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Radiation is a commonly used treatment modality for head and neck as well as CNS tumours, both benign and malignant. As newer oncology treatments such as immunotherapies allow for longer survival, complications from radiation therapy are becoming more common. Radiation-induced optic neuropathy is a feared complication due to rapid onset and potential for severe and bilateral vision loss. Careful monitoring of high-risk patients and early recognition are crucial for initiating treatment to prevent severe vision loss due to a narrow therapeutic window. This review discusses presentation, aetiology, recent advances in diagnosis using innovative MRI techniques and best practice treatment options based on the most recent evidence-based medicine.

Improving diversity in residency programs has been increasingly emphasized as a means to address gender, racial, and ethnic disparities in medicine. However, limited attention has been given to the potential benefits of training physicians with differences other than gender or race and ethnicity. Americans with a disability represent about 27% of the U.S. population, whereas 1-3% of physician trainees report having a disability. In 2013, a national survey identified only 86 physicians or trainees reporting deafness or hearing loss as a disability. To date, there are no published strategies on how to create an inclusive program for Deaf trainees. Herein, the authors report on the development of a Deaf and American Sign Language (ASL) inclusive residency training program that can serve as an academic model for other programs, in any medical specialty, seeking to create an accessible training program for Deaf physicians and that can be adapted for trainees with other disabilities. In March 2017, the radiation oncology residency program at Johns Hopkins University matched an ASL-signing Deaf resident who would begin the program in July 2018. In preparation, department leadership engaged key stakeholders and leaders within the university's health system and among the department faculty, residents, and staff as well as the incoming resident to create an ASL inclusive program. A 5-step transition process for the training program was ultimately developed and implemented. The authors focused on engaging the Deaf trainee and interpreters, engaging health system and departmental leadership, contracting a training consultant and developing oral and written training materials for faculty and staff, and optimizing the workspace via accommodations. Through collaborative preparation, a Deaf and ASL-signing resident was successfully integrated into the residency program. The proposed 5-step transition process provides an effective, engaging model to encourage other institutions that are seeking to employ similar inclusivity initiatives.

Purpose The purpose of this study is to assess the current status of gender disparities in academic radiation oncology departments in the United States and the associated factors. Methods and Materials The data were collected from publicly available resources, including websites of individual radiation oncology programs, the Fellowship and Residency Electronic Interactive Database, the Accreditation Council for Graduate Medical Education, and the Association of American Medical Colleges. We collected data on the gender information of residents in each year (postgraduate years 2-5) and of the faculty (attendings, program director, and chair) during the academic year 2018 to 2019. Spearman’s rho test, Pearson’s chi-squared test, and Fisher exact tests were used for evaluating the correlation among variables using SPSS version 24. Results Women constituted 30.8% of radiation oncology residents in the United States in 2019. Eight programs (12.5%) did not have any female residents in their programs, whereas 6 programs (9%) had women constituting more than half of their resident class. The fraction of female medical students applying to radiation oncology over the last 7 years varied between 27% and 33%. Female attending physicians accounted for 30.5% of all the attending physicians in the academic programs. In the leadership positions of the department, the gender gap was wider where only 19 (20%) and 11 (12%) of programs had female program director or chair, respectively. There was a positive correlation between the number of attending physicians and the number of female residents in programs (P = .01). Conclusions A significant gender disparity continues to exist among the residents and physicians in the academic radiation oncology departments in the US. This disparity is pronounced in the leadership positions. The results of this study could be used as a benchmark to evaluate the progress that has been made by the efforts to improve gender disparities in radiation oncology.

Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (4 BMV), intermediate (4-13 BMV), and high-risk groups (13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS.Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV 4, BMV 4-13, and BMV 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p 0.0001) remained predictive of BMV (adjusted RThis multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.

