Clinical and Translational Radiation Oncology

Definitive radiotherapy (RT) for prostate cancer (PC) with dose intensification and/or focal boosting has excellent oncologic outcomes, but many patients experience adverse events. Dose escalation to the whole prostate improves outcomes at the expense of increased late adverse events. Intraprostatic recurrence after definitive RT typically occurs at the site of the primary tumor, suggesting that dose to the site of the dominant lesion is an important predictor of future failure. The efficacy and safety of tumor-focused RT compared to that of standard RT for definitive treatment of localized PC has not been assessed. RadTARGET (RAdiation Dose TAiloRing Guided by Enhanced Targeting) is a phase II randomized trial that aims to demonstrate superior safety of image-guided, tumor-focused RT compared to standard RT for acute genitourinary (GU) or gastrointestinal (GI) in the setting of definitive RT for intermediate- and high-risk PC. The study intervention is image-guided, tumor-focused RT with dose intensification of cancer visible on imaging and dose de-intensification to remaining prostate. Patients will be randomized to two arms: those who receive standard RT dose and those that receive tumor-focused RT. The study population will be patients with intermediate- or high-risk PC planning to undergo definitive RT with or without systemic therapy. The primary endpoint to compare between randomized arms is acute GU or GI grade [≥]2 adverse events. Participant and study duration are 5 years and 8 years, respectively. RadTARGET will compare the efficacy and safety of tumor-focused RT to that of standard RT for definitive treatment of localized PC. We hypothesize that the tumor-focused approach will substantially reduce adverse events after prostate RT while retaining high efficacy. If this hypothesis is confirmed, we will conclude that a phase III randomized control trial is warranted to formally establish oncologic non-inferiority compared to the current standard of whole-gland dose escalation.

BackgroundMen with aggressive, localized prostate cancer (PC) undergo definitive radiotherapy (RT) with androgen deprivation therapy (ADT). The prospective, phase II ARIEL trial evaluates a quantitative MRI biomarker, Restriction Spectrum Imaging restriction score (RSIrs), at three time points (before treatment, after ADT and after RT) for treatment response assessment. RSIrs highlights intracellular restricted diffusion and is correlated with high-grade PC. DesignParticipants are men with unfavorable-intermediate-risk or high-risk localized PC undergoing definitive RT with neoadjuvant and concurrent ADT, and MRI-RSI acquisitions at three time points: before therapy, after neoadjuvant ADT but before RT, and after RT. The primary aim is to evaluate performance of RSIrs for identifying patients who will experience early biochemical recurrence. Change in RSIrs within visible tumors after ADT and RT is the primary independent variable. Results97 patients met inclusion criteria and received [&ge;]1 MRI. On central review, visible PI-RADS lesions were identified in 88 patients: 80 patients had one lesion, and 8 patients had two lesions. After neoadjuvant ADT, 40% of lesions were not clearly visible. Those still visible had shrank by median 55.8% (IQR: 42.8-69.0%), much more than the prostate volume decrease of 21.5% (11.9-31.6%). RSIrs maximum within visible lesions decreased from mean 329 (SD:185) pre-ADT to 209 (SD:125) pre-RT (p<0.01), and to 107 (SD:61) post-RT (p<0.01). Conventional apparent diffusion coefficient (ADC) changes were less consistent. Follow-up is ongoing to assess whether imaging response is related to future recurrence risk. ConclusionARIEL has completed accrual and preliminary results demonstrate changes in RSIrs after treatment, which may indicate tumor response. Primary results will be presented when the primary endpoint is reached. With neoadjuvant ADT, both pre- and post-ADT MRI are likely necessary for accurate focal RT boost targeting. Concurrent commencement of ADT and RT simplifies workflows and facilitates accurate gross tumor volume delineation.

