Clinical and Translational Radiation Oncology

Purpose: Radiation-associated lower cranial neuropathy (LCNP) is a debilitating late complication among head and neck cancer (HNC) survivors, leading to progressive dysphagia, aspiration, and loss of nutritional independence. No proven therapies exist to reverse LCNP. This Phase I dose-finding trial (XXXX, XXXX) and parallel registry study prospectively evaluated the safety, feasibility, tolerability, and symptomatic response of high-dose corticosteroid therapy for radiation-associated LCNP. Methods and Materials: Eligible participants were disease-free oropharyngeal cancer survivors [≥]2 years post-radiotherapy with LCNP involving CN XII +/- X and no structural or malignant etiology. Phase I trial participants received oral prednisone 1 mg/kg (Dose 1, n = 3) or 3 mg/kg (Dose 2, n = 5) daily for 5 days followed by a 2-week taper. A parallel registry (n = 6) enrolled broader HNC survivors treated with 1 mg/kg. Phase I dose escalation decisions were based on the balance of tolerability and symptom response. The primary endpoint was change in MDASI-HN Top 5 mean symptom score from baseline to 1-2 weeks post-taper; a [≥] 1.315 unit decrease indicated clinically meaningful improvement. Secondary endpoints included clinician-graded measures of bulbar function, electromyography (EMG) and patient-report outcome measures. Results: All regimens were feasible and well tolerated. Insomnia (n = 4, Grade 1) was the most frequent adverse event and there were no treatment discontinuations. At 1-2 weeks post-taper, the median MDASI-HN Top 5 change was -0.2 in Dose 1 and -1.6 in Dose 2; three of five Dose 2 patients achieved clinically meaningful improvement versus one in Dose 1. By 6-10 weeks, symptom improvement persisted in a subset but diminished overall. Dose 2 met pre-specified criteria for Phase II progression. No consistent improvements were observed in objective functional or electrophysiologic measures, though exploratory trends favored higher dosing. Conclusions: High-dose corticosteroid therapy at 3 mg/kg/day was feasible and tolerable in long-term HNC survivors with LCNP and showed preliminary evidence of short-term symptomatic benefit. Phase II evaluation is warranted.

Background: Deep Inspiration Breath Hold (DIBH) is a widely used respiratory motion management technique for minimizing cardiac dose in left-sided breast radiotherapy. In the Breast HYPORT Adjuvant study, DIBH was employed for cardiac sparing in patients without nodal irradiation using a standardized institutional protocol with the Varian Real-time Position Management (RPM) system. Both moderate-hypofractionation (control arm - 40Gy in 15 fractions) and one-week hypofractionation (experimental arm - 26 Gy in 5 fractions) regimens were delivered using this protocol. This study aimed to evaluate the robustness of DIBH by analyzing intra-fraction stability and inter-fraction reproducibility of breath-hold amplitude across the two treatment regimens. Methods: Respiratory waveforms acquired during each treatment session were analyzed to determine the median breath-hold amplitude and its standard deviation during beam delivery. Intra-fraction stability was assessed from vari- ations within individual treatment sessions, while inter-fraction reproducibility was evaluated relative to the simula- tion waveform amplitude across all treatment sessions. These parameters were compared between the two HYPORT regimens to examine breath-hold consistency during treatment delivery. Moreover, an additional comparison was made between the one-week hypofractionation regimen and the first five fractions of the moderate-hypofractionation regimen to evaluate the effect of treatment duration . Lung volumes from free-breathing and DIBH CT scans were analyzed to assess the effectiveness of patient breath-hold training. Results: Both arms demonstrated an average 1.7-fold increase of air volume in lung during the breath-hold position, confirming the effective implementation of DIBH during treatment planning and delivery. Structured training resulted in increased breath-hold amplitudes, with gains of 22.87% and 24.16% with respect to the first trial session in the experimental and control arms, respectively. Both regimens receive equivalent doses for approximately the same air volume in lung . Despite the different prescription doses in the two arms (26 Gy vs. 40 Gy), the experimental arm achieved an equivalent mean heart dose of 2.91% (75.6 cGy) compared with 2.95% (118.51 cGy) in the control arm, suggesting a similar cardiac preservation protocol adopted during treatment planning. Intra-fraction stability was similar between the control arm and the experimental arm, with median amplitude variations of 1.006 mm (95% CI: [0.998-1.015]) and 1.079 mm (95% CI: [1.067-1.097]), respectively. In contrast, inter-fraction reproducibility improved in the experimental arm, with lower deviation from simulation amplitude (0.44 {+/-} 0.24 mm vs. 0.66 {+/-} 0.25 mm) for the entire treatment schedule. The stability and reproducibility of experimental arm were further compared with the first five fractions of the control arm. The results were similar to those of the experimental arm. Conclusion: In this study, we compared two treatment regimens in terms of intra-fraction stability and inter-fraction reproducibility during DIBH radiotherapy. Both regimens demonstrated comparable intra-fraction stability, indicating effective motion management irrespective of treatment duration. However, the experimental arm showed better inter- fraction reproducibility, suggesting more consistent breath-hold performance throughout the treatment course. Based on stability and reproducibility, a reasonable narrowing of the DIBH gating window may be implemented with minor changes to the institutional protocol. The observed trend highlights the potential for improved consistency with the experimental approach and supports further investigation to better understand the underlying factors and strengthen these findings in future studies.

