International Journal Of Radiation Oncology, Biology, Physics[JOURNAL]
Sun
200 papers
A 10-Year Patterns of Use Analysis for the World's First Commercial Compact Pencil Beam Scanning Proton Therapy System.
Walter YA, Wu HT, Durci M … +12 more , Katz S, Wang CJ, Jeffery K, Chen KLG, Speir DB, Johnson M, Broekhoven B, Robinson D, Speir A, Clark H, Hoffnung K, Rosen L
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41856438 · Publisher ↗
PURPOSE: The miniaturization of treatment delivery systems has accelerated the global democratization of pencil beam scanning (PBS) proton beam therapy (PBT). The first clinically installed commercial compact PBS-PBT sys...
PURPOSE: The miniaturization of treatment delivery systems has accelerated the global democratization of pencil beam scanning (PBS) proton beam therapy (PBT). The first clinically installed commercial compact PBS-PBT system was brought online in September 2014 at the Willis Knighton Cancer Center, part of a community health system. Here, we detail our 10-year experience with the world's first compact PBS-PBT system. METHODS AND MATERIALS: Records of patients initiating PBT between September 2014 and September 2024 were reviewed. Patient demographic and treatment planning data were collected for each treatment course. Pearson correlation was used to assess trends over time. RESULTS: A total of 1382 PBT courses were initiated over the 10 years. On average, 138.2 ± 29.3 courses were treated annually. Year 10 had the most treated courses (N = 188), whereas only 114 courses were treated in year 8, partially because of an unexpected 3-month machine downtime. A total of 415 courses were initiated during the COVID-19 pandemic (March 2020-May 2023). In each year, the prostate was the most treated body site (N = 582 total), followed in most years by the brain (N = 208 total). A total of 121 courses used PBT in a reirradiation setting. Thirty-seven courses used PBT in a stereotactic ablative radiation therapy setting, although 20 of these courses were treated in year 10. Pearson correlation showed decreasing fractionation over time (r[1380] = -0.25; P < .01). Nearly 90% of patients lived within a 100-mile radius of the facility. CONCLUSIONS: Trends demonstrate stable patterns of use over time, despite the occurrence of global events such as the COVID-19 pandemic. Modern hypofractionation has driven steady decreases in fractionation, reducing travel burden and potential financial toxicity. Continued growth in the body of clinical evidence, paired with legislation and health policy supporting particle therapy, will allow further expansion and critical evaluation of PBT indications. Results demonstrate the feasibility and longevity of PBT in a community hospital setting.
Multi-lead Monitoring to Deduce Translations and Rotations of the Heart Through Respiration and Its Geometric Implications for Motion Management in Cardiac Radioablation.
Marshall J, Karan T, Bergman A … +3 more , Schellenberg D, Deyell MW, Thomas S
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41850495 · Publisher ↗
PURPOSE: To investigate the time-resolved translations and rotations of the heart through respiration and their impact on target localization accuracy in cardiac radioablation (CR). METHODS AND MATERIALS: Twelve patient...
PURPOSE: To investigate the time-resolved translations and rotations of the heart through respiration and their impact on target localization accuracy in cardiac radioablation (CR). METHODS AND MATERIALS: Twelve patient data sets, from 6 patients, were acquired with 5 Hz, biplanar kV, fluoroscopy for 15 to 20 seconds in preparation for CR. Each patient was imaged twice, with and without abdominal compression. Included patients undergoing CR had implanted cardiac leads in the right ventricle (RV), right atrium (RA), and left ventricle (LV). Time-resolved respiratory motion for each cardiac lead was determined by monitoring the lead tip in biplanar images, triangulating its 3D position, and low-pass filtering its motion. The following 3 motion compensation strategies to model the target's position were simulated: (1) no respiratory motion compensation; (2) RV lead respiratory compensation; and (3) 6-degree-of-freedom (6DoF) respiratory motion modeling using all 3 cardiac leads. The 6DoF model also enabled quantification of the time-resolved translation and rotations of the cardiac lead cluster due to respiration. Each scenario was evaluated on its ability to predict the position of an independent pseudotarget, represented by the most proximal LV lead electrode, on the lateral wall of the LV. RESULTS: The average rotational amplitude of the cardiac lead cluster through respiration was 2.4±0.6° (right-left), 1.3° ± 0.4° (superior-inferior), and 1.7° ± 0.7° (anterior-posterior). For each patient, 6DoF respiratory motion compensation significantly (P≤.001) reduced respiratory motion localization errors compared with no motion compensation and RV lead only compensation. The average magnitude of 3D localization errors in respiratory motion compensation was 2.8 ± 1.1 mm without motion compensation, 2.0 ± 1.0 mm with RV lead compensation, and 0.8 ± 0.4 mm with 6DoF motion modeling. CONCLUSIONS: The rotation of the heart through respiration in CR, and its importance for real-time motion monitoring, is presented for the first time. For each patient data set, 6DoF modeling significantly improved the accuracy of respiratory motion localization for pseudotargets on the lateral wall of the LV.
Pretreatment Radiation Esophagitis Prediction Using Quantum Machine Learning in Patients With Esophageal Cancer.
Xie C, Shen Y, He J … +9 more , Guo M, Mu Y, Li L, Wang W, Dou M, Zhou Y, Zhang J, Ai Y, Jin X
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41850494 · Publisher ↗
PURPOSE: To introduce a hybrid quantum-classical machine learning approach and validate its feasibility and accuracy for pretreatment radiation-induced esophagitis (RE) prediction in patients with esophageal cancer under...
