Musculoskeletal disorders, particularly tendinitis and bursitis, are major contributors to global disability and healthcare burden. Low-dose radiotherapy (LDRT) has emerged as a promising treatment for refractory cases, demonstrating anti-inflammatory and anti-proliferative effects, especially in inflammatory conditions. However, the lack of standardized treatment volumes hampers reproducibility, radiation safety, and broader clinical adoption. To address this gap, an international panel of experts applied the Delphi method to develop consensus-based target volumes for LDRT in common indications such as shoulder bursitis, lateral elbow tendinitis, trochanteric pain syndrome, achilles tendinitis, and plantar fasciitis. Utilizing a standardized CT-based homunculus, target volumes were delineated in a 3D Cartesian coordinate system to enable precise definition of gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Additionally, associated ICD-10 codes were defined to facilitate clinical documentation, billing, and future research. This structured approach provides a foundation for consistent treatment protocols, improved radiation protection, and future prospective trials to refine LDRT application in benign musculoskeletal conditions.
Purpose Wilms tumor (WT) survivors face increased mortality due to cardiovascular-related diseases. Cardiovascular risk factors include adiposity, insulin resistance, dyslipidemia, and hypertension, clustered as metabolic syndrome (MetS). We assessed the prevalence and determinants of MetS in the first XXXX national WT survivor cohort. Method This cross-sectional 1:3 age and sex-matched case-control study, using the Lifelines-cohort, analyzed WT survivors treated between 1963-2002, recruited within XXXX study (2016-2020). MetS prevalence was assessed using the modified NCEP-ATP-III 2005 classification. Multivariable logistic regression models, adjusted for age and sex, assessed associations between the presence of MetS (components) and abdominal radiotherapy. Dosimetry was performed to estimate the mean dose to the abdominal fat, liver, pancreas (head ± tail), and contralateral kidney ± vessels and to estimate a normal tissue complication probability. Results Among 265/491 participating WT survivors (median age 33.9y; median follow-up: 29.8y), MetS prevalence was 18.8% and 7.3% in matched controls (OR:95%CI) (2.94:1.92-4.49). WT survivors showed increased levels of triglycerides (2.39:1.65-3.49) and fasting glucose (1.67:1.03-2.70), and decreased HDL-cholesterol (2.79:2.00-3.91). Univariable analyses identified abdominal radiotherapy to be the main determinant associated with increased risk for MetS (2.42:1.24-4.75). Multivariable analysis identified a significant increased risk of high fasting glucose levels (3.14:1.14-9.56) after abdominal radiotherapy. NTCP estimation identified radiation exposure of the pancreas and intra-abdominal fat as potential contributors to this association. A median dose between 10-20 Gy to the organs-at-risk results in a 5% risk of developing one or more components of MetS, increasing to 25% at 20-30 Gy. Conclusion WT survivors, particularly those treated with abdominal radiotherapy >20 Gy, have an increased risk of developing components of the MetS.