Purpose/Objective: Genitourinary (GU) adverse events (AEs) are common during and after pelvic radiation therapy (RT) for prostate cancer and can substantially impact quality of life. We convened an international committee to establish consensus in the prevention, mitigation, and management of radiation-related acute and late GU AEs, as there are no relevant evidence-based consensus guidelines to inform treating providers. Materials/Methods: A systematic evidence review focused on mitigation and management of radiation-related acute and late GU AEs was performed in PubMed, Embase and Cochrane. The following topics were addressed: management of acute GU AEs in the intact and post-operative settings; RT techniques; bladder outlet obstruction procedures; and indications for urology referral or hyperbaric oxygen therapy (HBO). Evidence-based consensus recommendations were developed using a Delphi process. We highlight the current state of evidence and evidence gaps worthy of future study. Results: Consensus was reached for 31 key questions. For management of lower urinary tract symptoms (LUTS), most evidence comes from trials in patients without cancer and not undergoing RT. A consensus algorithm for medical management of acute GU AEs was developed with the following highlights: (a) alpha blockers as 1st-line for obstructive symptoms in the intact setting, (b) anti-spasmodics as 1st -line for irritative symptoms in the intact setting, and (c) anti-spasmodics as 1st -line in the post-operative setting. The consensus algorithm provides an ordered list of medications to offer if 1st -line options afford inadequate relief. For RT fractionation, randomized clinical trial (RCT) data are available. 40% of panelists rarely or never use standard fractionation over moderate hypofractionation for patients with baseline LUTS, but most consider moderate hypofractionation over SBRT for AUA IPSS > 15. For patients with severe obstructive LUTS (most commonly AUA IPSS >20), the panel recommends a prophylactic bladder outlet obstruction procedure and, if obstructive symptoms improve, consideration of moderate hypofractionation or SBRT, based on retrospective data. There is one RCT supporting use of HBO for late radiation cystitis. Conclusions: The consensus guideline synthesizes available evidence and expert opinion across key clinical decision points to provide practical guidance in the prevention, mitigation, and management of radiation-related acute and late GU AEs in prostate cancer RT. Envisioned as a living document with periodic updates, this guideline serves as a resource for practicing radiation oncologists by outlining expert-derived consensus recommendations of evidence-based care in areas where high-quality data is limited.

