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Purpose Keratinocyte carcinoma (KC, previously nonmelanoma skin cancer) represents the most common cancer worldwide. While surgical treatment is commonly utilized, various radiation therapy techniques are available including external beam and brachytherapy. As such, the American Brachytherapy Society has created an updated consensus statement regarding the use of brachytherapy in the treatment of KCs. Methods Physicians and physicists with expertise in skin cancer and brachytherapy created a consensus statement for appropriate patient selection, data, dosimetry, and utilization of skin brachytherapy and techniques based on a literature search and clinical experience. Results Guidelines for patient selection, evaluation, and dose/fractionation schedules to optimize outcomes for patients with KC undergoing brachytherapy are presented. Studies of electronic brachytherapy are emerging, although limited long-term data or comparative data are available. Radionuclide-based brachytherapy represents an appropriate option for patients with small KCs with multiple techniques available. Conclusions Skin brachytherapy represents a standard of care option for appropriately selected patients with KC. Radionuclide-based brachytherapy represents a well-established technique; however, the current recommendation is that electronic brachytherapy be used for KC on prospective clinical trial or registry because of a paucity of mature data.

BACKGROUND/AIM Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

PURPOSE/OBJECTIVE(S) Patients with recurrent head and neck squamous cell carcinoma (HNSCC) who present with carotid encasement (CE) > 180˚, skin involvement and/or require bolus are not eligible for SBRT per RTOG 3507. The objective of this study was to characterize our institutional experience of SBRT for patients ineligible for RTOG 3507. MATERIALS/METHODS Patients with recurrent HNSCC treated with SBRT from 2010-2020 with a history of prior radiation were extracted from an IRB approved database. Patients were evaluated based on CE > 180˚ or ≤180˚ and if there was skin involvement and/or use of bolus. The primary outcome was incidence of treatment related carotid bleeding event (CBE) and skin toxicity after SBRT in the absence of disease. RESULTS Thirty-one patients were treated with SBRT to 37 sites with a median follow up of 8 months (mo) (range 2-47). The median time from prior radiation to SBRT was 13 mo (range 2-257). SBRT fractionation included 35 Gy (13%), 40 Gy (57%), and 45 Gy (30%) in 5 fractions. SBRT was delivered every other day (76%) or 2 fractions (24%) per week. Concurrent immunotherapy was given in 11% and cetuximab in 8%. A total of 30% (N = 11) of sites treated exhibited CE > 180˚ and 70% (N = 26) ≤180˚. There were no CBE related to SBRT, however 18% (N = 2) of patients with CE > 180˚ experienced fatal CBE related to progressive disease at 2.3 mo and 7.6 mo from SBRT. The risk of CBE was potentially related to CE > 180˚ (P = 0.08). Skin involvement and/or use of bolus was present in 43% (N = 16) of sites treated and absent in 57% (N = 21). The rate of treatment related skin toxicity was 19% (N = 3) and only occurred in those with pre-SBRT skin involvement and/or use of bolus. The cumulative incidence of treatment related skin toxicity at 3 mo and 6 mo was 13% (95% CI 1.9-33.6) and 27% (95% CI 4.0-58.8), respectively. Of the 3 treatment related skin toxicities there was one each of grade 2, 3, and 5. Grade 5 toxicity was related to untreated SBRT wound infection as the patient transitioned to hospice. The risk of treatment related skin toxicity was possibly related to pre-SBRT skin involvement and/or use of bolus (P = 0.007). Of the 13 sites with pre-SBRT skin involvement, 31% (N = 4) completely resolved, 54% (N = 7) had residual ulceration attributed to disease, and 15% (N = 2) had ulceration related to SBRT toxicity. The cumulative incidence of local failure at site of SBRT at 3 mo and 6 mo was 13% (95% CI 4-27.3) and 38% (95% CI 20.5-55.9), respectively. The median time of local and regional recurrence free survival were 7 and 5.5 mo, respectively. Median OS was 8 mo and the estimated 1-year OS was 25% (95% CI 9.9-40.9). CONCLUSION The risk of toxicity following SBRT for patients with > 180˚ CE, skin involvement and/or use of bolus appears to be largely related to persistent or recurrent disease. There were no CBE related to SBRT in the absence of disease and 31% of patients with pre-SBRT skin involvement exhibited complete healing after SBRT. Consideration of SBRT may still be beneficial for such patients with appropriate counselling.

