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Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB).We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans.Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Radiation therapy (RT) is essential to managing many pediatric malignancies but can provoke anxiety, fear, and discomfort for children owing to prolonged treatment time, extended course, and restrictive immobilization. Patients younger than 10 years frequently require daily general anesthesia (GA), which is resource intensive, expensive, potentially toxic, and anxiety and fear provoking. Audio-Visual Assisted Therapeutic Ambience in Radiation Therapy (AVATAR), a video streaming device, has been proposed as an alternative to anesthesia in patients aged 3 to 10 years. A pilot study evaluating the efficacy of this novel innovation is accruing, but patients younger than 3 years are ineligible.We simulated a 2-year-old with stage IV Wilms tumor for bilateral whole-lung and left-flank irradiation without GA. Using AVATAR, we attempted to deliver RT to this patient without sedation. Patient anxiety at the time of simulation and at the beginning, middle, and end of the treatment course was characterized using the validated Modified Yale Preoperative Anxiety Score (mYPAS) measurement tool.Although the patient tolerated computed tomography simulation without GA or AVATAR use, his mYPAS of 14 out of 18 indicated significant anxiety. Using AVATAR, all treatments were delivered without GA; his mYPASs were 5 and 4 (the lowest possible) and 4 at the first, midcourse, and final treatments, indicating no significant anxiety and a decrease from the pre-AVATAR baseline. Without GA, the time to deliver RT decreased by 66% from 90 to 30 minutes.We describe an expanded, previously unreported indication for AVATAR by demonstrating the feasibility of this approach to reduce or omit anesthesia in appropriate younger patients currently excluded from ongoing trials. The financial and quality-of-life benefits (including decreased stress, anxiety, toxic effects, cost, and appointment time) of AVATAR use may be extendable to a younger patient population than previously thought. In older children, prospective validation is ongoing, but additional study in patients younger than 3 years is needed.

Background: The response rates to immune checkpoint inhibitors (ICI) remain low (13-20%) in metastatic head and neck cancer patients and better understanding of factors predictive of response to these agents is urgently needed. Here we explore the impact of smoking status, marijuana use and alcohol on treatment outcomes in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with ICI. Methods: We performed a retrospective analysis of 201 R/M HNSCC patients treated with ICI between January 15th 2016 and April 9th 2020 at a single institution. Results: Gender: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), nivolumab+ipilimumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), larynx 26 (13%), other sites 46 (23%). p16 tumor status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Overall response rate: 36 (18%). Median OS: 12 months (95% CI: 9.4-14.8). Tobacco: former (HR: 0.75, 95% CI: 0.50, 1.11), current (HR: 0.58, 95% CI: 0.33, 1.02). Marijuana: yes (HR: 0.93, 95% CI: 0.58, 1.49). Alcohol: yes (HR: 1.04, 95% CI: 0.72, 1.49). Conclusion: In our cohort, smoking status, marijuana use and alcohol consumption did not have a statistically significant impact on OS in patients with R/M HNSCC treated with ICI. Trial registration: retrospectively registered.

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Patients with Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) have been shown to have a favorable prognosis and excellent overall survival, and studies have demonstrated these findings in predominantly White cohorts. Racial/ethnic (R/E) minorities, particularly Black patients, with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. In this study, we aimed to determine if Black patients with HPV-OPSCC have a similar favorable prognosis to the White population.his was a population based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database from 2010-2016. We identified patients with Stage I-IV HPV-associated OPSCC who were treated with radiation, surgery, chemotherapy, or a combination of modalities. Patient outcomes were stratified by R/E groups including White Versus Black patients. The main outcome in this study was overall survival (OS). Analyses for proportions of categorical variables were performed using a Chi-Square or Fisher's Exact test. Univariate and multivariate time-to-event survival analyses were performed using Kaplan Meier product limit estimates and log-rank test to test the differences between strata. A Cox proportional hazards regression model was used to assess the association between covariates and risk of death (OS).We identified 9,256 OPSCC patients who met inclusion criteria and were treated between 2010-2016, of which 7,912 were white (85.5%) and 1,344 were Black (14.5%). 1,727 were HPV-OPSCC, of which 1598 were White (92.5%) and 129 (7.5%) were Black. By race, the 5-year OS for White Vs Black OPSCC patients was 42% versus 23%, respectively (log-rank, p0.0001). Among HPV-Positive OPSCC patients, the 5-year OS for White vs Black patients was 65% versus 39% (log-rank, p0.0001). Among HPV negative patients the 5-year OS for White vs Black patients was 36% versus 13% (log-rank, p0.0001). On multivariate analysis, after accounting for age, sex, insurance status, income, Charlson-Deyo score, receipt of surgery, distance from facility, and total treatment time, Black race trended towards, but was not associated with worse survival. (HR:1.24, 95% CI 0.85-1.81, p=0.255) CONCLUSIONS: This national cohort study of OPSCC patients demonstrates that Black patients with HPV-OPSCC have a poor prognosis and overall survival similar to HPV-negative White patients. This may be partly due to socioeconomic barriers such as insurance and income. Further work is needed to better understand the specific drivers of inferior survival outcomes in this specific patient population. This article is protected by copyright. All rights reserved.