Background: Cognitive impairment is a prevalent long-term sequela in glioma patients, yet its cerebrovascular correlates remain poorly characterized. Arterial spin labeling (ASL) perfusion MRI offers a non-invasive means to quantify cerebral blood flow (CBF) and may serve as a sensitive correlate of radiotherapy (RT)-induced neurovascular injury. Methods: Fifty WHO Grade 2/3 glioma patients and 50 matched healthy controls underwent pseudo-continuous ASL (pCASL) MRI and a standardized cognitive test battery. Regional CBF was compared between patients (n=44, after quality control) and controls (n=50) using ANCOVA with age, sex, and deep white matter CBF as covariates. In irradiated patients (~5 years post-RT), RT dose-CBF associations were assessed using region-wise regression, and regional CBF was compared among controls and low-dose ([&le;]15 Gy) versus high-dose ([&ge;]40 Gy) regional RT exposure groups. Cognition-CBF associations were evaluated in a priori domain-specific regions of interest. Results: Compared with controls, patients showed frontoparietal cortical hypoperfusion, with significantly lower CBF in middle frontal and superior/inferior parietal cortices (all q<0.01; partial -squared=0.128-0.147). Region-wise regression showed no significant linear RT dose-CBF associations after correction. However, subgroup analyses identified RT dose-sensitive regions with [&ge;]40 Gy exposure that showed lower adjusted CBF than controls, most prominently in the left precentral and caudal middle frontal cortices (q<0.01; adjusted-{Delta}CBF{approx}-27.2--28.8 mL/100g/min). Perfusion in the left precentral and postcentral gyri of irradiated patients correlated positively with motor performance. Conclusions: pCASL reveals persistent cortical hypoperfusion in glioma patients that spatially corresponds with RT dose exposure and associates with cognitive performance, positioning ASL as a promising non-invasive biomarker of RT-related neurovascular injury.

Purpose: Glioblastoma (GBM) remains associated with poor outcomes, with most recurrences occurring within the high-dose radiation field, suggesting persistent radioresistance. Exportin 1 (XPO1) inhibition with Selinexor has demonstrated radiosensitizing effects in preclinical models. We conducted a phase I trial to evaluate the safety, tolerability, and preliminary efficacy of Selinexor in combination with standard chemoradiation for newly diagnosed GBM. Methods: This investigator-initiated phase I dose-escalation trial (3+3 design) enrolled adults with newly diagnosed GBM or gliosarcoma. Patients received standard radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide and escalating doses of Selinexor. Three dose levels were evaluated: 80 mg weekly (weeks 1, 2, 4, 5); 60 mg twice weekly (weeks 1, 2, 4, 5); and 60 mg twice weekly (weeks 1-6) throughout radiotherapy. The primary endpoint was determination of the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), patterns of failure, and patient-reported outcomes (MDASI-BT). Results: Eleven patients were enrolled. Median age was 58 years, and median KPS was 90. The MTD was established at Selinexor 60 mg twice weekly during weeks 1, 2, 4, and 5 of chemoradiation. Dose level 3 exceeded the MTD with two DLTs. Treatment compliance was high, with minimal missed radiotherapy fractions. Median PFS was 15.9 months (95% CI, 6.2 28.5), and median OS was 17.4 months (95% CI, 14.1 not reached). Most recurrences were central (5/6 evaluable patients). Notably, multiple cases of delayed pseudoprogression were observed at 5, 9, 10, and 23 months post-radiotherapy. Patient-reported symptom burden remained stable over time. Conclusions: Selinexor can be safely combined with standard chemoradiation in patients with newly diagnosed GBM, with an MTD of 60 mg twice weekly during select treatment weeks. Preliminary efficacy signals and an increased incidence of delayed pseudoprogression suggest a potential radiosensitizing effect. These findings support further investigation of Selinexor in larger, prospective studies.

Background and purpose. Patients with oropharyngeal cancer (OPC) treated with radiotherapy (RT) exhibit heterogeneous courses of radiation-associated dysphagia (RAD) during recovery, yet most survivorship models typically treat RAD uniformly. This study aimed to identify distinct, data-driven RAD longitudinal Phenotypes based on imaging-graded swallow function from pre-treatment to 30 months post-RT and to characterize their baseline predictors. Materials and methods. Heterogeneous linear mixed-effects latent class trajectory modeling was applied to longitudinal DIGEST scores from the Stiefel MDA-OPC prospective registry. Eligible patients had [&ge;]3 Modified Barium Swallow (MBS) assessments between baseline and 30 months post-RT. Models were evaluated across functional forms and 1-5 latent classes; final selection used the Bayesian Information Criterion. Baseline predictors of class membership were identified via binary logistic regression. Results. The cohort comprised 650 OPC patients (2,116 MBS assessments; mean age 61 years, 89% male, 93% HPV-positive). Four RAD Phenotypes were identified: No/Minimal RAD (n=385/650, 59%), Mild/Moderate RAD (n=104/650, 16%), Moderate/Severe Transient RAD (n=94/650, 15%), and Moderate/Severe Progressing RAD (n=67/650, 10%). Classification quality was acceptable (mean posterior probabilities 0.78-0.89; entropy 0.69). Baseline DIGEST impairment, base-of-tongue primary, advanced T stage, and age [&ge;]60 independently predicted membership in higher-burden Phenotypes (AUC=0.845; 10-fold CV-AUC=0.835). Conclusion. RAD following RT for OPC comprises four biologically and clinically distinct longitudinal Phenotypes, predictable from pre-treatment characteristics. These findings support trajectory phenotyping as outcome framework for RAD research and risk-adaptive survivorship care.

