Rwigema, Jean‐Claude M.

Importance Standard adjuvant therapy for human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is radiation therapy 60 Gy with or without cisplatin delivered in 30 fractions during 6 weeks. A phase 3 randomized clinical trial demonstrated decreased toxic effects and improved patient-reported outcomes with de-escalated adjuvant radiation therapy (DART) compared with standard therapy; however, outcomes for patients treated in the clinical practice setting following trial adoption remain unknown. Objective To compare characteristics and oncologic outcomes of patients treated with DART during clinical trials (on study) and in clinical practice settings (off study) and report progression-free survival (PFS) by risk category. Design, Setting, and Participants This retrospective cohort study included patients treated with DART in the MC1273 and MC1675 trials and in clinical practice after study completion at a multisite tertiary care center. Patients with surgically resectable HPV-OPSCC who underwent margin-negative resection between August 20, 2013, and March 21, 2023, and were treated with DART were included in the analysis. Those with prior head and neck cancer, pT0 or pT4 disease, unknown HPV status, metastatic disease at presentation, synchronous primary tumors, induction chemotherapy, or treatment at an outside institution were excluded. Data were analyzed from July 1, 2024, to July 18, 2025. Interventions DART consisting of 30 to 36 Gy in 1.5- to 1.8-Gy fractions twice daily with docetaxel 15 mg/m 2 on days 1 and 8. Main Outcomes and Measures Progression-free survival as measured via Kaplan-Meier analysis. Results A total of 282 patients were included in the analysis: 176 (62.4%) in the on-study group and 106 (37.6%) in the off-study group (252 [89.4%] male; mean [SD] age, 59.1 [9.3] years). Both groups were predominantly male (157 [89.2%] and 95 [89.6%], respectively) and consisted mostly of never smokers (118 [67.0%] and 62 [58.5%], respectively). Pathologic features were similar between groups except for nodal stage (pN1: 155 [88.1%] on study vs 102 [96.2%] off study; pN2: 21 [11.9%] on study vs 4 [3.8%] off study; P = .02). The median follow-up times were 5.2 years (95% CI, 5.2-5.8 years) in the on-study group and 2.2 years (95% CI, 1.9-2.4 years) in the off-study group. Two-year PFS was similar (93% [95% CI, 88%-97%] on study vs 93% [95% CI, 88%-99%] off study). For patients with pN1 and no extranodal extension (ENE), 2- and 5-year PFS were 97% (95% CI, 93%-100%) and 96% (95% CI, 92%-100%), respectively. Patients with pN1 and ENE had a 2- and 5-year PFS of 93% (95% CI, 89%-98%) and 87% (95% CI, 81%-94%), respectively. Conclusions and Relevance In this retrospective cohort study of patients receiving DART on and off study, oncologic outcomes were similar between the 2 groups. Fewer patients with pN2 received DART off study, given the interim results of MC1675. Patients with pN1 and no ENE treated with DART had excellent 2- and 5-year PFS, supporting DART as a compelling treatment option in well-selected patients. An additional study that is currently underway will evaluate biomarker risk-stratified treatment of patients with pN1 and ENE receiving DART.

Abstract Purpose: Head and neck (HN) radiotherapy contour quality directly impacts local control (LC) and survival; however, few departments peer review (PR) contours prior to radiotherapy planning (RTP). This study reports outcomes of a single institution’s formal HN contour PR process. Methods: A formal HN contour PR process was implemented. Prior to RTP, HN radiation oncologists reviewed contours, provided feedback and assigned contour grades as follows: R0 (no change), R1 (minor revision, not high risk) or R2 (major revision; high risk). The PR task was completed and the contour grade was recorded. Cochran-Armitage trend test was performed. Results: Pilot PR process was performed over a 7-month period for 88 patients, followed by a maintenance phase. Contours were graded as follows: R0 ( N = 51), R1 ( N = 20) and R2 ( N = 17). Over time, the number of R2 revisions decreased ( p = 0.0001); month 1 ( N = 7), month 2 ( N = 3), month 3 ( N = 5), month 4 ( N = 2) and months 5–7 ( N = 0). Conversely, the number of R0 revisions improved over time ( p = 0.0203); month 1 ( N = 5), months 2–3 ( N = 9), month 4 ( N = 5), month 5 ( N = 8), month 6 ( N = 12) and month 7 ( N = 3). Each radiation oncologist demonstrated reduction in R2 revisions during the pilot. During maintenance, all 3 radiation oncologists demonstrated low rates of R2 revisions of less than 3 cases per year. Conclusion: Incorporation of HN contour PR into routine clinical workflow is feasible. The collective experience of multiple high-volume HN radiation oncologists led to improved contour quality in the pilot for each radiation oncologist and continued to ensure high quality in the maintenance phase.