PURPOSE: To introduce a hybrid quantum-classical machine learning approach and validate its feasibility and accuracy for pretreatment radiation-induced esophagitis (RE) prediction in patients with esophageal cancer undergoing radiation therapy or chemoradiotherapy. METHODS AND MATERIALS: This study enrolled 218 patients with esophageal cancer from hospital 1 for training and internal validation and 55 patients with esophageal cancer from hospital 2 for external validation, with grade ≥2 RE incidences of 64 and 20, respectively. Dose distribution images were converted into quantum states via angle encoding. Quantum features (Qs) were extracted using 3 quantum models: (1) classical convolutional neural network (CNN) with quantum convolution (Q-CNN), (2) Q-CNN plus classical attention (Q-CNN + attention), and (3) Q-CNN plus quantum attention (Q-CNN + Q-attention). The hybrid machine learning model integrates handcrafted dosiomic features (Ds), Qs, and clinical factors (C) through a feature-level concatenation. The concatenated feature vector was processed by a Random Forest classifier for RE prediction. RESULTS: Models using only Qs achieved an accuracy of 0.70 (Q-CNN), 0.83 (Q-CNN + attention), and 0.80 (Q-CNN + Q-attention) in external validation, respectively. Feature fusion (Q + D + C) improved the accuracy of models in comparison with Qs alone. Q (Q-CNN + Q-attention) + D + C demonstrated optimal performance, achieving accuracy, sensitivity, and specificity of 0.85, 0.83, 0.92 (training); 0.80, 0.73, 0.84 (internal validation); and 0.83, 0.73, 0.89 (external validation), respectively. The Random Forest model using fused features Q + D + C extracted via Q-CNN + Q-attention achieved AUCs of 0.89 (training), 0.89 (internal validation), and 0.83 (external validation), outperforming models using only Q-CNN + Q-attention (AUCs: 0.78 training, 0.78 internal validation, and 0.80 external validation). CONCLUSIONS: This study proposes a novel quantum-classical machine learning method for pretreatment RE prediction. By integrating quantum amplitude encoding, quantum attention mechanisms, and multimodal feature fusion (Q + D + C), the model enhances prediction accuracy and reliability, demonstrating significant potential for clinical application.
Radiation Therapy Accessibility in Cambodia and Mongolia-Geospatial Modeling Analysis in Low- and Middle-Income Countries Within the Asia-Pacific Region.
Leow BYJ, Mel M, Chhoeurt K … +6 more , Minjgee M, Bayasgalan U, Vanchinbazar E, Koh ES, Delaney GP, Yap ML
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41845995 · Publisher ↗
PURPOSE: Cambodia and Mongolia, both low- and middle-income countries within the Asia-Pacific region, face significant challenges in geographic accessibility to radiation therapy facilities (RTFs). This study aimed to qu...
PURPOSE: Cambodia and Mongolia, both low- and middle-income countries within the Asia-Pacific region, face significant challenges in geographic accessibility to radiation therapy facilities (RTFs). This study aimed to quantify the current accessibility of RTFs in Cambodia and Mongolia, evaluating the potential benefits and challenges of establishing RTFs in regional provinces. METHODS AND MATERIALS: Population and RTF location data were sourced from online databases. Local radiation oncologists identified potential sites for future RTF development. Geographic accessibility was determined by Euclidean distances from province centroids to existing and proposed RTFs. Isochrone maps were generated to measure the percentage of the population residing within 2 hours of driving time to RTFs. RESULTS: In Cambodia, existing RTFs are centralized in Phnom Penh. With proposed developments in Siem Reap and Kampong Cham, the median Euclidean distance would decrease from 135 to 99 km. The Cambodian population within 2 hours of an RTF is projected to rise from 37% to 50%. The sole RTF in Mongolia is in Ulaanbaatar. A first regional RTF is planned in the Western regional province of Khovd. Three additional sites were modeled in Khangai, Central, and Eastern regions. The current median Euclidean distance of 439 km would decrease to 273 km with the planned RTF in Khovd and to 186 km with developments across all health regions. The Mongolian population within a 2-hour driving time would increase from a baseline of 55% to 56% with the development in Khovd, and to 63% if all regional RTFs were developed. CONCLUSIONS: Geospatial modeling demonstrated an improvement in geographic accessibility with proposed RTF development in regional areas. Improvements in driving time are more significant in Cambodia; however, this still leaves a large proportion of the population with unacceptable travel burden. This study demonstrates the utility and limitations of geospatial analysis in resource planning for Asia-Pacific region low- and middle-income countries and advocates for further research into the relationship between accessibility and oncological outcomes in such settings.
Radiation-Induced Acute Cardiac Injury in Patients With Left-Sided Breast Cancer: A Cardiac Magnetic Resonance Study on the Dose-Response Relation.
Zheng L, Yang M, Luo C … +11 more , Lv X, Yuan K, Xu K, Xu W, Hu Y, Dai Q, Xu J, Li J, Lang J, Zhou P, Yin J
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41842879 · Publisher ↗
PURPOSE: Radiation therapy (RT) for breast cancer (BC) increases long-term cardiovascular risk; however, the early identification of acute cardiac injury remains critically underexplored. This study aimed to prospectivel...
