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Background Li‐Fraumeni Syndrome (LFS) is a rare cancer‐predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well‐characterized. Here we describe the risk of subsequent malignancy and cancer‐related death in LFS patients after undergoing RT for a first or second primary cancer. Methods We reviewed a multi‐institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non‐RT group). Results Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow‐up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative‐intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non‐RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy. Conclusion We found that four of14 patients treated with RT developed in‐field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT‐induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion., Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. We found that four of 14 patients treated with RT developed in‐field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT‐induced malignancies.

Càncer de cap i coll; Radioteràpia; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Cáncer de cabeza y cuello; Terapia de radiación; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Head and Neck Cancer; Radiation Therapy; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Purpose Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. Methods and Materials A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. Results In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

BACKGROUND Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.

OBJECTIVES: To compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression. RESULTS: Of 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes > 2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227). CONCLUSION: Within the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort SETTING: Population-based SUBJECTS AND METHODS: 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow up were compared with 7,796 controls matched for age, sex and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2–5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2–5 years increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% CI 5.08 −17.87) and 12.57 (7.17–22.04) respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45 – 197.33) to 35.2 (7.81–158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50–4.42) to 2.12 (1.63–2.75). Treatment with radiation therapy and age over 65 were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data supports our hypothesis that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Parotid tumors are rare, and no clinical trial data exists to guide postoperative radiation therapy (PORT) usage. We sought to determine the impact of PORT on the overall survival (OS) of patients with parotid malignancies. Patient data was queried from the National Cancer Database. Patients with surgical resection of parotid gland carcinomas from 2004 to 2012 were analyzed. Kaplan-Meier and Cox proportional hazards were used to assess OS among those receiving PORT or not. Additionally, variables affecting OS and use of PORT were evaluated. A total of 12,439 patients were identified for analysis. Increasing T stage, N stage, tumor grade, and positive margin status were predictive of PORT. Survival for patients receiving PORT versus surgery only at 5 and 10 years was 65.5% and 50.3% versus 74.4% and 61.2% for surgery only (p ≤ 0.001). After multivariable adjustment, PORT improved OS (adjusted hazard ratio 0.79, 95% confidence interval 0.70–0.89). In subgroup analysis, PORT provided benefit for certain histologic subtypes and all other patient groups except those with T1 tumors and undifferentiated/anaplastic tumor grades. Our data suggests that PORT was associated with improved survival. Additionally, some subgroups may receive additional benefit and patients with small (T1), low-grade disease may be able to forgo PORT.

Adult head and neck (HN) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes. This study uses the National Cancer Database (NCDB) to investigate whether PORT improves overall survival (OS) in adult HN sarcomas with a positive margin and how utilization has changed.Patients (n = 1142) in the NCDB from 2004-2013 with adult HN sarcomas who underwent resection and had a positive margin.Factors significantly associated with increased utilization of PORT were: having insurance, salivary gland primary site, high-risk histology, poor differentiation, and a macroscopic positive margin. Treatment with PORT was associated with improved 5-year OS for all patients with a positive margin (57% vs 48%; P = .002), both microscopic (57% vs 49%; P = .010) and macroscopic (57% vs 41%; P = .036). Improved OS was significant after controlling for other known covariates on multivariate analysis (HR: 0.76; [0.64-0.90]; P = .002). Treatment at a community-based facility was an independent predictor for reduced OS (HR: 1.37; [1.15-1.64]; P .001). The percentage utilization (53%) of PORT for these patients did not change significantly over time.PORT provides a significant survival benefit for adult HN sarcoma patients with either a microscopic or macroscopic positive margin; however, PORT is underutilized. Treatment at academic/research cancer programs was associated with increased utilization of PORT and improved survival outcomes.

Background Primary prostate sarcomas (PPS) are rare. Outcomes for this cancer have not been well characterized. Materials and methods Subjects with a PPS diagnosed between 1973 and 2014 were identified in the SEER database. Subjects were stratified by disease stage and types of therapies received. Disease-specific survival (DSS) and Overall survival (OS) was estimated by Kaplan-Meier analysis and cohorts were compared with a univariate and multivariable Cox regression. Results The incidence of PPS among all prostate cancer diagnoses was 0.02%. Subjects younger than age 26 years at diagnosis represented 29% of cases, and 32% of primary prostate sarcomas were rhabdomyosarcoma histology. Rhabdomyosarcoma histologies The median age at diagnosis was 9 years. Between age 0-25 years rhabdomyosarcoma accounted for 96.4% of primary prostate sarcoma diagnoses, after age 25 rhabdomyosarcoma represented 15% of new diagnoses. The 10-year DSS and OS for rhabdomyosarcoma was 47% and 44%. Non-rhabdomyosarcoma histologies The median age at diagnosis was 71 years. The most common diagnoses were leiomyosarcoma (33%) and carcinosarcoma (28%). Localized, regional, or distant disease occurred in 40%, 34%, and 26% of cases. The 10-year DSS and OS were 26% and 14%. In locally advanced cases, RT added to surgery trended toward improved DSS (P = 0.10). Conclusions Disease-specific survival and OS for non-rhabdomyosarcoma histologies appear inferior to those of rhabdomyosarcoma. The addition of RT to surgical resection may improve DSS in locally advanced non-rhabdomyosarcoma. This is the largest report of the incidence, stage distribution, and survival for this extremely rare urologic malignancy providing valuable prognostic information.

