, Saltz LB, Garcia-Aguilar J, Wu AJ
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42142103 · Publisher ↗
PURPOSE: The Organ Preservation in Patients with Rectal Adenocarcinoma trial was a randomized clinical trial investigating the optimal sequencing of total neoadjuvant therapy for patients with rectal cancer desiring orga...
PURPOSE: The Organ Preservation in Patients with Rectal Adenocarcinoma trial was a randomized clinical trial investigating the optimal sequencing of total neoadjuvant therapy for patients with rectal cancer desiring organ preservation (OP). An optional higher-dose radiation boost was allowed on this trial. We aimed to determine whether a higher radiation boost dose was associated with the probability of clinical complete response and OP. METHODS AND MATERIALS: Patients with clinical stage II/III rectal adenocarcinoma were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Radiation therapy was delivered to the primary tumor and involved nodes to 4500 cGy with concurrent chemotherapy. The standard boost dose to the primary tumor was 500 to 540 cGy, but the treating physician was allowed to give an optional higher-dose boost of 900 to 1100 cGy. Post-total neoadjuvant therapy restaging assessment with flexible sigmoidoscopy and magnetic resonance imaging stratified patients into 3 tiers of clinical response. Patients with a clinical complete or near-complete response were offered OP, whereas those with an incomplete clinical response were recommended for total mesorectal excision. In a post hoc analysis, OP rates by radiation boost dose (standard-dose [SD] vs high-dose [HD] boost) were estimated using the Kaplan-Meier method and tested for statistical significance using the log-rank test. Tumor clinical response rates were estimated using proportions and tested for statistical significance using the Fisher exact test. RESULTS: Of the 324 patients randomized in the Organ Preservation in Patients with Rectal Adenocarcinoma trial, 303 patients were eligible for the present analysis, including 93 patients in the SD boost group (median total dose, 5000 cGy) and 210 in the HD boost group (median total dose, 5400 cGy). Clinical T3/T4 stage at presentation was more common among HD patients (83% and 10%, respectively) compared with SD patients (62% and 18%, respectively) (P < .001); otherwise, the 2 groups were comparable in all other measured aspects. Rates of restaging endoscopic clinical complete response and near-complete response were similar among SD patients (41% and 44%, respectively) and HD patients (44% and 39%, respectively) (P = .5). The median follow-up for patients with OP was 5.14 (IQR, 3.75-5.67) years. The 3- and 5- year probability of OP were both 52% (95% CI, 43-64) for SD patients, and 47% (95% CI, 41-54) and 45% (95% CI, 38-52) for HD patients, respectively. CONCLUSIONS: In the prospective phase 2 Organ Preservation in Patients with Rectal Adenocarcinoma trial of total neoadjuvant therapy for locally advanced rectal cancer, a higher radiation boost dose was not significantly associated with the probability of achieving a clinical complete response or the durability of OP.
Peripheral PD-1⁺CD8⁺ T-cell TCR Dynamics During Radiation Therapy Predict Survival in Unresectable Locally Advanced Non-Small Cell Lung Cancer.
Jiang Y, Yang Y, Wu L … +9 more , Wang J, Wu Y, Wang X, Wang H, Bai J, Xia X, Wang Z, Zhang L, Bi N
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42142102 · Publisher ↗
PURPOSE: Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, reliable biomarkers for predicting response to immunothe...