PURPOSE Radiotherapy (RT) treatment at public hospitals in Nigeria is often interrupted by prolonged periods of machine breakdown because of insufficient funds for maintenance and repair. These delays have prompted the uptake of public-private partnerships (PPPs) to acquire and maintain RT equipment. This study aimed to understand Nigeria's current RT capacity and the impact of PPPs on RT availability and cost. METHODS Eleven radiation oncologists, each representing one of the 11 RT centers in Nigeria (eight public and three private), were invited to complete a survey on the type, status, acquisition, and maintenance plan of existing RT equipment, cost incurred by patients for external-beam radiation (EBRT) and brachytherapy treatment, and number of patients treated per year on each machine. Type and status of equipment at nonresponding facilities were obtained through literature review and confirmed with the facility. RESULTS A total of eight (81%) respondents completed the survey, all representing public centers, three of which reported PPP use. They reported 11 megavoltage units in total (seven linear accelerators [LINACs] and four Cobalt-60s) and 10 brachytherapy afterloaders. Of those, 57% (4/7) of the LINACs, 100% (4/4) of the Cobalt-60s, and 63% (7/11) of the afterloaders were in clinical use. All commissioned equipment supported by PPPs (three LINACs and one afterloader) were in operation. The public EBRT equipment were nonfunctional 35% of the year (resulting in 60% fewer patients treated per year). The PPP EBRT and afterloaders did not experience any periods of breakdown, but PPP costs were 338% higher than public equipment. CONCLUSION This study characterizes the use of PPP as a more reliable method of RT delivery in Nigeria, albeit at higher costs.

Several studies evaluating stereotactic radiosurgery (SRS) for patients with4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM.A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling.In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P .01).Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy.

Modern medicine, including the care of the cancer patient, has significantly advanced, with the evidence-based medicine paradigm serving to guide clinical care decisions. Yet we now also recognize the tremendous heterogeneity not only of disease states but of the patient and his or her environment as it influences treatment outcomes and toxicities. These reasons and many others have led to a reevaluation of the generalizability of randomized trials and growing interest in accounting for this heterogeneity under the rubric of precision medicine as it relates to personalizing clinical care predictions, decisions, and therapy for the disease state. For the cancer patient treated with radiation therapy, characterizing the spatial treatment heterogeneity has been a fundamental tenet of routine clinical care facilitated by established database and imaging platforms. Leveraging these platforms to further characterize and collate all clinically relevant sources of heterogeneity that affect the longitudinal health outcomes of the irradiated cancer patient provides an opportunity to generate a critical informatics infrastructure on which precision radiation therapy may be realized. In doing so, data science-driven insight discoveries, personalized clinical decisions, and the potential to accelerate translational efforts may be realized ideally within a network of institutions with locally developed yet coordinated informatics infrastructures. The path toward realizing these goals has many needs and challenges, which we summarize, with many still to be realized and understood. Early efforts by our group have identified the feasibility of this approach using routine clinical data sets and offer promise that this transformation can be successfully realized in radiation oncology.

Purpose: Pleomorphic adenoma is a benign salivary tumor that may recur multifocally. In case series, the benefit of radiation therapy (RT) for recurrent pleomorphic adenoma remains unclear. We hypothesized that the combination of surgery and adjuvant RT reduces risk of subsequent recurrence compared with surgery alone for recurrent pleomorphic adenoma. Methods and Materials: Patients who received diagnoses of recurrent pleomorphic adenoma between 1980 and 2016 were identified using an institutional pathology database. Medical records were retrospectively reviewed to determine clinical, operative, pathologic, and imaging characteristics. Kaplan-Meier methods were used to estimate local control after surgery, stratified by completeness of resection and receipt of adjuvant RT. The association of variables with risk of subsequent local recurrence was analyzed using Cox proportional hazards model, and variance estimates were calculated to account for multiple recurrences in the same patient. Toxicities were prospectively recorded in a departmental database. Results: A total of 49 patients presented with at least 1 recurrence, of which 28 were managed with surgery alone, and 21 were treated with surgery and RT. The median follow-up time after the initial recurrence was 48 months (range, 6-531 months). There were 35 subsequent recurrences; 34 after surgery alone and only 1 after surgery with RT. On multivariate analysis, adjuvant RT was associated with decreased risk of recurrence (hazard ratio, 0.09; 95% confidence interval, 0.02-0.41, P = .002), whereas increasing number of prior recurrences was associated with increased risk (hazard ratio, 1.23; 95% confidence interval, 1.13-1.35, P < .001). Common toxicities of RT included dermatitis, xerostomia, and mucositis. Conclusions: For patients with recurrent pleomorphic adenoma, the addition of adjuvant RT after surgery is associated with a significant decrease in risk of subsequent tumor recurrence.

oronavirus (COVID-19) has caused marked impact on graduate medical education for all medical specialties. Radiation Oncology and the American Board of Radiology have also had to rapidly adapt to converting education and examinations to virtual platforms. We describe our small pilot experience in transitioning our in-person mock oral examinations to a virtual platform. Survey-based assessment revealed excellent feedback regarding ease of use and educational usefulness. Our mock oral examinations pilot experience adds to evidence that virtual mock oral examinations are an important considerationfor Radiation Oncology education and a feasible alternative to an in-person oral examination.