Objectives To investigate clinicopathologic and treatment factors associated with survival in adult head and neck sarcomas in the National Cancer Database (NCDB). To analyze whether treatment settings and therapies received influence survival outcomes and to compare trends in utilization via an aggregated national data set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods The study comprised a total of 6944 adult patients treated for a head and neck sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary outcome. Results Increased age and tumor size, nodal involvement, and poorly differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma, malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and rhabdomyosarcoma histologic subtypes had significantly reduced OS, while liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001). Utilization of surgical therapy was associated with improved OS, while positive surgical margins were associated with treatment at a community-based cancer program and had reduced OS ( P < .001). On multivariate analysis, treatment with radiation and/or chemotherapy was not significantly associated with OS; however, primary treatment with definitive chemoradiotherapy had significantly reduced OS. Patients treated at academic/research cancer programs (n = 3874) had significantly improved 5- and 10-year OS (65% and 54%, respectively) when compared with patients treated at community-based cancer programs (n = 3027; 49% and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did not change over the study period. Conclusion For adult head and neck sarcomas, treatment at an academic/research cancer program was associated with improved survival; however, despite increasing medical specialization, the percentage utilization of these programs for this rare tumor remains constant.

Purpose Although several feasibility studies have demonstrated the safety of adjuvant concurrent chemoradiotherapy (CRT) for locally advanced or incompletely resected non–small-cell lung cancer (NSCLC), it remains uncertain whether this approach is superior to sequential chemotherapy followed by postoperative radiotherapy (C→PORT). We sought to determine the most effective treatment sequence. Patients and Methods Using the National Cancer Database, we selected two cohorts of patients with nonmetastatic NSCLC who had received at least a lobectomy followed by multiagent chemotherapy and radiotherapy; cohort one included patients with R0 resection and pN2 disease, whereas cohort two included patients with R1-2 resection regardless of nodal status. Overall survival (OS) was examined using a propensity score–matched analysis with a shared frailty Cox regression. Results A total of 747 patients in cohort one and 277 patients in cohort two were included, with a median follow-up of 32.8 and 27.9 months, respectively. The median OS was 58.8 months for patients who received C→PORT versus 40.4 months for patients who received CRT in cohort one (log-rank P < .001). For cohort two, the median OS was 42.6 months for patients who received C→PORT versus 38.5 months for patients who received CRT (log-rank P = .42). After propensity score matching, C→PORT remained associated with improved OS compared with CRT in cohort one (hazard ratio, 1.35; P = .019), and there was no statistical difference in OS between the sequencing groups for cohort two (hazard ratio, 1.35; P = .19). Conclusion Patients with NSCLC who undergo R0 resection and are found to have pN2 disease have improved outcomes when adjuvant chemotherapy is administered before, rather than concurrently with, radiotherapy. For patients with positive margins after surgery, there is not a clear association between treatment sequencing and survival.

Background To assess the effectiveness and outcomes of adjuvant radiotherapy regimens for nonmelanoma skin cancers (NMSC) of the head and neck, particularly for elderly patients. Methods A retrospective review of patients with head and neck NMSC was conducted. Radiotherapy dose per fraction regimens included ≤200, 240–250, 300–400, and 500–600 cGy. Demographics, tumor characteristics, local control (LC), regional control (RC), and survival outcomes were analyzed. Results Of the 90 patients with 140 disease sites, 76.6% were squamous cell carcinoma, 15.5% were basal cell carcinoma, and 7.7% were other histologies. The mean age at diagnosis was 72.1 years old. The most common location was preauricular (20.0%), followed by temple, scalp, cheek, and forehead. The overall LC and RC rates were 88.8% and 88.8%, respectively by patients, and 92.8% and 86.4%, respectively by treatment sites. Age, primary tumor location, T classification, N classification, overall stage, perineural invasion, comorbid disease, skull base invasion, and radiotherapy subgroup were significantly associated with disease-free and overall survival (P < 0.05). LC and RC were not significantly different among the radiotherapy dose subgroups. The mean survival was longer in patients treated with 240–250 cGy/fraction (50.3 months). There was no significant difference in radiotherapy toxicity between the subgroups. Conclusion Short-term radiotherapy regimens for patients with locally or regionally advanced head and neck NMSC appear feasible and effective, particularly in elderly patients or those that cannot tolerate the length of standard regimens.