PURPOSE: Radiation therapy (RT) for breast cancer (BC) increases long-term cardiovascular risk; however, the early identification of acute cardiac injury remains critically underexplored. This study aimed to prospectively assess radiation-induced acute cardiac injury after postoperative left-sided BC RT using cardiac magnetic resonance (CMR) strain analysis. METHODS AND MATERIALS: Patients with left-sided BC undergoing RT were prospectively enrolled. Radiation doses to cardiac structures were calculated. CMR scans were performed within 2 weeks before and after RT. RESULTS: Among 64 enrolled patients, 41 received whole-breast RT (40.5 Gy/15 fractions; whole-breast RT [WBRT] group) and 23 received chest wall plus nodal RT (50 Gy/25 fractions; chest wall RT [CWRT] group). The mean cardiac dose in the CWRT group was higher than that in the WBRT group (mean heart dose [MHD]: 8.93 ± 2.67 Gy vs 2.80 [2.25 to 3.61] Gy, P < .001; left ventricle [LV]: 9.50 ± 3.49 Gy vs 2.85 [2.06 to 3.86] Gy, P < .001). The CWRT group demonstrated an increasing gradient of radiation dose from the basal to apical LV layers and a significant reduction in global longitudinal strain (GLS) (-17.50 [-15.73 to -17.85]% vs -15.32% ± 2.58%; P = .020) and global circumferential strain (GCS) (-20.34% ± 1.89% vs -19.22% ± 2.14%; P < .001) after RT, with similar alterations in the apical and middle layers, whereas the WBRT group showed no such changes. Among all patients, cardiac dosimetric parameters were independently associated with decreases in GLS and GCS (P < .05). Moreover, 10 patients (15.6%) developed cancer therapy-related cardiac dysfunction after RT; the combination of cardiac dose and the Systematic Coronary Risk Evaluation 2 risk index accurately predicted cancer therapy-related cardiac dysfunction (area under the curve, [AUC] = 0.931; AUC = 0.925). CONCLUSIONS: High-dose radiation exposure increases susceptibility to acute cardiac injury after left-sided BC RT. CMR-derived myocardial strain is a sensitive indicator of radiation-related acute cardiac dysfunction.
Carbon Ion Radiotherapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of Single-arm Studies.
Liu S, Hu X, Tong R … +8 more , Yan J, Jiang R, Zeng Y, Zhang Y, Wang H, Zhang X, Yao Z, Lu Y
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41839377 · Publisher ↗
PURPOSE: The role of carbon ion radiation therapy (CIRT) in treating locally advanced pancreatic cancer (LAPC) lacks high-level medical evidence. This study aimed to assess the efficacy and safety of CIRT for LAPC throug...
PURPOSE: The role of carbon ion radiation therapy (CIRT) in treating locally advanced pancreatic cancer (LAPC) lacks high-level medical evidence. This study aimed to assess the efficacy and safety of CIRT for LAPC through a pooled analysis of single-arm studies. METHODS AND MATERIALS: Prospective or retrospective clinical studies of CIRT for LAPC with or without chemotherapy before, concurrent, and/or after CIRT were included in the analysis. A systematic search of the Embase, PubMed, and Cochrane Library databases was conducted for studies until September, 2025. These articles were independently screened, and data were extracted by 2 researchers. Statistical analysis of outcomes was performed using STATA 15.1. RESULTS: A total of 522 related articles were retrieved, and 9 single-arm studies with a total of 406 patients with LAPC were included. The pooled local control (LC) rates at 1 and 2 years were 84% and 64%, respectively, with higher prescribed doses showing improved LC compared with lower doses (89% vs 69% at 1 year; 72% vs 30% at 2 years). The overall survival rates at 1 and 2 years were 65% and 38%, respectively. A clear survival benefit of CIRT was observed in studies with concurrent chemotherapy than without (73% vs 53% at 1 year; 44% vs 22% at 2 years). Prior chemotherapy administration reduced the incidence of distant metastases (69% vs 85%). Regarding toxicities above G3, the pooled incidences of nonhematological toxicity and hematological toxicity were 8% and 24%, respectively. CONCLUSIONS: Encouraging LC and overall survival outcomes were observed in this pooled analysis of CIRT as a plausible treatment strategy for LAPC. Subgroup analyses suggested that higher doses, concurrent chemotherapy, and prior chemotherapy may further enhance the efficacy. Meanwhile, CIRT has acceptable toxicities even when it is administered concurrently with chemotherapy.
Tumor Purity as a Prognostic and Predictive Biomarker of Postoperative Radiation Therapy Outcomes in Stage IIIA-N2 Non-Small Cell Lung Cancer: A Transcriptomic Analysis From the Lung ART Trial.
Zrafi WS, Albarrán-Artahona V, Dall'Olio FG … +9 more , Ghigna MR, Signolle N, Cozic N, Adam J, Lacroix L, Pechoux CL, Gautheret D, Besse B, Levy A
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41833910 · Publisher ↗
PURPOSE: Tumor purity (TP), the proportion of malignant cells within a tumor sample, is an important feature of the tumor microenvironment. Using transcriptomic data from the Lung ART-IFCT 0503 trial, we investigated the...
PURPOSE: Tumor purity (TP), the proportion of malignant cells within a tumor sample, is an important feature of the tumor microenvironment. Using transcriptomic data from the Lung ART-IFCT 0503 trial, we investigated the relevance of TP and its potential to predict benefit from postoperative radiation therapy (PORT). METHODS AND MATERIALS: RNA sequencing was successfully performed on 285 samples. TP was inferred using the ESTIMATE algorithm. Associations with overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier and multivariable Cox models. RESULTS: Among 285 patients with resected stage IIIA-N2 non-small cell lung cancer, 144 received PORT. The median age was 61 years, 31% were women, and 80% had nonsquamous histology. Baseline characteristics were well balanced between arms. The median TP was 0.64 (range, 0.41-0.92) and was slightly higher in the PORT arm (0.65 vs 0.63; P = .006). TP correlated with H&E pathologist-estimated cellularity (r = 0.23, P < .001), was higher in squamous tumors (0.68 vs 0.63, P < .001), and increased with necrosis (r = 0.31, P < 10). Transcriptomic analysis confirmed associations with proliferation-related pathways and reduced hypoxia signatures (false discovery rate < 0.001). TP inversely correlated with T-cell immune infiltration by immunohistochemistry (CD3⁺ r = -0.52; CD8⁺ r = -0.45). High-TP was associated with worse OS (48.5 vs 106.5 months, P < .001) and DFS (18.4 vs 48.0 months, P = .017). A TP × PORT interaction was observed for OS (P = .049) and a trend for DFS (P = .07). CONCLUSIONS: TP reflects proliferative and tumor microenvironment features; a lower TP is independently associated with improved prognosis in resected stage IIIA-N2 non-small cell lung cancer. PORT may be more effective in tumors with lower TP; however, this finding is exploratory and requires independent validation.