Purpose Recent studies indicate that lung function can change significantly during radiation therapy (RT) course. However, additional function imaging scans are not part of routine RT workflow, limiting the use of functional avoidance for adaptive therapy. To bridge this gap, we aimed to develop a deep learning model to synthesize functional maps directly from fractional cone-beam computed tomography (CBCT) images, enabling potential functional image-guided adaptive radiotherapy (FIGART). Methods Data were prospectively collected from 60 lung cancer patients who underwent intensity-modulated radiation therapy. In addition to standard planning CT and fractional cone-beam computed tomography (CBCT) scans, all patients received a baseline single-photon emission computed tomography (SPECT) perfusion scan before radiotherapy. A subset of 16 patients also underwent a follow-up SPECT scan after completing RT. A three-dimensional Gated-Attention U-Net (GAU-Net) was developed to synthesize perfusion maps directly from CBCT images. To address the challenges of inherent CBCT noise and artifacts, the network architecture was augmented by integrating gated attention modules and 3D deformable convolutions within the skip-connection pathways. This design enhances multi-scale feature fusion for more robust image synthesis. The synthesized perfusion images were quantitatively compared to the reference SPECT scans using cross validation. Voxel-wise agreement was assessed using the Spearman correlation coefficient (R), structural similarity index (SSIM) and mean squared error (MSE), while functional region agreement was evaluated using the Dice similarity coefficient (DSC). The potential clinical benefit was assessed through dosimetric evaluation. Results Quantitative analysis demonstrated CBCT-based functional images strong agreement with ground-truth SPECT, with a R of 0.68±0.09, SSIM of 0.75±0.09, MAE of 0.15±0.03, MSE of 0.04±0.02, and DSC values of 0.76±0.07 and 0.85±0.05 for high- and low-functional regions, respectively. Regarding dose sparing of the lung high-function region, CBCT-based functional imaged guided plan significantly reduced the mean dose by 6.97±4.22 Gy and V20 by 13.54±8.66% compared to anatomical plan, while achieving a better target dose homogeneity index of 5.26±0.65. Conclusion We developed a CBCT-based lung function imaging method using a deep learning model. The evaluation demonstrated its feasibility for functional guidance planning in FIGART. A larger cohort study is warranted in the future.
PURPOSE:Respiratory motion increases setup uncertainty in thoracic and abdominal tumor radiotherapy and elevates dose exposure to organs at risk (OARs), such as the heart and lungs. Deep inspiration breath-hold (DIBH) can reduce OARs dose, but clinical deployment requires accurate, real-time, low-burden monitoring of breath-hold stability and tidal volume. This study proposes a contactless tidal volume estimation system for DIBH-guided radiotherapy. METHODS:A depth camera captured three-dimensional thoracoabdominal surface motion to construct a surface-based volumetric surrogate. A state-aware, surrogate-guided time-series regression model incorporating dynamic state gating, steady-state anchor modeling, adaptive baseline correction, and subject-specific calibration was developed for tidal volume estimation. In this prospective model-development and pilot internal-validation study, synchronized depth-camera data and tidal volume signals from an Active Breathing Coordinator (ABC) system were collected from 22 volunteers. ABC-derived tidal volume served as the reference signal, and performance was evaluated using subject-independent leave-one-subject-out cross-validation. Real-time respiratory feedback was provided through a head-mounted visualization interface. RESULTS:Predicted tidal volume strongly correlated with the ABC reference signal (pooled r=0.968; subject-level Fisher z-transformed mean r=0.966, 95% CI: 0.954-0.975, p<0.001), with an overall MAE of 0.098 L. Phase-specific MAE/MAPE were 0.1059 L/17.27% during breath hold and 0.0967 L/16.68% during normal breathing. GPU-side algorithmic latency was 12.55 ms per frame. CONCLUSION:The proposed contactless framework enables stable tidal-volume estimation and real-time visual feedback during DIBH while minimizing patient encumbrance, supporting low-burden respiratory monitoring for radiotherapy workflows.
Purpose To determine which baseline and treatment-planning factors best predict severe radiation-induced lymphopenia during rectal cancer chemoradiation and whether an early on-treatment absolute lymphocyte count (ALC) measurement refines risk. Methods and Materials We studied 179 curative-intent rectal cancer patients treated with long-course fluoropyrimidine-based chemoradiation from 2018 to 2024. Baseline models compared baseline ALC, age, sex, 23 complete blood count parameters, 6 inflammatory markers, and 600 dosimetric variables; a day-14 ALC update was also evaluated. Results Severe lymphopenia (nadir ALC <0.5 × 10^9/L) occurred in 44% of evaluable patients. Baseline ALC was the dominant predictor; risk showed a fourfold incidence gradient across baseline quartiles, from 67% in Q1 to 17% in Q4, and a three-variable nomogram using ALC, age, and sex achieved a corrected C-index of 0.746. Female sex independently increased risk (adjusted odds ratio 3.44, 95% CI 1.69-7.27). No platelet index, erythrocyte parameter, inflammatory marker, or dosimetric variable improved prediction; published pelvic bone marrow V10 and Dmean constraints were met in 98% and 100% of patients, respectively, while V20 compliance was 86%, limiting dose-constraint discrimination in these standardized fields. ALC fell 71% to a nadir at day 33, and only 19% of patients recovered to at least 1.0 × 10^9/L by 3 months. Week-2 ALC improved cross-validated area under the curve from 0.737 to 0.827. Severe lymphopenia was not associated with pathological complete response, tumor regression, or T-downstaging (all p>0.20). An unadjusted nadir-based survival association (hazard ratio 0.22) disappeared after time-dependent correction (hazard ratio 0.93). Conclusions A routine baseline ALC, refined by a day-14 checkpoint, outperformed dosimetric and inflammatory profiling for severe lymphopenia risk assessment. The nomogram appears to identify toxicity susceptibility rather than treatment efficacy and supports anticipatory monitoring rather than treatment modification.