PURPOSE/OBJECTIVE(S) Laryngeal preservation with definitive chemoradiation (CRT) in patients with advanced laryngeal cancer has been established through various prospective randomized trials. However, it is unclear what the optimal treatment approach for patients with T3N0M0 glottic cancer is and whether chemotherapy is needed in conjunction with radiation. We sought to evaluate survival differences in patients with T3N0M0 glottic cancer treated with radiation alone (RT) versus chemoradiation. MATERIALS/METHODS Patients with T3N0M0 glottic cancer diagnosed from 2004 through 2017 were identified from the National Cancer Database. Patients treated definitively with RT or CRT were selected. Patients receiving adjuvant RT or CRT were excluded. Baseline differences among treatment groups were identified. Overall survival was estimated with the Kaplan-Meier method and reported as median survival (MS). A multivariable cox proportional hazards model was constructed to identify variables associated with survival. RESULTS A total of 3785 patients were included in the cohort, with 942 (25%) patients who received RT alone and 2843 (75%) who received CRT. With a median follow up of 75.2 months, median survival was significantly longer in patients treated with CRT than in patients treated with RT alone (82 months [m], 95% CI 76-87m vs 29m, 95% CI 25-33m). On multivariable cox model, patient factors associated with decreased overall survival (OS) included omission of chemo (hazard ratio [HR] 1.69, 95% CI 1.52-1.87), age > 70 (HR 1.66, 95% CI 1.15-2.42), comorbidities (HR 1.66, 95% CI 1.15-2.42, and treatment at non-tertiary academic cancer centers (HR 1.24, 95% CI 1.04-1.48). Patients age > 70 and those with multiple comorbidities were significantly less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI 0.25-0.37 and OR 0.48 95% CI 0.31-0.76, respectively). When limiting analysis to patients under 70 with no comorbidities, the survival benefit persisted in favor of CRT (MS 113m, 95% CI 102-124m vs. MS 65, 95% CI 47-85m). CONCLUSION Optimal treatment for T3N0M0 glottic cancer has not fully been established in prospective clinical trials. This is the first study to evaluate survival outcomes in this group of patients comparing RT to CRT. Median survival appears to be significantly increased with the use of CRT, and this benefit persists when controlling for age and performance status. This study supports the use of definitive CRT for appropriately selected patients with T3N0M0 glottic cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Facial nerve (FN) palsy and perineural invasion (PNI) are adverse features in carcinomas of the parotid gland. FN sacrifice at the time of surgery is associated with significant morbidity. The role of adjuvant radiotherapy in patients with high-risk features, including FN involvement, remains unclear. Analyze the disease-free survival (DFS) and overall survival (OS) and the impact of tumor characteristics, including FN involvement, for patients treated with surgical resection for carcinoma of the parotid gland. This is a retrospective chart review. University of Utah and Intermountain Healthcare, Utah. A total of 129 patients who were treated with primary surgery for nonmetastatic primary malignancies of the parotid gland from 1988 to 2006. Parotidectomy with or without adjuvant therapy. Kaplan-Meier analysis was used to obtain 5-year estimates of DFS and OS. Recurrence risk factors, particularly the impact of FN involvement, were analyzed. Five-year DFS and OS rates were 79% and 78%, respectively. Thirty-two (28%) patients developed recurrent disease. Disease recurrence occurred in 64% of patients with both FN palsy and PNI, in 43% with FN palsy without PNI, in 27% with only PNI, and in 16% without either feature. FN involvement, particularly FN palsy, is a predictor of increased risk of recurrence and death. Radiotherapy cannot substitute for FN sacrifice in high-risk patients.

We appreciate the comments from Zhao and Ng (1) regarding our recent National Cancer Database (NCDB) study comparing survival outcomes after postoperative adjuvant concurrent chemoradiotherapy (CRT) versus sequential chemotherapy followed by postoperative radiotherapy (C→PORT) for locally advanced or incompletely resected non-small cell lung cancer (NSCLC).

Purpose To present our preliminary experience with the recently released Calypso lung beacons to track lung tumor location during stereotactic body radiation therapy (SBRT). Materials/methods Five recent lung SBRT patients had Calypso lung beacons implanted for tumor tracking during treatment. Beacons were placed by a pulmonologist using fluoroscopic navigation within 1 week prior to planning four-dimensional computed tomography (4DCT) acquisition. Patients were immobilized in a full-body double-vacuum bag. For the first three patients, a verification 4DCT was obtained prior to the first fraction with the patient in the treatment position to assess both beacon migration and motion of tumor and beacons relative to planning day. For each treatment fraction, Calypso was used to position the patient. A verification cone-beam CT (CBCT) confirmed the Calypso-defined target position was appropriate. Real-time Calypso tracking information was also acquired and compared to an action level that was used to determine if the tumor migrated outside of the planning target volume. Results For four patients, the implant procedure was well tolerated, with average CBCT-based shifts being within 0.2 mm of the shifts reported by Calypso at the time of imaging. The other patient had a small pneumothorax due to very peripheral tumor location and experienced beacon migration. However, the patient quickly recovered from the pneumothorax, and after deactivating that beacon, motion tracking was possible throughout his treatment. Conclusions All patients were successfully treated with SBRT using the newly released Calypso lung beacons, with initial positioning confirmed by this clinic's current clinical standard of CBCT. The system allowed us to validate, with real-time confirmation, that the planned internal target volumes were appropriate to each day's extent of actual tumor motion. An efficient and effective workflow for utilizing the new lung beacons for SBRT treatments was developed.

Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluated for recurrence risk. One hundred and fifty-six patients total had an average follow-up of 5.6 years. Twenty-nine (18.6%) patients underwent cartilage-sparing surgery and 99 (63.5%) patients underwent SLNB, 14.1% of whom had micrometastatic disease. Ten (6.4%) patients recurred loco-regionally. Recurrence was associated with Breslow depth, initial stage at diagnosis, and SLNB status. Cartilage-sparing surgery was not associated with increased recurrence. Sentinel lymph node identification rate was 100% based on clinical detection with use of lymphoscintigraphy. In addition to confirming established risk factors for melanoma recurrence, we confirm the feasibility of SLNB in stratifying recurrence risk. Although we did not see an increased recurrence risk with surgical technique and cartilage-sparing approaches, these findings are limited by small sample size.

Toxic leadership is associated with a number of negative consequences to the long-term health and welfare of people in organizations. Destructive leader styles redirect employee efforts from mission accomplishment to self-protection and survival behaviors, undermining the organization. Increased demand and decreased funding are characteristic of the nonprofit sector. Therefore, successful nonprofit organizations tend to rely on creativity and irrnovation to ensure their communities are appropriately and sufficiently sustained. Supportive, not toxic, leadership helps foster organizational environments that encourage prudent risk-taking and innovation. This concurrent mixed methods study explored the relationship between toxic leadership and organizational citizenship and turnover behaviors among 471 survey respondents from a sample of San Diego nonprofit paid staff, and considered the influence commitment has on those relationships. An open ended question for those who reported experiencing toxic leadership provided additional context and depth as to why employees stayed in an organization in spite of abusive supervision. The findings of the study are of interest to leaders and managers of nonprofit organizations to develop policies and training processes as they strive to recruit, retain and develop talented employees. Toxic supervision was found to exist in San Diego nonprofit organizations. However, its effect on organizational citizenship (OCB) and turnover behaviors was inconclusive, as was the influencing effect of commitment, in this study. However, both commitment and OCB-like ideas emerged as stated reasons that participants did not leave the organization, as did career, resilience and opportunity concepts. These identified variables suggest complex relationships that act in concert to influence staff retention indicating possible important opportunities for future research. ACKNOWLEDGEMENTS As noted by my USD colleague, COL James Dobbs, the process of completing this course of study is not possible without help, support and guidance from many. To all of you who have done so for me over the last many years, thank you all. Particularly, I must thank my Chair, Dr. George Reed for his enthusiasm and balanced approach to the myriad aspects ofleadership, Dr. Fred Galloway, a truly supportive and encouraging educator, who inspires all of us, his students, to think and consider rather than react and repeat, Dr. Zachary Green who engages my unfocussed excitement about leadership, its connections and applications, elevates my thinking and challenges me to bring forward my underlying reasoning a skill not easily taught (or learned) and always superbly offered, and Dr. Linnea Axman a good friend whose gentle guidance helped me understand this work at a much deeper level. Thank you all for your steadfast support. I owe a special debt of gratitude to my advisor, Dr. Robert Donmoyer, who brought me into research in the nonprofit sector and opened up a new path for me. Mostly, though, he reminded me what I could and should bring to the table. For that, I will always be grateful. A special thank you to Lenore Lowe and Stephanie McCullers, this study could not have happened without them, and for recognizing good leadership is important to the sector. This process can have many barriers to progress. No one helped me break them down as well as Dr. Mary McDonald a gifted and gentle teacher There are many friends and colleagues at USD who have supported, helped and inspired me through a very long journey, especially, Dr. Owen Smith who made me think harder and everything more fun, Dr. Nathaniel Dunigan, a stalwart friend and supporter, Dr. Lyn Taylor Peyton Roberts who makes "the data" an exciting dive every time, Elaine Lewis, a good friend, who gives me my own advice when I need it better than I do, Elizabeth Castillo who has an inspiring message and started me in my new career thank you, Alma Ortega whose unique approach to the subject helps me stretch my understanding, and, Heather Gibb, who has endless patience and such good humor. I want to thank those from the The Caster Family Center for Nonprofit and Philanthropic Research where my many passionate colleagues led me to the third sector, particularly Dr. Laura Deitrich, Dr. Heather Carpenter, Dr. Audrey Barrett, Dr. Jennifer Jones, Dr. Lindsey McDougle, Bethan Theunissen, Jennifer Y ebba and Pat Libby. I also greatly appreciate my many United Way colleagues and friends who have had such great confidence in me, especially my boss, Ryan Morris, who with such good grace gave me time to finish this, talk about it and supported me throughout. I also