To identify the proportion of Emergency Department (ED) visits in cancer patients associated with a mental and substance use disorder (MSUD) and the subsequent healthcare costs.Nationally representative data on ED visits from 2009 to 2018 was obtained from the Nationwide Emergency Department Sample (NEDS). We identified cancer-related visits with or without a MSUD using the Clinical Classifications Software diagnoses documented during the ED visit. Survey-adjusted frequencies and proportions of ED visits among adult cancer patients with or without a MSUD was evaluated. Survey-adjusted multivariable logistic regression models were used to examine demographic and clinical predictors of the presence of an MSUD and the likelihood of hospital admission for patients with a primary MSUD.Among 54,004,462 ED visits with a cancer diagnosis between 2009 and 2018, 11,803,966 (22%) were associated with a MSUD. Compared to a primary diagnosis of cancer, patients who presented to the ED with a chief complaint of MSUD were more likely to be female (54% vs. 49%), younger (median: 58 vs. 66), more likely to have Medicaid insurance, and more likely to be discharged home. The three most common MSUD diagnoses among cancer patients were alcohol-related disorders, anxiety disorders, and depressive disorders. The total costs associated with a primary MSUD from 2009 to 2018 was $3,133,432,103, of which alcohol-related disorders claimed the largest majority. Younger age (OR per 10-year increase: 0.86, 95% CI: 0.85, 0.86) and female sex (OR: 1.34, 95% CI: 1.33-1.35) were associated with higher odds of having an MSUD.Our findings demonstrate a high burden of psychiatric and substance use illness in the cancer population and provide the rationale for early psychosocial intervention to support these patients.

Background Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. Methods A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. Results 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79. Conclusions Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

Wound care accounts for more than $6 billion of health expenditure in the United States annually. In addition, Medicare reimbursement per relative value unit has remained flat with respect to inflation over the past 20 years. Yet, physicians face increasing operating costs. The economic effects of declining inflation-adjusted Medicare physician reimbursement on the use of wound debridement procedures have yet to be elucidated. This study describes trends in Medicare reimbursement, utilization, and total Medicare expenditure for wound debridement procedures. Using Medicare claims data, we aggregated the volume of services and average Medicare reimbursement for wound debridement procedures over the calendar years 2012 to 2017. For each billing code, we estimated inflation-adjusted total Medicare expenditure by multiplying the average inflation-adjusted Medicare reimbursement by the aggregate volume of services. The average inflation-adjusted payment for wound debridement procedures decreased by 6% from 2012 to 2017. Over this time period, the utilization of wound care procedures increased 32%. Total inflation-adjusted annual Medicare expenditure on wound care increased 24% from 2012 to 2017. Therefore, despite declining physician reimbursement rates, total Medicare expenditure on wound debridement increased from 2012 to 2017. This increase in total Medicare expenditure was driven by higher utilization of wound debridement procedures.

Background Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy (RT). Proton RT (PRT) enables superior sparing of critical structures compared with photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT. Methods One hundred fifty patients ( Results Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n = 145) at 7 years were 63.4%, 82.6%, and 76.1%. Fifty-one patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. One hundred sixteen patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR. Conclusion PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with >54 Gray relative biological effectiveness (GyRBE) versus ≤54 GyRBE.

In pediatric brain tumors, the intensification of chemotherapy has allowed for a reduction in radiotherapy (RT) volume to an involved field approach, particularly in patients with medulloblastoma. For patients with low-grade gliomas, the trend has remained to delay RT with chemotherapy; however, when RT is used, typically smaller clinical target volume margins are used. For patients with extracranial tumors, intensive chemotherapy to address systemic disease with local control is considered standard. Proton beam therapy shows significant promise in addressing both short-term and long-term toxicities in both central nervous system (CNS) and non-CNS pediatric tumors.

Background: Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. Patients and Methods: This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000–2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan–Meier product limit estimates and the log-rank test to evaluate the differences between strata. Results: There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (

Background Survivors of pediatric medulloblastoma experience long-term morbidity associated with the toxic effects of postoperative radiotherapy (RT). Proton RT limits radiation dose to normal tissues thereby reducing side effects of treatment while maintaining high cure rates. However, long-term data on disease outcomes and long-term effects of proton RT remain limited. Methods One hundred seventy-eight pediatric medulloblastoma patients treated with proton RT between 2002 and 2016 at the Massachusetts General Hospital comprise the cohort of patients who were treated with surgery, radiation therapy, and chemotherapy. We evaluated event-free survival (EFS), overall survival (OS), and local control using the Kaplan-Meier method. The cumulative incidence of brainstem injury and secondary malignancies was assessed. Results Median follow-up was 9.3 years. One hundred fifty-nine patients (89.3%) underwent a gross total resection (GTR). The 10-year OS for the entire cohort, standard-risk (SR), and intermediate/high-risk (IR/HR) patients was 79.3%, 86.9%, and 68.9%, respectively. The 10-year EFS for the entire cohort, SR, and IR/HR cohorts was 73.8%, 79.5%, and 66.2%. The 10-year EFS and OS for patients with GTR/NTR were 75.3% and 81.0% vs 57.7% and 61.0% for subtotal resection (STR). On univariate analysis, IR/HR status was associated with inferior EFS, while both anaplastic histology and IR/HR status were associated with worse OS. The 10-year cumulative incidence of secondary tumors and brainstem injury was 5.6% and 2.1%, respectively. Conclusions In this cohort study of pediatric medulloblastoma, proton RT was effective, and disease outcomes were comparable to historically treated photon cohorts. The incidence of secondary malignancies and brainstem injury was low in this cohort with mature follow-up.