Purpose/Objective(s) The outcomes of second primary head and neck malignancies in survivors of HPV associated OPSCC treated with radiation have not been well documented. The purpose of this study was to review the rate, management, and outcomes of non-metastatic second head and neck malignancies in patients with a history of HPV positive OPSCC treated with definitive or postoperative radiation (RT). Materials/Methods This is a single institution IRB approved retrospective study of patients with HPV positive OPSCC treated from 2001-2017 with definitive radiation and at least 3 years of follow up. Diagnoses were considered to be a second head and neck malignancy if they were distinct from index OPSCC with the exclusion of a primary or regional recurrence, primary site > 2 cm from the index OPSCC, and occurred at least 2 years from prior RT. Patients with second malignancies involving the thyroid were excluded. Actuarial analysis was used to calculate overall survival and disease control rates. Results There were a total of 418 patients who met inclusion criteria with a median follow up of 88.5 months (50.9-150.9 months). A total of 11 patients (2.6%) developed a second primary malignancy in the head and neck (2 larynx, 1 nasal cavity, 6 oral cavity and 2 oropharynx) and all were treated with definitive surgery. Median time between first and second cancers was 73 months (25-123 months). Median follow up for these patients was 25.4 months (7.7-69 months) and the median age at second malignancy was 65 years (range 54-73 years). 64% of patients were former smokers (quit > 3 months) and 36% were never smokers. Pathological tumor stage of the second cancer was T1 in 36%, T2 in 27%, T4a in 36%. The histology was squamous cell carcinoma in 9 patients, spindle cell squamous carcinoma in 1 patient, and adenosquamous carcinoma 1 patient. HPV status was negative in 45.5%, positive in 18.2% and unknown in 36.4%. Post-operative re-irradiation was given in 55%, of which 50% received concurrent chemotherapy. Locoregional control rates at 12 and 24 months were 100% and 62.5% (95% CI: 28.9-96.1%), respectively. Of the 2 patients with local failure, which occurred at 18 and 33 months after diagnosis, salvage therapy with surgery was successful. Regional failure was diagnosed in 2 patients at 13 and 16 months after diagnosis, and both of these patients ultimately died as a result of regional failure. There were no distant failures. One additional patient had died at last follow up which was unrelated to cancer. Estimated 2-year overall survival from the second head and neck malignancy was 78.9% (95% CI: 53.0-100%). Conclusion The risk of a second head and neck malignancy in survivors of HPV associated OPSCC is low, but as the incidence of HPV related OPSCC remains elevated and the likelihood of cure is excellent, secondary malignancy is an important long-term risk. Despite prior RT, consideration of post-operative re-irradiation is important as regional failure may carry a poor prognosis.

Brain metastases are often associated with a poor prognosis; however, with earlier detection and increasingly available therapies, including wider use of stereotactic radiosurgery and targeted therapies, the prognosis appears to be improving. This chapter reviews the epidemiology, diagnosis, and prognostic systems for brain metastases.