BACKGROUND: Cisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss. METHODS: We examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Among patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P < 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01). An adjusted odds ratio (OR) analysis indicated that an atorvastatin user is 53% less likely to acquire a cisplatin-induced hearing loss than a nonstatin user (OR = 0.47; 95% CI, 0.30–0.78). Three-year survival rates were not different between atorvastatin users and nonstatin users (P > 0.05). CONCLUSIONS: Our data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and neck cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03225157. FUNDING: Funding was provided by the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders (1 ZIA DC000079, ZIA DC000090).

Objective: To discuss some of the challenges that can arise in the treatment of patients with oropharyngeal carcinoma and scleroderma, by presenting an illustrative case. Methods: We report a case of a patient with scleroderma who was treated with surgery, radiation and systemic therapy for oropharyngeal squamous cell carcinoma. We also review the literature on treatment of head and neck squamous cell carcinoma (HNSCC) in scleroderma patients. Results: The patient tolerated treatment well, with a typical degree of toxicity and no evidence of recurrence at 3.5 years following adjuvant therapy. Conclusion: Patients with oropharyngeal cancer and scleroderma should be evaluated on a case-by-case basis in conjunction with a rheumatologist to determine the ideal treatment plan. Patients with limited or well-controlled scleroderma may tolerate treatment better than expected based on historical reports in the literature. Keywords: Scleroderma, Connective tissue disorder, Squamous cell carcinoma, Autoimmune, Transoral robotic surgery

The Functional Assessment of Cancer Therapy (FACT) instrument is comprised of a group of related and overlapping quality of life (QoL) questionnaires including a core general form, head and neck cancer (HNC)-specific items, and an expert-selected index (FACT-HNSI). Understanding how these relate to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in clinical trials.HNC patients concurrently completed MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015-2016). Spearman correlation coefficients were calculated between each FACT instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed to identify clusters of similar QoL responses. Principal component analysis (PCA) identified the degree of variability explained by each instrument.We identified 631 instances (363 patients) where the questionnaires were completed concurrently. Correlations between the various FACT measures and SSQ or MDADI were all significant (p 0.001), but FACT HNC-specific subscale and FACT-HNSI showed the strongest correlation with MDADI and SSQ. Clustering identified 3 distinct groups of responses when combining instruments either pairwise or three-way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and likely redundant information.FACT HNC-subscale and FACT-HNSI may be preferable over other FACT measures for use in clinical trials where patient-reported swallow function is evaluated. MDADI and FACT provide similar insights into HNC patient QoL while SSQ provides additional, complementary information which could serve to better stratify patients into groups with high, medium, and low QoL outcomes.

Introduction: Radiation-associated soft tissue sarcomas of the neck (RASN) constitute a rare and aggressive tumor type. Methods: A retrospective chart review at the authors’ institution revealed 3 patients with RASN. A systematic review of the literature was also conducted using MEDLINE, Ovid, the Cochrane Library, and Embase. Results: Patients within the authors’ institutional chart review presented from 6 to 26 years after neck radiation with neck masses. All patients underwent surgical resection with clear margins, and adjuvant radiation was offered when feasible. Patients had no evidence of disease at most recent follow-up. A total of 867 articles were screened for systematic review, revealing 9 articles detailing outcomes of RASN. Studies were small and heterogeneous, precluding pooled data. The importance of complete surgical extirpation was noted. Conclusions: Complete surgical resection appears to be the mainstay of therapy, but there are limited data on management and outcomes of patients with RASN.

Objective We explore whether a knowledge–discovery approach building a Classification and Regression Tree (CART) prediction model for weight loss (WL) in head and neck cancer (HNC) patients treated with radiation therapy (RT) is feasible. Methods and materials HNC patients from 2007 to 2015 were identified from a prospectively collected database Oncospace. Two prediction models at different time points were developed to predict weight loss ≥5 kg at 3 months post-RT by CART algorithm: (1) during RT planning using patient demographic, delineated dose data, planning target volume–organs at risk shape relationships data and (2) at the end of treatment (EOT) using additional on-treatment toxicities and quality of life data. Results Among 391 patients identified, WL predictors during RT planning were International Classification of Diseases diagnosis; dose to masticatory and superior constrictor muscles, larynx, and parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage, nausea, pain, dose to larynx, parotid, and low-dose planning target volume–larynx distance were significant predictive factors. The area under the curve during RT and EOT was 0.773 and 0.821, respectively. Conclusions We demonstrate the feasibility and potential value of an informatics infrastructure that has facilitated insight into the prediction of WL using the CART algorithm. The prediction accuracy significantly improved with the inclusion of additional treatment-related data and has the potential to be leveraged as a strategy to develop a learning health system.