Accurate segmentation of thin-wall organs-at-risk (OARs)-the cochlea, vestibular semicircular canals, internal auditory canal, tympanic cavity, and middle ear-is clinically relevant for head-and-neck radiotherapy planning, yet these small, thin-wall structures remain among the most challenging targets for automated delineation. Dual-frequency feature fusion is a promising direction for boundary-sensitive representation, but under the investigated FP16 FFT-FcaNet setting, we observe an approximately 863-fold activation-scale mismatch between the FFT and FcaNet branches, causing a nominal 5 percent residual coefficient to behave as an approximately 43-fold dominant term. We propose FreqFuseNet, which resolves this mismatch by normalizing the FcaNet branch to the FFT activation scale before residual injection with a fixed low-amplitude coefficient (beta = 0.05), restoring beta as an interpretable 5 percent residual-amplitude coefficient relative to the FFT feature scale. Under a controlled binary per-OAR ROI protocol on the SegRap2023 head-and-neck CT benchmark across 10 clinically prioritized thin-wall OARs, FreqFuseNet achieves Dice of 0.849, HD95 of 0.824 mm, and SDice@1mm of 0.959 in the primary seed, with comparable performance in an independent second seed (Dice 0.843, HD95 0.823 mm). FreqFuseNet yields statistically significant case-level aggregate improvements over 3D U-Net and MedNeXt-S (Wilcoxon p < 0.01 and p < 0.05, respectively), using only 29.7 million parameters versus 414.6 million for the full wavelet baseline.

Background: Independent end-to-end verification of adaptive radiotherapy on MR-Linac systems is limited by the lack of patient-specific phantoms able to reproduce imaging and dosimetric properties from CT and MRI scanners. We present a method for automated generation of 4D, patient-specific, multi-material 3D-printable phantoms for quality assurance of adaptive radiotherapy on a 1.5T MR-Linac. Methods: Patient images were automatically segmented using a pretrained deep learning model. The segmented structures were converted into high-resolution 3D meshes and assembled into printable phantoms. A dosimeter holder was inserted at user-defined anatomical locations, with orientation optimized to avoid traversal across heterogeneous tissue interfaces. Physiological motion was incorporated by generating phantoms from images at different timepoints and interpolating deformation fields to create continuous 4D models. Multi-material organs designed by mixing a set of six polymers at various proportions were used to reproduce tissue-specific imaging properties. The properties of material mixtures were evaluated in a clinical CT simulator and a 1.5T MR-Linac. Results: The proposed workflow enables automated generation of anatomically realistic phantoms with several types of embedded dosimeters. A discrete search method was designed for placement and immobilization of OSLD, film, and ion chamber dosimeters. Calibration curves for Hounsfield units were derived through variations in radiopaque material content, while MR signal intensity was modulated by gel and tissue matrix mixtures. Patient-derived abdominal phantoms were fabricated at multiple scales while replicating internal anatomical detail. Multi-dimensional phantom generation enabled continuous representation of motion states with consistent mesh topology across phases. Conclusions: We demonstrate an end-to-end workflow for automated generation of 4D patient-specific phantoms for MR-Linac quality assurance. The method combines realistic anatomy, embedded dosimetry, multimodal imaging properties, and physiological motion within a single fabrication framework. This approachmay enable an improved validation of adaptive radiotherapy workflows in MR-guided treatment devices.

