Dagan, Roi

Importance Standard treatment for human papillomavirus (HPV)–associated oropharyngeal carcinoma (OPC) often includes 7 weeks of intensive chemoradiotherapy with substantial toxic effects. Lowering the radiation dose to gross disease may maintain cancer control with fewer toxic effects. Objective To evaluate long-term oncologic outcomes among patients with HPV-associated OPC treated with definitive deintensified (chemo)radiotherapy. Design, Setting, and Participants This cohort study evaluated consecutive patients treated with (chemo)radiotherapy between September 2014 and August 2022 at multiple institutions under one academic hospital system. Eligible patients had p16-positive OPC with a clinical stage from T0 to T3 and N0 to N2c (according to the American Joint Committee on Cancer [AJCC] Staging Manual, seventh edition ) and favorable smoking history. Data were analyzed between August 2023 and October 2025. Interventions Treatment was 60-Gy intensity-modulated radiotherapy with first-choice concurrent chemotherapy of weekly cisplatin, 30 mg/m 2 , or weekly cisplatin, 40 mg/m 2 . Patients with OPC with a clinical stage from T0 to T2 and N0 to N1 (according to AJCC, seventh edition ) were recommended 60-Gy radiotherapy alone. Main Outcomes and Measures Evaluation of locoregional recurrence was the primary outcome. Distant recurrence, progression-free survival (PFS), and overall survival (OS) were secondary outcomes. Results A total of 240 patients received definitive deintensified (chemo)radiotherapy (207 receiving prospective protocol-adherent treatment and 33 receiving non–protocol-adherent treatment). Mean (SD) patient age was 60.3 (9.9) years (range, 33.0-84.0 years); 206 (85.8%) were male, and 34 (14.2%) were female. The cohort included 139 never smokers (57.9%) and 101 former smokers (42.1%) (median smoking history, 9.0 pack-years [range, 0.25-50.0 pack-years]). Concurrent chemotherapy was prescribed for 205 patients (85.4%), with 185 (77.1%) receiving cisplatin, and 165 (68.8%) receiving weekly cisplatin, 30 mg/m 2 . Median follow-up for surviving patients was 6.5 years (range, 0.44-11.0 years; 208 of 210 [99.0%] with minimum 2-year follow-up). Outcomes were as follows: 2-year OS was 97.9% (95% CI, 96.1%-99.7%), and 5-year OS, 92.4% (95% CI, 89.0%-96.0%); 2-year PFS, 94.1% (95% CI, 91.2%-97.2%), and 5-year PFS, 86.5% (95% CI, 82.1%-91.0%); 2-year locoregional recurrence, 1.3% (95% CI, −0.2% to 2.7%), and 5-year locoregional recurrence, 3.4% (95% CI, 1.1%-5.8%); 2-year distant recurrence, 4.6% (95% CI, 1.9%-7.3%), and 5-year distant recurrence, 7.3% (95% CI, 3.9%-10.7%). The median time to progression events was 1.9 years (range, 0.3-5.1 years); 12 of 26 recurrences (46.2%) occurred after 2 years. Thirty-three patients with low-risk disease (clinical stage T0-T2, N0-N1, according to AJCC, seventh edition ) received radiotherapy alone, which resulted in a 5-year PFS of 93.8%, with no patients experiencing a locoregional recurrence. Conclusions and Relevance In this cohort study, modest dose deintensification of 60-Gy radiotherapy in patients with HPV-associated OPC shows favorable rates of locoregional control. These findings provide support for ongoing investigations of deintensified radiotherapy.

AbstractBackgroundPediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT).ProcedureUsing an IRB‐approved prospective outcomes registry, we evaluated patient, tumor, and treatment‐related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT.ResultsFifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow‐up was 4.8 years. No patients were lost to follow‐up. Five‐year disease‐free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in‐field basal cell skin cancer.ConclusionsA multimodality approach for pediatric EN results in excellent local control. Despite the moderate‐dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow‐up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

Purpose: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. Methods: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. Results: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. Conclusion: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

Abstract Purpose: To determine the rate of rib fracture in a cohort of patients with breast cancer treated with proton therapy and enrolled on a prospective registry. In series investigating photon therapy for breast cancer, the rib fracture rate ranges from 0.3-13% Methods: From a prospective database, we identified patients treated with proton therapy for breast cancer at our institution between January 1, 2012 and December 31, 2020. Clinical and dosimetric data was extracted from the electronic medical record. The cumulative incidence method assessed rib fracture rate; the Fine-Gray test statistic assessed prognostic significance select variables. Results: 225 patients were identified, 223 women and 2 men. Median age at the time of radiation was 57.8 years (range, 25 – 87). 26% of patients were black, 69% white and 5% were other races or race not disclosed. 5% were Hispanic. 74% of patients had left-sided breast cancer, 5% bilateral, and 21% right-sided. DEXA scan was normal in 20%, showed osteopenia in 34%, osteoporosis in 6%, and not performed in 40%. 57% of patients received antiendocrine therapy with an aromatase inhibitor. For 16% of patients, the breast +/- internal mammary nodes (IMN) were treated, while 32% underwent proton therapy to treat the breast and comprehensive regional lymphatics. 1% of patients had chest wall +/- IMN treated, while 51% underwent proton therapy to treat the chest wall and comprehensive regional lymphatics. 41% of patients were treated with passive scatter proton therapy (n=92); 52% of these had mastectomy. 58% of patients received treatment with pencil beam scanning (PBS) proton therapy (n=131); 53% of these had mastectomy. A combination of passive scatter and PBS was used for 2 patients (1%). 85% of patients received a boost. Median follow-up was 3.1 years (range, 0.2 – 9.1). 97% of patients had > 12 months of follow-up. The 3 year cumulative incidence of in-field rib fracture was 3.7% (95%CI: 1.6%-7.1%). In total, 8 patients developed in-field rib fractures, one symptomatic and 7 identified incidentally on surveillance imaging, for a 0.4% rate of symptomatic rib fracture. Median time from completion of radiation to identification of rib fracture was 1.8 years (range, 0.4-7.4 years). Rib fractures occurred within 2.2 years from radiotherapy completion for seven of the eight patients who experienced this side effect. Three patients developed rib fractures outside of the radiation field, for a cumulative incidence of out-of-field rib fracture of 0.9% (95%CI: 0.2-3.0%). No variables were associated with rib fracture on univariate analysis. Of those with in-field rib fractures, 3 had low and 3 had normal bone density while 2 had not undergone testing; of those with out-of-field rib fractures, 2 had osteopenia and 1 did not have testing. Conclusions: Although a proton beam has higher biological dose deposition at end-of-range than the assumed constant RBE=1.1, the 3 year rate of any in-field rib fractures in our series remains low at 3.7%, with a 0.4% rate of symptomatic rib fracture. Contouring ribs as an OAR and establishing a dose constraint warrants further investigation as a means to maintaining a low rate of rib fracture with proton therapy. Citation Format: Julie Bradley, Xiaoying Liang, Raymond Mailhot Vega, Chunbo Liu, Eric Brooks, Teena Burchianti, Emma Viviers, Roi Dagan, Oluwadamilola Oladeru, Christopher Morris, Nancy Mendenhall. Incidence of rib fracture following treatment with proton therapy for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-08.

AbstractBackgroundVenous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node‐negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain.MethodsA total of 105 consecutive lymph node‐negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow‐up data were recorded.ResultsOf 37 patients with venous invasion, 19% had loco‐regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence‐free survival in the presence of venous invasion (log‐rank [Mantel‐Cox] test P‐value .025).ConclusionIdentification of VI is greatly aided by elastic stain. In patients with node‐negative HNSCC, presence of VI resulted in decreased recurrence‐free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.