Long-Term Analysis of One Versus Three Fractions of Stereotactic Body Radiation Therapy for Peripheral Stage I to II Non-Small Cell Lung Cancer: A Randomized, Multi-Institution, Phase 2 Trial.
Singh AK, Farrugia MK, Stephans KL … +4 more , Bogart JA, Yu H, Groman A, Videtic GM
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41833909 · Publisher ↗
PURPOSE: Stereotactic body radiation therapy is standard of care for inoperable early-stage non-small cell lung cancer. Here, we report the long-term outcomes of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (a...
PURPOSE: Stereotactic body radiation therapy is standard of care for inoperable early-stage non-small cell lung cancer. Here, we report the long-term outcomes of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2). METHODS AND MATERIALS: This was a multi-institutional randomized, phase 2, 2-arm clinical trial. Medically inoperable patients with peripheral clinical T1-T2/N0M0 disease were enrolled. All patients had biopsy-confirmed disease. Patients were stratified by performance status and randomized to arm 1 or arm 2. The primary endpoint was thoracic grade 3 or higher adverse events per the Common Terminology Criteria for Adverse Events. Secondary endpoints included freedom from local failure, freedom from distal failure, progression-free (PFS) and overall survival (OS). RESULTS: Between September 2008 and April 2015, 98 patients were randomized. Median survival was 40.3 months. There were no new attributable adverse events within the additional follow-up period. There were no differences in time to local failure, time to distant failure, PFS, or OS (P = .14, .17, .98, and .78, respectively). CONCLUSIONS: This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, local failure, distant failure, PFS, and OS.
A New Predictive Model for Radiation Necrosis Risk Based on PTV-Enriched Blood Inflammatory Biomarkers in Patients With Brain Metastases Treated With Stereotactic Radiosurgery.
Jablonska PA, Serrano D, Galán N … +12 more , Barranco J, Leon S, Zelaya V, Robledano R, Echeveste JI, Rico M, Flamarique S, Cuenca T, Moreno-Jiménez M, Bosch-Barrera J, Calvo A, Aristu J
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41831794 · Publisher ↗
PURPOSE: Radiation necrosis (RN) is an adverse event following stereotactic radiosurgery (SRS) for brain metastases (BMs). The planning target volume (PTV) size is a potential yet suboptimal predictor of RN, unlike V12,...
PURPOSE: Radiation necrosis (RN) is an adverse event following stereotactic radiosurgery (SRS) for brain metastases (BMs). The planning target volume (PTV) size is a potential yet suboptimal predictor of RN, unlike V12, which remains independent of the number of fractions delivered. Prior authors demonstrated that radiation-induced brain injury can be traced in peripheral blood. This study aimed to identify predictive biomarkers of symptomatic RN at the time of SRS to develop a risk prediction model based on inflammatory proteomic plasma markers and the PTV as dosimetric surrogate. METHODS AND MATERIALS: A retrospective study design was conducted using plasma samples from patients with BMs treated with SRS (single fraction) or fractionated stereotactic radiation therapy (3-6 fractions). The Olink 96 Target Immuno-Oncology Panel was used to analyze 92 related human proteins using oligonucleotide-bound antibodies and real-time polymerase chain reaction. Statistical analyses included receiver operating characteristic curves and multivariable Cox proportional hazards regression to evaluate clinical parameters, PTV, and blood biomarkers to predict RN risk. Multiplex immunophenotyping was performed on available RN tissue samples to assess immune infiltration. RESULTS: A total of 47 patients with BMs were analyzed (21 cases with RN and 26 without). Cox regression analysis identified PTV and the inflammation-related blood biomarkers MUC-16 and CXCL11 as independent predictors of RN. A high Necrosis Predictive Index combining PTV with MUC-16 and CXCL11 was significantly associated with a higher risk (hazard ratio = 2.543 [1.615-4.005]; P < .0001) of RN development. Receiver operating characteristic analysis demonstrated that the Necrosis Predictive Index effectively distinguished patients with RN, achieving an area under the curve of 0.808. An exploratory independent analysis found that baseline levels of other proinflammatory blood biomarkers (ie, CD8a and IL-8) were also associated with RN. Tissue analysis confirmed a proinflammatory microenvironment in RN compared with tumor recurrence. CONCLUSIONS: This hypothesis-generating study suggests the combination of PTV, CXCL11, and MUC-16 may predict the development of RN, warranting further validation.
Combined Real-time Liquid Biopsy With TNM Stage to Guide Induction Chemotherapy Cycles in Nasopharyngeal Carcinoma: A Development and Validation Study.
Ji P, Shen J, He D … +10 more , Chen L, Huang C, Huang S, Wang G, Li K, Du X, Ma J, Guo R, Zong J, Tang L
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41831793 · Publisher ↗
PURPOSE: The optimal number of induction chemotherapy (IC) cycles for locally advanced nasopharyngeal carcinoma (LA-NPC) is uncertain. This retrospective study proposes and validates a strategy combining clinical staging...