Xerostomia is the most common late toxicity after head and neck radiation. We demonstrate injection of a hydrogel spacer anteriorly displacing the submandibular gland. This procedure enables reduced dose to the displaced submandibular gland in cadaveric models of oropharynx cancer treated with IMRT, with potential implications in reducing xerostomia risk.

// Natalie Alphonse-Sullivan 1 , Glen B. Taksler 2 , Thomas Lycan 3 , Kathryn E. Weaver 4 , Emory R. McTyre 1 , Rachel F. Shenker 5 , Brandi R. Page 6 , Scott Isom 7 , Adam Johnson 1 , Michael T. Munley 1 , Adrian W. Laxton 8 , Stephen B. Tatter 8 , Kounosuke Watabe 9 , Michael D. Chan 1 and Jimmy Ruiz 3 1 Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA 2 Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA 3 Department of Medicine (Hematology and Oncology), Wake Forest School of Medicine, Winston-Salem, NC, USA 4 Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA 5 Wake Forest School of Medicine, Winston-Salem, NC, USA 6 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA 7 Division of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA 8 Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA 9 Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA Correspondence to: Jimmy Ruiz, email: jruiz@wakehealth.edu Keywords: brain metastases; sociodemographics; stereotactic radiosurgery Received: June 19, 2017 Accepted: October 13, 2017 Published: November 07, 2017 ABSTRACT Background: Patient sociodemographic factors such income, race, health insurance coverage, and rural residence impact a variety of outcomes in patients with cancer. The role of brain metastasis at presentation and its subsequent outcomes have not been well characterized in this patient population. Results: Multivariate analysis revealed that median income lower than $50,000 was associated with higher presenting symptom grade for brain metastasis (mean RTOG grade 1.2 vs 1.0, SE = 0.1, p = 0.04) and higher chronic symptom grade (mean RTOG grade 1.3 vs 0.9, SE = 0.1, p = 0.002). Higher area-level median income was associated with a lower symptom grade at diagnosis of brain metastasis ( p = 0.0008) and likelihood of hospitalization ( p = 0.004). Other sociodemographic factors were not significantly associated with survival, neurologic death, or patterns of failure after stereotactic radiosurgery for brain metastases. Conclusions: Lower median income was associated with a greater symptom burden at the time of diagnosis and need for hospitalization for patients with brain metastases, suggesting a delayed time to presentation. These differences in symptom burden persisted during treatment. Methods: Between January 2000 and December 2013, we identified 737 patients treated with stereotactic radiosurgery for brain metastases. They were characterized by 4 sociodemographic factors: median income, race, rural-urban residence, and health insurance status. Clinical outcomes included stage at diagnosis, symptom grade at presentation, likelihood of hospitalization from brain metastasis, overall survival, local failure, distant brain failure, and neurologic death. Multivariate cox proportional hazards model for each outcome was performed controlling for age, sex, number of brain metastases, and dose to brain metastases.

