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.

BACKGROUND AND PURPOSE: ROAM/EORTC-1308 is an international (Europe and Australasia) phase III randomised controlled trial (RCT) comparing radiotherapy (60Gy/30#) to observation after surgery for atypical meningioma. The treatment plans of all the patients randomised to radiotherapy were reviewed and approved prior to treatment delivery, either by the UK RTTQA group (European sites) or the Australian TROG (Australia and New Zealand). Pretrial credentialling included outlining and planning a benchmark case (DR). MATERIALS AND METHODS: Variations from the guidelines were noted in quality assurance (QA) reports both for DR and for the on-trial Individual Case Reviews (ICRs) and classed as major or minor. After recruitment had finished, a random 10% of the ICRs were independently reviewed for audit purposes. We used the QA reports to analyse the variations in the DR and in the ICRs RESULTS: 56 sites (20 UK, 25 EORTC, 11 TROG) undertook the DR of which 13 (23%) had major variations. During the trial 64 patients at 28 sites received radiotherapy, the median being 2 patients per site. Overall, 25 (39%) patient cases needed resubmitting: 22 (36%) sets of outlines (2 cases twice) and 12 (14%) treatment plans (1 plan twice). CONCLUSIONS: For complex radiotherapy of rare tumours, a DR is insufficient and prospective ICRs of all patients is required. The consistent high-quality radiotherapy in ROAM/EORTC1308 ensures the primary outcome (progression free survival) will be a robust assessment and any difference between treatment arms cannot be attributed to variation in radiotherapy treatment.

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.

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.

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.

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.

BackgroundAfferent baroreflex failure (ABF) is an underrecognized but debilitating complication among head and neck cancer survivors, especially in oropharyngeal cancer (OPC), a malignancy with excellent prognosis. ABF is mainly caused by radiation therapy (RT), with neck surgery and some chemotherapies also contributing. It manifests as blood pressure lability, including severe hypertension or hypotension, syncope, and arrhythmias. ObjectivesTo determine the prevalence and predictors of ABF-associated manifestations among OPC survivors treated with modern RT. MethodsWe retrospectively studied OPC patients treated with RT at a tertiary cancer center between 2016-2019. Clinical data were collected from RT initiation to last follow-up or death. ABF-associated manifestations included new or worsening hypertension, hypotension requiring intervention, arrhythmias, and syncope. Secondary endpoints included new or worsened carotid artery atherosclerosis, stenosis, transient ischemic attack (TIA), stroke, and all-cause mortality. ResultsAmong 393 patients (88% men, 91% White, mean age 61{+/-}10 years), 9.4% developed hypertension, 5.3% hypotension, 3.8% syncope, and 3.3% arrhythmias over median 6.3-year follow-up. Overall, 19.1% developed at least one ABF-associated manifestations. New or worsened carotid atherosclerosis occurred in 38.9%, with 7.1% developing >50% stenosis and 2.3% experiencing TIA or stroke. Mortality was 21.4%. On cause-specific multivariable Cox analysis, older age (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI] 1.01-1.06), valvular disease (aHR 2.85; CI 1.03-7.92), T4 cancer (aHR 1.90; CI 1.10-3.27), and platinum-taxane chemotherapy (aHR 1.86; CI 1.13-3.05) independently increased risk of ABF-associated manifestations. ConclusionsNearly 1 in 5 OPC survivors treated with RT develop ABF-associated manifestations, highlighting the need for early recognition and surveillance.

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.

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.

