OBJECTIVES:Cutaneous adnexal carcinomas (CACs) are rare skin cancers with no established treatment guidelines. Given the limited data, this study aims to explore the characteristics and outcomes of patients with CAC treated with radiation therapy (RT). METHODS:Patients diagnosed with CAC between 2000 and 2020 who received RT were included. Kaplan-Meier methods measured time to local recurrence (LR), regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), and progression-free survival (PFS). Fisher exact test compared frequency distributions. RESULTS:Forty-nine patients with an average age of 65 years were studied. Most were White males with head and neck tumors. Common subtypes were adnexal adenocarcinoma, sebaceous carcinoma, and microcystic adnexal carcinoma. Patients received RT diagnosis or recurrence. The median overall survival was 44 months, with a median follow-up of 41 months for surviving patients. For patients with de novo cancer treated with surgery and adjuvant RT (n=22), 2-year PFS, LR, RR, LRR, DM, and OS were 77%, 5%, 0%, 5%, 10%, and 95%, respectively, with all LRR occurring outside the irradiated area. Patients with de novo cancer who received definitive RT (n=9) experienced 2-year PFS, LR, RR, LRR, DM, and OS of 30%, 46%, 13%, 55%, 40%, and 67%, respectively, with all LRR events occurring within the irradiated area. LR within the irradiated volume was associated with immunosuppression (95% CI: 19-99). Patients treated at recurrence had inferior outcomes. CONCLUSIONS:Surgical resection and adjuvant RT effectively control CAC, while definitive RT shows lower disease control. Novel strategies are needed to improve outcomes in patients receiving definitive RT.

IntroOne main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors including air-tissue interface, anatomical uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. Additionally, the elevated relative biological effectiveness (RBE) at the Bragg peak's distal end can also increase hot spots within and outside the target area.Purpose/MethodsThe purpose of this study was to evaluate for a difference in PET SUV uptake following definitive treatment, between IMPT or IMRT. Additionally, we compared the biologic dose between PET areas of high and low uptake within the CTV-primary of patients treated with IMPT. This work is assuming that the higher SUV uptake may potentially result in higher toxicities. For the purposes of this short communication, we are strictly focusing on the SUV uptake, and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month post-treatment FDG PET scans for 100 matched oropharyngeal cancer patients treated definitively without surgery using either IMPT (n=50) or IMRT (n=50).ResultsOur study found a significant difference in biologic dose between the high and low-uptake regions on 3-month post-treatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the CTV-primary at 3 and 6-months follow-up between IMPT and IMRT patients. Conclusion: Studies propose proton's higher RBE at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.

Background and Objective: We aim to summarize and discuss the literature on intensity-modulated proton therapy (IMPT) in head and neck cancer and elucidate its benefits and limitations in a clinical setting. Head and neck cancer treatment involves a multi-disciplinary approach, with radiation therapy playing an integral role. Historically, photon therapy techniques, such as intensity-modulated radiation therapy (IMRT), have been utilized to manage head and neck cancer. In recent years, proton therapy has grown in popularity as a potential radiotherapy to provide favorable outcomes and limit toxicities in an aging patient population. The physical properties of protons provide a dosimetric advantage, where protons are deposited at a narrow range of tissue depth, termed the "Bragg peak". Localization of the Bragg peak onto the desired target volume and the minimal to no exit dose of protons limit healthy tissue radiation. IMPT is the most recently developed delivery method of delivering protons, where it uses a pencil beam manipulated by magnets. In hopes to improve treatment outcomes and reduce toxicities, studies on IMPT have gained traction in its role in treating head and neck cancers. including oropharyngeal, nasopharyngeal, and sinonasal cancer.

IMPORTANCE Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret. OBJECTIVE To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects. EXPOSURES Proton therapy reirradiation. MAIN OUTCOMES AND MEASURES Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS. RESULTS A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8%(95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6%(95% CI, 46.4%-73.6%) and the 1-year OS was 28.5%(95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P =.046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P =.005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P <.001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects. CONCLUSIONS AND RELEVANCE The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck. Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities. Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities. Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

ObjectiveLimited data is available to guide non‐surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long‐term therapeutic and functional outcomes.MethodsWe reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA).ResultsThe 2‐/5‐year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non‐intensity‐modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease‐free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow‐up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither.ConclusionWe report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery.Level of Evidence4 Laryngoscope, 133:1138–1145, 2023

Proton beam therapy has gained popularity over recent years. This is likely due to improved affordability; that is, lower cost, and increasing reports on excellent patient‐reported outcomes. Protons’ physical properties provide dosimetric advantages over photon therapy due to the unique ability to have little‐to‐no “exit” dose, potentially translating to reduced toxicities and improved patient quality of life. The increased delivery of proton beam therapy to treat numerous head and neck cancers, including oropharynx, nasopharynx, sinonasal, in the re‐irradiation setting, and unilateral malignancies, has led to more studies elucidating the clinical risks and benefits. In this review, we aim to summarize the recent literature on proton beam therapy utilization in head and neck cancer. In addition, we discuss the process of treatment and planning, clinical treatment toxicities and outcomes, limitations, and future directions.

Background Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Methods Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Results Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. Conclusion In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

Background Numerous studies and guidelines suggest an outcome detriment from radiation treatment breaks (rTBs) and the need for compensatory dosing in patients with head and neck cancer. Methods In a consecutive cohort of 521 patients with oropharyngeal squamous cell carcinoma (OPSCC), we investigated the impact of rTBs and prolongation of overall treatment time (OTT) on OS, DFS, LRC, and cancer recurrence using competing risk and multivariate analyses. Results Neither OTT prolongation by <= 2 days nor rTBs of <= 3 days were associated with detriments to clinical outcomes. Consecutive breaks of >= 3 days were also not significantly associated with detriment to clinical outcomes. There was significantly increased competing mortality in those with longer breaks. Conclusions In OPSCC patients treated with definitive concurrent chemoradiotherapy, there is no significant association between disease failure and total rTBs of <= 3 consecutive or scattered days. Further investigation is needed for longer breaks.