Background and Objectives: Are some brain regions intrinsically more vulnerable to metastatic colonization? We sought to characterize the spatial distribution of brain metastases and determine whether regional patterns vary according to primary tumor origin. Methods: We analyzed baseline MRI scans and expert tumor segmentations from 906 patients with 3,492 brain metastases treated with stereotactic radiosurgery. Lesions were normalized to MNI152 standard space and superimposed to generate probabilistic atlases of metastatic occurrence. Regional metastatic burden was quantified using anatomical and vascular atlases. Spatial distributions were additionally compared between lung cancer and melanoma metastases. Results: Metastatic burden was distributed nonuniformly throughout the brain. The cerebellum demonstrated the strongest enrichment relative to its anatomical volume (fold change 1.61, p < 0.001), accompanied by overrepresentation of the vertebrobasilar circulation (fold change 1.49, p < 0.001). Spatial distribution also varied by primary tumor type. Lung cancer metastases demonstrated greater infratentorial involvement than melanoma metastases (16.6% vs. 8.7%, p < 0.05), with a corresponding increase in cerebellar burden (14.8% vs. 6.8%, p < 0.05), whereas melanoma metastases were relatively concentrated within the frontal lobe (37.7% vs. 24.6%, p < 0.01). Infratentorial enrichment was observed across all carcinoma subgroups, with the greatest enrichment seen in gastrointestinal metastases (32.9% infratentorial). Conclusion: Brain metastases exhibit nonrandom spatial distributions, with preferential involvement of posterior and infratentorial structures. Regional patterns vary according to primary tumor origin, supporting the existence of region-specific vulnerability to metastatic disease.

Sentinel lymph node biopsy (SLNB) is increasingly omitted in early-stage breast cancer, often prompting whole-breast irradiation (WBI). We evaluated partial-breast irradiation (PBI) without axillary surgery among 78 clinically node-negative patients (median age 75) treated from 2014 to 2022. After 53-month median follow-up, no ipsilateral, regional, or distant recurrences occurred. These results demonstrate excellent outcomes and suggest PBI is a feasible, safe alternative to WBI when SLNB is omitted.

Abstract Background: The lack of effective biomarkers and therapeutic targets to overcome radioresistance in cervical cancer remains a major clinical challenge. Tumor necrosis factor receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase pivotal in immune and inflammatory signaling, has been implicated in various malignancies. However, its role in radioresistance in cervical cancer remains unclear. Methods: TRAF6 expression was evaluated in cervical cancer tissues from 162 patients who underwent postoperative radiotherapy at our institution and in 304 cases from the TCGA-CESC cohort. The prognostic significance of TRAF6 was assessed using Kaplan-Meier and Cox regression analyses. A nomogram integrating TRAF6 expression with clinicopathological factors was constructed to predict overall survival (OS) and progression-free survival (PFS). The functional role of TRAF6 in malignant phenotypes and radiosensitivity was investigated using shRNA-mediated knockdown in HeLa and C33A cervical cancer cells. Immune cell infiltration patterns associated with TRAF6 expression were analyzed using ssGSEA and xCELL algorithms based on TCGA data. Results: TRAF6 expression was significantly elevated in cervical cancer tissues compared with adjacent normal tissues (70.99% vs. control, P < 0.001) and was higher in radioresistant than in radiosensitive patients (P < 0.001). High TRAF6 expression was associated with shorter OS (HR = 18.73, P = 0.004) and PFS (HR = 8.44, P < 0.001) and was identified as an independent risk factor for radiotherapy resistance (OR = 8.44, P < 0.001). The TRAF6-integrated nomogram demonstrated good predictive accuracy for OS (C-index = 0.7351) and PFS (C-index = 0.7444). TRAF6 knockdown in cervical cancer cells significantly suppressed proliferation, migration, and invasion, while substantially enhancing radiosensitivity of tumor cells. Functional enrichment analysis revealed that TRAF6-related genes were enriched in autophagy, mitophagy, and HPV infection pathways. Immune cell infiltration analysis showed that TRAF6 expression correlated with distinct immune cell profiles, characterized by enrichment of activated dendritic cells, M1 macrophages, and regulatory T cells, alongside depletion of cytotoxic effectors such as CD8+ T cells and {gamma}{delta} T cells. Conclusions: TRAF6 could be a prognostic biomarker associated with poor outcomes and indicator of radiotherapy resistance in cervical cancer, TRAF6 represents a potential therapeutic target for overcoming radioresistance in cervical cancer.