Purpose/Objective(s): Microbiome has been shown to affect tumorigenesis by promoting inflammation. However, the association between the upper aerodigestive microbiome and head and neck squamous cell carcinoma (HNSCC) is not well established. Hypoxia is a modifiable factor associated with poor radiation response. Our study analyzed the HNSCC tumor samples from The Cancer Genome Atlas (TCGA) to investigate the relationship between different HNSCC tumor subsites, hypoxia, and local tumor microbiome composition. Results: A total of 357 patients were included [Oral cavity (OC) = 226, Oropharynx (OPx) = 53, and Larynx/Hypopharynx (LHPx) = 78], of which 12.8%, 71.7%, and 10.3%, respectively, were HPV positive. The mean (SD) hypoxia scores were 30.18 (11.10), 24.31 (14.13), and 29.53 (12.61) in OC, OPx, and LHPx tumors, respectively, with higher values indicating greater hypoxia. The hypoxia score was significantly higher for OC tumors compared to OPx (p = 0.044) and LHPx (p = 0.002). There was no significant correlation between hypoxia and HPV status. Pseudomonas sp. in OC, Actinomyces sp. and Sulfurimonas sp. in OPx, and Filifactor, Pseudomonas and Actinomyces sp. in LHPx had the strongest association with the hypoxia score. Materials/Methods: Tumor RNAseq samples from TCGA were processed, and the R package “tmesig” was used to calculate gene expression signature, including the Buffa hypoxia (BH) score, a validated hypoxia signature using 52 hypoxia-regulated genes. Microbe relative abundances were modeled with primary tumor location and a high vs. low tertile BH score applying a gamma-distributed generalized linear regression using the “stats” package in R, with adjusted p-value < 0.05 considered significant. Conclusions: In our study, oral cavity tumors were found to be more hypoxic compared to other head and neck subsites, which could potentially contribute to their radiation resistance. For each subsite, distinct microbial populations were over-represented in hypoxic tumors in a subsite-specific manner. Further studies focusing on an association between microbiome, hypoxia, and patient outcomes are warranted.

Some patients elect for self-pay proton radiation therapy (PT) in the United States, but price transparency is a significant concern. The U.S. government recently declared that hospitals must provide a comprehensive list of "standard" charges for all services. Yet, the proportion of compliant proton centers is unknown, as is the extent to which prices vary nationally.We obtained online chargemasters from U.S. proton centers. Technical charges for per fraction delivery of PT of varying complexity were obtained by billing code (77520, 77522, 77523, 77525) and keyword searches. Prices were adjusted for cost-of-living differences using the Medicare geographic cost price index. The relationship between prices for each PT billing code and cost of living was assessed. The interrelationship in cost between codes was examined. The effect of geographic region and other key variables on pricing was explored.Thirty-six proton centers were identified. Twenty-eight (78%) had accessible chargemasters with 20 (56%) listing at least one PT charge. The median prices for billing codes 77520, 77522, 77523, 77525 were $4707, $4712, $5904, and $6690, respectively, with a trend toward greater cost for more complex therapy (77523, 77525; P = .056). Large ranges ($16,863, $16,059, $18,414, $22,143) resulted in ratios of maximum/minimum prices of 5 to 10x. Only prices for code 77522 were associated with cost of living (P = .039). Across institutions, prices for all 4 codes were positively interrelated (all P.0001). Prices differed between regions (P.0001) but not by National Cancer Institute designation.List prices for PT differ dramatically between institutions and regions without obvious explanation, raising the concerning possibility that such variation is largely arbitrary. Policy solutions that promote rationalized pricing would greatly benefit this patient population.

Objective: The objective of this study is to report disease outcomes and toxicity with the use of stereotactic body radiation therapy (SBRT) in the treatment of pediatric metastatic disease. Methods: All pediatric and adolescent young adult (AYA) patients’ who received SBRT were included between the years 2000 and 2020. Study endpoints included local control (LC), progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The end points with respect to survival and LC were calculated using the Kaplan–Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. Results: 16 patients with 36 lesions irradiated met inclusion criteria and formed the study cohort. The median OS and PFS for the entire cohort were 17 months and 15.7 months, respectively. The 1 year OS for the entire cohort was 75%. The 6- and 12 month local control was 85 and 78%, respectively. There were no local failures in irradiated lesions for patients who received a BED10≥100 Gy. Patients who were treated with SBRT who had ≤5 metastatic lesions at first recurrence had a superior 1 year OS of 100 vs 50% for those with >5 lesions. One patient (6.3%) experienced a Grade 3 central nervous system toxicity. Conclusion: LC was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with five or fewer metastatic sites have a significantly better OS compared to >5 sites. Advances in knowledge: This study demonstrates that SBRT is safe and efficacious in the treatment of pediatric oligometastatic disease.