BackgroundNon-small cell lung cancer (NSCLC), the most common type of lung cancer, often leads to brain metastases (BMs) with a poor prognosis. Radiotherapy is the main treatment for BMs, which despite decades of development, still results in radiation of healthy tissue. Neural stem cells (NSCs), crucial for the establishment and preservation of the nervous system, are sensitive to radiation, therefore radiation damage to NSCs may affect overall survival (OS). NSCs are primarily located in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the hippocampus (HPC). Our study aims to evaluate the impact of radiotherapy dose on NSCs on OS in patients with BMs from NSCLC. MethodsWe have retrospectively included 138 NSCLC patients with BMs, irradiated at a single academic institute. NSC regions were delineated on the non-enhanced T1 MR images with CAT12 and SPM. The association between regional mean doses in the SVZ and HPC and OS was examined using a Cox regression model. Additionally, survival differences between lesion contact and no direct contact with SVZ and HPC were investigated with Kaplan-Meier (KM) analysis. FindingsMultivariable Cox regression of dose on the SVZ and HPC showed a significant negative correlation, with a hazard ratio (HR) of 1.366 (p = 0.041 [95% (CI) 1.013- 1.842]) and 1.194 (p = 0.037 [95% CI 1.010 - 1.411]), respectively. KM analysis did not find a relationship between lesion contact with NSC-regions and OS. InterpretationRadiotherapy dose on the neurogenic niches is correlated with poorer OS and we found no association between direct lesion contact to NSC-regions and OS. We recommend further investigation into the impact of radiation on OS and neurocognitive function in a prospective study design in order to develop treatment approaches that minimize the potential harm to NSCs while maximizing effectiveness. FundingReceived no funds, grants, or support.

PURPOSEWe aimed to quantify the sublocal geometric uncertainties of the neck prophylactic clinical target volume (CTVprophy) during image-guided radiotherapy for nasopharyngeal cancer (NPC). MATERIALS AND METHODSTwenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) followed by six weekly CT (CTrepeat) scans during chemotherapy and intensity-modulated radiation therapy. The sternocleidomastoid muscle (SCM) and its anterior, middle, and posterior parts, as well as the body contours at the 1st (C1) and 2nd (C2) cervical vertebrae, hyoid bone (HB), and cricoid cartilage (CC) in transverse CT sections, were manually delineated in the CTplan and each CTrepeat. The residual error and 2D or 3D vector displacements of each sublocation were calculated, and the planning target volume (PTV) margins were estimated using the PTV margin formula. RESULTSThe left- and right-sided SCM volume decreased by 3.7 {+/-} 9.6% (1.9-5.4%) and 5.1 {+/-} 6.7% (3.9-6.3%), respectively, and the center of mass shifted medially 0.8-0.9 mm. An anisotropic PTV margin of 2-4 and 1-5 mm was needed in the left-right and anterior-posterior directions, respectively. The geometric changes in the upper neck at the C1 and C2 sections were smaller than those in the middle-lower neck at the HB and CC levels. At the same sublocation, the margin needed in the anterior-middle part was smaller than that needed in the posterior part of the neck. The rigid imaging registration-induced anatomical errors in the upper neck were < 1.9%, and those in the middle and lower neck level were 0.6-3.8%. CONCLUSIONSThe surface geometrical changes of the neck prophylactic CTV in the sublocations are substantial and an anisotropic PTV margin of 1-5 mm is needed in the context of image-guided radiotherapy for NPC.

BackgroundDynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This work sought to determine if a significant difference exists in post head and neck cancer (HNC)-RT DCE-MRI quantitative parameters Ktrans and ve between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose. MethodsDCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI quantitative parameters Ktrans and ve were obtained through Tofts model fitting. Four mandible sections (left ramus, left body, right ramus, and right body) were delineated on subject mandible contours. Two Kruskal-Wallis tests comparing the mean Ktrans and ve in low dose ([&le;] 60 Gy) areas of the four mandible regions were computed. Next, two Wilcoxon signed-rank tests were used to determine if the means of Ktrans and ve between high dose (> 60 Gy) and low dose ([&le;] 60 Gy) mandible regions were significantly different. To account for multiple statistical tests, a Bonferroni corrected significance level for all statistical tests was used [Formula]. Results48 HNC subjects were included in the analysis. The Kruskal-Wallis tests showed no inherent significant difference in Ktrans means between mandible regions [Formula] and no inherent significant difference in ve means between mandible regions [Formula]. No significant difference was found between high and low dose Ktrans mandible means (W=392, p=0.044). A significant difference was found between high and low dose ve mandible means (W=214, p=0.00013). ConclusionsNo inherent difference in DCE-MRI quantitative parameters was observed within subject mandibles, but a significant difference was observed between ve means of high and low radiation dose mandible regions. These results provide evidence of the utility of DCE-MRI to monitor mandible vasculature changes resulting from head and neck cancer radiation therapy. Monitoring post HNC-RT mandible vasculature changes is important to initiate earlier toxicity management and ultimately improve HNC survivor quality of life. Simple SummaryDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can detect relative differences in anatomical blood perfusion and vessel permeability. Differences in vascularity should occur between mandible regions receiving a large radiation dose and regions receiving a low radiation dose during head and neck cancer radiation therapy. In this study, we determined if DCE-MRI can be used to detect vasculature differences between mandible regions irradiated with high and low amounts of radiation. The results indicate that one of the DCE-MRI parameters was significantly different between irradiated mandible regions receiving high and low radiation dose. This parameter may be used as an early marker for mandible radiation damage from head and neck radiation therapy.

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.

Background and purposeIn the last 20 years, it has become well-documented that incidental cardiac exposure to ionizing radiation is associated with a clinically relevant increased risk of cardiovascular morbidity. In parallel, radiation therapy technologies have been developed to provide target dose coverage with less exposure to adjacent organs at risk. In the current work, we investigate trends in cardiac exposure among patients treated with curative intent radiotherapy from a single institution between 2009 to 2020. Materials and methods10,215 treatment courses were analyzed from 9,966 patients treated with curative intent for intrathoracic or breast cancers in the period 2009-2020. All hearts were re-delineated using an AI model to ensure consistency over time. Cardiac doses were extracted in 3D from the record-and-verify system and converted, voxel-by-voxel, to equi-effective doses in 2 Gy fractions (EQD2) using /{beta}=2 Gy. Mean heart dose (in EQD2) and volume exposed to 5 and 40 Gy (V5 and V40Gy), respectively, were extracted. Time trends in these cardiac dose-volume metrics were investigated for each diagnosis. ResultsPatients with esophageal cancer had the highest mean heart dose (median = 11.67 Gy; IQR = 2.85, 18.18), while the lowest was observed in patients with breast cancer (median = 0.60 Gy; IQR = 0.30, 1.08) and lymphoma (median = 0.01 Gy; IQR = 0.00, 0.38). A decreasing trend over time was seen most clearly for patients with esophageal and lung cancers (p<0.05). Among patients with breast cancer, V40 decreased from 2009-2015 after which we observed an increase. ConclusionThere has been a significant reduction in radiation exposure to the heart in patients treated in the period 2009-2020, likely due to increased awareness of cardiovascular toxicity and technological developments. The study also found a significant increase in V40 from 2015 to 2020 for patients with breast cancers, possibly related to increased prioritization of target coverage. HighlightsO_LI10,215 radiation therapy plans extracted and analyzed C_LIO_LIHearts were re-delineated with machine learning on the therapy CT-scan to ensure time-independent delineations C_LIO_LICardiac doses were found to decrease over time, especially high dose exposure of intrathoracic lesions C_LIO_LIAn unexpected increase in cardiac high dose volume (V40Gy) for breast cancer treatment plans in recent years was observed C_LI