Abstract Purpose Radiologic surveillance is essential for oropharyngeal cancer (OPC) survivors, guiding recurrence detection and follow-up strategies. The Neck Imaging Reporting and Data System provides a standardized framework for post-treatment risk reporting at both the primary tumor site (pNI-RADs) and cervical lymph nodes (nNI-RADS). Comprehensive surveillance additionally requires assessment of disease status, including the primary tumor, nodal involvement, and distant metastases. These clinical results are often embedded as unstructured data within free-text radiology reports. We hypothesized that a large language model (LLM) can reliably extract NI-RADS score criteria and summarize key imaging features from unstructured radiology text, achieving high concordance with expert review. Methods Previously untreated OPC patients who received definitive cancer therapy were identified. Eligible imaging reports included post-treatment head and neck CT, MRI, or FDG PET/CT scans containing narrative and impression text. Examinations lacking narrative or impression text, containing pre-existing NI-RADS annotations, or involving non-surveillance imaging modalities were excluded. A total of 200 reports were randomly selected from 7,076 eligible examinations for manual abstraction using a three-reviewer consensus framework to establish a reference dataset. Using the Palantir Foundry Pipeline Builder, a GPT-5-based LLM was deployed to extract pNI-RADS and nNI-RADS scores, and key imaging features of disease status from these reports. Performance was evaluated using exact agreement and F1-based metrics. Results Agreement for no evidence of disease (score of 1) was 93.3% (126/135; F1 = 0.94) and 90.3% (130/144; F1 = 0.93) for pNI-RADS and nNI-RADS, respectively. For NI-RADS [&ge;]2, exact category agreement was 73.1% (38/52; macro-F1 = 0.75) for pNI-RADS and 64.3% (27/42; macro-F1 = 0.56) for nNI-RADS. Quadratic weighted {kappa} was 0.81 and 0.59, respectively. For post-treatment disease surveillance variables, agreement was 94.9% (149/157; F1 = 0.87) for primary tumor presence, 89.1% (164/184; F1 = 0.87) for nodal disease presence, and 94.7% (126/133; F1 = 0.70) for distant metastasis detection. Specificity was high across disease-status variables (0.95-0.99), with negative predictive values of 0.95 for primary tumor, 0.87 for nodal disease, and 0.99 for distant metastasis. Conclusions Our LLM-based information retrieval and classification approach for radiographic treatment response from unstructured, multidimensional imaging reports achieved high performance for disease exclusion and moderate performance for detecting suspected residual and/or new disease. This pipeline supports scalable and standardized surveillance data capture for longitudinal monitoring, clinical analytics, and survivorship research in head and neck oncology.

PurposeTo develop and evaluate a multi-model consensus deep learning approach for automated gold fiducial marker (FM) segmentation in T1-weighted prostate MRI. Materials and MethodsIn this retrospective study, T1-weighted MRI and CT-derived reference standard segmentations were collected from 127 prostate cancer patients (all male; mean age, 70 years {+/-} 7 [standard deviation]; age range, 50-88 years; collected between October 2020 and January 2026) who each had three implanted gold FMs. A 3D U-Net was trained on 93 subjects using four random seeds to produce an ensemble. At inference, marker-class probability maps were averaged across models and the top three connected components selected. Performance was evaluated on 34 temporally held-out subjects (9 tuning, 25 test) using marker-level sensitivity and precision with exact (Clopper-Pearson) 95% confidence intervals (CIs). A model count ablation study was performed. The pipeline was deployed for on-scanner processing on Siemens MRI systems via the OpenRecon framework and as a browser-based application using WebAssembly, executing entirely client-side. ResultsThe four-model consensus achieved 96% (70 of 73) sensitivity and 95% (70 of 74) precision on 25 test subjects, with 29 of 34 (85%) subjects achieving perfect marker detection. Single models had a mean sensitivity of 84% (SD, 9%), improving to 96% with four-model consensus (SD, <1%). ConclusionMulti-model consensus deep learning substantially improved FM segmentation reliability over individual models, achieving high sensitivity and precision using only routinely acquired T1-weighted MRI.