The advent of proton beam therapy (PBT) has initiated a paradigm shift in the field of pediatric radiation oncology, with increasing promise to alleviate both short-term and long-term toxicities. Given the dramatic rise in proton therapy centers in the United States, a discussion of the quality of evidence supporting its use in pediatric cancers is warranted.Proton radiotherapy appears to decrease the incidence and severity of late effects with the strongest evidence in pediatric brain tumor cohorts that shows benefits in neurocognitive, hearing, and endocrine outcomes. However, emerging data has shown that more conservative brainstem dose limits with protons compared with photons are required to limit brainstem toxicity; these modified recommendations have been incorporated into national cooperative group studies. Decreased toxicity in tumors outside of the CNS for PBT have also been reported in sarcomas, Hodgkin disease and neuroblastoma. Similarly, QoL outcomes are improved in brain tumor and other cohorts of patients treated with PBT.The collective findings demonstrate improved understanding and refinement of PBT in pediatric cancers. Data on QOL, toxicity and disease outcomes with PBT should continue to be collected and reported in order to understand the full extent of the risks and benefits associated with PBT.

Purpose/Objective(s) Radiotherapy (RT) is a cornerstone modality in treating head and neck cancers in the primary and salvage settings. Maximum tolerated dose to the brachial plexus and other factors contributing to brachial plexus injury in the re-irradiation setting are poorly understood. To define radiation dose and other clinical factors associated with the brachial plexus injury in patients treated with re-irradiation for recurrent head and neck cancers. Materials/Methods We analyzed 47 brachial plexus re-irradiation between 2015 and 2020. A first course of radiation for head and neck cancer, developed recurrent disease, and then underwent salvage re-irradiation. DICOM plans and contours for all patients were reviewed by two authors and via a prospective multidisciplinary chart rounds. Common terminology criteria for adverse events (CTCAE) was used to define the brachial plexus injury after the second course of radiation. We used ROC curves to evaluate the cutoff values. Kaplan-Meier and logistic regression were used to test the correlation between the variables and the outcome. Results Median prescription dose from the 1st course was 70 Gy (range: 60-70) and from the 2nd course was 66 Gy (46-70) in 2 Gy per fraction. All patients received photon volumetric modulated arc therapy; 74% received concurrent chemotherapy (CRT) during the 1st course (Cisplatin 30%, Carboplatin +/- Paclitaxel 23% and Cetuximab 21%), 74% received CRT during the 2nd course (Carboplatin/Paclitaxel 40%, Cetuximab 17%, Cisplatin 13% and Nivolumab 4%) and 53% received CRT twice. The median time interval between the two RT courses was 24 months (range, 8-221 months). The median cumulative maximum dose (Dmax) to brachial plexus was 97 Gy (range, 64-144 Gy). At a median follow-up of 9 months (range, 1-47 months), the cumulative incidence of brachial plexopathy (CIBPP) was 17% at 1 year. This consisted of two cases with pain alone, one case with numbness alone, two cases with weakness alone and one case with combination of pain and numbness. The median time to development of symptoms was 8.2 months (range, 1-15 months). Among patients with a Dmax greater than vs less than 106 Gy, the 1-year cumulative incidence of BPP was 42% vs 4% P = 0.005. V80 > 1cc (1-yr CIBPP 34% vs 4% P = 0.03) and V90 > 0.3cc (32% vs 4%, P = 0.046) associated with increased risk of BPP. The use of concurrent cisplatin during re-irradiation was associated with increased risk of BPP (OR 39 CI 4.263-356.81, P = 0.001). Other variables like gender, history of neck surgery, use of other kind of systemic therapy, use of cisplatin during the first course of RT, mean cumulative dose, V60, V70, V100 and the interval between the first and the second courses of radiation were not associated with increased risk of BPP. The 1-year OS was 78% and the 1-year PFS was 52%. Conclusion Cumulative incidence of radiation-induced BPP after re-irradiation was 17% at 1 year. Dmax > 106 Gy, higher V80/V90, and the use of concurrent cisplatin during re-irradiation, were associated with increased risk of BPP.

Purpose/Objective(s) Pediatric patients with metastatic solid tumors historically have a poor overall survival. Some pediatric patients may still be potentially curable with aggressive local therapy to metastatic disease, and adult trials have defined a group of oligometastatic patients, where the use of stereotactic body radiation therapy (SBRT) has an overall survival benefit. The purpose of this study is to report results of the use of SBRT in the treatment of pediatric metastatic disease. Materials/Methods All pediatric and adolescents and young adult (AYA) patients age 3-40 years who received SBRT were included between the years 2000-2020. SBRT included radiation treatments with 3-5 fractions and ablative doses above conventional palliative radiation. Study endpoints included local control (LC), progression free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The endpoints with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. Toxicity was scored using CTCAE v5.0. Results Thirty-six lesions in 16 patients were treated with SBRT and comprised the overall cohort. The most common pediatric solid tumors treated were Ewing's Sarcoma (n = 3), Osteosarcoma (n = 3), and Rhabdomyosarcoma (n = 2). The majority of lesions irradiated were in the spine (n = 11), lung (n = 8), pelvis (n = 7), and brain (n = 5). The median follow up was 12 months. The median OS and PFS for the entire cohort were 17 months and 15.7 months, respectively. Patients were treated to a median dose of 25 Gy in 5 fractions. The 1-year OS for the entire cohort was 75%. The 6- and 12-month local control was 85% and 78%, respectively. There were no local failures in irradiated lesions for patients who received a BED10≥100 Gy. Patients treated with SBRT who had ≤5 metastatic lesions at first recurrence had a superior 1-year OS of 100% versus 50% for those with > 5 lesions. No patients experienced a grade 4 or 5 toxicity in our cohort. One patient (6.3%) experienced a CTCAE grade 3 toxicity (seizure) which resolved after anti-epileptic medications. Conclusion Local control was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with 5 or fewer metastatic sites have a significantly better OS compared to > 5 sites. Future prospective trials with multi-institutional collaboration will be necessary to evaluate appropriate patient selection and the optimal radiation dose regimen.