PurposeThere is currently no consensus on the role of proton therapy in head and neck cancers. We conducted a retrospective dosimetric comparison of delivered photon-based intensity modulated radiation therapy (IMRT) plans with simulated intensity-modulated proton therapy (IMPT) plans. Patients and MethodsIn this single-institution retrospective review, we included patients with primary tumors from all head and neck sites treated with unilateral IMRT, who experienced worsened dysphagia and xerostomia symptoms post-radiation. MD Anderson Dysphagia Inventory (MDADI) and Xerostomia Questionnaire (XQ) scores were prospectively collected. We compared target coverage (V95%) for high-dose and low-dose clinical target volumes (CTVs) and maximum/mean doses for organs-at-risk (OARs) between delivered IMRT plans and simulated IMPT plans. Statistical analysis was performed using Wilcoxon signed-rank tests, with Bonferroni-corrected significance level of 0.003. ResultsA total of 23 patients were included in the study. Both IMRT and IMPT plans provided appropriate target coverage of the high-dose CTV (median V95 99.91% for both) and low-dose CTV (median V95 99.71% and 99.90%, respectively). IMPT plans allowed for significant reduction in maximum dose to critical OARs, including the spinal cord (6.4Gy vs 37.3Gy IMRT, p<0.001) and brainstem (5.6Gy vs 33.0Gy IMRT, p<0.001). Furthermore, mean dose to the oral cavity and contralateral pharyngeal constrictors were significantly reduced in IMPT plans (19.7Gy vs 33.6Gy IMRT oral cavity, p<0.001; 20.4Gy vs 26.2Gy IMRT contralateral pharyngeal constrictor, p<0.001). IMPT spared dose to the contralateral parotid (0.04Gy vs 7.6Gy IMRT, p<0.001) and contralateral submandibular gland (1.4Gy vs 15.4Gy, p<0.001). ConclusionIMPT spares dose to OARs compared to IMRT plans in head and neck cancers treated with unilateral radiation. We hypothesize that IMPT can reduce acute and long-term toxicity for these patients, even in locally advanced cancers. Future prospective comparison between these treatment modalities is indicated.

BackgroundThe abscopal effect is a phenomenon where a tumor that is not the intended site of treatment also shrinks in response to therapy; and is one of the most coveted and rare effects of cancer therapies. Previous attempts to summarize literature on the abscopal effect have focused on specific disease sites or been done on a limited basis. We performed a comprehensive review of every publication and case report regarding the abscopal effect induced by radiotherapy from the 1950s to February 2023 to identify potential trends and patterns in its induction based on specific disease/ treatment site, radiation dose, and other factors. MethodsLiterature that described the abscopal effect was identified through search of online databases: Pubmed, Medline, and Google Scholar for all published articles from 1953 leading to February of 2023 that included the terms "Abscopal Effect" and "Radiation" or "Radiotherapy." Demographics (patient and tumor characteristics), radiation and abscopal effect analysis, outcome and treatment analysis, and risk of bias were reported and summarized. ResultsA final total of 92 papers corresponding to 99 separate lesions or cases were included in the meta-analysis. The most common site of induction of the abscopal effect and of the target of the abscopal effect was the lung. One manuscript reported a nonstandard treatment protocol, the remainder of cases received radiation within reasonable treatment guidelines. The majority of manuscripts included most important information (cancer site, number of prior treatments, histopathology, outcome information, and dose). ConclusionAdditional research is urgently needed to understand how and why some treatment regimes are able to induce the abscopal effect. For the time being, this remains a rare phenomenon.