OBJECTIVES Positive margins can increase the risk of local recurrence of soft tissue sarcomas (STS). Utilizing a national registry, we investigated patterns of care and overall survival (OS) of patients with margin-positive non-retroperitoneal STS who received preoperative radiation therapy, adjuvant radiation therapy, or both. METHODS Adult patients with non-retroperitoneal STS who underwent resection and RT from 2004 to 2015 were included. Kaplan-Meier, log-rank analysis, and Cox regression analysis were performed. RESULTS We identified 5726 patients. Most had a tumor size >5 cm (60%), grade 3 disease (67%), and microscopically positive margins (57%). Compared to ≤50.4 Gy, a dose of 66 to 69.99 Gy was associated with decreased risk of death on multivariate analysis (HR 0.69, 95%; CI, 0.50-0.94). Receipt of a boost was associated with decreased risk of death on univariate analysis (HR 0.54, 95%; CI, 0.29-0.99). In patients with grade 2 to 3 tumors without the gross disease, there was an OS benefit associated with a boost on multivariate analysis (HR 0.39, 95%; CI, 0.16-0.97). CONCLUSION This analysis appears to show an OS benefit of dose escalation to 66 to 69 Gy for margin-positive non-retroperitoneal STS. A Postoperative boost is associated with higher OS in grade 2 to 3 STS without the gross disease.

Background National guidelines support both surgical and radiotherapy (RT) as initial treatment options for early-stage oral cavity squamous cell carcinoma (SCC). There remains limited data evaluating the survival outcomes of RT and the current practice patterns for these lesions. Methods We conducted a retrospective review of 8274 patients in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2008 with T1 to T2N0M0 oral cavity SCC. Primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Results Surgical therapy had significantly improved OS (140 months; p < .001) and DSS (217 months; p < .001) compared to surgery with adjuvant RT (104 and 163 months, respectively) and definitive RT (68 and 136 months, respectively). The use of radiation alone was associated with an increased T classification, hard palate, retromolar trigone primary site lesions, and advanced patient age. Conclusion Primary radiation without surgery continues to be used in a subset of early-stage oral cavity SCCs, in which it is associated with decreased OS and DSS. © 2017 Wiley Periodicals, Inc. Head Neck 39: 876–880, 2017

Importance The benefit of adjuvant radiation in surgically treated T1-2N1 oropharyngeal cancer without adverse pathologic features remains unclear Objectives To compare population-level survival outcomes in surgically-treated T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC) with and without the use of adjuvant radiation. Study Design Retrospective population-based study using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1998–2011. Setting Population-level study. Participants Patients with T1-2N1 OPSCC treated with surgical resection and neck dissection with or without adjuvant radiation. Intervention(s) for Clinical Trials or Exposure(s) for observational studies The use of postoperative adjuvant radiation. Main Outcome(s) and Measures Overall and disease-specific survival. Results Radiation was utilized in 74% of patients and was positively associated with extracapsular extension and well-differentiated histology. The use of radiation was associated with improved mean overall survival (124 v. 108 months, p=0.023) and a non-significant increase in mean disease-specific survival (138 v. 131 months, p=0.053). Conclusions and Relevance The use of adjuvant radiation is associated with improved survival in surgically-treated T1-2N1 squamous cell carcinoma of the oropharynx with unknown HPV status. Level of Evidence IV

We aimed to evaluate if use of brachytherapy (BT) is associated with improved survival in patients with oral cavity cancer who do not receive surgery and to analyze patterns of care.We queried the Surveillance, Epidemiology, and End Results database for patients who received radiation therapy for squamous cell carcinoma of the oral cavity between 1973 and 2012. Patients were grouped by treatment modality: external beam radiotherapy alone vs. external beam radiotherapy + BT. Surgical patients were excluded. Trends in BT utilization over the study period and patterns of care were analyzed. Propensity scores were generated, and a nearest-neighbor matching algorithm was used to balance the 2 groups. Cox regression modeling was used to estimate the effect of BT on overall survival. Sensitivity analysis was conducted to estimate the effect of unmeasured confounders on the analysis.Of 5,161 patients with squamous cell carcinoma of the oral cavity who received radiotherapy, 12% of patients received BT. The rate of BT use has decreased by 0.58% per year (p 0.001). Factors that predicted for omission of radiation therapy included age ≥ 65 years (adjusted odds ratio [aOR], 0.56; p0.001), regional nodal disease (aOR, 0.57; p0.001), and black race (aOR, 0.45; p0.001). Use of BT was associated with a decreased risk of death (hazard ratio, 0.75; p0.001).The use of BT is associated with improved survival in oral cavity tumors treated with definitive radiotherapy. Rates of BT utilization have declined by 0.58% per year and are currently very low.