PURPOSE: The optimal number of induction chemotherapy (IC) cycles for locally advanced nasopharyngeal carcinoma (LA-NPC) is uncertain. This retrospective study proposes and validates a strategy combining clinical staging with post-cycle-2 plasma Epstein-Barr virus (EBV)-DNA status to guide IC cycle selection. METHODS AND MATERIALS: Patients with LA-NPC from Sun Yat-sen University Cancer Center (center 1) formed the training cohort, and those from Fujian Cancer Hospital (center 2) comprised the external validation cohort. All received 2 to 3 IC cycles plus (chemo)radiation therapy, with plasma EBV-DNA measured after cycle-2 (post-IC2-EBV-DNA). Failure-free survival (FFS) was compared between 2- versus 3-cycle IC and stratified by recursive partitioning analysis. RESULTS: The training and validation cohorts comprised 794 and 448 patients, evenly divided between 3- and 2-cycle IC. In the training cohort, recursive partitioning analysis stratified patients into 3 distinct prognostic groups. Among the low-risk group (undetectable post-IC2-EBV-DNA), FFS was comparable between the 3- and 2-cycle IC (83.8% vs 87.3%, P = .647). In the detectable cohort, patients with stage IVA disease (high-risk group) who received 3-cycle IC had improved 5-year FFS versus 2-cycle (74.0% vs 56.8%; P = .013), whereas no difference was observed in stage III (intermediate-risk group) (75.9% vs 83.1%; P = .269). Findings were confirmed in the external validation cohort. CONCLUSIONS: This retrospective study indicates that patients with stage IVA LA-NPC with detectable EBV-DNA after 2 IC cycles benefit from a third cycle, whereas no clear benefit of a third cycle is observed in patients with stage III or in those with undetectable post-IC2-EBV-DNA.
Cognitive Outcomes After Radiation Therapy for Medulloblastoma: A Voxel-based Analysis.
Aznar MC, Davey A, Wilson LJ … +13 more , Vasquez Osorio E, Bulbeck H, Thomson A, Watson-Wood K, Goddard J, Pirlepesov F, Gajjar A, van Herk M, Ashford JM, Conklin HM, Vaughan K, McCabe MG, Merchant TE
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41831792 · Publisher ↗
PURPOSE: For children treated for medulloblastoma, reducing the radiation dose to specific brain substructures may be crucial for preserving cognitive function. However, it remains unclear which substructures are most cr...
PURPOSE: For children treated for medulloblastoma, reducing the radiation dose to specific brain substructures may be crucial for preserving cognitive function. However, it remains unclear which substructures are most critical and what the optimal dose levels should be. Voxel-based analysis (VBA) enables the study of dose-response relationships in patients without requiring a priori hypotheses about which substructures are most relevant. METHODS AND MATERIALS: In a cohort of 141 children treated for medulloblastoma with photon radiation therapy between 1996 and 2013, we used VBA to investigate the relationship between radiation dose and neurocognitive outcomes. Specifically, the outcomes of interest were the decline of cognitive test scores, representing the longitudinal change in processing speed (PS) or working memory. RESULTS: VBA identified an association between a decline in PS and increased radiation dose in a region in the frontal lobe and anterior midline structures. This relationship remained significant in multivariable analysis, with a change in the age-adjusted PS decline per year of -0.11 units/y/Gy increase in dose to the region. Additionally, older age at treatment was found to be protective, whereas the use of a shunt for managing hydrocephalus was associated with a decline in PS. However, no association was found between radiation dose and working memory. CONCLUSIONS: Our analysis shows the potential of VBA in identifying new dose-response relationships in pediatric brain tumor radiation therapy. Improving our understanding of which brain regions are more sensitive to radiation could help inform future radiation therapy planning. Alongside considerations of disease control and other treatment effects, this could support the preservation of cognitive function in long-term survivors.
Prophylactic Recombinant Human Thrombopoietin Prevents Cancer Therapy-Induced Thrombocytopenia During Concurrent Chemoradiation Therapy in Limited-Stage Small Cell Lung Cancer: A Prospective, Multicenter, Phase II Clinical Trial.
Wang S, Zhao F, Wang J … +15 more , Hua Y, Ji Y, Wang C, Man L, Zhang Z, Chen J, Chen J, Li H, Ma X, Liang Z, Meng X, Wang J, Zhang X, Yu J, Wang L
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41831791 · Publisher ↗
PURPOSE: Concurrent chemoradiation therapy is the standard therapy for limited-stage small cell lung cancer (LS-SCLC) but induces cancer therapy-induced thrombocytopenia (CTIT), which leads to treatment delays. This stud...
PURPOSE: Concurrent chemoradiation therapy is the standard therapy for limited-stage small cell lung cancer (LS-SCLC) but induces cancer therapy-induced thrombocytopenia (CTIT), which leads to treatment delays. This study aims to assess the efficacy and safety of prophylactic recombinant human thrombopoietin (rhTPO) in preventing CTIT in this patient population. METHODS AND MATERIALS: This prospective, multicenter, phase II trial was conducted across 14 Chinese centers. LS-SCLC patients receiving etoposide plus cisplatin or carboplatin chemotherapy with concurrent radiation therapy were given subcutaneous rhTPO (300 IU/kg/d) on days 1-5, 8-12, and 15-19 during radiation therapy. rhTPO treatment was stopped if platelet count reached ≥300 × 10/L or increased by ≥100 × 10/L from baseline. Primary endpoints were the nadir and peak platelet count. RESULTS: From March 8, 2024, to October 10, 2024, 56 LS-SCLC patients were enrolled. During the rhTPO treatment period, nadir platelet count (×10/L) was 128.54 ± 54.15, and peak platelet count reached 409.23 ± 173.50. Overall incidence of CTIT was 33.9% (19/56), including 8.9% (5/56) grade 3, and no grade 4-5 events. A total of 78.9% of patients (15/19) experienced platelet count recovery to ≥100 × 10/L during the rhTPO treatment period. Median time for platelet count recovery from <100 × 10/L to ≥100 × 10/L was 8 days (95% CI, 6-14). Multivariable logistic regression analysis revealed that low baseline platelet count (<150 × 10/L) was an independent risk factor for developing CTIT (odds ratio, 4.26; 95% CI, 1.08-16.78; P = .038). No patients required platelet transfusions or experienced radiation therapy interruptions, and only one patient required a reduction in the dose of chemotherapy throughout the entire study. Moreover, no serious adverse events were reported. rhTPO-related adverse reactions were infrequent and predominantly grade 1 (eg, transient platelet elevation). CONCLUSIONS: Prophylactic rhTPO during concurrent chemoradiation therapy for patients with LS-SCLC demonstrated a potential benefit in maintaining platelet counts with a low incidence of CTIT. These findings support further investigation of rhTPO as a preventive strategy for high risk CTIT patients.