PURPOSE:Detection and offline correction of proton range errors due to incorrect Hounsfield Unit-to-stopping power conversion with minimal (5-10 minute) extension of the patient-facing clinical workflow using a cable-free thermoAcoustic Range Verifier (tARV). MATERIALS:The accelerator (Mevion Hyperscan) delivered at a conventional dose rate. To generate quantitative results, the target was a multi-modality anthropomorphic phantom (Sun Nuclear) composed primarily of hydrogels with known stoichiometry. The tARV includes six sonar receivers packed around the active imaging face of a wireless ultrasound probe (Clarius PAHD3). METHODS:Two dual-field plans were computed using Raystation 2023b's Monte Carlo engine. "Clinical MC" and "stoichiometric MC" plans were generated using clinical settings and by applying stoichiometry and range measurements (IBA Zebra) of phantom hydrogels. We evaluated the posterior-anterior field that delivered approximately 2 Gy (maximum 27 proton pulses/spot) to seven energy layers (135.6-162.8 MeV). The tARV was positioned anteriorly and distal to the Bragg peak, nearly in-line with the posterior-to-anterior beam trajectory, and rotated to collect a sagittal ultrasound image. Acoustic paths to receivers 5-6 were frequently obstructed by ribs. Measured thermoacoustic pulses generated by each spot were averaged to increase SNR. Time shifts between measured and simulated pulses were used to compute range errors. Range errors were averaged with respect to energy layer. Clinical MC dose was recomputed by shifting each beamlet by the layer's average range error, and imported back into the treatment planning system. RESULTS:Overall, thermoacoustic estimates of range errors for clinical and stoichiometric dosemaps were 6.7±1.7mm and 0.5±1.6mm, respectively. DVHs of recomputed and stoichiometric MC dosemaps were indistinguishable from each other but were clearly distinguishable from the clinical MC DVH. CONCLUSION:Using thermoacoustic range estimates to recompute largely corrected the clinical dosemap. This preliminary, but quantitative study demonstrates that the tARV warrants and is poised for efficient evidence development, such as noninterventional patient safety and offline adaptive studies.
