Radiotherapy Deserts: The Impact of Race, Poverty, and the Rural-Urban Continuum on Density of Providers and the Use of Radiation Therapy in the US.

PURPOSE: Prior efforts to characterize disparities in radiation therapy access and receipt have not comprehensively investigated interplay between race, socioeconomic status, and geography relative to oncologic outcomes. This study sought to define these complex relationships at the US county level for prostate cancer (PC) and invasive breast (BC) cancer to build a tool that facilitates identification of "radiotherapy deserts"-regions with mismatch between radiation therapy resources and oncologic need. METHODS AND MATERIALS: An ecologic study model was constructed using national databases to evaluate 3,141 US counties. Radiation therapy resources and use densities were operationalized as physicians to persons at risk (PPR) and use to persons at risk (UPR): the number of attending radiation oncologists and Medicare beneficiaries per 100,000 persons at risk, respectively. Oncologic need was defined by "hot zone" counties with ≥2 standard deviations (SDs) above mean incidence and death rates. Univariable and multivariable logistic regressions examined links between PPR and UPR densities, epidemiologic variables, and hot zones for oncologic outcomes. Statistics are reported at a significance level of P < .05. RESULTS: The mean (SD) PPR and UPR densities were 2.1 (5.9) and 192.6 (557.6) for PC and 1.9 (5.3) and 174.4 (501.0) for BC, respectively. Counties with high PPR and UPR densities were predominately metropolitan (odds ratio [OR], 2.9-4.4), generally with a higher percentage of Black non-Hispanic constituents (OR, 1.5-2.3). Incidence and death rate hot zones were largely nonmetropolitan (OR, 0.3-0.6), generally with a higher percentage of Black non-Hispanic constituents (OR, 3.2-6.3). Lower PPR density was associated with death rate hot zones for both types of cancer (OR, 0.8-0.9); UPR density was generally not linked to oncologic outcomes on multivariable analysis. CONCLUSIONS: The study found that mismatch between oncologic need with PPR and UPR disproportionately affects nonmetropolitan communities with a higher percentage of Black non-Hispanic constituents. An interactive web platform (bit.ly/densitymaps) was developed to visualize "radiotherapy deserts" and drive targeted investigation of underlying barriers to care in areas of highest need, with the goal of reducing health inequities in this context.

Evaluation of the Clinical Utility of the Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP): A Case-Based Pilot Assessment.

PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.

Improving providers' survival estimates and selection of prognosis- and guidelines-appropriate treatment for patients with symptomatic bone metastases: Development of the Bone Metastases Ensemble Trees for Survival Decision Support Platform.

RATIONALE, AIMS AND OBJECTIVES: In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render individualised treatment decisions, yet no such tools are available for use in this setting. Thus, we describe the development of the Bone Metastases Ensemble Trees for Survival-Decision Support Platform (BMETS-DSP), which aims to optimise selection of evidence-based, individualised palliative RT regimens. METHOD: The Ottawa Decision Support Framework was used as the theoretical basis for development of BMETS-DSP. First, we utilised stakeholder input and review of the literature to assess determinants underlying the provider decision. Based on this assessment and iterative stakeholder feedback, we developed the web-based, provider-facing BMETS-DSP. Consistent with the underlying theoretical framework, our design also included assessment of decision quality using the International Patient Decision Aids Standards (IPDAS) certification checklist. RESULTS: Stakeholder input and review of 54 evidence-based publications identified the following determinants of the provider decision: estimated prognosis, characteristics of the target symptomatic lesion and the primary cancer type, consideration of alternative interventions, access to patient-specific recommendations, and patient preferences. Based on these determinants, we developed the BMETS-DSP that (1) collects patient-specific data, (2) displays an individualised predicted survival curve, and (3) provides case-specific, evidence-based recommendations regarding RT, open surgery, systemic therapy, and hospice referral to aid in the decision-making process. The finalised tool met IPDAS quality requirements. Preliminary results of a pilot assessment suggest impact of clinical outcomes. CONCLUSIONS: We describe the successful development of a provider-facing decision support platform to aid in the provision of palliative RT in better alignment with patient and disease features. Impact of the BMETS-DSP on decision outcomes will be further assessed in a randomised, controlled study.

External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases.

PURPOSE: The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown. PATIENTS AND METHODS: Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set. RESULTS: A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 v 62 years; P < .001), had more primary breast (27% v 19%; P = .03) and prostate cancer (20% v 12%; P = .01), and survived longer (median, 10.7 v 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained > 0.79. CONCLUSION: BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.