PurposeThis study evaluated the safety and effectiveness of an intraoral light-emitting diode (LED)-based photobiomodulation (PBM) device to reduce the incidence and severity of oral mucositis (OM) from intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC). MethodsThis randomized, double-blind, sham-controlled trial enrolled patients with HNC undergoing high-dose IMRT over 6-8 weeks, with or without concurrent chemotherapy. Participants received daily 10-minute PBM or sham treatments immediately before IMRT sessions. Assessments were conducted at baseline, daily and weekly during IMRT, and two weeks post-IMRT. ResultsEighty-five participants (42 PBM; 43 sham) were enrolled across 12 US sites. No device-related adverse events were observed, and 99.5% of initiated sessions were completed. In the intent-to-treat population, severe OM (WHO Grade [&ge;]3) incidence was significantly lower with PBM across six weeks of IMRT (36.8% vs 57.1%; p = 0.046) and at two weeks post-treatment (10.8% vs 36.4%; p = 0.042). In the per-protocol population, the PBM arm reported significantly greater taste preservation (p = 0.034), lower increases in mouth/throat soreness (p = 0.029) and throat pain (p = 0.028) and needed fewer feeding tube placements (p = 0.073) than the control arm. ConclusionDaily intraoral PBM therapy using an LED-based device was safe, well tolerated, and significantly reduced the incidence of severe OM and associated complications in HNC patients undergoing IMRT with or without concurrent chemotherapy. These findings align with guidelines recommending daily intraoral PBM therapy for preventing cancer therapy-related OM, a dose-limiting toxicity for which effective preventive interventions are needed. Trial RegistrationClinicalTrials.gov Registration Number NCT03972527. Registered on June 3, 2019. Concise SummaryDaily intraoral PBM therapy using an LED-based device was safe, well tolerated, and significantly reduced the incidence of severe OM and associated complications in HNC patients undergoing IMRT with or without concurrent chemotherapy. These findings align with guidelines recommending daily intraoral PBM therapy for preventing cancer therapy-related OM, a dose-limiting toxicity for which effective preventive interventions are needed.

BackgroundLattice radiotherapy (LRT) delivers heterogeneous dose distribution through a three-dimensional array of vertices within the tumor. It is typically applied in 1[~]5 fractions for patients with large tumor volumes. However, conventional LRT generally employs only a single vertex set, which may limit the biological advantages of this technique in multi-fraction treatments. PurposeThis study proposes a novel vertex arrangement strategy in LRT aimed at improving intratumoral dose homogeneity and enhancing coverage of high-dose regions through alternating irradiation of different vertex sets. Materials and methodsPatients with the gross tumor volume (GTV) between 300 cm3 to 2000 cm3 who received radiotherapy treatment at our institution were considered for inclusion. An "NaCl"-type structure was employed. Two sets of vertices ("Na"-type and "Cl"-type) were distributed within the tumor volume following a face-centered cubic (FCC) close-packed pattern analogous to the NaCl crystal structure. For each of the 10 patients with large tumor volumes (range: 319.23-1649.47 cc), two plans were generated: Plan A (optimized for "Na" vertices) and Plan B (optimized for "Cl" vertices). Each plan delivered 15 Gy per fraction to the vertices. Physical doses from Plans A and B were converted to EQD2 (/{beta} = 10 for GTV, /{beta} = 3 for normal tissues) and summed into three composite plans: A+A, A+B, and B+B. Plan quality was assessed using generalized equivalent uniform dose (EUD), homogeneity index (HI), D2, D98, and mean normal tissue dose (Dmean of NT). ResultsThe alternating composite plan (A+B) achieved significantly greater dose homogeneity compared to non-alternating plans (A+A and B+B), with a lower HI (1.23 {+/-} 0.08 vs. 1.70 {+/-} 0.08 and 1.70 {+/-} 0.09, p < 0.05) and higher EUD (3.76 {+/-} 0.38 Gy vs. 3.48 {+/-} 0.40 Gy and 3.42 {+/-} 0.25 Gy, p < 0.05). The low-dose metric D98 was also higher in A+B (4.23 {+/-} 0.27 Gy) than in A+A (3.92 {+/-} 0.25 Gy) and B+B (3.94 {+/-} 0.25 Gy). No significant difference was observed in NT Dmean among the three composite plans. ConclusionAlternating irradiation of two geometrically complementary vertex sets significantly improves dose coverage in high-dose regions and overall dose homogeneity without increasing normal tissue toxicity and potentially enhances therapeutic efficacy in spatially fractionated radiotherapy for large tumors.

