OBJECTIVE:Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS:This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS:At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm3; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm3 had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm3 (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80-0.99; p = 0.036). CONCLUSIONS:In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Abstract Background Early detection of melanoma recurrence and progression remains a clinical challenge, which relies on physical examination and imaging. Circulating tumor DNA offers a noninvasive, dynamic biomarker that may identify molecular recurrence before clinical progression. We aimed to evaluate the prognostic and predictive value of longitudinal, tumor-informed ctDNA testing across multiple melanoma care settings. Methods We retrospectively analyzed 56 consecutive melanoma patients who underwent serial ctDNA testing using a tumor-informed assay (Signatera™) at a single institution. Fifty-six patients with evaluable ctDNA results were stratified into three cohorts based on the treatment context at the time of ctDNA testing: (A) no active treatment (n = 20), (B) adjuvant therapy (n = 14), and (C) active treatment for known disease (n = 22). We evaluated disease-free survival (DFS), overall survival (OS), and longitudinal ctDNA dynamics in relation to clinical outcomes. Results Median clinical follow-up was 48.0 (IQR 24.7–94.1) months. In Cohorts A and B (HR 12.3, 95% CI 1.1–1138.6), detectable ctDNA at any timepoint was significantly associated with inferior DFS. Conversely, 90% of patients in Cohorts A and B combined with undetectable ctDNA remained recurrence-free. In Cohort C, rising or persistently positive ctDNA was seen in 81.8% of patients who progressed. Longitudinal ctDNA trends were more informative than isolated timepoints, with increases preceding radiologic progression by a median of 11.4 (IQR 5.0–13.1) months. Conclusions and relevance Tumor-informed ctDNA testing offers clinically meaningful insight across melanoma care settings. Rising or positive ctDNA frequently anticipates disease progression, supporting its use for MRD surveillance and treatment response monitoring in dermatology and oncology practice.

BACKGROUND AND OBJECTIVES:Pediatric large-volume brain arteriovenous malformations (AVMs) carry a substantial lifelong hemorrhage risk, neurological symptoms, and treatment morbidity. Single-session stereotactic radiosurgery (SRS) is often unsuitable due to constraints on dose-volume toxicity. Volume-staged SRS (VS-SRS) enables sequential dosing of large nidus volumes, potentially enhancing safety while maintaining efficacy. Evidence in children remains limited. We aimed to evaluate outcomes of VS-SRS for large AVMs in pediatric patients. METHODS:A multicenter retrospective cohort was assembled from 21 centers, including patients aged younger than 21 years treated with VS-SRS for AVMs >10 cm3. Clinical and radiological end points included obliteration, hemorrhage, and permanent symptomatic radiation-induced changes (RIC). RESULTS:A total of 103 patients were included (median age 14 years; IQR, 12-17). The median nidus volume at first stage was 18.2 cm3 (IQR, 12.3-25.6). Median prescription dose per stage was 17 Gy (IQR, 16-18). The median clinical follow-up from the first stage was 57.5 months (IQR, 25-138). Obliteration occurred in 42 of 103 patients (40.8%), with actuarial rates of 6.9% (95% CI: 2.8-14) at 3 years and 29% (95% CI: 20-39) at 5 years. Hemorrhage occurred in 17 of 103 patients (16.5%) during follow-up, and permanent RIC was observed in 9 of 103 patients (8.7%). CONCLUSION:VS-SRS is a reasonably safe, selected option for pediatric large-volume AVMs when microsurgical or endovascular cure is not feasible or prudent. Delivering ≥17 Gy per stage while limiting each treatment volume to <15 cm3 supports durable nidus control with acceptable toxicity. VS-SRS represents a key modality in multidisciplinary management of this historically difficult-to-treat population.

