Mai WX, Huang KZ, Kuo J
… +26 more, Wang E, Wong S, Yauger A, Langer J, Free D, Gebeyehu P, Kathiravan A, Swamy A, Flores KZ, Merrill S, Sianez-Torres D, Kokinos A, Pranoto A, Lao O, Guerrero T, Bedi H, Sala M, Bourhis J, Durham A, Skinner L, Vitzthum LK, Kastelowitz N, Chin A, Diehn M, Loo BW, Blomain ES
PURPOSE: Tumor motion during respiration presents a challenge in delivering high-precision stereotactic ablative radiation therapy (SABR) for lung cancer. While inspiratory breath-hold techniques can minimize motion, the...PURPOSE: Tumor motion during respiration presents a challenge in delivering high-precision stereotactic ablative radiation therapy (SABR) for lung cancer. While inspiratory breath-hold techniques can minimize motion, they are often limited by the patients' ability to sustain prolonged breath-holds and the variability that comes with repeat breath-holds. We present the first-in-human demonstration of the feasibility and safety of percussive ventilation breath-hold (PVB) to eliminate the uncertainty of breath-hold reproducibility between confirmatory volumetric image guidance and delivery of lung tumor SABR by completing both within the same assisted breath-hold. Here, we report that 4 patients were successfully treated as initial observations from a prospective clinical trial of PVB-SABR. METHODS AND MATERIALS: Four patients with lung tumors were treated in a prospective, institutional review board-approved study in which they underwent an education and evaluation session to assess their tolerance for PVB, followed by treatment with PVB-SABR. RESULTS: All 4 patients successfully completed PVB-SABR. The mean PVB duration per fraction from the beginning of the final cone beam computed tomography image verification to the end of SABR delivery was 6 minutes 56 seconds in a single PVB. Within that time, the mean delivery time per fraction was 2 minutes 22 seconds and the mean duty cycle was 93.5%. CONCLUSIONS: These initial observations in a first prospective trial of PVB-SABR demonstrate the feasibility of PVB to enable completion of SABR delivery within the same effective breath-hold as confirmatory volumetric imaging, eliminating the uncertainty of interbreath-hold reproducibility.
Elsharief MM, Pan S, Wang Y
… +12 more, Abutaleb MK, Fatimilehin A, Hanafi H, Thorp N, Reynolds D, France A, Wylie J, Sharma S, Ebrahim M, Venkata VG, Brennan B, Smith E
PURPOSE: We report survival and disease-specific outcomes, prognostic factors, and impact of radiotherapy timing in patients with non-metastatic rhabdomyosarcoma (RMS) treated with definitive proton beam therapy (PBT) at...PURPOSE: We report survival and disease-specific outcomes, prognostic factors, and impact of radiotherapy timing in patients with non-metastatic rhabdomyosarcoma (RMS) treated with definitive proton beam therapy (PBT) at a national UK centre. PATIENTS AND METHODS: We retrospectively reviewed patients with non-metastatic, pathologically confirmed RMS treated with definitive PBT at the XX Proton Beam Therapy Centre between December 2018 and May 2025. All patients were treated according to RMS 2005 or FaR-RMS protocols. Time-to-event outcomes included local control (LC), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). Kaplan-Meier methods were used for survival estimates. Prognostic factors were assessed using Firth-penalised Cox regression due to limited event numbers. Multivariable models adjusted for dominant prognostic variables. RESULTS: Eighty-four patients were included with a median age of 7.6 years (range, 1-70). Parameningeal primaries accounted for 51% of cases, and 75% of patients had high or very high-risk disease. Median time from chemotherapy initiation to PBT was 13 weeks (range, 10-22). After a median follow-up of 48 months, 4-year OS, DFS, LC, and DMFS were 81.2%, 70.8%, 75.4%, and 89.7%, respectively. Fifteen patients developed local failure, all occurring in-field within the high-dose region. On univariate analysis, parameningeal primary site and advanced T stage (T3-4) were significantly associated with inferior OS and DFS. Radiotherapy initiation at ≥14 weeks was not independently associated with worse outcomes after adjustment for other variables. Within the parameningeal subgroup, intracranial extension was associated with significantly inferior OS. CONCLUSIONS: Definitive PBT for non-metastatic RMS resulted in disease control and survival outcomes comparable to those reported in cooperative group trials and other proton therapy series. Prognosis appears to be primarily driven by disease-related factors, particularly parameningeal location, intracranial extension, and advanced T stage. Radiotherapy timing was not independently associated with outcomes after adjustment for these factors; however, these findings should be interpreted with caution, particularly in relation to disease-free survival. Further validation in larger, multi-institutional datasets is warranted.