BackgroundDefinitive (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) consists of treatment of the macroscopic tumor and prophylactic irradiation of large parts of the lymphatic drainage system: the elective clinical target volume (CTV). There is limited data and quantification of (occult) lymphatic spread and the required extent of the elective CTV. De-escalation of the irradiated volume could result in less early and late toxicity and less affection of the immune system. In this study, we reduce the elective CTV based on the personalized factors T-stage, clinical lymphatic involvement, and lateralization of the primary tumor. MethodsThe primary objective is to evaluate the efficacy and safety of an individualized de-escalation of elective node irradiation volumes. We collected a multi-institutional dataset of 598 oropharyngeal SCC patients in whom detailed lymph node involvement was reported. The data can be explored on the publicly available online platform LyProX.org. Based on the data, we developed a model of lymphatic tumor progression to estimate the probability of occult metastases in the clinically negative lymph node levels (LNLs). Metastatic lymphatic progression is described via a hidden Markov model. The patients state of lymph node involvement is described by hidden binary random variables, and the transition matrix describes the probabilities of lymphatic spread. Based on this model and clinical judgement, we created tables that define the personalized elective CTV for different combinations of T-stage, midline extension and clinical LNL involvement. The elective CTV is defined such that the cumulative risk of occult metastases in all non-irradiated LNLs is below 10%. The primary endpoint of this multicentric, prospective, single-arm trial is the rate of out-of-field nodal recurrences after 2 years. The study will be conducted in 6 centers across Switzerland and 120 patients will be enrolled. DiscussionThis study sets out to personalize the elective CTV in oropharyngeal SCC patients, with the goal to de-escalate radiotherapy for patients and herewith improve therapy-associated toxicity and quality of life. The results of this study may be used to personalize treatment in oropharyngeal SCC patients. Trial RegistrationThis study sets out to personalize the elective CTV in oropharyngeal SCC patients, with the goal to de-escalate radiotherapy for patients and herewith improve therapy-associated toxicity and quality of life. The results of this study may be used to personalize treatment in oropharyngeal SCC patients.

PurposeParotid whole-gland magnetic resonance (MR) T1 intensity, thresholded at the 90th percentile (T1 P90), has been previously reported to be a candidate MR imaging biomarker (MR-IBM) for improved prediction of xerostomia development after radiotherapy. Although P90 was previously derived from the parotid glands of T1-weighted MRI, in this study, we aim to validate P90 in an external cohort using fat only images reconstructed from a T1 Dixon MRI sequence, as well as determining alternative T1 intensity thresholds for potential qualification as predictive FDA BEST biomarkers of xerostomia development 6 months after radiotherapy (Xero6m). MethodsMR-IBMs derived from T1 Dixon intensity-normalized scans from 76 head and neck cancer (HNC) patients were extracted from pre-treatment MR images. Scans were normalized to fat tissue, and imaging characteristics were quantified. A reference model and MR-IBM models were created using multivariable logistic regression to predict Xero6m. External validation was performed using the model coefficients described in a previous study. The area under the curve (AUC) of the resulting models were compared. Stepwise forward feature selection was performed to discover additional MR-IBMs for improved predictions of xerostomia. ResultsThe external validation of a previous model coefficients against our cohort showed decreased performance of the P90 MR-IBM model (AUC of 0.73 (CI 0.61-0.85)). The reference model exhibited improved performance when P90 was incorporated (AUC of 0.78 (CI 0.67-0.89)). Feature selection demonstrated the P10 MR-IBM provided performance improvements (AUC of 0.79 (CI: 0.69-0.90)). ConclusionOur findings validated P90 as predictive biomarker for radiation-induced xerostomia and showed MR-IBMs derived from Dixon sequences can improve Xero6m prediction when compared to the reference model. Formal biomarker qualification should be considered for T1 sequences/relaxometry via formalized approaches.