ABSTRACT Objective Limited literature focuses on delays in accessing head and neck cancer (HNC) care across the entire care continuum. This study aims to describe the time to care from symptom onset to treatment completion and identify predictors of delays for oral cavity cancer patients. Methods We reviewed patients with oral cavity squamous cell carcinoma (OCSCC) treated with curative surgery followed by adjuvant treatment at a tertiary center. Delays were defined per published thresholds for: time to treatment initiation (TTI, diagnosis to surgery), time to adjuvant treatment (stratified by whether adjuvant treatment was at the same or different facility as surgery), and total treatment package time. We also measured symptom duration, reported median times, and used logistic regression to assess predictors of delay. Results Among 93 patients, median (IQR) symptom duration was 17.4 weeks (IQR: 6.8–42.8); TTI 6.9 weeks (IQR: 4.4–10.4); time to adjuvant radiation 8.4 weeks (IQR: 7.4–9.3) at the same institution as surgery was performed and 9.3 weeks (IQR: 7.4–14) at a different facility; and total treatment package time 15.4 weeks (IQR: 12.6–20) for surgery and adjuvant radiation, and 16.3 weeks (IQR: 15–18.6) for surgery and adjuvant chemoradiation. 73% of patients experienced delays in reaching a healthcare facility, 39% in TTI, 89% in starting adjuvant treatment, and 64%–81% in total treatment time. In univariate analyses, late‐stage disease, residing in a community with higher social vulnerability index (SVI), longer time from surgery to pathology report, need for free flap, and social worker interaction were associated with higher odds of delay in any care interval following diagnosis. Higher SVI was associated with delays in multivariate analyses. Conclusion HNC patients experience delays during all phases of cancer care. Interventions and future research need to address social determinants of health and health system factors that contribute to multifactorial delays across the care continuum.

11123 Background: We tested the primary question whether the addition of cetuximab to postoperative radiotherapy (IMRT) results in poorer patient reported outcomes (PROs) at 12 months compared to IMRT alone. We also examined changes in PROs over time. Methods: Randomized and eligible patients who consented to quality of life (QOL) assessment completed PROs measured by 5 instruments, prior to treatment (baseline) and at 3, 12, and 24 months after IMRT. Instruments included: 1) Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN), a multidimensional QOL instrument for use with head and neck cancer patients; 2) University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) covering mouth/throat dryness and its impact on oral health-related QOL; 3) Dermatology Life Quality Index (DLQI) for skin-related changes; 4) EuroQol (EQ-5D-3L) covering usual activities and perceived current health state; 5) Performance Status Scale for Head and Neck Cancer (PSS-HN) assessing normalcy of diet, public eating, and understandability of speech. Higher scores on XeQOLS and DLQI indicate worse QOL; otherwise higher scores indicate better QOL for other measures. For FACT-HN, XeQOLS, DLQI, and EQ-5D-3L, changes from baseline were compared by Van Elteren test, and for PSS-HN, the % ≤ 50 was compared by Z test. 158 patients per arm provided 80% power to test the difference between IMRT + cetuximab and IMRT alone. Changes in PROs over time were evaluated using mixed models. Two-sided tests were used with α=0.05. Results: 499 of 577 eligible patients (86%) consented to QOL. There were no significant differences between treatment arms (IMRT vs. IMRT + cetuximab) for all PRO measures in change from baseline to 3 or 12 months post-IMRT (see table). At 24 months, the change from baseline was significantly different for DLQI (p=0.02), but the difference was not clinically meaningful; other PROs were not significantly different. There were no significant differences between treatment arms for PSS-HN diet, eating, or speech at any time point (see table). Regarding treatment effect over time, in both treatment groups, all PRO measures showed greatest decline at 3 months followed by improvement towards baseline by 24 months. Conclusions: Treatment with IMRT + cetuximab was not associated with worse PROs compared to IMRT alone. Furthermore, findings demonstrate important recovery trends in QOL with return to baseline for most measures in both study arms. Clinical trial information: NCT00956007 . Results at 12 months. Instrument (score range) IMRT IMRT+Cetuximab p-value FACT-HN (0-148) n 122 132 Mean change -0.41 1.31 0.94 XeQOLS (0-4) n 105 114 Mean change 0.52 0.46 0.99 DLQI (0-30) n 121 133 Mean change -0.07 0.44 0.23 EQ-5D-3L (0-1) n 108 117 Mean change 0.01 0.02 0.87 PSS-HN diet (0-100) n 130 141 % ≤ 50 37.7 39.7 0.73 PSS-HN eating (0-100) n 130 141 % ≤ 50 20.0 15.6 0.34 PSS-HN speech (0-100) n 131 140 % ≤ 50 10.7 7.9 0.42