INTRODUCTION: Management of recurrent glioblastoma remains a major challenge, with no treatment shown to meaningfully prolong survival. Reirradiation may offer local control but is often constrained by concerns regarding...INTRODUCTION: Management of recurrent glioblastoma remains a major challenge, with no treatment shown to meaningfully prolong survival. Reirradiation may offer local control but is often constrained by concerns regarding dose to critical normal tissues. We evaluated clinical outcomes, toxicity, and cumulative dosimetric parameters in patients with recurrent glioblastoma treated with hypofractionated proton reirradiation. MATERIALS AND METHODS: We retrospectively identified patients with recurrent glioblastoma treated with hypofractionated reirradiation courses of 35 Gy in 10 fractions. Cumulative composite dosimetry was calculated using EQD2 (α/β = 2) for organs at risk (OARs). Overall survival (OS) was estimated using Kaplan Meier methods. Cox proportional hazards modeling was performed to identify factors associated with OS. A contemporaneous cohort treated with hypofractionated photon reirradiation was identified for comparison. RESULTS: A total of 89 patients were treated with hypofractionated proton reirradiation for recurrent glioblastoma between 2015 and 2025 with median follow up of 7.2 months. Median age was 58 years (IQR 48-68), and 48% underwent reresection prior to reirradiation. Composite dosimetry demonstrated that the initial radiation course accounted for the majority of cumulative OAR dose, with proton reirradiation contributing limited additional exposure. Median OS from reirradiation in the proton cohort was 8.3 months (95% CI 6.27-9.47), with 6 and 12 month OS of 62.6% and 24.9%, respectively. On multivariable analysis, increasing age was independently associated with worse OS. A comparator cohort of 49 patients treated with photon reirradiation was identified. OS did not differ between proton and photon reirradiation cohorts. 8 (5.8%) patients experienced Grade 3 or 4 radiation necrosis. No Grade > 4 toxicities were observed. CONCLUSIONS: Hypofractionated proton reirradiation was feasible and associated with favorable toxicity outcomes, supporting its use as a retreatment option. Prospective studies are needed to further define optimal patient selection.
PURPOSE: To simulate motion and evaluate its dosimetric interplay from gastrointestinal (GI) motility in pancreas pencil-beam scanning (PBS) proton therapy, and to assess how fractionation and motility amplitude affect t...PURPOSE: To simulate motion and evaluate its dosimetric interplay from gastrointestinal (GI) motility in pancreas pencil-beam scanning (PBS) proton therapy, and to assess how fractionation and motility amplitude affect target coverage and organ-at-risk (OAR) doses. METHODS AND MATERIALS: A novel, physiology-informed GI motion simulator was developed to quantify GI motion by generating time-resolved motion modes (peristalsis, rhythmic segmentations, and high-amplitude propagated contractions (HAPC)) parameterized along organ centerlines (stomach, duodenum, and small bowel). The simulator was integrated with an in-house 4D dose accumulation tool to evaluate dose interplay between GI motion and PBS delivery. Seven clinically treated pancreatic adenocarcinoma patients receiving proton PBS were studied to assess correlations between motion characteristics and the resulting dosimetric interplay effects. Two motion settings were studied: MODERATE (small magnitude) and MAX (large magnitude). Endpoints were dosimetric differences (Δ) relative to static plan (no GI motion), e.g., CTV D95% and OAR D2%. Single-fraction (1-fx) and full-treatment with multiple fractions (full-tx) deliveries were compared. Dosimetric Δ and dose range (defined as the difference between the maximum and minimum values across motion scenarios) are reported as percentages relative to the prescribed dose (mean [min, max] in %). RESULTS: GI motility alone produced measurable interplay effect that degraded the target coverage and increased critical OAR dose. For 1 MAX/1-fx (1 fraction with MAX motion), CTV D95% changed by -1.34% [-5.52%, +0.08%] across prescription doses ranging from 30 to 59.4 Gy. For OARs, relative dose ranges were 6.90% [4.48%, 13.45%] for duodenum, 6.74% [0.43%, 25.57%] for small bowel, and 8.47% [3.08%, 12.63%] for stomach. MAX motion yielded larger Δ and wider dose ranges than MODERATE. For full treatment, conventional fractionation substantially reduced the dose interplay effect and pulled Δ toward zero, whereas hypofractionation provided only partial averaging. CONCLUSIONS: GI motility is a dosimetrically relevant, geometry-contingent source of interplay in pancreas PBS. We present the first plan-specific replay of clinical PBS deliveries on motility-only time-resolved anatomies. Fractionation mitigates this interplay effect.