Opsoclonus is a pathological eye movement phenomenon in hich the eyes experience involuntary, arrhythmic, rapid, multidiectional, conjugate movements. It occurs in all eye positions and uring smooth pursuit, and can also persist during sleep. It is diferentiated from nystagmus in that there is no slow eye movement hase, and it differs from ocular flutter because the eye movement s multidirectional and not confined to the horizontal. Opsoclonus an be accompanied by tremors, cerebellar ataxia, myoclonic jerks, r encephalopathy. In addition to paraneoplastic etiologies, it is ometimes autoimmune, but frequently without an identifiable ntibody [1].

Background National guidelines support surgical-based treatment and offer nonsurgical therapy as an alternative for advanced-stage oral cavity squamous cell carcinoma (SCC). There are limited data evaluating current utilization of these therapies and their survival outcomes. Methods A total of 5856 patients were found in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2008 with resectable advanced-stage oral cavity SCC tumors. Outcomes were disease-specific survival (DSS) and overall survival (OS). Results Surgical therapy had significantly improved mean DSS and OS (115 and 71 months, respectively) compared to nonsurgical therapy (63 and 35 months, respectively; p < .001). The use of nonsurgical therapy was significantly associated with the hard palate, and patients who were single, divorced, and black, with T3, T4, and N3 tumors, and the percent utilization has significantly increased from 12% to 20% (p < .05). Conclusion Utilization of nonsurgical therapy for advanced-stage oral cavity SCC is increasing and is independently associated with a reduction in survival, as well as patient factors traditionally associated with reduced access to medical care and advanced T and N classifications. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Purpose Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume–to–planning target volume (CTV-to-PTV) margin. Methods and materials Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. Results The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations ( P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction ( P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. Conclusions The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

Objectives: Parathyroid carcinoma is rare and treatment for these cancers varies between institutions. The primary purposes of this study were to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate current practice patterns in the use of adjuvant radiation for parathyroid cancers and to investigate the efficacy in a population-based setting. Methods: There were 508 patients treated surgically for parathyroid cancer from 1973 to 2013 identified in the SEER database. Patients with metastatic disease and other prior malignancies were excluded. Three hundred and twenty-one patients (63%) had local disease, while 187 had regional lymph node involvement (37%). Of these patients, 78 (15%) were treated with adjuvant radiation. 5-year disease-specific survival (DSS) and overall survival (OS) were the primary outcomes. Results: Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (94% versus 89%; p=0.045) and OS (81% versus 74%; p=0.036). Improved DSS and OS were significant after controlling for other known covariates on multivariate analysis (HR 0.59, 95% CI 0.44-0.87, p Conclusion: Adjuvant radiation appears to provide a survival benefit for patients with parathyroid carcinoma. Utilization of adjuvant radiation is increasing over time for these patients. Citation Format: Richard B. Cannon, Patrick S. Carpenter, Luke O. Buchmann, Jason P. Hunt, Shane Lloyd, Ying Hitchcock, Marcus M. Monroe. Increasing use of adjuvant radiation for parathyroid carcinoma is associated with improved survival outcomes: A population-based study [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A21.

Evaluate current practice patterns in the use of adjuvant radiation for T1-2N1 OCSCC patients and investigate its efficacy in the population-based setting.This study extracted patients who were treated surgically for T1N1 and T2N1 OCSCC without adverse nodal features from the SEER database from 2004 to 2013. Patients with distant metastatic disease, unknown surgery or radiation status, or prior malignancies were excluded. Patients were divided into those who underwent surgical resection with and without adjuvant radiation. Disease-specific survival (DSS) and overall survival (OS) were the primary outcomes measured.746 patients met inclusion criteria and 70% received adjuvant radiation therapy. Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (65% versus 51%; p 0.001) and OS (54% versus 44%; p = 0.007) for T1N1 tumors. Likewise, improved 5-year DSS (58% versus 38%; p = 0.009) and OS (48% versus 28%; p = 0.004) was shown in T2N1 tumors. Patients with T2N1 tumors wer significantly more likely to receive adjuvant radiation (75% versus 63%; p 0.001). Those with insurance and high risk primary subsites: buccal, retromolar trigone, and hard palate were more likely to receive adjuvant radiation. The percent utilization of adjuvant radiation remained constant through the study period for T2N1 tumors (72-74%) but significantly decreased for T1N1 (71-55%) (p = 0.047).Adjuvant radiation therapy is independently associated with a significant survival benefit for patients with both T1N1 and T2N1 OCSCC. However, this study demonstrates that patients with T1N1 cancer are less likely to receive adjuvant radiation and utilization is decreasing.