PURPOSE:To evaluate the protective effects and therapeutic efficacy of FLASH proton therapy (FR) compared with standard dose-rate proton therapy (SR) in a preclinical model of ocular irradiation. METHODS AND MATERIALS:Mice received bilateral ocular irradiation with SR (≤1 Gy/s) or FR (>40 Gy/s) at identical doses. Longitudinal ocular structure and function were assessed over five months using spectral-domain optical coherence tomography, confocal scanning laser ophthalmoscopy, electroretinography (ERG), and histopathological analysis. Tumor control was evaluated in an intraocular B16F10 melanoma model using bioluminescence imaging and histopathology. RESULTS:Dose-response studies identified 24 Gy as the optimal dose, producing substantial visual impairment with SR (39.5% reduction in rod a-wave amplitude, p<0.001) without inducing complete blindness. SR induced progressive ocular injury, with significant corneal edema evident by 1 month (p<0.0001), advancing to ulceration by 5 months, whereas FR maintained corneal transparency comparable to non-irradiated controls. Consistent with these findings, TUNEL analysis demonstrated markedly increased corneal apoptosis following SR, whereas FR showed minimal apoptotic activity. ERG analysis revealed profound SR-induced functional deterioration by 5 months, with a 76% reduction in rod a-wave, 69% in rod b-wave, and 74% in cone b-wave amplitudes (all p<0.0001), reflecting extensive photoreceptor and bipolar cell dysfunction. FR eyes retained near-normal responses across retinal layers. Histopathology confirmed severe SR-associated pathology, including corneal perforation, uveal inflammation, and retinal disorganization, whereas FR largely preserved ocular architecture. Importantly, FR maintained short-term antitumor efficacy equivalent to SR, with comparable reductions in tumor burden (both p<0.05 vs. controls; p>0.05 SR vs. FR). CONCLUSIONS:FR provides substantial normal tissue protection across multiple ocular compartments while preserving therapeutic efficacy, effectively expanding the therapeutic window for ocular radiotherapy. These findings establish proof-of-principle for clinical translation of FR to improve visual outcomes in patients with ocular and orbital malignancies without compromising tumor control.
PURPOSE:Five to 7 weeks of whole-larynx radiation (RT) is standard for treatment of early-stage glottic cancer. Previous studies evaluated CT-guided hypofractionated/SBRT treatment to a smaller volume. Magnetic resonance-guided radiotherapy (MRgRT) allows real-time motion tracking and gating by continuously imaging the larynx. We performed the first prospective study of MRgRT in patients with early-stage glottic cancer with quantification of laryngeal motion. METHODS AND MATERIALS:This phase 1 trial evaluated MRgRT in patients with stage I/II squamous cell glottic cancer undergoing definitive RT. The RT prescription was either 42.5 Gy/5 fractions (treatment volume < 10cc, not actively smoking) or 58.08 Gy/16 fractions (treatment volume > 10cc / smokers). Treatment was delivered using gated 0.35 T MRgRT with continuous tracking. Coprimary endpoints were feasibility and safety (grade 3+ toxicity rate). Patient-reported outcome measures (PROMs), voice quality, MRgRT treatment parameters, and local control were assessed. Intrafraction cine-MRI quantified laryngeal motion. RESULTS:MRgRT was feasible in all patients. Median time on study was 10.9 months. Treatment was well tolerated with no acute or late grade 3+ toxicities. There was no change in PROMs over the course of the study. Two patients who received 42.5 Gy experienced locoregional failure, one in-field only and one in-field and nodal. MR tracking resulted in 20/94 (21%) of treatment fractions requiring ≥ 1 shift necessitating intra-fraction re-imaging. In 19/94 (20%) of treatment fractions, the beam was off more than 20% of the treatment time due to stochastic beam interruption events (BIEs). During BIEs, larynx displacement exceeded 3 mm in 53% of cine-MRI frames. CONCLUSIONS:MRgRT targeting gross disease instead of the whole larynx is feasible and safe for patients with early-stage glottic cancer with minimal treatment-associated toxicity and no detriment in PROMs. MRI guidance provides real-time verification of larynx position. Data regarding real-time intrafraction motion has important implications for patients receiving standard laryngeal RT.
INTRODUCTION:In this systematic review and associated guidelines, the American Radium SocietyTM (ARS) thoracic and gastrointestinal oncology expert panels worked together to thoroughly evaluate current literature and provide treatment recommendations for best outcomes for resectable esophagus or gastroesophageal junction adenocarcinoma. To represent a diverse group representing all key specialties, thoracic and gastrointestinal radiation and medical oncologists, gastroenterologists, and thoracic surgeons were included in development of these consensus guidelines. METHODS:Using the Population, Intervention, Comparator, Outcome, Timing and Study Design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included randomized Phase II and III trials and retrospective subset analyses of randomized controlled trials published between January 1, 2019 and July 7, 2025 in the Ovid Medline database. These references were assessed via ARS Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of various treatments. RESULTS:For patients with adenocarcinoma of the esophagus or gastroesophageal junction, the standard treatment approach has been trimodality therapy including chemotherapy, radiation, and surgery which is associated with significant long-term toxicity. Recent randomized controlled trials have compared perioperative chemotherapy to trimodality therapy affording the omission of radiotherapy for suitable patients and a resulting reduction in associated treatment-related toxicities. Recommendations for adjuvant and neoadjuvant therapies are provided, including chemotherapy, immunotherapy, targeted therapy and radiation therapy, and active surveillance after chemoradiation is also detailed. CONCLUSIONS:The updated 2026 ARS AUC for Operable Esophageal and Gastroesophageal Junction Adenocarcinoma is presented in this manuscript.