PURPOSE: Intra-fractional respiratory motion management encounters trade-offs between target coverage, organ at risk (OAR) sparing, and treatment efficacy. Real-time tracking is promising but hindered by invasiveness ris...PURPOSE: Intra-fractional respiratory motion management encounters trade-offs between target coverage, organ at risk (OAR) sparing, and treatment efficacy. Real-time tracking is promising but hindered by invasiveness risks, lack of global deformations, or inadaptability to irregular respiration. Currently respiratory modeling-based adaptive tracking may offer ideal solutions, but is limited by discrete clinical priors, highly-sparse observations, and complex motion variability. This study advances the constrained modeling toward a synergistic knowledge- and information-augmentation-driven paradigm (KIADP), thereby bridging sparse real-time observations with voxel-wise anatomical deformations. METHODS AND MATERIALS: Four multi-center cohorts were enrolled comprising 35 cases (10 prospective and 25 retrospective), including 7 patients undergoing re-irradiation. KIADP was instantiated as MorphTracking, a patient-specific respiratory modeling framework that synergistically leveraged prior clinical materials and external-and-internal surrogates-optical surface images (OSIs) and single-view X-ray projections-to estimate 3D deformation vector fields (DVFs). MorphTracking incorporated a comprehensive data augmentation pipeline to enhance phase diversity with irregular variability. To enforce physical-consistency and anatomical-plausibility, we performed optimization spanning deformation, image, and surrogate domains. MorphTracking was compared with three state-of-the-art (SOTA) methods and further validated through full-cycle evaluations, ablation studies, and simulated 4D treatment scenarios. RESULTS: Across thoracic (n=24) and abdominal (n=11) cohorts, MorphTracking significantly outperformed SOTA methods in CT reconstruction and tracking of gross tumor volume (GTV) and OARs. It exhibited high consistency with ground-truths spanning full-cycle phases, operating at an average inference time of 15.622±0.001 ms/frame. Comprehensive ablation studies substantiated the individual and synergistic contributions of data augmentation, multimodal configuration, and cross-domain optimization. In simulated treatment scenarios, compared to the standard internal GTV (IGTV) approach, MorphTracking-driven 4D delivery effectively maintained GTV's dosimetric indices while enhancing OAR (spinal cord and lungs) sparing. CONCLUSIONS: MorphTracking provides an innovative solution for intra-fractional respiratory modeling, potentially enhancing voxel-wise geometric confidence for motion-aware highly-conformal dose delivery with real-time, robust, and adaptive anatomical tracking.
PURPOSE: Proton plans are often very homogenous with minimal hotspots compared to the prescribed dose, which may not be ideal for ablative stereotactic body radiation therapy (SBRT). A treatment planning approach for ste...PURPOSE: Proton plans are often very homogenous with minimal hotspots compared to the prescribed dose, which may not be ideal for ablative stereotactic body radiation therapy (SBRT). A treatment planning approach for stereotactic body proton therapy (SBPT) is proposed to match the characteristics of photon SBRT dose distributions, namely a Gaussian-shaped curve with high centralized doses in the gross tumor volume (GTV) and rapid dose falloff in healthy tissues. METHODS AND MATERIALS: The semi-automated technique is derived from a desired maximum dose value, or hotspot. The GTV is divided into concentric shells, and treatment plans are optimized to drive the hotspot to the innermost shell while using the remaining target shells to shape falloff within the GTV. The algorithm is tested in a cohort of 10 patients who previously received SBPT to the liver at our institution. The Gaussian approach is compared to standard homogeneous SBPT planning for both dosimetric and deliverability results. RESULTS: Achieved hotspots on Gaussian plans matched pre-specified hotspot within 2.2% on average. Gaussian-based planning led to a statistically significant increase in biologically effective dose of 20 Gy (α/β=10) compared against the homogenous plans. On nominal plans, healthy liver and gastrointestinal organ-at-risk and planning-risk-volumes showed no statistically significant differences, though liver D trended lower with the Gaussian approach (10.8 Gy vs 11.9 Gy, p=0.01). In evaluating plan robustness, Gaussian plans had slightly higher dose spill outside of the PTV, but lower dose to GI OARs. In a subset of 3 plans evaluated for deliverability, Gaussian plans took 10 seconds longer to deliver per field and patient-specific QA results passed institutional criteria. CONCLUSIONS: A mathematically driven treatment planning technique was developed and tested for generating liver SBPT plans. The proposed technique was derived to mirror photon SBRT dose distributions, allowing for enhanced harmonization of SBPT with historical SBRT clinical data and potentially allowing safe radiation dose escalation during SBPT.