PURPOSE: Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, reliable biomarkers for predicting response to immunotherapy remain limited. Among circulating immune cells, PD-1⁺CD8⁺ T cells represent an activated subset that directly responds to PD-1 blockade. Profiling the T-cell receptor (TCR) repertoire within this population may reflect antitumor immune activity and holds promise as noninvasive, blood-based biomarker. METHODS AND MATERIALS: We prospectively enrolled 63 patients with unresectable LA-NSCLC who underwent chemoradiation therapy. Peripheral blood PD-1⁺CD8⁺ T cells were isolated from peripheral blood mononuclear cells obtained by density gradient centrifugation at 3 time points: before radiation therapy, during radiation therapy (on-RT, approximately at the 20th fraction), and after radiation therapy (post-RT), yielding a total of 141 blood samples. TCR sequencing was performed to assess repertoire diversity. Dynamic changes in TCR diversity metrics across time points were analyzed and correlated with progression-free survival (PFS). RESULTS: A higher D50 index on-RT was significantly associated with improved median PFS (not reached vs 21.95 months; P = .0246), regardless of the timing of immunotherapy. Patients with more stable TCR diversity and clonality on-RT experienced significantly longer PFS. Specifically, patients with low D50 index variation between on-RT and post-RT had a median PFS that was not reached (95% CI, 30.72-NA), compared with 21.95 months (95% CI, 17.84-NA; P = .018) in the high-variation group. Similarly, patients with low clonality variation demonstrated longer PFS from pre-RT to on-RT (30.72 vs 21.95 months; P = .0425) and from on-RT to post-RT (not reached vs 22.21 months; P = .0331). Clonal tracking analyses revealed that patients with short-PFS exhibited a higher proportion of markedly decreased TCR clones, particularly among high-frequency clones, suggesting impaired antitumor immune responses. CONCLUSIONS: Peripheral PD-1⁺CD8⁺ TCR diversity and its dynamic changes on-RT are associated with PFS in patients with LA-NSCLC. These findings suggest that TCR repertoire profiling of circulating PD-1⁺CD8⁺ T cells may serve as a noninvasive biomarker to identify patients less likely to benefit from consolidation immunotherapy. Further validation in larger, prospective cohorts is warranted.
Long-Term Locoregional Control and Pattern of Recurrences After Implementation of Highly Conformal Flank Target Volumes and Image-Guided Intensity Modulated Arc Therapy for Pediatric Wilms Tumors.
Ding M, Radu AM, Spijkerman R … +16 more , van Grotel M, Littooij AS, van Tinteren H, Davila-Fajardo R, Tytgat GAM, Mavinkurve-Groothuis AMC, van der Steeg AFW, van de Ven CP, Wijnen MHWA, de Krijger RR, Seravalli E, Bosman ME, Roy P, Maspero M, van den Heuvel-Eibrink MM, Janssens GO
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42140503 · Publisher ↗
PURPOSE: Excellent outcomes in patients with Wilms tumors (WT) have allowed efforts to reduce toxicity and treatment burden while sustaining effectiveness. Concerning radiation therapy, "conventional" flank target volume...
PURPOSE: Excellent outcomes in patients with Wilms tumors (WT) have allowed efforts to reduce toxicity and treatment burden while sustaining effectiveness. Concerning radiation therapy, "conventional" flank target volumes combined with 2 opposing photon beams are now being replaced by highly conformal flank target volumes combined with image-guided intensity modulated arc therapy, allowing better sparing of the organs-at-risk, but outcome descriptions based on large cohorts are scarce. Previously, a cohort of 36 patients with excellent locoregional control at 2 years from diagnosis using "modern" flank irradiation has been described. This study aims to investigate locoregional control outcomes, patterns of recurrence, and toxicity in an extended national cohort of patients with WT with a longer follow-up (FU) period. METHODS AND MATERIALS: Newly diagnosed patients with a WT, irradiated on the flank between January 01, 2015 and August 08, 2025 using highly conformal target volumes, as defined by the International Society for Pediatric Oncology - Renal Tumor Study Group consensus statement, combined with IMAT, were eligible for analysis. The 4-year locoregional control rate (LCR), disease-free interval, event-free survival, overall survival, and acute and estimated late toxicity were assessed. For each locoregional recurrence, image co-registration and dose reconstruction were performed to classify each recurrence as "infield" if ≥99% of the gross tumor volume at recurrence received ≥95% of the prescribed dose at initial irradiation (V95%, ≥99%), "marginal" (V95%, 20.0%-98.9%), or "outfield" (V95%, ≤19.9%). RESULTS: Seventy patients received postoperative flank irradiation only (n = 50) or combined with metastatic site irradiation (n = 20). With a median FU of 4.7 years, the estimated 4-year LCR, disease-free interval, event-free survival, and overall survival were 93.7%, 86.4%, 83.7%, and 93.7%, respectively. Four patients developed a locoregional recurrence, of whom one (marginal recurrence) could have been better covered by the conventional approach. Nausea ± vomiting requiring antiemetics developed in 34 of 63 (54%) patients. In 24 of 70 patients (34%), major constraint violations, mainly involving the pancreatic tail and spleen, were observed. CONCLUSIONS: This extended national cohort of patients with WT confirms the excellent LCR, using modern flank irradiation, even after a long-term FU.