Background/Objectives: The accurate delineation of primary tumors (GTVp) and metastatic lymph nodes (GTVn) in head and neck (HN) cancers is essential for effective radiation treatment planning, yet remains a challenging and laborious task. This study aims to develop a deep-learning-based auto-segmentation (DLAS) model trained on external datasets with false-positive elimination using clinical diagnosis reports. Methods: The DLAS model was trained on a multi-institutional public dataset with 882 cases. Forty-four institutional cases were randomly selected as the external testing dataset. DLAS-generated GTVp and GTVn were validated against clinical diagnosis reports to identify false-positive and false-negative segmentation errors using two large language models: ChatGPT-4 and Llama-3. False-positive ruling out was conducted by matching the centroids of AI-generated contours with the slice locations or anatomical regions described in the reports. Performance was evaluated using the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), and tumor detection precision. Results: ChatGPT-4 outperformed Llama-3 in accurately extracting tumor locations from the diagnostic reports. False-positive contours were identified in 15 out of 44 cases. The DSCmean of the DLAS contours for GTVp and GTVn increased from 0.68 to 0.75 and from 0.69 to 0.75, respectively, after the ruling-out process. Notably, the average HD95 value for GTVn decreased from 18.81 mm to 5.2 mm. Post ruling out, the model achieved 100% precision for GTVp and GTVn when compared with the results of physician-determined contours. Conclusions: The false-positive ruling-out approach based on diagnostic reports effectively enhances the precision of DLAS in the HN region. The model accurately identifies the tumor location and detects all false-negative errors.

ImportanceThe De-escalated Adjuvant Radiation Therapy (DART) phase 3 randomized clinical trial (RCT) showed that in patients with human papillomavirus (HPV)−associated oropharyngeal squamous cell carcinoma, postoperative minimal residual disease (MRD), detected through circulating tumor HPV DNA (ctHPVDNA), was associated with a higher risk of disease progression. When considered along with pathologic factors, postoperative ctHPVDNA assessment may improve patient selection for adjuvant treatment de-escalation; however, more data are needed to demonstrate how it may be used in personalizing treatment intensity.ObjectiveTo determine the association of postoperative MRD status with progression-free survival (PFS) after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Design, Setting, and ParticipantsThis was a secondary analysis of the DART RCT, which was conducted from October 2016 to August 2020 in multiple sites in the US. Participants from the de-escalated adjuvant radiation therapy group and the standard of care group with available blood specimen data were included. Reports from 3-month posttreatment surveillance visits were used to assess associations and outcomes. Data analyses were performed from March 2023 to March of 2025.InterventionsThe DART group received 30 to 36 Gy of radiation therapy in 1.5 to 1.8 Gy twice daily, plus docetaxel, 15 mg/m2, on days 1 and 8. The standard of care group received 60 Gy with or without weekly cisplatin, 40 mg/m2.Main Outcome and MeasurePFS.ResultsThe analysis included 140 patients (mean [SD] age, 59.1 [8.4] years; 12 [8.6%] females and 128 [91.4%] males; 97 [69.3%] with no smoking history); characteristics were similar to the overall DART RCT population. Of these, 17 patients (12.1%) had postoperative MRD (13 of 96 [13.5%] receiving DART and 4 of 44 [9.1%] receiving standard of care). For all patients, postoperative MRD positivity was strongly associated with worsened PFS at 24 months (MRD positivity, 69.5%; MRD negativity, 95.9%; hazard ratio [HR], 0.19; 95% CI, 0.06-0.59). MRD positivity was associated with PFS when evaluating only those patients in the DART group, where 24-month PFS was 68.4% compared to 92.6% for MRD-negative patients (HR, 0.28; 95% CI, 0.08-0.93). Three months after completion of all treatment, 8 of 117 patients (6.8%) had detectable ctHPVDNA, whereas 109 of 117 (93.2%) did not, and detection was highly associated with PFS (HR, 20.48; 95% CI, 6.91-60.67).Conclusions and RelevanceThis secondary analysis of the DART RCT found that patients with detectable ctHPVDNA after surgery had a higher risk of disease progression. When added to the pathologic factors considered, ctHPVDNA assessment may improve selection of patients for treatment de-escalation. In addition, the 3-month posttreatment time point, early in surveillance, may identify a sizable portion of patients with progression and may guide intervention and surveillance after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Trial RegistrationClinicalTrials.gov Identifier: NCT02908477