Summary Background A thorough understanding of the local sources, risks, and antibiotic resistance for Escherichia coli bloodstream infection (BSI) is required to focus prevention initiatives and therapy. Aim To review the sources and antibiotic resistance of healthcare-associated E. coli BSI. Methods Sources and antibiotic resistance profiles of all 250 healthcare-associated (post 48 h) E. coli BSIs that occurred within our secondary and tertiary care hospital group from April 2014 to March 2017 were reviewed. Epidemiological associations with urinary source, gastrointestinal source, and febrile neutropenia-related BSIs were analysed using univariable and multivariable binary logistic regression models. Findings E. coli BSIs increased 9% from 4.0 to 4.4 per 10,000 admissions comparing the 2014/15 and 2016/17 financial years. Eighty-nine cases (36%) had a urinary source; 30 (34%) of these were classified as urinary catheter-associated urinary tract infections (UTIs). Forty-five (18%) were related to febrile neutropenia, and 38 (15%) had a gastrointestinal source. Cases were rarely associated with surgical procedures (11, 4%) or indwelling vascular devices (seven, 3%). Female gender (odds ratio: 2.3; 95% confidence interval: 1.2–4.6) and older age (1.02; 1.00–1.05) were significantly associated with a urinary source. No significant associations were identified for gastrointestinal source or febrile neutropenia-related BSIs. Forty-seven percent of the isolates were resistant to ciprofloxacin, 37% to third-generation cephalosporins, and 22% to gentamicin. Conclusion The gastrointestinal tract and febrile neutropenia together accounted for one-third of E. coli BSI locally but were rare associations nationally. These sources need to be targeted locally to reduce an increasing trend of E. coli BSIs.

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (HN the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Curative treatment for base-of-tongue squamous cell carcinoma (BOT SCC) has evolved over time; however, comparative outcomes analysis for various treatment strategies is lacking. The authors reviewed the evolution of treatment modality and radiotherapy (RT) technique for 231 consecutive BOT SCC patients at our institution between 1981 and 2011. Treatment modalities included definitive chemoradiotherapy (chemoRT) (42%), definitive RT (33%), surgery followed by RT (20%), and surgery alone (5%). RT techniques included external beam plus interstitial brachytherapy (EBRT + IB) (37%), conventional EBRT (29%), intensity-modulated radiation therapy ± simultaneous integrated boost (IMRT ± SIB) (34%). Clinical characteristics and outcomes were stratified by modality or RT technique. Treatment modality evolved from definitive RT (1980s–1990s) to definitive chemoRT (1990s–2000s). RT technique evolved from EBRT + IB (1980s–1990s) to conventional EBRT (1990s–2000s) to IMRT + SIB (2000s). With median alive follow-up of 6 years (0.3–28 years), the 5-year LC, LRC, and OS rates were 80%, 73%, and 51%. There was no difference in distribution of gender, age, stage among treatment modalities. Definitive chemoRT had improved LRC (HR 1.6) and OS (HR 1.7) compared to definitive RT. IMRT + SIB had improved LRC (HR 3.2), DFS (HR 3.4), and OS (HR 3.0) compared to conventional EBRT. Over the past 30 years, BOT SCC treatment has undergone major paradigm shifts that incorporate nonsurgical functional preservation, concurrent chemotherapy, and advanced RT techniques. Excellent locoregional control and survival outcomes are associated with accelerated IMRT with chemotherapy.

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group. Patient demographics, primary tumor characteristics, and clinical outcomes were analyzed. A total of 123 patients with BM were matched by initial presenting stage to 237 patients without BM. The characteristics of the primary melanoma tumor associated with BM development included location on the scalp (P=0.030), nodular histologic type (P=0.020), and Breslow depth more than 4 mm (P=0.048), whereas location on the leg was associated with decreased BM risk (P=0.006). In patients with BM, time to first recurrence for melanomas of the scalp was significantly shorter (10.8 vs. 24.8 months, P=0.007) than nonscalp head and neck tumors. Patient stage, tumor depth, nodular type, and ulceration were also associated with worse clinical outcomes. There were no differences in the clinical outcomes between patients whose BM were detected upon routine screening versus those detected upon symptomatic presentation. In summary, factors predictive of development of BM included primary scalp location, nodular type, and depth. In BM patients, scalp location, stage, tumor depth, nodular type, and ulceration, but not detection setting, were associated with worse clinical outcomes.