A Meta-Analysis-Based Risk Score for Predicting Radiation Pneumonitis After Thoracic Radiation Therapy for Lung Cancer.
Yang J, Zhu T, Zhou J … +12 more , Ni C, Ma R, Xu Q, Zhou Y, Dai X, Tao Q, Gong S, Ye X, Ge X, Cheng H, Ren J, Lou P
Int J Radiat Oncol Biol Phys · 2026 May · PMID 42140502 · Publisher ↗
PURPOSE: To develop and validate a risk score for predicting radiation pneumonitis (RP) in lung cancer patients following thoracic radiation therapy. METHODS AND MATERIALS: The linear predictor was first derived from a m...
PURPOSE: To develop and validate a risk score for predicting radiation pneumonitis (RP) in lung cancer patients following thoracic radiation therapy. METHODS AND MATERIALS: The linear predictor was first derived from a meta-analysis. Risk factors with consistent definitions and statistical significance were identified, and their pooled odds ratios were converted to β-coefficients and then linearly transformed to construct the initial scoring items. An independent Asian calibration cohort (cohort 1, n = 218) was used to estimate the model's intercept and to determine the optimal risk stratification cut-off via receiver operating characteristic analysis. The discrimination capability and clinical applicability of the model were subsequently evaluated in 2 independent Asian external validation cohorts (cohort 2, n = 69; cohort 3, n = 81). The primary endpoint was grade ≥2 RP (National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0). RESULTS: The final score for predicting RP included 7 variables: smoking, chemotherapy, tumor location, pulmonary comorbidities, use of renin-angiotensin system inhibitors, percentage of lung volume receiving ≥5 Gy (V5), and percentage of lung volume receiving ≥20 Gy (V20), with a total possible score of 107. It demonstrated an area under the curve of 0.831 (95% CI, 0.768-0.894) in the calibration cohort, establishing 53.5 points as the optimal cut-off value for risk stratification. Discriminative performance remained robust in external validation, with areas under the curve of 0.881 (95% CI, 0.799-0.962) and 0.845 (95% CI, 0.749-0.942), respectively. At this threshold, positive likelihood ratios (LR+) across the 3 cohorts were 3.097, 2.934, and 3.492, and negative likelihood ratios (LR-) were 0.224, 0.159, and 0.212. The high-risk group showed significantly elevated relative risks for RP (7.270, 5.143, and 5.884; all P < .001). To facilitate clinical use, this scoring system has been made available as a web-based calculator. CONCLUSIONS: We developed a meta-analysis-based risk score for RP and independently validated it in Asian cohorts. This tool provides reliable risk stratification that may aid in personalized management and optimization of resource allocation for this population.
In Reply to Delaney.
Bentzen SM, Paradis KC
Int J Radiat Oncol Biol Phys · 2026 Jun · PMID 42140259 · Publisher ↗
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In Reply to DeLaney.
Marks LB, Mayo CS, Dawson LA … +7 more , Andratschke N, Jackson A, Xiao Y, Gabrys D, Appelt AL, Osorio EV, Yorke ED
Int J Radiat Oncol Biol Phys · 2026 Jun · PMID 42140258 · Publisher ↗
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In Regard to Marks et al and Mayo et al.
DeLaney TF
Int J Radiat Oncol Biol Phys · 2026 Jun · PMID 42140257 · Publisher ↗
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In Regard to Pratx et al.
Pratx G, Yang W, Scarpelli ML
Int J Radiat Oncol Biol Phys · 2026 Jun · PMID 42140256 · Publisher ↗
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In Reply to Knol et al.
Grilj V, Böhlen TT
Int J Radiat Oncol Biol Phys · 2026 Jun · PMID 42140255 · Publisher ↗
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