IntroductionBrain metastases (BMs) affect an increasing number of cancer patients and are typically managed with stereotactic radiosurgery (SRS). Our institution advocates the use of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR), where radiation is delivered in high-dose pulses at extended intervals allowing for treatment adaptation and easy concurrent systemic therapy integration. We explore the integration of PULSAR with central nervous system (CNS)-active drugs (CNS-aDs) compared to traditional fractionated stereotactic radiotherapy (FSRT). MethodsThis study involved a retrospective evaluation of patients treated with either PULSAR or FSRT using Gamma Knife from 2018-2024. We collected demographic, clinical, and specific treatment details, outcomes such as local failure (LF) and toxicity rates. Cumulative incidence analysis for local failure and toxicity, considering death a competing risk, and Kaplan-Meier survival analysis for overall survival (OS) were conducted. Multivariate (MV) Cox proportional hazard models assessed failure and toxicity rates. ResultsAnalysis included 166 lesions treated with FSRT and 109 with PULSAR, predominantly in patients with lung and breast cancer. The median follow-up and OS were 1.88 and 1.48 years. 1- and 2-year LF rates were similar; 5%/8.9% vs 8.2%/12.3% for PULSAR and FSRT and 3.4%/5.5% vs 10.1%/12.3% with concurrent CNS-aDs (cCNS-aDs). BMs > 2 cm LF rates were 9.4% and 17.3% at two years for PULSAR and FSRT (p=0.1). No LFs were observed in BMs > 2 cm treated with PULSAR+CNS-aDs at 2.5 years. The two-year grade 3+ toxicity rate for PULSAR (8.7%) and FSRT (11.7%), without an increase in toxicity when combined with cCNS-aDs. BMs treated with PULSAR+cCNS-aDs were less likely to fail (HR 0.15, p=0.048) on MV analysis (MVA). ConclusionThe integration of PULSAR with cCNS-aDs appears to offer excellent local control for larger brain metastases without increased toxicity. These promising results merit further prospective investigation to validate the findings and potentially establish new treatment protocols.

Background and purposeRadiation-induced changes in brain tissue may relate to post-radiotherapy (RT) cognitive decline. Our aim is to investigate changes of the brain microstructural properties after exposure to radiation during clinical protocols of RT using diffusion MRI (dMRI). Methods and MaterialsThe susceptibility of tissue changes to radiation was investigated in a clinically heterogenic cohort (age, pathology, tumor location, type of surgery) consisting of 121 scans of 18 patients (10 females). The imaging dataset included 18 planning CTs and 103 dMRI scans (range 2-14, median = 6 per patient) assessing pre-operative, post-operative pre-RT and post-RT states. Diffusion tensor imaging (DTI) metrics were estimated from all scans for a region-of-interest based linear relation analysis between mean dose and change in DTI metrics, while partial volume effects were regressed out. ResultsThe largest regional dose dependency with mean diffusivity appear in the white matter of the frontal pole in the left hemisphere by an increase of 2.61 %/(Gy x year). Full brain-wise, pooled results for white matter show fractional anisotropy to decrease by 0.85 %/(30Gy x year); mean diffusivity increase by 9.17 %/(30Gy x year); axial diffusivity increase by 7.30%/(30Gy x year) and radial diffusivity increases by 10.63%/(30Gy x year). ConclusionsWhite matter is susceptible to radiation with some regional variability where diffusivity metrics demonstrate the largest relative sensitivity. This suggests that dMRI is a promising tool in assessing microstructural changes after RT, which can help in understanding treatment-induced cognitive decline.