BACKGROUND: Though pathologic evidence for non-small cell lung cancer (NSCLC) is preferred, many patients do not receive a biopsy prior to treatment with stereotactic body radiation therapy (SBRT). This study seeks to analyze the overall survival (OS), local control, and toxicity rates for such patients. METHODS: This retrospective review included patients empirically treated with SBRT for presumed non-metastatic NSCLC at a single institution. Inclusion criteria included a hypermetabolic pulmonary lesion noted on positron emission tomography (PET) imaging but no pathological evidence of NSCLC. Patients with another known metastatic tumor were excluded. Statistical analysis was conducted with Cox proportional hazards analysis, univariate analysis, and the Kaplan-Meier method. RESULTS: Ninety-one treatments in 90 unique patients met inclusion criteria. Patients were a median 77.9 years at the start of treatment and had a median Charlson score of 7. Pre-treatment standardized uptake value (SUV) was a median 4.5 and 1.5 after treatment. At a median follow-up of 12.9 months, 36-month local control of 91.3% was achieved. Twenty-four-month OS and progression-free survival were 65.4% and 44.8%, respectively. On univariate analysis, biologically effective dose (BED) ≥120 Gy was predictive of improved OS (P=0.001), with 36-month OS of 50.5% for patients with BED ≥120 Gy and only 31.6% for patients with BED

This cohort study describes recent trends in use and payment rates and in overall expenditure for skin cancer procedures in the Medicare Part B population in the United States.

The importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs).The National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan-Meier estimator was used to estimate the association between RT duration (≤45 days or45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS.Six-hundred twenty-five patients met inclusion criteria, of which 181 were assigned to the "RT long" (45 days) cohort (29.0%) and 444 (71.0%) to the "RT short" group (≤45 days). The five-year OS for the "RT short" compared with "RT long" cohort was 82.2% versus 70.9%, respectively (log-rank, P0.0037). For average risk patients, the five-year OS was 84.6% versus 86.4% for "RT short" and "RT long," respectively (log-rank, P = 0.40). However, for high-risk patients, five-year OS was 77.7% versus 51.0% (log-rank, P0.0001) in the "RT short" and "RT long" cohorts.For patients with high-risk medulloblastoma and CNS PNETs, RT duration45 days was associated with inferior OS.

The treatment of skin cancers represents a growing share of healthcare expenditures. At the same time, Medicare reimbursement rates for physician services have declined with respect to inflation. The objective of this study was to describe the economic effects of declining Medicare reimbursement for skin cancer procedures. In this ecological study, we used the Medicare Physician Supplier and Other Provider Public Use File (POSPUF) to analyze trends in Medicare reimbursement rates, use rates, and overall Medicare expenditures for skin cancer procedures from 2012 to 2017. We adjusted reimbursement rates for inflation by converting payment amounts into units of 2017 dollars. From 2012 to 2017, overall inflation-adjusted Medicare expenditure on skin cancer procedures increased 9%. Over this time period, inflation-adjusted Medicare reimbursement rates declined for each procedure class, with the exception of shave excision. Concurrently, the use rate of Mohs micrographic surgery increased 23%, while the use rate for all other skin cancer procedure classes declined. In summary, this study describes trends suggesting declining Medicare reimbursement rates have been associated with increasing use rates for higher cost skin cancer procedures. Clinicians and policy makers should collaborate to develop value-based payment models that incentivize patient outcomes rather than procedural volumes.

Purpose Despite high response rates, there has been reluctance to use radiation therapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17% to 24% (≥grade 2) even with intensity modulated radiation therapy. Proton therapy (PT), which has no exit radiation dose, is associated with a lower dose to lung compared with other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT. Methods and Materials Within an international, multi-institutional cohort, we retrospectively evaluated the incidence and grade of radiation pneumonitis (National Cancer Institute Common Terminology Criteria for Adverse Events v4) among patients with r/r HL or NHL treated with PT. Results A total of 85 patients with r/r lymphoma (66% HL, 34% NHL; 46% primary chemorefractory) received thoracic PT from 2009 to 2017 in the consolidation (45%) or salvage (54%) setting. Median dose was 36 Gy(RBE). Before PT, patients underwent a median of 1 salvage systemic therapy (range, 0-4); 40% received PT within 4 months of transplant. With a median follow-up of 26.3 months among living patients, 11 patients developed symptomatic (grade 2) pneumonitis (12.8%). No grade 3 or higher pneumonitis was observed. Dose to lung, including mean lung dose, lung V5, and V20, significantly predicted risk of symptomatic pneumonitis, but not receipt of brentuximab, history of bleomycin toxicity, sex, or peritransplant radiation. Conclusions PT for relapsed/refractory lymphoma was associated with favorable rates of pneumonitis compared with historical controls. We confirm that among patients treated with PT, pneumonitis risk is associated with mean lung and lung V20 dose. These findings highlight how advancements in radiation delivery may improve the therapeutic ratio for patients with relapsed/refractory lymphoma. PT may be considered as a treatment modality for patients with relapsed/refractory lymphoma in the consolidation or salvage setting.