The NCCN Guidelines for Testicular Cancer provide recommendations for the multidisciplinary approach to the diagnostic workup, treatment, and follow-up for testicular germ cell tumors, including both seminoma and nonseminoma. These NCCN Guidelines Insights discuss the current treatment recommendations and supporting clinical data for seminomas as presented in Version 2.2025 of the NCCN Guidelines for Testicular Cancer.

Abstract Background Inter‐fractional and intra‐fractional positioning and motion monitoring based on implanted fiducials through kilovoltage (kV) imaging is a cost‐effective approach to enhance intact prostate radiotherapy treatment accuracy. However, comprehensive studies for three‐dimensional (3D) position extraction and the corrective action threshold are lacking. Purpose To develop and verify a fiducial motion monitoring system with 3D position information based on triggered kV images taken during treatment delivery, and to comprehensively evaluate the recommended thresholds for corrective action during treatment. Methods An in‐house fiducial triangulation algorithm was developed to monitor fiducial positions using subsequent kV triggered images. The precision of fiducial triangulation and motion detection was validated on a pelvis phantom with four fiducial inserts. A retrospective study was conducted on prostate cancer patients who received either moderately hypofractionated radiotherapy (MHRT, n = 16) or stereotactic body radiotherapy (SBRT, n = 12), categorized by endo‐rectal balloon (ERB) use. Intra‐fractional positions relative to isocenter were computed, and these positions were analyzed in comparison to the original marker locations of the patient's treatment plan. A linear regression fit was used per fraction to determine correlation coefficients between motions in the left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions. Average fraction time (AFT) of treatment was reported based on the observed average time spent on steps in the workflow and the percentage of fiducials caught outside of the current two‐dimensional (2D) tolerance threshold of 5 mm. The observed 3D offsets were used to estimate AFT for various 3D tolerance thresholds. Results Overall, our triangulation method proved to be very precise for static cases, where phantom measurements revealed a fiducial position triangulation precision of mm for stationary targets, but had a spread of mm for targets with 1 mm of motion. Employing triangulation, true motion exceeding 5 mm was detected above 4.0 mm in magnitude 90.9% of the time, a noticeable improvement in comparison to the 28%–65% successful detection rate reported by 2D projection methods. Most detection errors were attributed to depth disparity. Similar to other reports, correlation coefficients for intra‐fractional motion generally indicated no LR/SI, no LR/AP, and weak positive SI/AP correlations for MHRT and SBRT patients. Offsets beyond a 3D tolerance threshold of 5 mm were observed at a rate of 4.25%–5.25%, while the 5 mm 2D out‐of‐tolerance catch‐rate was 1.6%. The AFT was 8.1–8.2 min using the 2D tolerance threshold of 5 mm. In comparison, the estimated AFT for the proposed 3D tolerance monitoring of offsets beyond 2–5 mm was slightly higher at 8.2–10.9 min due to the higher amount of out‐of‐tolerance instances for the higher precision intra‐fractional motion management. Conclusions Our study showcases a promising subsequent kV‐based triangulation method for intra‐fractional prostate motion monitoring. Acquiring 3D motion information results in higher out‐of‐tolerance catch‐rates particularly in the depth dimension of the kV images, which is perpendicular to the treatment beam. Failure to properly observe and catch these offsets would result in sub‐optimal conformality and accuracy of the dose delivery.

