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Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.

Stereotactic body radiation therapy (SBRT) is a relatively new technology, and its use among patients with benign spinal tumors has limited prospective data. Similar to intracranial benign tumors treated successfully with SBRT, benign spinal tumors of the same histology can also develop, and SBRT may be an effective treatment alternative in inoperable or recurrent cases. Outcomes in patients with neurofibromatosis type 1, neurofibromatosis type 2, or schwannomatosis treated with SBRT have also been reported. Single institution reports have shown local control rates over 90% and improvement in clinical symptoms. The optimum dose and fractionation to maximize local control and minimize toxicity is unknown, with few incidences of radiation treatment-related toxicities. Given the location and benign nature of these tumors, careful management of dose to critical organs is essential. With continued follow-up, the optimum use of SBRT in patients with benign spinal tumors can be better defined.

PurposeTo compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events.MethodsWe identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (ω) using the Akaike Information Criterion.ResultsIn each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8.ConclusionCompared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality.

PurposeAdjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer.Methods and materialsA total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes.ResultsPatients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality.ConclusionsFor women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques.

Background and purposeIn cost-effective healthcare systems, the cost of services should parallel patient complexity or quality of care. The purpose of this study was to determine whether the cost of radiotherapy correlates with patient-related outcomes among a large cohort of breast cancer patients treated with adjuvant breast radiation.Materials and methods23,127 women with non-metastatic breast cancer undergoing radiotherapy after breast conservation surgery were identified from the Surveillance, Epidemiology, and End Results database from 2000 to 2009. Medicare reimbursements were used as a proxy for cost of radiotherapy, and Medicare claims were examined to identify local toxicities, and breast cancer-related endpoints. The impact of cost on these outcomes was studied with multivariable Fine-Gray models to account for competing risks.ResultsThe median cost (and interquartile range) of a course of breast radiation was $8100 ($6700-9700). Increased radiation costs were not associated with the occurrence of treatment-related toxicities (all p-values>0.05), ipsilateral breast recurrence (p=0.55), or breast cancer-related mortality (p=0.55).ConclusionHigher costs for adjuvant radiation in breast cancer were not associated with a decreased risk of patient-related outcomes suggesting inefficiency in Medicare reimbursements. Future efforts should focus on prospective evaluation of alternative payment models for radiotherapy.

PurposeRadiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries.Patients and methodsWe identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy.ResultsFor breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300), $9,000 ($7,500 to $11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor-related factors accounted for < 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer.ConclusionIn this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices.

BackgroundAspiration pneumonia represents an under-reported complication of chemoradiotherapy in patient with head and neck cancer. The objective of the current study was to evaluate the incidence, risk factors, and mortality of aspiration pneumonia in a large cohort of patients with head and neck cancer who received concurrent chemoradiotherapy.MethodsPatients who had head and neck cancer diagnosed between 2000 and 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Aspiration pneumonia was identified from Medicare billing claims. The cumulative incidence, risk factors, and survival after aspiration pneumonia were estimated and compared with a noncancer population.ResultsOf 3513 patients with head and neck cancer, 801 developed aspiration pneumonia at a median of 5 months after initiating treatment. The 1-year and 5-year cumulative incidence of aspiration pneumonia was 15.8% and 23.8%, respectively, for patients with head and neck cancer and 3.6% and 8.7%, respectively, for noncancer controls. Among the patients with cancer, multivariate analysis identified independent risk factors (P

Purpose: To develop a high-density isocenter packing (HDIP) approach utilizing hundreds of isocenters that are optimally placed inside a 3D target volume to achieve equivalent dose distribution of a dynamic dose painting delivery previously reported by our group (c.f., Phys Med Biol. 2009 Mar 21;54(6):1579-91). Method: HDIP sequentially places a large number isocenters inside a target volume similar to solving a “3D lawn-mowing problem”, a variation of the traveling salesman problem. In our algorithm, a dose kernel always “paints” the outermost surface of the target volume first before moving to the next outermost surface area of the remaining unpainted volume. Once finished, the locations, weights, and sizes of the dose kernels were further finetuned by optimization and the final dose distribution was calculated in a clinical treatment planning system. For this study, technical feasibility and potential benefits of HDIP were investigated on a Leksell Gamma Knife (LGK) unit for hypofractionated radiosurgery of large (>3 cm) brain tumors such as gliomas. Results: Since LGK requires a minimum beam-on time of ~0.02 min per isocenter, HDIP was delivered by lowering the effective collimator size with a slightly increased beam-on time. As a result, the total beam-on time was increased by approximately 5 min for each treatment fraction under a nominal dose rate of 2.5 Gy/ min. Compared to the conventional delivery which uses 20% of the number of isocenters, HDIP significantly reduced the dose hot spots by 56% within the 2-mm GTV-to-PTV margin area with substantial normal brain tissue while achieving identical target volume coverage, Paddick conformality index and dose fall-off gradient outside the target. Furthermore, HDIP was found to be significantly more robust against intrafractional residual target shifts on the order of 0-1 mm that are generally unaccounted for in the current treatment delivery. Conclusion: HDIP rivals ideal dynamic dose painting delivery and it is potentially advantageous in achieving better normal brain sparing, more accurate delivery with improved robustness against residual target shifts. Adaptions of the technique for other modalities are under further investigations. [ABSTRACT FROM AUTHOR]

Purpose: Radiation oncology has been facing an evolving crisis in recruitment for several years, and the events of 2020 to 2021 will certainly add to that crisis with the urgency of addressing systemic racial injustice amid a global pandemic. The purpose of this study is to examine applicant data to gain insight on residency match trends and evaluate these findings within the backdrop of a novel match year., Methods and Materials: National Residency Matching Program (NRMP) data between 2009 and 2020 were assessed for the number of applicants, programs, and positions available, number of ranked applicants needed to fill positions, and successfully matched applicant data. Additionally, Electronic Residency Application Service data were evaluated for race/ethnicity identification among applicants., Results: The number of applicants who ranked radiation oncology as their preferred specialty has declined for 3 consecutive years from 223 in 2017 to 155 in 2020. In 2020 the applicant-to-position ratio was at an all-time low at 0.82, and the unmatched position rate increased to 18.5%. The percentage of Black or African American applicants applying to radiation oncology has also declined to 4.9%, and this population represents 7.2% of all applicants. The number of ranked applicants needed to fill the available radiation oncology PGY2 positions increased from 4.0 in 2010 to 6.0 in 2020., Conclusion: Declining interest in radiation oncology among applicants, and an even further decline of black applicants, along with the challenges of interview and travel restrictions during the pandemic provide heightened concern for this year's match. Innovative efforts to expand the reach of radiation oncology to prospective applicants is needed to engage diverse, bright, and committed students for the continued progress of radiation oncology and most importantly, our patients., (© 2020 The Author(s).)