Background: A subset of uveal melanomas can be treated using either enucleation or proton beam therapy (PBT), which offer similar oncological outcomes. The most appropriate treatment depends on a patient's preference. To allow patients to genuinely determine their preference, it is recommended to describe options as neutrally as possible. This study assesses to what extent ocular oncologists use and perceive non-neutral framing behaviour, and if it is related to patient satisfaction with decision-making. Methods: Consultations of ocular oncologists with patients newly-diagnosed with uveal melanoma were audio recorded, transcribed verbatim, and coded for ocular oncologists' explicit and implicit non-neutral framing behaviours. Explicit non-neutral framing was defined as: explicitly mentioning a preferred option at least once, without relating it to the patient. Implicit non-neutral framing was defined as: describing an option (un)favourably, without providing a medically substantive clarification alongside. Results: 110 patients provided consent for the audio recordings. Non-neutral framing was found in 84% (n=92/110) of consultations. We found explicit behaviour in 38% (42/110) and implicit behaviour in 76% (84/110, median=1, range, 0-4) of consultations. The most frequent implicit framing was presenting options by positively or negatively emphasizing one option. Non-neutral framing behaviours were not significantly related to patient satisfaction with decision-making. Conclusion: This study shows that in most consultations some non-neutral framing was present, which did not impact patients' satisfaction with decision-making. Nonetheless, ocular oncologists should be aware that how they describe options may influence preferences in ways that do not align with the patient's values.

Background: Nuclear medicine and radiopharmaceutical development require coordinated radiochemistry, dosimetry, molecular imaging, radiation-safety and clinical decision processes. Current workflows remain fragmented, difficult to audit and poorly standardised for evaluating domain-specific AI support. Methods: We developed RadGuide AI, a nuclear medicine agent built around a traceable data-model-tool loop. Patent, literature and clinical-trial records were converted into 15,596 initial QA items; relevance screening, completeness checks, semantic deduplication and cross-validation retained 5,474 core QA items. MedGemma-27B-Instruct served as the foundation model and was adapted with LoRA. The system incorporated 55 MCP-wrapped tools covering radiopharmaceutical R&D, clinical decision support, imaging analysis and radiation-safety/dosimetry. Evaluation used a locked N=200 benchmark with predefined denominators, leakage control, expert scoring, statistical procedures, factuality audits and tool-execution metrics. Results: RadGuide-LLM achieved 88.5% answer accuracy (177/200; 95% CI, 83.3-92.2%) and a Macro-Average score of 21.5/25 (bootstrap 95% CI, 20.9-22.0), exceeding GPT-4o, DeepSeek-V3.2 and the base MedGemma model in this technical evaluation. Supplementary audits reported guideline compliance, terminology recall, knowledge coverage, tool-routing success and preclinical/phantom dosimetry agreement with explicit denominators and confidence intervals. Interpretation: RadGuide AI converts nuclear medicine queries into auditable retrieval, tool selection, calculation, verification and reporting workflows. The findings support technical feasibility, not definitive patient-level clinical validation; prospective multicentre studies and external benchmark release remain required before clinical deployment.

Background: GBM is one of the most common and most aggressive brain tumors in adults, and upfront standard of care treatment has limited efficacy. Immune checkpoint inhibitor strategies have significantly improved outcomes in various solid tumors but have not proven effective in GBM, suggesting other strategies may be needed to realize their full potential. Methods: GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation. Results: 90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe. Conclusions: Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy. Trials Registration: ClinicalTrials.gov identifier: NCT03018288

Background: Three-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. Methods: This in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. Results: OCT-only models consistently outperformed the BF baseline (median R2 0.77 to 0.85 versus 0.61 to 0.69; p<0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest (p=0.026, power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. Conclusions: OCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition.