PURPOSE:This study sought to evaluate the outcomes and toxicities from oral cavity (OC) and oropharynx (OP) high-dose-rate brachytherapy (HDRBT) for re-irradiation (reRT) of head and neck squamous cell carcinoma (HNSCC). METHODS:Patients who previously received curative-intent external beam radiotherapy for primary HNSCC and were treated with OC/OP reRT with HDRBT from January 2000 to December 2021 were included. Patients were selected by a multidisciplinary tumor board to be appropriate candidates for HDRBT for one of two reRT indications: (1) definitive reRT or (2) postoperative reRT. Survival outcomes were estimated using the Kaplan-Meier method. Efficacy and toxicity outcomes were analyzed for the entire cohort and separately based on reRT indication. RESULTS:27 patients were evaluated with a median follow up of 20 (IQR 12-41) mo. 14 (52%) and 13 (48%) patients were treated for a recurrent or second primary OC and OP HNSCC, respectively. Median dose of prior EBRT was 68.4 (IQR 60-70) Gy. Median interval between completion of EBRT to HDRBT reRT was 42 (IQR 14-85) mo. Median target volume was 16 (IQR 10-29) cc; median D90% was 31 (IQR 30-36) Gy. In cohorts A and B, 2-year LC/late grade ≥3 toxicity were 70%/57% and 60%/15%, respectively. CONCLUSIONS:HDRBT for reRT of small (<4 cm), recurrent, or second primary OC/OP HNSCC provided LC and late grade ≥3 toxicity rates similar to historical outcomes with EBRT reRT.

OBJECTIVE:In head and neck cancer (HNC) survivors not actively receiving dysphagia care, long-term dysphagia prevalence, dysphagia-related complications, and quality of life outcomes remain poorly understood. Understanding these outcomes is critical for creating effective HNC survivorship programs. METHODS:HNC survivors who completed cancer treatment > 2 years prior who had not undergone a swallow evaluation or therapy for > 1 year completed the MD Anderson Dysphagia Inventory (MDADI) and reported dysphagia-related complications. RESULTS:Of 722 invited participants who met inclusion criteria, 143 responded at a median of 5.9 years (IQR: 2.5-10.2 years) post-treatment, including 65 at 2-5 years, 42 at 5-10 years, and 36 at > 10 years. Median time since last speech-language pathologist visit was 2.8 years (IQR 2.1-4.9 years), and 27% had not received any swallow therapy since cancer treatment completion. The most common tumor subsite was oropharynx (n = 103), and most underwent definitive (n = 72) or adjuvant (n = 60) (chemo)radiation. The overall median MDADI score was 80 points (IQR: 62.1-91.6) and 49.6% (n = 71) had moderate to severe dysphagia (MDADI < 80). The most common complications within the 6 months prior to patient contact were unintentional weight loss (7.7%), current gastrostomy tube dependence (4.9%), aspiration pneumonia (1.4%), and dehydration requiring intravenous fluids (1.4%). An MDADI score ≤ 80 was associated with 7.7 times higher odds of dysphagia-related adverse events (95% CI 2.1-28.2, p = 0.002). CONCLUSIONS:Long-term dysphagia is prevalent among HNC survivors not actively receiving dysphagia care, highlighting the need for ongoing swallow function surveillance and proactive dysphagia management strategies tailored to this population. LEVEL OF EVIDENCE: 3:

ImportanceLimited evidence exists to guide the safe use of radiotherapy (RT) and concurrent disease-modifying antirheumatic drugs (DMARDs) in patients with collagen vascular disease (CVD).ObjectiveTo describe toxicity outcomes in patients with CVD receiving intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) and to evaluate whether concurrent DMARD use is associated with increased toxicity.DesignRetrospective cohort study.SettingSingle academic tertiary care center in the United States, from 2005 to 2022.ParticipantsTwenty-three adult patients with CVD [eg, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM)] and biopsy-proven HNC treated with curative-intent IMRT. Eligibility required available treatment records and ≥90 days of follow-up post-RT.Intervention or ExposuresDefinitive or postoperative IMRT for HNC. Exposure of interest was concurrent use of DMARDs during RT.Main Outcome MeasuresRates of acute (≤90 days) and late (>90 days) grade ≥2 and ≥3 toxicities, as graded by CTCAE v5.0. Fisher exact tests were used to compare toxicity rates by DMARD use.ResultsMedian follow-up was 56 months (IQR 9-98). Most common CVDs were RA (39%), SLE (17%), and DM (17%). Median RT dose was 66 Gy (range 48-70 Gy); 39% received concurrent chemotherapy. Acute grade ≥3 toxicity occurred in 35% (n = 8) and late grade ≥3 in 13% (n = 3). No grade ≥4 toxicities were observed. DMARD use during RT was not associated with higher rates of acute or late grade ≥2 or ≥3 toxicity (P > .1 for all comparisons).ConclusionsIMRT was associated with moderate rates of severe toxicity in patients with CVD, but DMARD use during RT did not increase risk.RelevanceConcurrent DMARDs may be safely continued during IMRT for HNC in patients with CVD. Prospective studies are needed to confirm these findings and refine risk stratification by CVD subtype and treatment regimen.