BackgroundThe benefit of immune checkpoint inhibitors (ICIs) in patients with leptomeningeal metastases (LMM) is unknown.MethodsWe undertook a phase II trial of pembrolizumab in patients with LMM from solid tumors. Eligible patients had radiologic/cytologic LMM and Eastern Cooperative Oncology Group performance status 0–1. Pembrolizumab was administered intravenously at 200 mg q3W until disease progression/unacceptable toxicity. The primary endpoint was central nervous system (CNS) response after four cycles, defined radiologically/cytologically/clinically. Serial cerebrospinal fluid (CSF) was assessed for tumor-derived DNA (t-DNA) aneuploidy and cytokines.ResultsThirteen of a planned 16 patients were treated between April 2017 and December 2019. The study closed early for poor accrual. Median age was 57 years (range: 22–79). Sixty-two percent of patients had tumors not traditionally ICI-responsive (hormone-receptor (HR)-positive breast carcinoma=39%; high-grade glioma=23%), while 38% had ICI-responsive tumors (non-small cell lung cancer (NSCLC)=23%, head and neck carcinoma=8%, cutaneous squamous carcinoma (CSC)=8%). CNS response was observed in 38% of patients at 12 weeks (95% CI 13.9% to 68.4%) by pre-defined criteria and LM-RANO, and 2 achieved durable complete responses (CSC=1, overall survival (OS) 3+ years; NSCLC=1, OS 9 months). Median CNS progression-free survival and OS was 2.9 months (95% CI 1.3 to NR) and 4.9 months (95% CI 3.7 to NR), respectively. Grade 3+ treatment-related adverse events occurred in 15% of patients. Sensitivity for LMM detection by t-DNA and cytopathology was 84.6% (95% CI 54.6% to 98.1%) and 53.9% (95% CI 25.1% to 80.8%), respectively. Pre-therapy and on-therapy CSF cytokine analysis demonstrated complete responders clustered together.ConclusionsPembrolizumab conferred a 38% CNS response rate in patients with LMM, a tolerable safety profile, and deep responses in selected patients with ICI-responsive tumors. CSF t-DNA may be sensitive for LMM detection, and immunologic subsets of CNS response warrant further study.Trial registration numberNCT03091478

Purpose Prior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS). Methods Between 2000–2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54 months (range, 0–106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher’s-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models. Results Of 149 patients, 21 (14%) developed LMF (median time of 11.9 months). None of the following predicted for LMF: Her2-status (HR = 0.49, p = 0.16), hormone-receptor status (HR = 1.15, p = 0.79), prior craniotomy (HR = 1.58, p = 0.42), prior WBRT (HR = 1.36, p = 0.55). Non-significant factors between patients that did (n = 21) and did not (n = 106) develop LMF included neurologic death (p = 0.34) and median survival (8.6 vs 14.2 months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p = 0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1 months (IQR 3.4–7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1 months) than in other (1.7 months) histologies Conclusion Breast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients.

Introduction Nigeria has the biggest gap between radiotherapy availability and need, with one machine per 19.4 million people, compared to one machine per 250,000 people in high-income countries. This study aims to identify its patient-level barriers to radiotherapy access. Material and methods This was a cross sectional study consisting of patient questionnaires ( n =50) conducted in January 2016 to assess patient demographics, types of cancers seen, barriers to receiving radiotherapy, health beliefs and practices, and factors leading to treatment delay. Results Eighty percent of patients could not afford radiotherapy without financial assistance and only 6% of the patients had federal insurance, which did not cover radiotherapy services. Of the patients who had completed radiotherapy treatment, 91.3% had experienced treatment delay or often cancellation due to healthcare worker strike, power failure, machine breakdown, or prolonged wait time. The timeliness of a patient's radiotherapy care correlated with their employment status and distance from radiotherapy center ( p Conclusions Barriers to care at a radiotherapy center in a low- and middle-income country (LMIC) have previously not been well characterized. These findings can be used to inform efforts to expand the availability of radiotherapy and improve current treatment capacity in Nigeria and in other LMICs.

OBJECTIVE: Review of the literature regarding hearing loss in patients with head and neck cancer treated with chemoradiation. DESIGN: Studies in the literature are reviewed that pertain to hearing loss sustained in head and neck cancer patients receiving cisplatin-based chemoradiation. Personal observations noted while treating these patients are also detailed. STUDY SAMPLE: PubMed was searched for pertinent articles regarding hearing loss in head and neck cancer patients receiving cisplatin chemotherapy and/or radiation. RESULTS: Studies on the incidence and severity of hearing loss in head and neck cancer patients are limited, but those studies suggest that the risk of hearing loss is greater with higher-dose regimens. CONCLUSIONS: Newer cisplatin chemotherapy regimens using lower, weekly doses may be associated with a lower incidence and severity of hearing loss; however, large prospective studies are needed. Such information will be paramount to effective pre-treatment counseling of head and neck cancer patients.