PurposeRadiotherapy-induced dysphagia can significantly impair head and neck (H&N) cancer patients quality of life. Despite the dose-dependent relationship between radiotherapy and dysphagia, swallowing structures are not routinely contoured due to time and labor demands. We evaluated atlas-based autosegmentation (ABAS) on MRI, identifying the optimal number of atlases required to efficiently and accurately delineate swallowing structures. MethodsThis study included pre-radiotherapy simulation T2-weighted MRIs from 60 H&N cancer patients enrolled in an IRB-approved observational trial. Scans were acquired on a 1.5T Siemens Aera scanner with H&N immobilization. Swallowing structures, including epiglottis, constrictors, digastric muscles, genioglossus, and others, were manually contoured for 25 atlas patients and 35 test patients. GTV-involved structures were excluded. ABAS was performed with increasing numbers of atlases (1-25) using a random-forest algorithm (ABAS-ADMIRE; Elekta) to determine the optimal atlas count. To mitigate variability from atlas selection, bootstrap resampling was implemented. Dice similarity coefficient (DSC), surface DSC (SDSC), average surface distance (ASD), and 95% Hausdorff distance (HD95) were calculated for each structure. Median computation times were calculated for each atlas count. Hsus MCB analysis identified the minimum atlas number statistically equivalent to the best-performing atlas range. ResultsAcross all structures and metrics, Hsus analysis demonstrated that 2-4 atlases performed similarly to the best-performing atlas count. All structures except constrictors achieved median DSC>0.75 with [&ge;]2 atlases. Computation times increased linearly with atlas count (range: [~]22-950 seconds for 1-25 atlases). These findings highlight that smaller atlas counts achieve comparable accuracy while significantly improving time efficiency. ConclusionAtlas-based autosegmentation is useful for delineating swallowing muscles in radiotherapy, especially with limited available contoured datasets. Utilizing 2-4 atlases achieves similar geometric accuracy to larger atlas counts, significantly reducing computational time without compromising clinical quality. This balance between efficiency and accuracy supports integration into workflows for better dysphagia prediction and treatment planning.

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 [&ge;]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 [&ge;] 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 and purposePrecise manual annotation of the left ventricular myocardial (LVM) wall is essential for cardiac substructure research, wall-specific radiation dosimetry, and segmentation model development. However, existing radiotherapy-oriented atlases and conventional CT viewing planes lack an explicit framework for reproducible, wall-level LVM delineation. To address this gap, we developed an anatomy-guided manual segmentation protocol for delineating the five LVM walls on non-contrast-enhanced CT (NECT) or contrast-enhanced CT (CECT) scans. Materials and methodsThis protocol was developed using 60 chest CT scans from two prospective cohorts at Heidelberg University Hospital, including 50 CECTs from IMRT-MC2 cohort and 10 NECTs from MAGELLAN cohort. Manual contouring was performed in 3D Slicer. Segmentation rules were established through review by a radiation oncologist and a cardiology expert, based on the American Heart Association 17-segment model, and were tested on additional CT scans before final protocol definition. ResultsThe protocol centers on three geometric steps: (1) defining the LV long axis using the endocardial apex and the center of the mitral annulus; (2) constructing an apical delimitation plane based on LV geometry; and (3) partitioning wall regions via intersections of the right ventricular and LV cavity centers in the short-axis view. This workflow enables structured segmentation of the anterior, septal, lateral, inferior, and apical LVM walls, supporting anatomically coherent 3D reconstruction. ConclusionThis study provides contouring steps and a representative atlas as a methodological basis for standardized annotation, with potential applications in dose-mapping cardiotoxicity analysis and deep-learning modeling for radiotherapy.

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.

Accurate delineation of orodental structures on computed tomography (CT) is critical for image-guided assessments of radiation-associated bone injury. This dataset comprises curated CT imaging and expert-defined segmentation masks for 60 patients with head and neck cancer treated with radiotherapy (RT), including delineations of mandibular and maxillary sub-volumes and individual teeth. Segmentation guidelines were informed by anatomical differences across sub-regions and aligned with the ClinRad osteoradionecrosis (ORN) staging system. The dataset includes converted NIfTI files of simulation CT images, RT dose distributions, and delineated structures. All segmentations were performed manually using a standardized protocol in a commercial treatment planning system and converted to research-ready formats using open-source tools. This dataset may facilitate the development and validation of automated segmentation tools, dose mapping applications, and image-based ORN detection pipelines in head and neck cancer survivors.