Purpose/objective(s) Hypofractionated intensity modulated radiation therapy (H-IMRT) is uncommonly used in head and neck cancers due to concern for toxicity. This study reviews our experience using H-IMRT for head and neck cancers and explores its tolerability and efficacy. Materials/methods This single institution IRB approved retrospective study includes patients with head and neck cancers treated with definitive or post-operative H-IMRT from 2011-2020. Patients treated with ≥50Gy in 20 fractions to the primary tumor site and/or neck with at least 3 months of follow up were included. Patients treated to a superficial target only without proximity to mucosal surfaces or coverage of the elective neck (e.g., scalp; skin only targets) were excluded. Patients undergoing re-irradiation were excluded. Toxicity was scored using CTCAE v4.0. Acute toxicity included events occurring within 90 days of H-IMRT completion. Late toxicities occurred any time thereafter. Multiple toxicities in the same patient were scored separately. Results Fifty-nine patients with a median follow up of 10.9 months (range 3.0-111.5) were included. The majority of patients were white (93%) and male (78%) with a median age of 79.1. The most common primary tumor sites were skin (42%), major salivary glands (22%), and oral cavity (9%). The most frequent histologies included squamous cell carcinoma (66%) followed by thyroid cancer (7%), melanoma (5%), and Merkel cell carcinoma (5%). Treatment was delivered post-operatively in 80% and definitively in 20% of patients. All patients were treated with ≥50 Gy in 20 fractions, with the most common dose being 50 Gy (53%) followed by 55 Gy (44%). In 64% of patients a secondary elective dose of 45-50 Gy was used. Site treated included primary tumor site/bed with unilateral neck (54%), primary tumor site/bed with bilateral neck (19%), primary tumor site/bed alone (14%), unilateral neck (8%), and bilateral neck (5%). Five patients (8%) experienced a locoregional failure at a median time of 5.4 months (range 2.8-13.9). There were no grade 4 or 5 toxicities. Ten patients (17%) experienced acute grade 3 toxicity including mucositis (12%) and dermatitis (5%). Forty-six patients (78%) had an acute grade 2 toxicity, most commonly dermatitis (41%), pain (32%), fatigue (32%), dysgeusia (31%) and xerostomia (22%). Five patients (8%) experienced grade 2 late complications including neck fibrosis in three patients and trismus, aspiration pneumonia, and osteoradionecrosis in one patient each. No patient experienced grade 3 or higher late toxicity. No patients required the placement of a feeding tube or tracheostomy. Conclusion Hypofractionated IMRT in the definitive or post-operative treatment of head and neck cancers using ≥50Gy in 20 fractions appears safe and well tolerated with modest toxicity. Prospective studies comparing the safety and efficacy of H-IMRT to conventionally fractionated IMRT are warranted.

This study examines the utility of surveillance imaging in detecting locoregional failures (LRF), distant failures (DF) and second primary tumors (SPT) in patients with human papillomavirus (HPV) associated oropharyngeal cancer (OPC) after definitive chemoradiotherapy (CRT).An institutional database identified 225 patients with biopsy proven, non- metastatic HPV+ OPC treated with definitive CRT between 2004 and 2015, whose initial post-treatment imaging was negative for disease recurrence (DR). Two groups were defined: patients with2 scans/year Group 1 and patients with ≥2 scans/year Group 2. The Mann-Whitney test or Chi-square was used to determine differences in baseline characteristics between groups. FineGray regression was used to detect an association between imaging frequency, DR and diagnosis of SPT.Median follow up was 40.8 months. 30% of patients had ≥T3 disease and 90% had ≥ N2 disease (AJCC 7th edition). Twenty one failures (9.3%) were observed, 7 LRF and 15 DF. Six LRF occurred within 24 months and 14 DF occurred within 36 months of treatment completion. Regression analysis showed Group 2 had increased risk of DR compared to Group1 (HR 10.3; p = 0.002) albeit with more advanced disease at baseline. Five SPT were found (2 lung, 2 esophagus, and 1 oropharynx) between 4.5 and 159 months post-CRT.Surveillance imaging seems most useful in the first 2-3 years post treatment, and is particularly important in detecting DF. Surveillance scans for SPT has a low yield, but should be considered for those meeting lung cancer screening guidelines.