We evaluated the toxicity associated with stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) in elderly and very elderly patients with brain metastases, as the role of SRS in geriatric patients who would traditionally receive WBRT is unclear.We conducted a retrospective review of elderly patients (aged 70-79 years) and very elderly patients (aged ≥80 years) with brain metastases who underwent RT from 2010 to 2015 at Johns Hopkins Hospital. Patients received either upfront WBRT or SRS for metastatic solid malignancies, excluding small cell lung cancer. Acute central nervous system toxicity within 3 months of RT was graded using the Radiation Therapy Oncology Group acute radiation central nervous system morbidity scale. The toxicity data between age groups and treatment modalities were analyzed using Fisher's exact test and multivariate logistic regression analysis. Kaplan-Meier curves were used to estimate the median overall survival, and the Cox proportion hazard model was used for multivariate analysis.A total of 811 brain metastases received RT in 119 geriatric patients. The median overall survival from the diagnosis of brain metastases was 4.3 months for the patients undergoing WBRT and 14.4 months for the patients undergoing SRS. On multivariate analysis, WBRT was associated with worse overall survival in this cohort of geriatric patients (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.9-7.0, P.0001) and age ≥80 years was not. WBRT was associated with significantly greater rates of any grade 1 to 4 toxicity (OR 7.5, 95% CI 1.6-33.3, P=.009) and grade 2 to 4 toxicity (OR 2.8, 95% CI 1.0-8.1, P=.047) on multivariate analysis. Elderly and very elderly patients did not have significantly different statistically acute toxicity rates when stratified by age.WBRT was associated with increased toxicity compared with SRS in elderly and very elderly patients with brain metastases. SRS, rather than WBRT, should be prospectively evaluated in geriatric patients with the goal of minimizing treatment-related toxicity.

PURPOSE To evaluate the utility of a clinical decision support system (CDSS) using a weight loss prediction model. METHODS A prediction model for significant weight loss (loss of greater than or equal to 7.5% of body mass at 3-month post radiotherapy) was created with clinical, dosimetric, and radiomics predictors from 63 patients in an independent training data set (accuracy, 0.78; area under the curve [AUC], 0.81) using least absolute shrinkage and selection operator logistic regression. Four physicians with varying experience levels were then recruited to evaluate 100 patients in an independent validation data set of head and neck cancer twice (ie, a pre-post design): first without and then with the aid of a CDSS derived from the prediction model. At both evaluations, physicians were asked to predict the development (yes/no) and probability of significant weight loss for each patient on the basis of patient characteristics, including pretreatment dysphagia and weight loss and information from the treatment plan. At the second evaluation, physicians were also provided with the prediction model’s results for weight loss probability. Physicians’ predictions were compared with actual weight loss, and accuracy and AUC were investigated between the two evaluations. RESULTS The mean accuracy of the physicians’ ability to identify patients who will experience significant weight loss (yes/no) increased from 0.58 (range, 0.47 to 0.63) to 0.63 (range, 0.58 to 0.72) with the CDSS ( P = .06). The AUC of weight loss probability predicted by physicians significantly increased from 0.56 (range, 0.46 to 0.64) to 0.69 (range, 0.63 to 0.73) with the aid of the CDSS ( P < .05). Specifically, more improvement was observed among less-experienced physicians ( P < .01). CONCLUSION Our preliminary results demonstrate that physicians’ decisions may be improved by a weight loss CDSS model, especially among less-experienced physicians. Additional study with a larger cohort of patients and more participating physicians is thus warranted for understanding the usefulness of CDSSs.

Xerostomia is a common consequence of radiotherapy in head and neck cancer. The objective was to compare the regional radiation dose distribution in patients that developed xerostomia within 6 months of radiotherapy and those recovered from xerostomia within 18 months post-radiotherapy. We developed a feature generation pipeline to extract dose volume histogram features from geometrically defined ipsilateral/contralateral parotid glands, submandibular glands, and oral cavity surrogates for each patient. Permutation tests with multiple comparisons were performed to assess the dose difference between injury vs. non-injury and recovery vs. non-recovery. Ridge logistic regression models were applied to predict injury and recovery using clinical features along with dose features (D10-D90) of the subvolumes extracted from oral cavity and salivary gland contours + 3 mm peripheral shell. Model performances were assessed by the area under the receiver operating characteristic curve (AUC) using nested cross-validation. We found that different regional dose/volume metrics patterns exist for injury vs. recovery. Compared to injury, recovery has increased importance to the subvolumes receiving lower dose. Within the subvolumes, injury tends to have increased importance towards D10 from D90. This suggests that different threshold for xerostomia injury and recovery. Injury is induced by the subvolumes receiving higher dose, and the ability to recover can be preserved by further reducing the dose to subvolumes receiving lower dose.