Li W, Li Z, Shi Y
… +38 more, Lam S, Xiao L, Cheung AH, Liu C, Liu S, Yang J, Zeng G, Yang X, Lee SWY, Nicol AJ, Liu Z, Zou L, Yin H, Li X, Liu X, Sun J, Li J, Zhu D, Li X, Sun R, Li B, Sun X, Ge H, Chen J, Li C, Wu X, Wang X, Zhang J, Liu C, Li T, Ren G, Teng X, Zhi S, Cheung AL, Lee FK, Lee VH, Fu J, Cai J
PURPOSE: Contrast-enhanced MRI imaging via administration of contrast agents is critical for diagnosis, staging, and treatment of nasopharyngeal carcinoma. However, gadolinium-based contrast agents can lead to severe adv...PURPOSE: Contrast-enhanced MRI imaging via administration of contrast agents is critical for diagnosis, staging, and treatment of nasopharyngeal carcinoma. However, gadolinium-based contrast agents can lead to severe adverse effects, especially in patients with compromised kidney function, necessitating a safer alternative for contrast enhancement. In this study, we aim to develop and assess the clinical feasibility of a federated learning model for synthesizing virtual contrast-enhanced MRI (VCE-MRI) images from contrast-free scans for patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this multicenter, retrospective study, we developed and clinically evaluated a federated learning-based VCE-MRI synthesis model (FL-VCE-MRI) using pre-treatment contrast-free T1-weighted and T2-weighted MRI scans. The model was trained using data from 14 centers involving 2,061 patients. External validation was performed with an independent dataset from 25 centers comprising 126 patients. Additionally, ten clinicians from eight centers assessed the quality of the synthetic images. RESULTS: The FL-VCE-MRI model demonstrated high generalizability in the external validation dataset, achieving a mean absolute error (MAE) of 45.85 (95% CI, 43.73-47.96). For centers facing challenges in developing well-performing single-center models, the FL-VCE-MRI improved the average MAE from 53.93 (95% CI: 49.21-58.65) to 45.93 (95% CI: 41.64-50.22). Clinical evaluations indicated that the synthesized VCE-MRI images are both reliable and clinically valuable, with no significant differences compared to gadolinium-enhanced MRI in disease diagnosis, tumor staging, and delineation. CONCLUSION: The FL-VCE-MRI model shows potential as a non-invasive alternative to gadolinium-enhanced MRI for NPC patients.
PURPOSE: Pencil beam scanning proton therapy of hepatocellular carcinoma (HCC) may reduce the risk of radiation-induced liver disease compared to photon radiotherapy, but tumor motion and anatomical changes can distort t...PURPOSE: Pencil beam scanning proton therapy of hepatocellular carcinoma (HCC) may reduce the risk of radiation-induced liver disease compared to photon radiotherapy, but tumor motion and anatomical changes can distort the dose. This was investigated through daily reconstruction of the delivered dose in a clinical trial of gated HCC proton therapy. METHODS AND MATERIALS: Sixteen patients with HCC included in a prospective phase II trial received 58-67.5 Gy (RBE) of proton therapy in 15 fractions with treatment planning in the exhale phase of a 4DCT and exhale gated treatment guided by an external gating block. CBCT-guided setup was based on 2-3 implanted fiducial markers. At 3-8 fractions per patient, the 3D tumor motion during pre-treatment and post-treatment CBCT acquisition was measured via the positions of the fiducial markers as a surrogate for the moving tumor. The tumor motion during treatment was estimated from the gating block motion using an external-internal motion correlation model constructed from the CBCTs. The delivered CTV dose was estimated by modelling tumor motion as proton spot position shifts and energy shifts in the treatment planning system. Effects of interfractional anatomical changes were assessed by dose recalculation on weekly control 4DCTs. RESULTS: The mean (±SD) root-mean-square tumor position error during spot delivery was 1.1±0.8mm (left-right), 2.9±1.2mm (cranio-caudal) and 1.6±0.7mm (anterior-posterior). Motion increased the CTV homogeneity index, defined as 100%⋅(D2%-D98%)/D50%, by 4.1±2.6 percentage points for individual fractions and 1.5±2.1 percentage points when accumulated over all analyzed fractions. Control 4DCTs demonstrated minimal CTV dose variations. CONCLUSIONS: Intrafractional motion affected single fraction tumor doses due to interplay effects that tended to smear out after more than three fractions. The tumor dose was robust to interfractional anatomical changes.