Children with medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and ependymoma are treated with a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Lower doses of craniospinal irradiation and tumor bed boost together with chemotherapy are the current standard of care for average-risk medulloblastoma in the Children's Oncology Group (COG). The International Society of Pediatric Oncology (SIOP) is examining the role of hyperfractionated craniospinal irradiation and chemotherapy in high-risk patients. The recent stratification of medulloblastoma into specific molecular risk groups has prompted both COG and SIOP to reexamine the role of these modalities in these different risk groups to maximize cure rates and minimize long-term complications. Proton therapy has shown lower rates of neurocognitive and endocrine complications compared with photons. Ependymomas are treated with maximal surgical resection and adjuvant radiation therapy. The role of chemotherapy in ependymoma is currently being studied in both COG and SIOP. Likewise, for ATRT the role of different high-dose chemotherapy regimens together with local radiation therapy in infants, or craniospinal radiation in older children, is the current focus of research.

Objective: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. Methods and materials: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. Results: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing’s sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. Conclusions: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. Advances in knowledge: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.

Renal cell carcinoma (RCC) is usually treated with surgery, with or without systemic therapy. For select patients, stereotactic body radiation therapy (SBRT) may be a suitable alternative. Although many reports exist on the successful use of SBRT, very few have described long term outcomes with regard to disease progression and renal function. We report a rare case of a single patient with primary, metastatic, and locally recurrent renal cell carcinoma who was successfully treated with SBRT. The patient has been disease-free for 8 years since treatment, with stable renal function even after two courses of SBRT to her solitary functioning kidney.

6030 Background: Immune checkpoint inhibitors (ICI) therapy is approved for patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will die within two years of diagnosis. We have shown that pretreatment clinical characteristics may predict overall survival (OS). Here, we expand our analysis to a total of 201 pts. Methods: Between January 15,2016 and April 9, 2020, 201 pts with R/M HNSCC were treated with ICI as first, second line and beyond. Data on p16 status, hemoglobin (Hb), albumin, lactate dehydrogenase (LDH), neutrophil, platelet and lymphocyte count was recorded initially. OS was defined from the start of ICI to death. Progression Free Survival (PFS) was defined from the start of ICI to disease progression (PD) or death. A nomogram was created using the rms package to generate individualized survival prediction. Results: 201 pts were analyzed, sex: 154 male (77%), 47 female (23%), median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), ipilimumab+nivolumab 10 (5%). Line of therapy: First: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), others 72 (36%). p16 status: negative 132 (66%), positive 69 (34%). Laboratory values: Median neutrophil count: 4.58 (IQR: 3.43-6.47), Median lymphocyte count: 0.69 (IQR: 0.47-1.08), Median Platelet count: 229 (IQR: 187-300), hemoglobin (Hb) normal/low 101/100 (50%/50%), albumin: normal/low 156/45 (78%/22%), LDH: normal/high 124/77 (62%/38%). Overall response rate: 36 (18%). Median OS: 12 months (CI: 9.4-14.8), median PFS: 4 months (CI: 3.5-5.7). The variables associated with OS were neutrophil count (high) [HR 1.28 (1.08 – 1.51), p=0.004], lymphocyte count (high) [HR 0.75 (0.60 – 0.95), p=0.015], albumin (low) [HR 2.06 (1.37 – 3.10), prd and 66th percentile. Median OS in the good risk group was 24 months (CI: 18.5-NR), average risk group 13.8 months (CI: 11-20), poor risk group 2.3 months (CI: 1.7-4.4). The discrimination of the model after internal validation was c-index of 0.72. Conclusions: A small percentage of R/M HNSCC pts treated with ICI have good long-term survival outcomes. In a larger cohort, we internally validated the utilization of a simple, inexpensive and widely accessible nomogram based on clinical and laboratory variables which can predict OS in this patient population.