BackgroundRadiation therapy (RT) is an essential component of definitive treatment for cancers of the prostate, rectum, cervix, and other pelvic malignancies. Despite its proven efficacy, pelvic RT is associated with a constellation of adverse effects, collectively referred to as pelvic radiation disease (PRD). Several clinical and preclinical studies have shown that dietary interventions, including time-restricted eating (TRE), may represent a novel approach to mitigate radiation and chemotherapy toxicity and, in some cases, promote oncologic efficacy, thereby enhancing quality of life, reducing morbidity and mortality, and improving disease outcomes. ObjectivesThis trial was designed to evaluate TRE feasibility/tolerability and test the hypothesis that TRE during RT or chemoradiation could reduce DNA damage accumulation in peripheral blood mononuclear cells over the course of treatment, as quantified by {gamma}H2AX foci. Secondary objectives include reduction in clinically observed toxicities, improvements in urinary or blood biomarkers of DNA damage, mitigation of microbiome dysbiosis and cytokine response during radiation, and improved metabolic parameters. MethodsA total of 48 individuals with prostate, cervical, or rectal cancer aged [&ge;]18 years with a BMI [&ge;]21 kg/m2 receiving pelvic radiation will be randomized to either TRE or nutritional counseling. Both groups of participants will receive dietary consultation with a registered dietician before and during RT, and the TRE group participants will be asked to restrict their caloric intake to a specific timeframe (fast at least 6-8 hours before and at least 4-6 hours after RT). Biospecimens (blood, urine, stool), quality-of-life surveys, physician-reported toxicities (CTCAEv5.0), and food intake and fasting logs will be collected biweekly during the study intervention and every 3-6 months up to one year follow-up. ResultsAccrual was completed in August 2025. Follow-up and biospecimen collection are ongoing, and correlative analyses are in progress. Final outcomes will be reported upon study completion. Trial registrationClinicalTrials.gov NCT05722288

Background and purposeBoron neutron capture therapy (BNCT) has been routinely practiced for treatment of head and neck cancer in Japan. However, differences in contouring the oral and pharyngeal mucosa can lead to discrepancies in treatment. This study aimed to introduce a standardized approach using an MRI-based atlas, aiming to minimize inter-observer error and improve dose precision. Materials and MethodsAn MRI atlas of the head and neck mucosa was developed using water/fat-separated images from a healthy man. Using CT images from three patients, seven radiation oncologists performed contouring of the head and neck mucosa twice over a 3-week period. Contouring was first performed using CT alone, then later using fused T2-weighted images with the mucosal atlas for guidance. Contouring errors were assessed and their impacts on tumor dose were evaluated. ResultsThe introduction of the MRI-based mucosal atlas significantly reduced inter-observer variation in mucosal volume (the coefficient of variation, abbreviated with COV, decreased from 0.61 with CT alone to 0.21 with the MRI atlas; p=0.003). Moreover, the atlas resulted in improved contour homology among observers and reduced variations in tumor dose. For all cases, COVs for maximum, mean, and minimum tumor doses were all below 5%. ConclusionUtilizing an MRI-based mucosal atlas in BNCT contouring can significantly reduce inter-observer variation, improve contour homology, and decrease variations in tumor dose. These findings suggest strong potential for standardizing and enhancing the quality of BNCT for head and neck cancer.

PurposeConformal dose distributions in proton radiotherapy promise to reduce normal tissue toxicity such as radiation-induced pneumonitis, but this has not been fully realized in clinical trials. To further investigate dose and toxicity, we employ voxel-based normal tissue evaluation techniques such as ventilation maps throughout treatment. We hypothesize that ventilation change after 1 week of treatment (WK1) predicts for ventilation change at the end of treatment (EOT). MethodsFor 48 photon and 23 proton lung cancer patients, 4DCT-based ventilation maps were generated using stress-based methods at planning, WK1, and EOT. Voxel-wise ventilation change from planning to WK1 and EOT was calculated and binned by planned dose, and median ventilation change at WK1 and EOT was calculated across all patients in each dose bin. Patients were stratified into 6 groups based on modality and increased, decreased, or stable ventilation at WK1. Mann-Whitney U tests were performed to determine if median ventilation change at WK1 and EOT in each dose bin was significantly different from zero. Univariate analysis was performed to correlate ventilation change at EOT with change at WK1 and other clinical factors. A linear regression model was developed to predict ventilation at EOT using a variety of input features including ventilation at planning, ventilation at WK1, tumor response information, and tumor location. Accuracy of the model was assessed through R2. ResultsFor patients that decreased in ventilation at WK1, 90% of photon patients and 92% of proton patients were stratified similarly at EOT. Patients that were stratified as increased ventilation at WK1 were stratified similarly (72% for photon, 80% for proton) at EOT. These patients were more likely to develop Grade 2+ pneumonitis though the difference was not significant when computing a Fishers exact test. Univariate analysis indicated that only ventilation change at WK1 was correlated with ventilation change at EOT. The linear regression model achieved R2 of 0.65. ConclusionVentilation changes at EOT can be predicted using ventilation information from planning and WK1. Patients that increased in ventilation at WK1 were more likely to develop pneumonitis. Further work is needed to characterize the relationship between ventilation change with pneumonitis development.