Background: Cutaneous squamous cell carcinoma (cSCC) accounts for a significant proportion of skin malignancies in India, yet data on patterns of failure, particularly for extremity and truncal primaries remain scarce. We audited a decade of surgically treated cSCC at a tertiary cancer center to characterize failure patterns and associated risk factors. Methods: This retrospective study included 161 patients with histopathologically confirmed cSCC treated surgically between January 2013 and December 2023, comprising 127 upfront/residual and 34 recurrent presentations. Primary sites were extremities (64%), head and neck (26%) and torso (10%). 21 patients had Marjolin's ulcer. Outcomes included local, regional and distant failure, recurrence-free survival and overall survival. Brigham and Women's Hospital (BWH) staging was applied to assess prognostic utility. Statistical analysis was done using Kaplan-Meier and competing-risk methods. Results: Median follow-up was 2.4 years. Regional recurrence was the predominant failure pattern seen in 26 patients, local recurrence was seen in 14 patients and distant metastasis in 13. The 3-year cumulative incidences of local, regional and distant failure were 11%, 19% and 8.4% respectively. Rates of regional recurrence were substantially higher than Western series. Extremity primaries accounted for 19/26 regional recurrences. BWH T2b disease showed the highest regional failure rate (27.6%), exceeding T3 (17.8%) and T2a (6%) with perineural invasion significantly associated with regional failure in T2b/T3 tumors (p<0.001). Median time to regional metastasis was 8.4 months. At 3 years, overall survival was 77% and progression-free survival was 64%. Conclusion: Regional recurrence is the dominant mode of failure in this cohort, at rates higher than most published series, with extremity primaries and BWH T2b staging identifying particularly high-risk subgroups. These findings highlight the need for a comprehensive staging system encompassing non head and neck cSCC and support prospective evaluation of elective nodal staging and adjuvant radiotherapy in high-risk patients, alongside intensified surveillance.

Background. Tertiary clinical genomics reports condense layered molecular findings into documents that treating oncologists must read, translate, and act upon; manual summarisation of these reports is time-consuming and variable. Tools that assist summarisation and translation into local languages are emerging, yet the field lacks an agreed methodology for evaluating such tools before any downstream clinical use. The appropriate first endpoint is fidelity of the generated summary to its source report, assessed by qualified human raters under blinded scoring, not downstream variant classification. Methods. QNOMX-VHIR-CPSP-001 Phase 1 is a single-site, non-interventional clinical performance study conducted at Vall d'Hebron Institut de Recerca (VHIR) under ISO 20916:2019 as a Clinical Performance Study Protocol. De-identified tertiary cancer genomics reports from pediatric oncology cases are summarised by the AI-assisted summarisation system under evaluation and, in parallel, by the standard manual workflow. Qualified raters score both summary types against the source genomics report using the Quality Summary Index (QSI), a six-dimension, five-point rubric adapted from the Provider Documentation Summarization Quality Instrument, under a blinded, counterbalanced, two-period crossover with a minimum fourteen-day washout. Two co-primary composite endpoints, content and presentation, are analysed for non-inferiority under a Bayesian hierarchical model, with a frequentist linear mixed model as the convergence check. Inter-rater reliability is reported as Krippendorff's ; a Monte-Carlo power analysis of the fixed clustered design is pre-specified. Discussion. The design isolates summarisation quality from clinical decision-making by scoring both summary types against the same source report under blinding, counterbalancing, and a fourteen-day washout. Conclusion. The QSI rubric, the counterbalanced crossover, and the pre-specified Bayesian primary with frequentist convergence check define a replicable protocol for early-stage evaluation of AI-assisted summarisation in tertiary genomics reporting; observed variance components will inform sample-size determination for Phase 2.

Clinical oncology datasets often store systemic therapy as a regimen label with a start date and an end date. Those records are clinically recognizable but can be analytically incomplete when the research question concerns whether a patient was exposed to a concurrent CNS-active drug (cCNS-aD) or an adjuvant CNS-active drug (aCNS-aD) around radiotherapy. Contemporary CNS-oncology studies usually define CNS activity by empiric drug lists and define concurrency by fixed calendar windows, although the literature shows substantial heterogeneity across both concepts. This paper proposes a generalizable framework for converting raw systemic therapy records into reproducible cCNS-aD and aCNS-aD variables, useful in subgrouping for clinical studies. The framework uses a transparent CNS scoring model based on three clinical evidence components: intracranial objective response rate, consensus CNS endorsement, and intrathecal route of administration. It then defines a pharmacokinetic exposure proxy as the recorded end date plus five half-lives. Concurrent exposure is classified by overlap with the radiotherapy interval, while post-radiotherapy exposure is classified by overlap with a prespecified post-RT attribution window. The framework separately identifies post-RT pharmacokinetic persistence and post-RT treatment initiation, allowing investigators to distinguish continued exposure from true adjuvant initiation. This is a methodological framework and reference implementation. Implementation audits and endpoint-specific sensitivity analyses remain necessary before use as a definitive exposure classifier