Constraints, Cumulative Doses and Toxicity Outcomes in Glioma Reirradiation: A Systematic Review and Radiobiological Comparison From the Reirradiation Collaborative Group (ReCog).
Slevin F, Chen XS, Rosen BS … +7 more , Shen CJ, Mayo C, Zhang L, Butala AA, Ajithkumar T, Kim MM, Murray L
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41831790 · Publisher ↗
There remains considerable uncertainty regarding normal tissue tolerances to reirradiation for recurrent brain tumours. This systematic review aimed to collate reirradiation constraints, planned cumulative organ at risk...
There remains considerable uncertainty regarding normal tissue tolerances to reirradiation for recurrent brain tumours. This systematic review aimed to collate reirradiation constraints, planned cumulative organ at risk (OAR) doses and corresponding toxicity outcomes for adults treated with reirradiation for recurrent glioma. The Medline, Embase, Cochrane, Web of Science and Scopus databases were searched for studies published up to 1 July 2025. To allow comparison between constraints, where necessary, equivalent doses in 2Gy fractions (EQD2Gy) were calculated. In total, 27 studies were included. Most patients had glioblastoma. Of the 24 studies that reported constraints, 17 employed flat constraints (i.e. applied to the reirradiation treatment alone), and 11 employed cumulative constraints (i.e. applied across the original and reirradiation treatments), without the use of tissue recovery factors (TRFs). None of the included studies used TRFs. Constraints were highly heterogenous. Planned cumulative doses were reported in seven studies and were also heterogeneous. No serious optic pathway, eye or brainstem toxicities were reported. Radionecrosis was infrequently reported, but severe cases did occur. No clear patterns emerged between cumulative constraints or planned cumulative doses and the occurrence of radionecrosis. Given the heterogeneity, it is not possible to recommend definitive OAR constraints for glioma reirradiation. That said, in patients with recurrent glioblastoma, for optic pathways and brainstem, candidate cumulative maximum or near-maximum EQD2Gy limits (α/β=2Gy) of 75-80Gy and 85-100Gy, respectively, are suggested as being associated with <5% risk of severe toxicity. For normal brain, 100-110Gy might be reasonable though larger volume constraints are likely relevant but, as yet, are undefined. In conclusion, there is heterogeneity in glioma reirradiation constraints. The lack of data on larger volume normal brain constraints and toxicity outcomes from centres using cumulative constraints with TRFs represent substantial gaps. Trials and standardisation of reporting are means to better define dose-toxicity relationships.
Quality of Life in Patients With p16+ Oropharyngeal Cancer Receiving Accelerated Radiation Therapy With Either Cisplatin or Cetuximab in the NRG/RTOG 1016 Randomized Controlled Trial.
Ringash J, Torres-Saavedra PA, Gillison ML … +16 more , Caudell JJ, Adelstein DJ, Harari PM, Sturgis EM, Basch E, Koyfman SA, Krempl GA, Blakaj DM, Bates JE, Galloway TJ, Jones CU, Beadle BM, Harris J, Le QT, Yom SS, Movsas B
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41825810 · Full text
PURPOSE: NRG/RTOG 1016 was a phase III randomized noninferiority de-escalation trial comparing cetuximab versus cisplatin, concurrent with accelerated radiation 70 Gy/6 weeks, in p16+ oropharyngeal cancer. Quality of lif...
PURPOSE: NRG/RTOG 1016 was a phase III randomized noninferiority de-escalation trial comparing cetuximab versus cisplatin, concurrent with accelerated radiation 70 Gy/6 weeks, in p16+ oropharyngeal cancer. Quality of life (QOL) was a secondary endpoint. METHODS AND MATERIALS: Eligible/consenting patients among the first 400 entered completed the EORTC QLQ-C30/H&N35 at baseline, end of treatment, 3, 6, and 12 months posttreatment, to provide 90% power to detect an effect size of 0.5 in the between-arm change in QOL scores from baseline to 6 months. We report completion, responsiveness, and patterns over time across domains between arms, considering a difference of >10 points as clinically significant. RESULTS: Consent to the QOL substudy was 91%, with analyzable data in 375 patients. No significant differences in patient/tumor characteristics were found by QOL participation status. Completion at the 5 timepoints did not differ by arm (intensity modulated radiation therapy [IMRT] + cisplatin/cetuximab) and was: 92/94%, 74/77%, 76/81%, 76/81%, and 73/74%. No significant difference was observed between arms for the 6-month change from baseline on any domain. At the end of treatment, all domains showed statistically and clinically significant mean worsening across both arms except emotional functioning, dyspnea, financial difficulties, diarrhea, and teeth. By 6 months, drops >10 points remained for: senses, social eating, opening mouth, dry mouth, sticky saliva; and at 12 months for senses, trouble with social eating, opening mouth, dry mouth, sticky saliva, pain killers, and weight gain. Pain killer reduced at both 6 and 12 months. CONCLUSIONS: Although replacing concurrent IMRT + cisplatin with IMRT + cetuximab did not improve global health status or swallowing at 6 months, this study supports the responsiveness of the EORTC QLQ-C30/H&N35 to the effects of IMRT + systemic therapy for oropharyngeal cancer. Dry mouth, sticky saliva, and senses showed large, significant, and persistent impairment, whereas domains related to eating (swallowing, appetite, nutritional supplements, social eating, and weight loss) did not show sustained significant impairment in this study.