Head and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers during treatment may improve earlier detection of responders versus non-responders during radiotherapy. In this study, patients with intact tumour of HNSCC were enrolled in the prospective PREDICT-HN study. Pre-, after first treatment, weekly, and post-treatment blood samples were collected. CTC was enumerated using the CellSearch system. cfDNA was quantified from cfNA isolated at pre-, mid- and post-treatment timepoints. Blood samples were collected from 45 patients. Of the 339 samples analysed for CTC, 31% had detectable CTCs. Nine patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment samples. After 1 fraction, 16 patients had CTCs detected, with 12 who had no pre-treatment CTC. Sixteen (36%) patients had detectable CTC in final week of treatment. There was no correlation between cancer stage, nodal status and tumour burden with CTC. cfDNA levels increased during treatment, with its highest level in the final week and lowest at post-treatment. Our results showed in HNSCC that CTCs can be detected during radiotherapy, suggesting mobilization into circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, and may indicate apoptotic change. Simple SummaryHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumour cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Although the detection of CTCs and cfDNA in patients with HNSCC has been described, there is minimal data on the kinetics of CTC counts and cfDNA levels during radiotherapy in patients with HNSCC. Here, our study prospectively describes the changes in CTC and cfDNA enumeration during radiotherapy in patients with HNSCC. Our results showed, for the first time to our knowledge, in HNSCC, that CTCs can be detected during radiotherapy, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.

BackgroundThe 1-week photon radiotherapy schedule of 26 Gy in 5 fractions is as safe and effective as the standard 3-week schedule of 40 Gy in 15 fractions for adjuvant local radiotherapy in early-stage breast cancer. Proton radiotherapy offers dosimetric advantages by sparing the heart and lung dose but may cause more acute skin toxicities than conventional fraction photon radiotherapy. The acute toxicity of ultra-hypofractionated proton therapy is currently unknown. Materials and MethodsIn this trial, non-metastatic breast cancer patients were randomly assigned to receive either proton or photon therapy with the same dose of 26 Gy in 5 fractions given on alternate days. The aim of this trial was to compare acute skin toxicity between proton radiotherapy and photon beam radiotherapy using ultra-hypofractionation. ResultsOut of 140 eligible patients, 72 were included in this initial analysis (36 proton, 36 photon). Only one patient in the proton arm experienced grade 2 radiation dermatitis, which was the highest recorded grade. The incidence of acute radiation dermatitis was significantly higher in the proton arm compared to the photon arm (97.2% vs. 75%, respectively, p=0.006). There was no significant difference in other acute toxicities between the two arms. Patients treated with photon had better cosmetic outcomes (41.7% vs. 13.9%, P= 0.007) and were more satisfied (80.6% vs. 58.3%, P=0.04) than those in the proton arm. At a median follow-up of 9 months (IQR: 6-11), no locoregional recurrence was observed between the two arms. ConclusionIn summary, this interim analysis found that ultra-hypofractionated proton therapy led to a higher rate of acute radiation dermatitis than the photon arm, although the dermatitis was mild. Patients in the photon arm had better cosmetic outcomes and higher satisfaction scores. However, further patient accrual and long-term follow-up are necessary to determine the long-term effects and effectiveness of proton therapy in breast cancer treatment.