AbstractPurposeTo assess the practicality of employing a commercial knowledge‐based planning tool (RapidPlan) to generate adapted intact prostate and prostate bed volumetric modulated arc therapy (VMAT) plans on iterative cone‐beam computed tomography (iCBCT) datasets.Methods and materialsIntact prostate and prostate bed RapidPlan models were trained utilizing planning data from 50 and 44 clinical cases, respectively. To ensure that refined models were capable of producing adequate clinical plans with a single optimization, models were tested with 50 clinical planning CT datasets by comparing dose‐volume histogram (DVH) and plan quality metric (PQM) values between clinical and RapidPlan‐generated plans. The RapidPlan tool was then used to retrospectively generate adapted VMAT plans on daily iCBCT images for 20 intact prostate and 15 prostate bed cases. As before, DVH and PQM metrics were utilized to dosimetrically compare scheduled (iCBCT Verify) and adapted (iCBCT RapidPlan) plans. Timing data was collected to further evaluate the feasibility of integrating this approach within an online adaptive radiotherapy workflow.ResultsModel testing results confirmed the models were capable of producing VMAT plans within a single optimization that were overall improved upon or dosimetrically comparable to original clinical plans. Direct application of RapidPlan on iCBCT datasets produced satisfactory intact prostate and prostate bed plans with generally improved target volume coverage/conformality and rectal sparing relative to iCBCT Verify plans as indicated by DVH values, though bladder metrics were marginally increased on average. Average PQM values for iCBCT RapidPlans were significantly improved compared to iCBCT Verify plans. The average time required [in mm:ss] to generate adapted plans was 06:09 ± 02:06 (intact) and 07:12 ± 01:04 (bed).ConclusionThis study demonstrated the feasibility of leveraging RapidPlan to expeditiously generate adapted VMAT intact prostate and prostate bed plans on iCBCT datasets. In general, adapted plans were dosimetrically improved relative to scheduled plans, emphasizing the practicality of the proposed approach.

Purpose: This study aimed to develop a retrained large language model (LLM) tailored to the needs of HN cancer patients treated with radiotherapy, with emphasis on symptom management and survivorship care. Methods: A comprehensive external database was curated for training ChatGPT-4, integrating expert-identified consensus guidelines on supportive care for HN patients and correspondences from physicians and nurses within our institution’s electronic medical records for 90 HN patients. The performance of our model was evaluated using 20 patient post-treatment inquiries that were then assessed by three Board certified radiation oncologists (RadOncs). The rating of the model was assessed on a scale of 1 (strongly disagree) to 5 (strongly agree) based on accuracy, clarity of response, completeness s, and relevance. Results: The average scores for the 20 tested questions were 4.25 for accuracy, 4.35 for clarity, 4.22 for completeness, and 4.32 for relevance, on a 5-point scale. Overall, 91.67% (220 out of 240) of assessments received scores of 3 or higher, and 83.33% (200 out of 240) received scores of 4 or higher. Conclusion: The custom-trained model demonstrates high accuracy in providing support to HN patients offering evidence-based information and guidance on their symptom management and survivorship care.

Abstract In radiotherapy, 2D orthogonally projected kV images are used for patient alignment when 3D-on-board imaging(OBI) unavailable. But tumor visibility is constrained due to the projection of patient’s anatomy onto a 2D plane, potentially leading to substantial setup errors. In treatment room with 3D-OBI such as cone beam CT(CBCT), the field of view(FOV) of CBCT is limited with unnecessarily high imaging dose, thus unfavorable for pediatric patients. A solution to this dilemma is to reconstruct 3D CT from kV images obtained at the treatment position. Here, we propose a dual-models framework built with hierarchical ViT blocks. Unlike a proof-of-concept approach, our framework considers kV images as the solo input and can synthesize accurate, full-size 3D CT in real time(within milliseconds). We demonstrate the feasibility of the proposed approach on 10 patients with head and neck(H\&N) cancer using image quality(MAE:<45HU), dosimetric accuracy(Gamma passing rate(2%/2mm/10%):>97%) and patient position uncertainty(shift error:<0.4mm). The proposed framework can generate accurate 3D CT faithfully mirroring real-time patient position, thus significantly improving patient setup accuracy, keeping imaging dose minimum, and maintaining treatment veracity.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. Conclusions: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.