Boss MK, Darragh LB, Georgiopoulou S
… +12 more, Hart C, Harrison LG, Hopkins S, Rivera MA, Danczik A, Trageser E, Chow L, Wang XJ, Dow S, Jordan KR, Regan D, Karam SD
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42379318
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PURPOSE: Head and neck cancer patients with high risks for regional metastasis receive radiation therapy targeted to their primary tumor and regional lymph nodes (RLN). RLN irradiation may alter cancer immunity. We inves...PURPOSE: Head and neck cancer patients with high risks for regional metastasis receive radiation therapy targeted to their primary tumor and regional lymph nodes (RLN). RLN irradiation may alter cancer immunity. We investigate the impact of RLN irradiation in a pilot study of dogs with sinonasal tumors undergoing stereotactic body RT (SBRT). We hypothesized that RLN irradiation would reduce effector lymphocyte populations in the local microenvironment and RLNs following SBRT compared to dogs treated with SBRT targeted to the tumor alone. Previously, we demonstrated that RLN irradiation resulted in decreased populations of local CD4 and CD8 T cells following SBRT compared to dogs whose RLNs were spared. In this expanded study, the effects of RLN irradiation on local sinonasal cytokines and RLN tissue are presented. METHODS AND MATERIALS: Dogs with sinonasal tumors were treated with SBRT targeted to the tumor alone or tumor + RLNs. The local microenvironment was serially sampled with nasal lavage and RLNs were removed and analyzed two weeks post-SBRT. RESULTS: Local sinonasal cavity cytokine levels increased in dogs whose RLN were spared from SBRT whereas cytokine levels from dogs treated with RLN irradiation did not. At two weeks post-treatment, multiplex immunofluorescence imaging revealed global increases in DNA damage, apoptosis, and density of dendritic cells in irradiated RLN compared to spared. Transcriptomic analysis of the RLN tissues two-weeks post-treatment indicated that RLN irradiation led to tissue microenvironmental immunomodulation and activation of cell death and damage pathways, whereas RLNs spared from RT had expression associated with effector T cell populations, regulation of immune cell migration and adhesion, and responses to stimuli and developmental pathways. CONCLUSIONS: We expand upon our previous canine results, which demonstrate that RLN irradiation can reduce local effector lymphocyte populations, and provide preliminary evidence that RLN irradiation can alter local cytokine shifts, as well as induce apoptotic and damage responses within irradiated nodal tissues.
Cao W, Lloyd I, Dichmann M
… +14 more, Halder N, Thomas D, Chen Z, Blomain E, Adejolu F, Beck K, Faherty P, Khan M, Simone N, Jain V, Storozynsky E, Dicker AP, Choi W, Vinogradskiy Y
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42373015
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PURPOSE: Cardiac toxicity is a significant concern for cancer patients undergoing radiotherapy. The complexity of evaluating cardiac events, the time required to parse the Electronic Health Record (EHR), and the need for...PURPOSE: Cardiac toxicity is a significant concern for cancer patients undergoing radiotherapy. The complexity of evaluating cardiac events, the time required to parse the Electronic Health Record (EHR), and the need for large datasets make cardiotoxicity studies time- and resource-intensive, limiting progress of cardio-oncology research. Large-language models (LLMs) have the potential to automatically identify cardiac events. This work aimed to develop and validate a novel LLM-based automated cardiac event identification framework using a two-institution dataset. METHODS: 411 lung and breast cancer patients from two institutions were analyzed. [Institution 1] data (n=266) were divided into a development cohort (lung, n=178) and an internal validation cohort (breast, n=88). External validation used [Institution 2]data (lung, n=145). Cardiac events were physician-adjudicated from the entire EHR patient history. Extracted EHR data comprised structured problem lists and unstructured clinical notes. We introduced the Two-phase Reasoning for Automated Cardiac Event Recognition (TRACER) framework, which combines structured term matching with LLM-based analysis of unstructured notes (including specialty-filtering, temporally aware queries, and few-shot examples). Following initial evaluation of six candidate models, the three top-performing open-source LLMs (DeepSeek-R1, Llama-3.3, Mistral-Large) were validated. Performance was evaluated against physician-adjudicated ground truth using accuracy and processing time. RESULTS: Of 411 patients, 220 had at least one cardiac event. The top three models achieved mean accuracies of 79.4%, 81.0%, and 79.3% for the development, internal validation, and external validation cohorts, respectively. DeepSeek-R1 achieved the highest accuracy on internal cohorts (83.4-85.2%), while Llama-3.3 reached 85.5% accuracy on external validation. TRACER processing time was 20-42 seconds per patient (2.3-4.8 hours total) versus 2 hours per patient for manual review (822 person-hours total). CONCLUSION: TRACER, a locally deployed LLM framework, accurately extracted cardiac events across institutions and disease sites. This approach enables scalable cardio-oncology research by substantially reducing the resources required for cardiac event identification.