Importance Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings. Objectives To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI). Design, Setting, and Participants Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885). Main Outcomes and Measures Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives. Results Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from −2.6% (1.2%) (95% CI, −5.6% to −0.3%) to −1.9% (1.1%) (95% CI, −4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts. Conclusions and Relevance Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.

INTRODUCTION Chronic neuro-inflammation after brain radiotherapy (RT) contributes to radiation-induced cognitive decline (RICD). The renin angiotensin system (RAS) may mediate this inflammatory cascade after RT. Ramipril is an angiotensin-converting enzyme inhibitor used to treat hypertension and has good blood-brain barrier penetration. By blocking RAS activation, ramipril reduces neuro-inflammation and preclinical data show that ramipril administration during RT can prevent RICD. METHODS WF-1801 is an ongoing feasibility study that will enroll a total of 75 patients. Patients ≥ 18 with newly diagnosed and pathologically confirmed GBM who will receive chemoradiation are eligible. All participants take ramipril daily during RT and for 4 months thereafter. Ramipril is titrated from 1.25mg to 5mg daily over 3 weeks. A cognitive battery that includes the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), and Controlled Oral Word Association test (COWA) is administered at baseline, end of RT, and 1-month and 4-months post-RT. The co-primary endpoints are retention rate (with retention defined as compliance with > 75% of drug therapy doses) and neurocognitive function at 1-month post-RT. To estimate the effect of ramipril on cognitive function, performance on the cognitive battery will be compared to a historical control (cognitive data from the control arm of RTOG 0825). ApoE genotyping is being performed as a correlative study. RESULTS 31 of a planned 75 participants have been enrolled over 14 months. 20 of 31 (64.5%) are male. 21 (67.7%) are between the age of 40-64. 20 (95.6%) are white and 29 (93.6%) are not Hispanic or Latino. CONCLUSION Despite a pause in accrual due to COVID-19, we are easily meeting planned accrual goals. Community oncology-based clinical trials of interventions to prevent cognitive toxicity appear to be feasible. GBM patients seem eager to enroll in studies seeking to prevent cognitive decline. Supported by NCI grant UG1CA189824.

Stereotactic radiosurgery (SRS) has become a widely available treatment option for patients with brain metastases. Recent clinical trials suggest that SRS can be used without upfront whole brain radiotherapy (WBRT), resulting in several clinical dilemmas in the current daily practice of SRS. The proper patient selection for SRS or WBRT continues to evolve. Statistical models to predict when new brain metastases will occur as well as who will experience neurologic death have been developed. The optimization of imaging continues for both detection of brain metastases and response assessment. Larger brain metastases continue to pose a challenge to practitioners to find options to optimize the therapeutic ratio. The current review addresses the current state of the scientific literature for these clinical dilemmas.

INTRODUCTION: Radiation-induced cognitive decline (RICD) is a late effect of radiotherapy (RT) occurring in 30–50% of irradiated brain tumor survivors. In preclinical models, pioglitazone prevents RICD but there are little safety data on its use in non-diabetic patients. We conducted a dose-escalation trial to determine the safety of pioglitazone taken during and after brain irradiation. METHODS: We enrolled patients > 18 years old with primary or metastatic brain tumors slated to receive at least 10 treatments of RT (≤ 3 Gy per fraction). We evaluated the safety of pioglitazone at 22.5 mg and 45 mg with a dose-escalation phase and dose-expansion phase. Pioglitazone was taken daily during RT and for 6 months after. RESULTS: 18 patients with a mean age of 54 were enrolled between 2010 and 2014. 14 patients had metastatic brain tumors and were treated with whole brain RT. Four patients had primary brain tumors and received partial brain RT and concurrent chemotherapy. No DLTs were identified. In the dose-escalation phase, there were only three instances of grade ≥ 3 toxicity: one instance of neuropathy in a patient receiving 22.5 mg, one instance of fatigue in a patient receiving 22.5 mg and one instance of dizziness in a patient receiving 45 mg. The attribution in each of these cases was considered “possible.” In the dose-expansion phase, nine patients received 45 mg and there was only one grade 3 toxicity (fatigue) possibly attributable to pioglitazone. CONCLUSION: Pioglitazone was well tolerated by brain tumor patients undergoing RT. 45 mg is a safe dose to use in future efficacy trials.

We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT).Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival.Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p0.001, 95% CI:3.4-7.8).WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS.

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p