PURPOSE:A radiotherapy boost to the internal mammary nodes (IMNs) is often recommended for patients with breast cancer and clinically positive IMNs at baseline but may increase treatment-related toxicity. Given the widespread use of neoadjuvant therapy (NAT), we investigated whether MRI-assessed IMN clinical complete response (icCR) after NAT could help inform response-adapted IMN boost strategies. METHODS AND MATERIALS:This retrospective study included 208 patients with baseline clinically positive IMNs. The association between IMN boost and outcomes was evaluated in the overall cohort and in subgroups defined by MRI-assessed post-NAT icCR status. Inverse probability of treatment weighting (IPTW) was used to improve balance in selected measured baseline characteristics and reduce observed treatment-selection bias. Effect modification by icCR status was assessed using IPTW-weighted Cox proportional hazards models with an interaction term. RESULTS:With a median follow-up of 36 months, the IMN boost was not associated with a significant improvement in disease-free survival (DFS) in the overall cohort (IPTW-adjusted HR = 0.66, 95% CI: 0.32-1.39, P = 0.277). However, a significant interaction was observed between IMN boost and icCR status (P for interaction = 0.042). In subgroup analyses, IMN boost was associated with improved DFS in patients without icCR (IPTW-adjusted HR = 0.36, 95% CI: 0.14-0.93, P = 0.034), whereas no significant DFS improvement was observed in patients who achieved icCR (IPTW-adjusted HR = 1.13, 95% CI: 0.47-2.74, P = 0.781). CONCLUSIONS:In this study, improved DFS was observed with IMN boost in patients without icCR, whereas no clear benefit was observed among those who achieved icCR. These findings support further evaluation of post-NAT icCR status as a potential indicator for response-adapted postoperative IMN radiotherapy boost selection, warranting prospective validation.
PURPOSE:Few reports address the use of incident learning systems (ILS) in low- and middle-income countries (LMICs). We hypothesize that ILS can support quality improvement (QI) needs in an LMIC clinic, and that a commitment to QI can overcome perceived barriers to ILS uptake. METHODS:A preliminary survey assessing safety culture and perceived barriers to ILS use was distributed to all clinical staff at a radiation oncology clinic in sub-Saharan Africa. An ILS was implemented based on the International Atomic Energy Agency taxonomy. After seven months, ILS reports were analyzed by type, clinic area, clinical role, and origin. Quality control quantification (QCQ) was used to determine the QA intervention most likely to prevent or detect each error. An interdisciplinary team of clinicians used failure modes and effects analysis (FMEA) to rank 23 representative failure modes by risk priority number (RPN). RESULTS:Survey responses indicated that "concern on the part of the reporter about their reputation or the effects of reporting a colleague" was a barrier to incident reporting. Despite this, the ILS collected eighty-four reports throughout the seven-month accrual period. Most were classified as near-misses (32, 38%). Although most reports were entered from the LINAC control rooms (41, 48.8%), treatment planning was the most common origin of errors (28, 33.3%). The most frequently identified QA intervention that would have prevented errors was a comprehensive physics plan check (29 reports). The highest-RPN failure mode was associated with a treatment delivery error related to the oncology information system (OIS). CONCLUSION:ILS reports indicate that QI needs center on treatment planning and technical plan review, as well as OIS implementation. This study, one of the few to explore the use of ILS in the LMIC setting, illustrates how a commitment to QI can overcome perceived barriers to ILS use.