Lui JCF, Chan JCH, Chow JCH
… +7 more, Tong J, Lee JCY, Lee FKH, Cheung GTC, Leung VWS, Lee VHF, Jimenez RB
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42373014
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PURPOSE: To identify cardiac substructure dosimetric predictors of major adverse cardiac events (MACE) following breast radiotherapy, and to develop a robust normal tissue complication probability (NTCP) model for person...PURPOSE: To identify cardiac substructure dosimetric predictors of major adverse cardiac events (MACE) following breast radiotherapy, and to develop a robust normal tissue complication probability (NTCP) model for personalized risk assessment using a cohort with over a decade of follow-up. METHODS AND MATERIALS: This retrospective study included 633 female breast cancer patients receiving postoperative radiotherapy (2011-2013) at two XXXX public hospitals. The heart and six cardiac substructures were retrospectively contoured on planning CTs, and dose-volume metrics were extracted and converted to EQD2. The primary endpoint was the first occurrence of MACE (cardiogenic death, myocardial infarction, coronary revascularization, unstable angina, or heart failure). Fine-Gray regression was used to identify predictors of MACE, with non-cardiogenic death as the competing event. Based on these predictors, an NTCP model was developed to quantify the 10-year excess MACE risk attributable to radiation. Model performance was evaluated using bootstrap optimism-corrected Harrell's C-index and 10-year time-dependent AUC. RESULTS: Over a median follow-up of 11.8 years, 29 patients (4.6%) developed MACE. In multivariable analysis, left anterior descending artery (LAD) V40 in EQD2 emerged as the strongest dosimetric predictor (sHR = 1.023 per %; p = 0.010). A threshold of LAD V40 ≥18% identified patients at more than 2-fold increased risk of MACE (sHR = 2.333; p = 0.033). The final NTCP model (incorporating LAD V40, age, and cardiac history) demonstrated excellent discrimination with an optimism-corrected C-index of 0.865. Compared with 3D-CRT, VMAT re-planning of high-risk cases substantially reduced LAD V40, translating to an average 5.7% absolute reduction in projected 10-year excess MACE risk. CONCLUSIONS: In this multicenter cohort with long-term follow-up, LAD V40 was identified as a superior predictor of MACE compared to whole-heart dosimetry. Pending external validation, the developed NTCP model offers a promising framework for personalized risk stratification to guide the use of cardiac-sparing techniques.