Aiming for 100% Local Control in Locally Advanced Cervical Cancer: The Role of Complex Brachytherapy Applicators and Intraprocedural Imaging.

The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity.

IMRT-based treatment of unknown primary malignancy of the head and neck: Outcomes and improved toxicity with decreased mucosal dose and larynx sparing.

BACKGROUND: Radiation therapy for squamous cell cancer of the head and neck with unknown primary (head and neck CUP) has been associated with significant levels of swallowing toxicity. We examined the effect of changes in mucosal dose on development of laryngeal strictures and percutaneous endoscopic gastrostomy (PEG) dependence. METHODS: Retrospective analysis of 58 patients with head and neck CUP treated with intensity-modulated radiation therapy (IMRT) at the Dana Farber Cancer Institute from August 2004 through July 2013. RESULTS: There were no significant differences between any recurrences for groups treated to 56 versus ≥60 Gy to the mucosal surfaces. However, mucosal dose and chemotherapy type were associated with stricture on multivariable analysis; median PEG dependence was decreased for patients treated to 56 Gy. A larynx-sparing approach was associated with improved outcomes for strictures and PEG use. CONCLUSION: In this single institution study, a 56 Gy IMRT-based mucosal dose demonstrated significant improvements in swallowing toxicity. Additional benefit was seen with larynx-sparing IMRT.

Strengthening palliative care delivery in developing countries: a training workshop model in Botswana.

BACKGROUND: The persistent global unmet need for palliative care continues to be felt acutely in Sub-Saharan Africa, where the volume is growing and access to palliative services remains underdeveloped. Recognizing the increasing urgency of bolstering palliative care infrastructure, several countries, such as Botswana, have established national policies and strategies to enhance care delivery. Given that education and training are essential components in pursuing this goal, we present a model for a training workshop that was successful in increasing the palliative care knowledge base and skill set in a group of nurses. METHODS: A 2-day palliative care workshop was conducted for 15 nurses in Gaborone, Botswana in October 2014. Ten nurses completed pre- and post-workshop tests consisting of 21 questions spanning palliative care topics and delivery skills. RESULTS: The survey category with the highest pre-test score of 70% was principles of palliative care. Ninety percent of participants demonstrated statistically significant improvement in post-test scores in comparison to pre-test results. The greatest increase in scores were observed in the categories of communication, end-of-life care and syringe driver use for administration of analgesic medications. The lowest post-test score category was spirituality, though it consisted of one survey question. CONCLUSIONS: Here we provide quantitative data that supports the success of the training workshop model presented. Improvement in palliative care knowledge and treatment skills, as evidenced by the increased scores from pre- to post-test results, suggests the efficacy of this 2-day training program in advancing palliative care education of nurses. Given the unmet need for healthcare workers trained in palliative care, this model could serve as a valuable tool for expanding and strengthening the delivery of care in settings where patients have limited access to palliative care services.

Palliative care in Botswana: current state and challenges to further development.

BACKGROUND: A rising tide of cancers and other chronic diseases, alongside the ongoing HIV/AIDS epidemic, has created an increasing demand for palliative care in Africa. Yet, few African nations have established effective palliative care programs. In Botswana, the escalating HIV/AIDS crisis revealed an unmet need for holistic care, prompting efforts to expand palliative care education and policy, and target curricular and health system integration in the years that followed. Despite numerous successes, Botswana continues to face barriers to palliative care development. In this paper, we examine the country's current state of palliative care and the challenges it must still overcome. METHODS: Data was collected from June to July of 2015, and includes interviews of physicians, nurses and hospice staff. RESULTS: Palliative care delivery in Botswana is primarily concentrated in the south, where the country's first palliative care clinic and three hospices are located. While 157 health care workers, students and lecturers received palliative care training from 2013 to 2014, 100% of participants felt that education remains a significant obstacle for palliative care expansion. Sixty-four percent commented on the need for increased palliative care understanding and awareness, while 91% noted the difficulty of achieving adequate access to pain medication. CONCLUSIONS: Several targets were identified that have persistently hampered efforts to advance palliative care in Botswana, including: infrastructural challenges such as access to pain medications, the strained size of the palliative care workforce, and a need for increased palliative care education and understanding. However, recent achievements in national strategy and policy offer promising avenues for moving past these historical barriers. With implementation of action plans already underway, Botswana may ultimately provide a model for successful palliative care implementation in continuing to strengthen palliative care services throughout the country.

Treatment-refractory ALK-positive inflammatory myofibroblastic tumour of the oral cavity.