BACKGROUND The available literature to guide treatment decision making in esthesioneuroblastoma (ENB) is limited. OBJECTIVE To define treatment patterns and outcomes in ENB according to treatment modality using a large national cancer registry. METHODS This study is a retrospective cohort analysis of 931 patients with a diagnosis of ENB who were treated with surgery, radiation therapy, and/or chemotherapy in the United States between the years of 2004 and 2012. Log-rank statistics were used to compare overall survival by primary treatment modality. Logistic regression modeling was used to identify predictors of receipt of postoperative radiotherapy (PORT). Cox proportional hazards modeling was used to determine the survival benefit of PORT. Subgroup analyses identified subgroups that derived the greatest benefit of PORT. RESULTS Primary surgery was the most common treatment modality (90%) and resulted in superior survival compared to radiation (P < .01) or chemotherapy (P < .01). On multivariate analysis, PORT was associated with decreased risk of death (hazard ratio [HR] 0.53, P < .01). PORT showed a survival benefit in Kadish stage C (HR 0.42, P < .01) and D (HR 0.09, P = .01), but not Kadish A (HR 1.17, P = .74) and B (HR 1.37, P = .80). Patients who received chemotherapy derived greater benefit from PORT (HR 0.22, P < .01) compared with those who did not (HR 0.68, P = .13). Predictors of PORT included stage, grade, extent of resection, and chemotherapy use. CONCLUSION Best outcomes were obtained in patients undergoing primary surgery. The benefit of PORT was driven by patients with stages C and D disease, and by those also receiving chemotherapy.

Copyright © 2014 by the National Comprehensive Cancer Network. All rights reserved. This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Background Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. Objective We sought to characterize survival and patterns of failure for patients with scalp melanoma. Methods Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases–free survival, and disease-free survival. Results Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases–free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. Limitations This is a retrospective review. Conclusion Distant metastases–free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods.

Purpose The phase 2 component of Radiation Therapy Oncology Group (RTOG) 0631 assessed the feasibility and safety of spine radiosurgery (SRS) for localized spine metastases in a cooperative group setting. Methods and Materials Patients with 1-3 spine metastasis with a Numerical Rating Pain Scale (NRPS) score ≥5 received 16 Gy single fraction SRS. The primary endpoint was SRS feasibility: image guidance radiation therapy (IGRT) targeting accuracy ≤2 mm, target volume coverage >90% of prescription dose, maintaining spinal cord dose constraints (10 Gy to ≤10% of the cord volume from 5-6 mm above to 5-6 mm below the target or absolute spinal cord volume Results Sixty-five institutions were credentialed with spine phantom dosimetry and IGRT compliance. Forty-six patients were accrued, and 44 were eligible. There were 4 cervical, 21 thoracic, and 19 lumbar sites. Median NRPS was 7 at presentation. Final pretreatment rapid review was approved in 100%. Accuracy of image guided SRS targeting was in compliance with the protocol in 95%. The target coverage and spinal cord dose constraint were in accordance with the protocol requirements in 100% and 97%. Overall compliance for other normal tissue constraints was per protocol in 74%. There were no cases of grade 4-5 acute treatment-related toxicity. Conclusions The phase 2 results demonstrate the feasibility and accurate use of SRS to treat spinal metastases, with rigorous quality control, in a cooperative group setting. The planned RTOG 0631 phase 3 component will proceed to compare pain relief and quality of life between SRS and external beam radiation therapy.

Background: “Abscopal response” refers to the spontaneous involution of untreated metastatic disease following local primary tumor-directed therapy. We report a case of an abscopal response of untreated lung metastasis in a man with pleomorphic sarcoma of the head and neck treated with hypofractionated radiotherapy. Methods: An inoperable pleomorphic sarcoma of the postauricular soft tissue was treated with 40 Gy of radiation in eight fractions. Untreated disease in the lungs was followed with CT scans. Results: At the two-month post-treatment follow-up, clinical exam and restaging CT demonstrated complete primary tumor involution. Additionally, CT chest images showed a dramatic disease response in the untreated pulmonary disease, which progressed to complete and persistent clinical response at one-year post-treatment follow-up. Conclusions: We report the first described case of a complete abscopal resolution of untreated lung metastases in a patient with a primary pleomorphic sarcoma of the head and neck treated with hypofractionated radiotherapy.

To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists.Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure.For the GTV, the minimum, maximum, mean (SD) volumes (mL) were 674, 798, 752±35 for the lower extremity case and 383, 543, 447±46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa=0.9 [p0.0001] and kappa=0.86 [p0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605±211 for the lower extremity case and 637, 1246, 1006±180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa=0.85 [p0.0001]) but only substantial in the upper extremity case (kappa=0.77 [p0.0001]).Almost perfect agreement existed in the GTV of these two representative cases. There was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.

To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS).A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included. Patients were also required to have known stage and grade. Prognostic factors for survival were identified using multivariate techniques. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p0.05) using the log-rank test.A total of 821 patients met inclusion criteria. The median follow-up time was 63 months. Age, stage, histology, gender, tumor size, and RT sequence were independent predictors for OS (p0.05). Preop RT was associated with significantly improved OS and CSS compared with postop RT (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.56-0.91, p0.01, and HR = 0.64, 95% CI 0.46-0.88, p0.01, respectively). The 5-year CSS was 79% and 74%, in favor of preop RT (log-rank, p0.05). Preop RT was also significantly associated with a reduced risk for local and distant relapse compared with postop RT.Preoperative RT is associated with a reduced cancer-specific mortality compared with postoperative RT in STS. The results of this study may serve as motivation to conduct future prospective studies with larger patient numbers.