Gharzai LA, Liu YA, Sun Z
… +5 more, Mullen M, Sadigh G, Pottow JA, Jagsi R, Mady LJ
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42364822
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OBJECTIVE: Patients undergoing radiotherapy (RT) often face substantial out of pocket costs (OOPC), putting patients at risk of going into debt. Unpaid medical debt sent to collections is a proxy for severe financial dis...OBJECTIVE: Patients undergoing radiotherapy (RT) often face substantial out of pocket costs (OOPC), putting patients at risk of going into debt. Unpaid medical debt sent to collections is a proxy for severe financial distress. METHODS: We identified patients treated with RT at a tertiary care center and its affiliated community sites in fiscal years 2023-2024. Charges for physician and hospital fees for RT, billed OOPC, and unpaid debt (i.e., billed OOPC that is not paid and sent to collections) were collected. Multivariable analyses (MVA) were performed to assess factors associated with unpaid debt. RESULTS: We identified 14,774 patients (mean age of 64 years (SD 14.7), 55.6% female (n=8,212), 6.3% Hispanic (n=932), and half never smokers (55.2%, n=7,863)). Most paid OOPC (61.1%, n=8,711), with mean of $1,350.70 (SD 2,569.3) and median $182.80 (IQR 29.7-1,894.7). A minority had debt sent to collections (2.7%, n=397), with a mean of $1109.90 outstanding (SD 4215.5) after a mean of 9.3 months (SD 3.9). On MVA, older patients (odds ratio (OR) 0.99 [0.98-1.00], p=0.005) were less likely to have debt sent to collections. Patients who were single (OR 1.32 [95% CI 1.06-1.64], p=0.012), current smokers (OR 2.20 [1.56-3.05], p<0.001; Figure 1), with commercial insurance (OR 1.95 [1.50-2.54], p<0.001; referent government insurance), living in more disadvantaged neighborhoods, or with higher OOPC (OR 1.08 per $1000 [1.05-1.12], p<0.001) were more likely to have unpaid debt. An OOPC threshold of $49.10 was associated with being twice as likely to have unpaid debt (AUC of 0.724; OR 2.36 [1.31-3.14], p<0.001). CONCLUSIONS: In patients undergoing RT, most patients pay OOPC for treatment and a minority of patients incur debt going to collections. Patients who are single, Hispanic, current smokers or with non-government issued insurance, and higher OOPC were more likely to incur unpaid debt.
Bellaye PS, Tavares A, Ladjohounlou R
… +12 more, Moreau M, Bernhard C, Dias A, Claron M, Froidurot L, Guillemin M, Collin B, Denat F, Truc G, Cochet A, Baude J, Mirjolet C
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42362068
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PURPOSE: Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide. Although external beam radiotherapy (RT) plays a growing role in primary and metastatic CRC, dose escalation may remai...PURPOSE: Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide. Although external beam radiotherapy (RT) plays a growing role in primary and metastatic CRC, dose escalation may remain limited due to the high dose received by neighboring organs which may cause toxicity. Targeted Radionuclide Therapy (TRT) selectively delivers cytotoxic radiation to tumor cells through a molecular vector that targets a specific protein overexpressed by cancer cells, and is linked to a therapeutic radionuclide. The present study aims to provide proof-of-concept for combining in vivo RT with anti-PDL1-targeted TRT delivered via an anti-PDL1 antibody. METHODS AND MATERIALS: An anti-PDL1 monocolonal antibody (mAb) was bioconjugated with a DOTAGA chelating agent and radiolabeled with either indium-111 (In) for imaging purposes (SPECT imaging) or lutetium-177 (Lu) for therapeutic purposes (TRT). In-mAb-PDL1 biodistribution and TRT evaluation were performed in CT26 tumor-bearing mice six days after RT (8Gy) by i.v. injection of In-mAb-PDL1 or Lu-mAb-PDL1. Epitope saturation assay was performed by co-administrating an excess of unconjugated mAb-PDL1. RESULTS: RT induced a significant increase in PDL1 expression in colon tumors in vivo enhancing the intratumoral uptake of radiolabeled anti-PDL1 mAb with In or Lu. A high uptake of radiolabeled anti-PDL1 mAb was found in the spleen that hampered the efficacy of the combination of RT with anti-PDL1 TRT by inducing a significant decrease in CD8 T lymphocytes infiltration in tumors. Epitope-saturation with a 15-fold excess of unlabeled anti-PDL1 mAb significantly reduced the spleen uptake of In-mAb-PDL1 while preserving tumor uptake. This restored the efficacy of the combination of RT with Lu-mAb-PDL1, compared to both treatments alone. CONCLUSIONS: The combination of RT and anti-PDL1 TRT shows promising synergistic effects but it requires the blockade of anti-PDL1 mAb uptake in the spleen.