6038 Background: Immune checkpoint inhibitors (ICI) are currently approved in the treatment of patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will progress on ICI. Little is known regarding the best treatment approach for this patient population. We previously showed that the combination of weekly carboplatin, paclitaxel and cetuximab was associated with reduced risk of grade 3/4 toxicities, which makes it an ideal regimen in this setting. Here; we report the outcomes of pts with R/M HNSCC who were treated with chemotherapy alone vs weekly chemotherapy plus cetuximab after progression on ICI. Methods: Between January 15th 2016 and April 9th 2020, 154 pts who progressed on ICI were analyzed. Among these pts, 64 had received subsequent systemic therapy and met the inclusion criteria. Progression Free Survival (PFS) was defined as the time elapsed between initiation of subsequent chemotherapy and tumor progression or death. Overall Survival (OS) was defined as the time elapsed between initiation of subsequent chemotherapy to death. Descriptive statistics and Cox regression were used to explore study variables. Results: 64 pts received subsequent chemotherapy after progression on ICI. 28 pts (44%) received a combination of weekly chemotherapy plus cetuximab. This regimen included carboplatin AUC 1.5, paclitaxel 45 mg/m2, and cetuximab loading dose of 400mg/m2 followed by weekly dose of 250 mg/m2. 36 pts (56%) received chemotherapy alone without cetuximab. These regimens included capecitabine, afatinib, and gemcitabine, among others. Sex: 51 males (80%), 13 females (20%), age (median): 61 (IQR: 53-66), tumor site: oropharynx 32 (50%), oral cavity 11 (17%), larynx 8 (12%), other sites 13 (21%). P16 status: negative 36 (56%), positive 28 (44%). Prior ICI drug: pembrolizumab 34 (53%), nivolumab 26 (41%), ipilimumab + nivolumab 4 (6%). Median follow up: 9 months (IQR: 5-13). Overall response rate: weekly chemotherapy plus cetuximab 32%, chemotherapy alone 22% (p = 0.4). Pts who received chemotherapy alone had a median PFS of 3.2 months (CI: 2-5) vs 5.6 months (CI: 4.3-10.1) in the weekly chemotherapy plus cetuximab group. After adjusting for p16 status and prior ICI drug, PFS was improved in the group that received weekly chemotherapy plus cetuximab vs. chemotherapy alone (HR: 0.52; CI: 0.28-0.98; p = 0.042). Median OS was 10 months (CI: 8.5-NR) in the weekly chemotherapy plus cetuximab group vs 8.7 months (CI: 5.7-13.8) in the chemotherapy alone group (HR: 0.84; CI: 0.4-1.8; p = 0.8). Conclusions: Pts with R/M HNSCC who progressed on ICI experience longer PFS with the addition of cetuximab to weekly chemotherapy. Further investigation in a larger cohort of pts is needed to fully assess the impact on survival for this treatment combination.

10016 Background: The impact of race and socioeconomic status (SES) on cancer mortality has been elucidated in adult patients, but is not well described in pediatric oncology. We hypothesize that racial and socioeconomic disparities exist in pediatric cancer patients, resulting in higher rates of hospitalization and mortality. Methods: We analyzed the Kids’ Inpatient Database (KID) which shows national estimates of inpatient stays for pediatric patients. Inclusion criteria included patients who were ≤20 with a cancer diagnosis identified through the Clinical Classifications Software (CCS). Variables analyzed were discharge status, patient demographics, hospital characteristics, expected payment source, total visit charge, and length of stay. Initial comparisons between cancer and non-cancer related discharges were performed using a chi-square test. To estimate disparities by race, clinical comparisons were performed across five racial groups: White, Black, Hispanic, Asian/Pacific Islander, and Native American/Other. A multivariable logistic regression model was used to examine predictors of hospitalization and mortality. Results: From 2006-2012, there were 9,488,477 non-cancer related pediatric inpatient stays and 242,489 cancer related stays. Patients with cancer related visits were more likely to be white, male (54.9% vs 46.1%, p < 0.0001), older at admission, have private insurance (52.5% vs 41.7%), and were from a higher income quartile (76th-100th percentile, 25.2% vs 19.9%, p < 0.001). These patients also had a higher rate of death during admission (1.2% vs 0.5%, p < 0.0001), higher cost of visit charge ($25,097 vs $8,267, p < 0.001), longer length of stay (4 vs 2 days), and were less likely to be discharged (85.5% vs 92.0%, p < 0.0001).The four most frequent cancer diagnoses associated with hospital admission were leukemia (n = 75,807), Other and Unspecified Primary (n = 50,076), bone/connective tissue tumor (n = 42,477), and central nervous system tumor (n = 27,958). Patients who were non-white were more likely to die during their inpatient stay (1.5% Non-white versus 0.9% White, p < 0.001). On multivariate logistic regression, Black (OR: 1.61, 95% CI: 1.57-1.66, p < 0.0001) and Native American (OR: 1.39, 95% CI: 1.34-1.44, p < 0.0001) race, as well as lower income quartile (OR: 1.24, 95% CI: 1.19-1.28, p < 0.001) were associated with increased odds of death during admission. Conclusions: This is the largest observational study to date to identify the impact of race and SES on pediatric cancer hospitalization and mortality in the United States. Non-white race and lower SES was associated with significantly increased odds of death during admission. Given the significant difference in mortality by race, healthcare policy makers and insurance companies should investigate the specific drivers of increased admission and mortality and develop strategies to address inequity in cancer care.

Trans-oral robotic surgery (TORS) has emerged as an important surgical treatment option in the management of human papillomavirus (HPV)-positive and -negative oropharynx cancer. However, treatment selection is paramount to ensure that patients will not require multimodality adjuvant therapy. In this study, we determined predictors of adjuvant therapy in TORS-treated patients. The National Cancer Database (NCDB) was used to identify patients with newly diagnosed clinical T1-T4, N0-N3 oropharyngeal squamous cell carcinoma who underwent TORS between 2010&ndash, 2016. Kaplan&ndash, Meier survival analysis was used to estimate overall survival (OS). A total of 2999 patients were studied, and the five-year OS for the entire cohort was 82.5%, and for HPV-positive and -negative cohorts it was 88.3% and 67.9%, respectively (p &lt, 0.001). Among all patients treated with TORS, 35.1% of patients received no additional treatment, 33.5% received adjuvant radiation alone (RT), and 31.3% received adjuvant chemoradiation. The N stage was pathologically upstaged in 629 (20.9%) patients after TORS. Patients treated at higher-volume centers were more likely to have negative surgical margins (OR: 0.96, 95% CI: 0.94, 0.98, p &lt, 0.001), but this did not influence the receipt of adjuvant therapy. The high rate of adjuvant multimodality treatment after TORS suggests a need for improved patient selection. Limitations of this study, including lack of data on loco-regional control, progression free survival, acute and late toxicities, and utilization of pretreatment PET/CT imaging, should be addressed in future studies.