We present a challenging case of a previously healthy 23-year-old man who developed an inflammatory myofibroblastic tumour of the hard palate, harbouring a rearrangement of the anaplastic lymphoma kinase (ALK) locus. Despite surgical intervention, radiotherapy and ALK-inhibition therapy, the tumour recurred locally and metastasised to regional lymph nodes, and the patient passed away roughly 9 months after diagnosis from local progression. The rapid progression of this patient's disease and its resistance to treatment demonstrate the potentially aggressive clinical course of inflammatory myofibroblastic tumours. ALK-inhibition therapy was unsuccessful in this ALK-positive tumour, highlighting the need for further investigation of markers predictive of disease progression and treatment response.

Cervical cancer in low and middle income countries: Addressing barriers to radiotherapy delivery.

The global cervical cancer burden falls disproportionately upon women in low and middle-income countries. Insufficient infrastructure, lack of access to preventive HPV vaccines, screening, and treatment, as well as limited trained personnel and training opportunities, continue to impede efforts to reduce incidence and mortality in these nations. These hurdles have been substantial challenges to radiation delivery in particular, preventing treatment for a disease in which radiation is a cornerstone of curative therapy. In this review, we discuss the breadth of these barriers, while illustrating the need for adaptive approaches by proposing the use of brachytherapy alone in the absence of available external beam radiotherapy. Such modifications to current guidelines are essential to maximize radiation treatment for cervical cancer in limited resource settings.

CanSupport: a model for home-based palliative care delivery in India.

BACKGROUND: According to the 2014 WHO Global Atlas of Palliative Care, there is insufficient access to palliative care services worldwide, with the majority of unmet need in low- and middle-income countries. In India, there are major disparities in access to palliative care, with the majority of services being offered by non-governmental organizations (NGOs) scattered throughout the country. The barriers to expanding palliative care services in India are common to many lower- and middle-income countries-a lack of financial resources, a paucity of trained staff, and a focus on curative rather than comfort care. In this paper, we describe a model of palliative care being used by CanSupport, a non-governmental organization based in Delhi that was formed in 1996. They offer home-based services provided by multidisciplinary teams consisting of a physician, nurse, and social worker who are trained in palliative care. METHODS: Data on patient demographics, services provided, and outcomes were collected retrospectively for patients treated by CanSupport for the year 2009-2010. Sources include CanSupport's population data and direct discussions with CanSupport staff. RESULTS: During the year 2009-2010, CanSupport served 746 patients, with an average of 10 home visits per patient. Only 29% of patients were referred from hospitals or physicians, with the rest being self-referred or referred from CanSupport's help line. Pain scales were administered on each visit and 31% of patients received morphine. Of the 514 patient deaths, 76% occurred at home and a majority of families received bereavement counseling for up to 6 months. CONCLUSIONS: CanSupport has shown that a home-based care model can be successful in India and is desired by patients at the end of life or with chronic illness. Their model of care saves the patients the cost of a hospital visit while still providing evaluation by staff with training in palliative care. In addition, the multidisciplinary nature of the teams allows for symptom management and emotional counseling for both the patients and their families. CanSupport has developed a way to provide reliable, cost-effective palliative care to patients that can serve as a model for building palliative care capacity in low- and middle-income countries.

Comparative genomics identifies the mouse Bmp3 promoter and an upstream evolutionary conserved region (ECR) in mammals.

The Bone Morphogenetic Protein (BMP) pathway is a multi-member signaling cascade whose basic components are found in all animals. One member, BMP3, which arose more recently in evolution and is found only in deuterostomes, serves a unique role as an antagonist to both the canonical BMP and Activin pathways. However, the mechanisms that control BMP3 expression, and the cis-regulatory regions mediating this regulation, remain poorly defined. With this in mind, we sought to identify the Bmp3 promoter in mouse (M. musculus) through functional and comparative genomic analyses. We found that the minimal promoter required for expression in resides within 0.8 kb upstream of Bmp3 in a region that is highly conserved with rat (R. norvegicus). We also found that an upstream region abutting the minimal promoter acts as a repressor of the minimal promoter in HEK293T cells and osteoblasts. Strikingly, a portion of this region is conserved among all available eutherian mammal genomes (47/47), but not in any non-eutherian animal (0/136). We also identified multiple conserved transcription factor binding sites in the Bmp3 upstream ECR, suggesting that this region may preserve common cis-regulatory elements that govern Bmp3 expression across eutherian mammals. Since dysregulation of BMP signaling appears to play a role in human health and disease, our findings may have application in the development of novel therapeutics aimed at modulating BMP signaling in humans.