Comparison of Computed Tomography Ventilation Imaging and Hyperpolarized He Magnetic Resonance Imaging in Patients With Lung Cancer.
Ito S, Nakajima Y, Fujita Y … +8 more , Capaldi DPI, Sheikh K, Parraga G, Kabus S, Palma DA, Yaremko B, Hoover D, Yamamoto T
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41802548 · Publisher ↗
PURPOSE: Computed tomography ventilation imaging (CTVI) has great potential for clinical translation and has been validated in numerous studies. However, previous studies focused on image comparisons, and little is known...
PURPOSE: Computed tomography ventilation imaging (CTVI) has great potential for clinical translation and has been validated in numerous studies. However, previous studies focused on image comparisons, and little is known about the dosimetric implications of "good" or "poor" image correlations or agreements in radiation therapy (RT). This study assessed the agreement of dose-function metrics between CTVI and hyperpolarized He magnetic resonance imaging (MRI) as a reference. METHODS AND MATERIALS: This study included 27 patients with non-small cell lung cancer who were randomized in a phase 2 trial examining He MRI-guided functional avoidance RT. All patients underwent 4-dimensional computed tomography and He MRI. CTVI was retrospectively created. Pearson correlation and Bland-Altman analyses were performed to assess the agreements between He MRI- and CTVI-based well-ventilated lung dose-function metrics, including functional V (fV) and functional mean lung dose, of RT plans. To assess the associations between dose-function metrics and clinical outcomes, we dichotomized patients by a clinically meaningful decline in Functional Assessment of Cancer Therapy-Lung: Lung Cancer Subscale (≥3-point) and the occurrence of grade ≥2 radiation pneumonitis and compared the dose-function metrics between the 2 groups. RESULTS: Correlation coefficients of dose-function metrics were 0.80 to 0.82 for both fV and functional mean lung dose. Bland-Altman analyses showed a mean difference < 1% for fV, with 95% limits of agreement of 8% to 10%, indicating that agreements varied among patients. Among Lung Cancer Subscale-evaluable patients (n = 20), those with a ≥3-point decline (n = 8) had higher fV than those without (CTVI: 28.2% vs 21.9%, P = .05; He MRI: 26.2% vs 22.3%, P = 0.24). Patients with grade ≥2 radiation pneumonitis (n = 4) also showed higher values than those without (CTVI: 28.2% vs 24.2%, P = .34; He MRI: 27.0% vs 23.5%, P = .25). CONCLUSIONS: CTVI demonstrated strong correlations and small bias in dose-function metrics with He MRI, including fV and functional mean lung dose. These findings support CTVI as a ventilation surrogate for functional avoidance RT.
Executive Summary of the American Radium Society Appropriate Use Criteria for Extranodal Natural Killer/T-cell Lymphoma.
Dandapani SV, Ahmed S, Robinson T … +13 more , Advani R, Bates J, Constine LS, Dabaja B, Ha CS, Hoppe BS, Vega RM, Peterson JL, Pinnix CC, Plastaras J, Shaaban SG, Wu SY, Milgrom SA
Int J Radiat Oncol Biol Phys · 2026 Mar · PMID 41785936 · Publisher ↗
Extranodal natural killer/T-cell lymphoma is a rare and aggressive extranodal non-Hodgkin lymphoma. These evidence-based recommendations for natural killer/T-cell lymphoma by the American Radium Society were developed by...
Extranodal natural killer/T-cell lymphoma is a rare and aggressive extranodal non-Hodgkin lymphoma. These evidence-based recommendations for natural killer/T-cell lymphoma by the American Radium Society were developed by a multidisciplinary panel of medical and radiation oncologists to propose treatment approaches. This guideline was based on a literature review with a consensus methodology to rate the appropriateness of treatment recommendations for each natural killer/T-cell lymphoma clinical presentation. Six variants highlight the recommended treatment strategies.
Pretreatment Risk Model for Radiation-Induced Lymphopenia Is Associated With Adjuvant Durvalumab Efficacy in Patients With Unresectable Stage III NSCLC.
van Rossum PSN, Damen PJJ, Cortiula F … +11 more , Hobbs BP, De Marchi L, Mohan R, Peters M, Schneiders FL, De Ruysscher D, Wijsman R, Verhoeff JJC, Xu T, Liao Z, Lin SH
Int J Radiat Oncol Biol Phys · 2026 Feb · PMID 41763495 · Publisher ↗
PURPOSE: Severe radiation-induced lymphopenia (RIL) during concurrent chemoradiation therapy (CCRT) for NSCLC has been associated with poorer outcomes and reduced immunotherapy efficacy. Because RIL often develops late d...