Rai Y, Hoseini-Ghahfarokhi M, Bright SJ
… +10 more, Da Silva Brito WA, Lee D, Reis MTF, Wasley MD, Fru LC, Salehpour M, Schori A, Alfassi A, Gebert E, Sawakuchi GO
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42362067
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PURPOSE: To characterize the biological effects of low-energy photons generated by a ∼60-keV quasi-monoenergetic focused convergent-beam system (patented X-ray converging lens) compared with orthovoltage and 6-MV clinica...PURPOSE: To characterize the biological effects of low-energy photons generated by a ∼60-keV quasi-monoenergetic focused convergent-beam system (patented X-ray converging lens) compared with orthovoltage and 6-MV clinical photon beams. METHODS AND MATERIALS: Human (NCI-H460, NCI-H2172) and murine (KLN-205 and LKR-13) lung cancer cell lines and a normal human bronchial epithelial cell line (Beas-2B) were irradiated with photons from a 6 MV linear accelerator (linac), an 180 kVp orthovoltage unit (average energy ∼60 keV), or a system that generates 60-keV quasi-monoenergetic convergent photons. Clonogenic cell survival was analyzed to assess dose-response metrics and relative biological effectiveness (RBE) in all cell lines. DNA damage and cell cycle analysis were assessed in the human-origin lung cancer cell lines. A human lung cancer (NCI-H460) xenograft model was used to test tumor growth delay in vivo. RESULTS: Relative to 6 MV photons, the 60 keV quasi-monoenergetic convergent and orthovoltage photons induced comparable cell kill effect and RBE for the LKR-13, KLN-205, and Beas-2B cell lines and higher cell kill effect and RBE for the NCI-H460 (significant) and NCI-H2172 (non-significant) cell lines. The enhanced biological response to orthovoltage and 60 keV quasi-monoenergetic convergent photons in NCI-H460 cells was also evidenced by increased DNA damage signaling and cell cycle checkpoint activation. Radiosensitivity differed considerably among cell lines, even for the same radiation type. The 60-keV quasi-monoenergetic convergent photons significantly delayed tumor growth, achieving effects comparable to 6-MV photons, in the NCI-H460 xenograft model. CONCLUSIONS: In vitro and in vivo evaluations confirmed that the biological effectiveness of 60 keV quasi-monoenergetic convergent photons is similar to that of photons from an orthovoltage unit (average energy ∼60 keV) and either comparable (three cell lines) or higher (two cell lines, but one was not significant) than photons from a 6-MV linac.
Dang A, Palma DA, Nichols AC
… +12 more, Warner A, Tran E, Bayley A, Sultanem K, Le H, Gaudet M, Karam I, Banerjee R, Tenenholz T, Winquist E, Theurer J, Goodman CD
Int J Radiat Oncol Biol Phys
· 2026 Jun · PMID 42349663
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PURPOSE: This study evaluates the impact of treatment de-escalation from 70 Gy to 60 Gy on patient-reported outcomes (PROs) and toxicity for patients with T1-2 p16-positive oropharyngeal squamous cell carcinoma (OPSCC) t...PURPOSE: This study evaluates the impact of treatment de-escalation from 70 Gy to 60 Gy on patient-reported outcomes (PROs) and toxicity for patients with T1-2 p16-positive oropharyngeal squamous cell carcinoma (OPSCC) treated with primary radiotherapy as part of the BLINDED-FOR-REVIEW trials. METHODS: Patients with p16-positive OPSCC treated with primary radiotherapy in the BLINDED-FOR-REVIEW randomized trials were included in this post-hoc analysis. Patient demographics, tumor and treatment characteristics were compared between patients who received radiation with 70 Gy (BLINDED-FOR-REVIEW, usually with cisplatin every 3 weeks) vs. 60 Gy (BLINDED-FOR-REVIEW, usually with weekly cisplatin). Outcomes examined included PROs and quality of life (QOL) metrics, including the MD Anderson Dysphagia Inventory (MDADI), European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 (C30) and Head-and-Neck 35 (H&N35) scales, toxicity, overall survival (OS) and progression-free survival (PFS). RESULTS: The cohort included 59 patients, 29 patients treated with 60 Gy and 30 patients with 70 Gy. Comparing QOL changes at 1-year in the 60 Gy vs. 70 Gy cohort respectively, the 60 Gy cohort demonstrated improved MDADI total (mean ± SD change: +1.9 ± 12.2 vs. -5.8 ± 11.3, p=0.035), and functional (+5.5 ± 12.7 vs. -3.3 ± 12.2, p=0.023) scores. The 60 Gy cohort demonstrated significantly better outcomes at 1-year in several EORTC QOL domains: global health status, fatigue, nausea/vomiting, appetite, constipation, pain, xerostomia, sticky saliva, and coughing (all p < 0.05). Patients treated with 60 Gy had significantly lower rates of grade 2-3 dysphagia and grade 2-3 mucositis (all p < 0.05). CONCLUSION: This comparison of arms from the separate ORATOR trials suggests that de-escalation from 70 Gy to 60 Gy for p16-positive patients with early-stage OPSCC may lead to better PROs across numerous domains, and reduced toxicity. Results from direct comparisons of these two doses are awaited.