BACKGROUND:This study aimed to evaluate swallow outcomes in head and neck cancer (HNC) survivors enrolled in a long-term dysphagia surveillance protocol following curative intent radiotherapy (RT). METHODS:We conducted a retrospective review of videofluoroscopic swallow studies from 2015 to 2023 in HNC patients treated with RT. Swallow kinematics and function were assessed at baseline, 0-1, 1-2, 2-5, and 5+ years post-RT. Logistic regression models assessed kinematic deviations beyond 2SD from normative and dichotomized outcomes. RESULTS:Among 638 patients with 1167 VFSS, 14.6% were 2 years post-RT, primarily oral cavity (29.6%) and oropharyngeal (46.7%) cancers treated with adjuvant (chemo) RT (53.3%). At 2 years, 51.3% exhibited abnormal hyolaryngeal movement, 27.5% had pharyngeal contraction abnormalities, and 9.0% had impaired pharyngoesophageal opening. Unsafe swallow was seen in 51.6% with moderate-to-profound dysphagia in 45%. CONCLUSION:Dysphagia surveillance revealed significant swallowing impairments in HNC survivors, with unsafe swallowing prevalent in over half of cases 2 years post-RT.

PURPOSE Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. METHODS Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)–negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. RESULTS We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. CONCLUSION RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.

BACKGROUND AND OBJECTIVES:Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS:This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS:The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2-4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION:VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

A 78-year-old man with a history of nonmelanoma skin cancers presented with left-sided upper and lower facial weakness. What is your diagnosis?

BACKGROUND:Neighborhood socioeconomic deprivation impacts outcomes in various cancers. We examined this association in nasopharyngeal carcinoma (NPC) patients using the area deprivation index (ADI).METHODS:We conducted a single-institution retrospective cohort study on NPC patients treated with definitive radiotherapy from 1980 to 2023. ADI was used as the primary exposure measure. Higher ADI indicates higher levels of socioeconomic deprivation.RESULTS:Of 561 patients, those with higher ADI (6-10 vs. 1-5) presented more commonly with AJCC stage III/IV compared to I/II (87% vs. 76%, p = 0.03). Increasing ADI decile score correlated with poorer overall survival (HR 1.14, 95% CI 1.01-1.28, p = 0.04). Local control was worse in patients from the most deprived quartile in the cohort ADI 5-10 (HR 2.11, 95% CI 1.01-4.41, p = 0.05).CONCLUSIONS:NPC patients from more disadvantaged neighborhoods undergoing radiotherapy had worse local control and survival outcomes. Interventions to address structural determinants of health and neighborhood disparities may improve these outcomes.

Background/Aim: Plasma Epstein-Barr virus (EBV) viral load measurement is prognostic in nasopharyngeal carcinoma (NPC) disease monitoring; however, a consensus measurement approach does not exist. This study characterized the clinical performance of metagenomic next-generation sequencing (mNGS), an unbiased sequencing-based assay distinct from polymerase chain reaction (PCR) or targeted sequencing approaches, in 73 peripheral blood specimens from 32 patients diagnosed with NPC. Patients and Methods: Samples were analyzed for plasma EBV viral load either by mNGS profiling or PCR-based assays (either LMP2 or BAMHI-W PCR) and compared to tumor presence by clinical assessment. Plasma mNGS-based EBV detection was quantified as reads per million (RPM). Results: Plasma mNGS displayed similar overall performance (100% sensitivity, 86% specificity, 92% accuracy) to BAMHI-W PCR (100% sensitivity, 86% specificity, 94% accuracy) and superior performance to the LMP2 PCR assay (36% sensitivity, 56% specificity, 45% accuracy). In a subset of 13 patients who underwent longitudinal analysis, plasma mNGS EBV RPM correlated with cancer recurrence (95%CI PreCRT=232.10 +/- 214; 95%CI Post-CRT=0.34 +/- 0.32; 95%CI difference=-231.70 +/- 214; *p=0.03, paired t-test), suggesting

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents ( N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested ( N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.