PURPOSE: Severe radiation-induced lymphopenia (RIL) during concurrent chemoradiation therapy (CCRT) for NSCLC has been associated with poorer outcomes and reduced immunotherapy efficacy. Because RIL often develops late during CCRT, identifying patients at risk before treatment may be clinically relevant. This study aimed to develop and validate a nomogram based on pretreatment predictors for severe RIL, and secondarily to explore associations between predicted RIL risk and adjuvant durvalumab-associated survival. METHODS AND MATERIALS: A retrospective development cohort of consecutive patients with NSCLC treated with CCRT (2010-2019) was established, along with an independent external validation cohort from other institutions. A multivariable logistic regression model was developed to predict severe RIL, with internal and external validation. Survival analyses (progression-free and overall survival) were performed as exploratory, hypothesis-generating analyses stratified by predicted RIL risk and durvalumab use. RESULTS: Severe RIL was defined as an absolute lymphocyte count nadir of <0.24 K/µL. Among 451 patients, 164 (36%) developed severe RIL. Independent predictors were older age, cN3-stage, larger planning target volume, >30 radiation therapy fractions, higher mean lung dose, and lower baseline absolute lymphocyte count (c-statistic: 0.70). External validation (130 patients, 41 [32%] with severe RIL) yielded similar discrimination (c-statistic: 0.69). In exploratory analyses, durvalumab use was associated with improved survival in patients with a low predicted risk of severe RIL, whereas no statistically significant association was observed in those with a high predicted risk, in both cohorts. CONCLUSIONS: We developed and externally validated a pretreatment prediction model for severe RIL during CCRT for NSCLC with consistent performance. In exploratory analyses, an association between durvalumab use and improved survival was observed in patients with a low predicted risk of severe RIL, but not in those with a high predicted risk. This model may help identify patients for lymphopenia-mitigating strategies and inform more personalized immunotherapy approaches, pending prospective validation.
Integrating Genomic and Nongenomic Data to Stratify the Risk of Contralateral Breast Cancer After Radiation Therapy.
Lee S, Shu X, Derkach A … +11 more , Reiner AS, Liang X, Woods M, Concannon P, Lynch CF, Malone KE, Knight JA, John EM, Deasy JO, Bernstein JL, Oh JH
Int J Radiat Oncol Biol Phys · 2026 Feb · PMID 41763494 · Full text
PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging because of the comple...
PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging because of the complex interplay of genomic, treatment, personal, and clinical factors. This study investigated computational methods that integrate genome-wide single-nucleotide polymorphisms and nongenomic data to develop a risk stratification model for developing CBC in women treated with RT for their first primary breast cancer. METHODS AND MATERIALS: This study used a subset of the population-based Women's Environmental Cancer and Radiation Epidemiology study that included 633 CBC cases and 1253 individually matched unilateral breast cancer controls who were treated with RT and had single-nucleotide polymorphism data available from a genome-wide association study. The study population was split into training, validation, and test sets for rigorous modeling and validation. Three data integration methods were compared in terms of their ability to stratify CBC risk: (1) naive integration; (2) sequential integration; and (3) sequential iterative integration. A biological analysis of the final model was performed using gene set enrichment analysis and protein-protein interaction analysis with gene annotation information informed by the model. RESULTS: The best-performing integration method was the sequential iterative integration equipped with the mixed-effect random forest algorithm. This approach achieved an area under the curve of 0.64 to stratify CBC risk in the test set, representing moderate predictive power. Calibration analysis showed good agreement between the lowest and highest risk bins stratified using sorted predicted values in the test set, resulting in an odds ratio of 3.27 for both predicted and observed CBC occurrence. Gene set enrichment analysis and protein-protein interaction analysis revealed that genes with high importance scores were associated with pathways relevant to lipid and fatty acid metabolism as well as breast cancer sensitivity to tamoxifen. CONCLUSIONS: The mixed-effect random forest approach demonstrated the potential for integrating high-dimensional genomic and low-dimensional nongenomic data to stratify CBC risk.
Early Safety of Ultra-Hypofractionated Whole Breast Irradiation and Sequential Tumor Bed Boost for Early Breast Cancer (SHIFT): A Multicenter, Phase 2 Trial.
Zheng SY, Huang JQ, Xie JR … +15 more , Gan L, Yu B, Shi YG, Jiang J, Zhang J, Dong ML, Qi WX, Cai G, Cai R, Xu C, Xu HP, Qian XF, Zhang YB, Cao L, Chen JY
Int J Radiat Oncol Biol Phys · 2026 Feb · PMID 41759682 · Publisher ↗
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...
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.
Integration of Breast Reconstruction and Radiation: How the Proton-Photon Debate Exposes Methodological Gaps, Analytical Bias, and Lack of Consensus.
Naoum GE, Taghian A, Kaidar-Person O … +5 more , Meattini I, Boersma L, Khan A, Colwell A, Poortmans P
Int J Radiat Oncol Biol Phys · 2026 Feb · PMID 41759681 · Publisher ↗
For breast cancer patients undergoing mastectomy and reconstruction, postmastectomy radiation therapy jeopardizes reconstruction outcomes, yet no universal consensus exists for integrating postmastectomy radiation therap...
For breast cancer patients undergoing mastectomy and reconstruction, postmastectomy radiation therapy jeopardizes reconstruction outcomes, yet no universal consensus exists for integrating postmastectomy radiation therapy with breast reconstruction. The recent expansion of proton therapy has intensified a debate over its role in this setting. Although protons offer superior dosimetry and cardiac sparing compared to photons, several studies, focusing on implant-based reconstruction, report higher rates of capsular contracture and reconstruction failure with protons, whereas others show comparable protons outcomes to photons. These discordant findings reveal not only questions about radiation modality but also deeper flaws in the reconstruction literature-heterogeneous inclusion criteria, inconsistent endpoint definitions, reliance on historical controls, and inadequate adjustment for surgical confounders. Such methodological weaknesses have tangible consequences: policy decisions (eg, payer coverage for proton therapy) may be based on incomparable outcomes; patient counseling becomes inconsistent, with surgeons and radiation oncologists quoting different risks; and trial design suffers, as discordant rates affect sample size calculations. In this review, we use the proton-photon debate as a lens to expose how inconsistent reporting and research methodological weaknesses in the field of breast reconstruction have hindered reaching a consensus. We advocate for methodological standardization through harmonized endpoints definitions and stratified cohort design. Establishing reporting frameworks that integrate surgical events and patient-reported outcomes is essential to generate interpretable evidence, inform reimbursement policy, and align practices across radiation oncology and reconstructive surgery fields.
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