BACKGROUND To assess the association between radiation therapy (RT) use and overall survival (OS) for patients with metastatic head and neck squamous cell carcinomas (HNSCC). METHODS We analyzed the National Cancer Database to identify patients with newly diagnosed metastatic HNSCC from 2004 to 2013 who were treated with up-front chemotherapy. Associations between the use of RT and OS were evaluated. RESULTS We identified 3516 patients with metastatic HNSCC who were treated with chemotherapy; 2288 (65%) were also treated with RT. The addition of RT to chemotherapy was associated with prolonged survival (median: 13.6 vs 11.3 months, log-rank P

To determine whether patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC) treated with Transoral Robotic Surgery (TORS) have similar survival to patients treated with definitive RT.Using the National Cancer Database (NCDB) registry, we identified patients with newly diagnosed clinical T1-T2, N0-N2b OPSCC between 2010 and 2014. A multivariable logistic regression was utilized to determine the association between chemotherapy use and primary treatment modality (TORS vs definitive RT). Kaplan Meier survival analysis was used to estimate overall survival. Propensity score matching was utilized to address selection bias.We identified 17,150 patients, of which 14,470 (84.4%) received primary RT and 2,680 (15.6%) underwent TORS. The median follow-up for the cohort was 31.4 months. Propensity score matching demonstrated similar 5-year OS for patients treated with either definitive RT or TORS (81% vs 84%, log rank p = 0.10). There was no difference in survival outcomes by treatment selection (TORS or definitive RT) in either HPV positive or HPV negative subtypes. Patients treated with TORS were less likely to receive chemotherapy compared to patients treated with definitive RT and this was also demonstrated in a propensity matched analysis (OR: 0.09, 95%CI 0.078-0.12, p 0.001). Only 68.4% of TORS treated patients underwent adjuvant RT, compared to 100% of patients in the primary RT cohort (p 0.001).For patients with OPSCC, TORS results in similar OS outcomes and is associated with decreased chemotherapy and RT use compared to definitive RT. Our results demonstrate the feasibility of TORS in a select subgroup of OPSCC patients.

Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen.We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT.10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100 GyFSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose-response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose-response relationship for LC in patients treated with FSRT for brain metastases.

The management of patients with recurrent head and neck cancers remains a challenging clinical dilemma. Concerns over toxicity with re-irradiation have limited its use in the clinical setting. Stereotactic Body Radiation Therapy (SBRT) has emerged as a highly conformal and precise type of radiotherapy and has the advantage of sparing normal tissue. Although SBRT is an attractive treatment modality, its use in the clinic is limited, given the technically challenging nature of the procedure. In this review, we attempt to provide a comprehensive overview of the role of re-irradiation in patients with recurrent head and neck cancers, with particular attention to the advent of SBRT and its use with systemic therapies such as cetuximab. In the second portion of this review, we present our systematic review of published experiences with SBRT in recurrent head and neck cancers in an attempt to provide data on response rates (RR), overall survival and toxicity. © 2016 Wiley Periodicals, Inc. Head Neck 39: 595-601, 2017.

6035 Background: The role of radiation therapy (RT) in the upfront management of patients with metastatic head and neck squamous cell carcinoma (HNSCC) is not clearly defined. In this study, we used the National Cancer Database (NCDB) to assess the association between RT use and overall survival (OS) for patients with metastatic HNSCC who received chemotherapy. Methods: We analyzed the NCDB to identify patients with newly diagnosed metastatic HNSCC from 2004-2013 who were treated with upfront chemotherapy. Associations between the use of RT and OS were evaluated using the Kaplan Meier method, univariate and multivariate cox regression, propensity score matching, and sequential landmark analysis. Survival outcomes were also compared for patients receiving a biologically effective dose (BED) ≥72 Gy10 and < 72 Gy10. Results: We identified 3,516 patients diagnosed with metastatic HNSCC who were treated with chemotherapy, of which 2,288 (65%) were also treated with RT. The median follow up was 11.9 months. The addition of RT to chemotherapy was associated with prolonged survival (median 13.6 v 11.3 months, logrank p < 0.001). On multivariate analysis, the use of RT remained associated with prolonged survival (HR = 0.71, 95% CI 0.61-0.82, p < 0.001). After propensity score matching, the addition of RT was associated with improved median survival (13.5 v 11.2 months) and 5-year (17% v 7%) OS compared to chemotherapy alone (log rank, p < 0·001). Landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis continued to demonstrate improved OS with the addition of RT. Among patients treated with RT, the use of RT schedules with a BED exceeding 72 Gy10 was associated with prolonged survival (median 18.0 versus 11.7 months, logrank p < 0.001). Conclusions: For patients with metastatic HNSCC, the addition of RT to chemotherapy was associated with improved OS in this population based study. These results provide rationale for prospective randomized trials to validate these findings and to determine the optimal radiation therapy dose/fractionation and treatment schedule for these patients.