PurposeWe developed QUANNOTATE, a new web-application for rapid review of radiotherapy (RT) target volumes, and used it to evaluate the relationship between target delineation compliance with the international guidelines and treatment outcomes in nasopharyngeal carcinoma (NPC) patients undergoing definitive RT. Methods and MaterialsThe dataset used for this study consists of anonymized CT simulation scans, RT structures, and clinical data of 332 pathologically confirmed NPC patients treated with intensity-modulated RT between July 2005 and August 2017. We imported the contours of intermediate risk clinical target volumes of the primary tumor (IR-CTVp) receiving 56 Gy into QUANNOTATE. We determined inclusion of anatomic sites within IR-CTVp in accordance with 2018 International guideline for CTV delineation for NPC and correlated the results with time to local failure (TTLF) using Cox-regression. ResultsAt a median follow-up of 5.6 years, 5-year TTLF and overall survival rates were 93.1% and 85.9% respectively. The most frequently non-guideline compliant anatomic sites were sphenoid sinus (n = 69, 20.8%), followed by cavernous sinus (n = 38, 19.3%), left and right petrous apices (n = 37 and 32, 11.1% and 9.6%), clivus (n = 14, 4.2%), and right and left foramen rotundum (n = 14 and 12, 4.2% and 3.6%). Among 23 patients with a local failure (6.9%), the number of non-compliant cases were 8 for sphenoid sinus, 7 cavernous sinus, 4 left and 3 right petrous apices, and 2 clivus. Compared to conforming cases, cases which did not contour the cavernous sinus had a higher local failure (LF) rate (89.1% vs 93.6%, p= 0.013). Multivariable analysis confirmed that lack of cavernous sinus contouring was prognostic for LF. ConclusionsQUANNOTATE allowed rapid review of target volumes in a large patient cohort. Despite an overall high compliance with the international guidelines, undercoverage of the cavernous sinus was correlated with LF.

Purpose/Objective(s)To determine diffusion-weighted imaging (DWI) MRI parameters associated with tumor response and oncologic outcomes in head and neck (HNC) patients treated with definitive radiation therapy (RT). Materials/MethodsEighty-six HNC patients enrolled in an active prospective imaging study at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients had MRIs pre-, mid-, and post-RT completion. Inclusion criteria included adults with histologic evidence of malignant head and neck neoplasm indicated for curative-intent treatment with RT with/without chemotherapy, good performance status (ECOG score 0-2), and with no contraindications to MRI. Patients were scanned using a MAGNETOM Aera 1.5T MR scanner (Siemens Healthcare, Germany) with two large four-channel flex phased-array coils. We used fat-suppressed T2-weighted turbo spin echo sequences for tumor segmentation which were co-registered to respective DWIs for extraction of apparent diffusion coefficient (ADC) measurements. Treatment response was assessed at mid-RT and at 8-12 weeks post-RT using RECIST 1.1 criteria and was defined as: complete response (CR) vs. non-complete response (non-CR). Pre-RT ADC was correlated with RT response (CR vs. non-CR) at mid- and post-RT. The Mann-Whitney U test was used to compare ADC values between the mid-treatment CR group and the non-CR group. Recursive partitioning analysis (RPA) was performed to identify ADC threshold associated with relapse. Cox proportional hazards models were done for clinical vs. clinical and imaging parameters and internal validation was done using bootstrapping technique. ResultsEighty-one patients were included in this analysis. Median follow-up was 31 months. Pre-treatment ADC was not correlated with tumor response or oncologic outcomes (P>0.05). For patients with post-RT CR, there was a significant increase in mean ADC at mid-RT compared to baseline ((1.8 {+/-} 0.29) x 10-3 mm2/s versus (1.37 {+/-} 0.22) x 10- 3 mm2/s, p < 0.0001), while patients with non-CR had no statistically significant increase (p >0.05). RPA identified GTV-P delta ({Delta}) ADCmean <7% at mid-RT as the most significant parameter associated with worse LC and RFS (p=0.01). Univariable and multivariable analysis of prognostic outcomes showed that GTV-P {Delta}ADCmean at mid-RT [&ge;]7% was significantly associated with better LC and RFS. The addition of {Delta}ADCmean significantly improved the c-indices of LC and RFS models compared with standard clinical variables (0.85 vs. 0.77 and 0.74 vs. 0.68 for LC and RFS, respectively, p<0.0001 for both). ConclusionADC change at mid-RT is a strong predictor of oncologic outcomes in HNC patients. Patients with no significant increase of primary tumor site ADC at mid-RT relative to baseline values are at high risk of disease relapse. Multi-institutional data are needed for validation of our results.

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

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.