Estimating the Practice-Level and National Cost Burden of Treatment-Related Prior Authorization for Academic Radiation Oncology Practices.

PURPOSE: Prior authorization (PA) imposes significant time burdens on radiation oncology practices, but its financial impact has not been characterized. We used time-driven activity-based costing (TDABC) to assess the cost burden of treatment-related PA events at an academic radiation oncology practice. We then estimated annual costs for an academic practice and academic practices nationally. METHODS AND MATERIALS: Using internal analyses, we created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. Using published compensation data, internal workhour estimates, and supervisory requirements, we calculated the cost of each PA event and annual costs. Using data from the 2017 American Society for Radiation Oncology Workforce Survey and the 2018 American Society for Radiation Oncology Prior Authorization Survey, we estimated annual PA costs for academic medical centers nationally. RESULTS: We successfully created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. There were significant time and cost burdens for all events (range: 51-95 minutes, $28-$101 US dollars [USD]), with significant increases when peer-to-peer discussion was required (range: 92-95 minutes, $75-$101 USD). Annual treatment-related PA departmental costs were estimated to be $491,989 USD, with approved treatments accounting for the majority (94%; $463,027 USD). Nationally, annual treatment-related PA costs were estimated to be $40,125,848 USD, with approved treatments accounting for the majority (86%; $34,632,620 USD). CONCLUSION: TDABC can be used to estimate the cost burden of PA events. These burdens are significant and translate into massive organizational costs. Our national estimates highlight the tremendous cost of PA for academic radiation oncology practices, with the majority of costs related to approved treatments.

Radiation Therapy Adherence Among Patients Experiencing Homelessness.

PURPOSE: Radiation therapy is a valuable, yet time- and resource-intense therapy. Patients experiencing homelessness (PEH) face many barriers related to the timely receipt of radiation therapy. Owing to a paucity of data regarding cancer treatment and homelessness, clinicians have a limited evidence base when recommending therapy to PEH. This study was performed to evaluate adherence to radiation therapy treatment regimens in PEH with cancer. METHODS AND MATERIALS: The study cohort was primarily derived from the Vanderbilt University Medical Center Homeless Health Services program. Patients in the Homeless Health Services program with radiation oncology visits were identified by query of the electronic medical record. Manual chart review was performed to gather standard treatment parameters and data describing missed appointments. A comparison group of patients not experiencing homelessness (non-PEH) was generated by aggregating appointment data for all other patients receiving similar treatments at Vanderbilt University Medical Center during multiple, consecutive years. RESULTS: In the study, 3408 PEH were identified, of whom 48 underwent radiation oncology consultation. Thirty-two were prescribed at least 1 course of radiation therapy, for a total of 54 unique courses. Out of these courses, 34 (62.9%) were completed as prescribed without delay, 12 (22.2%) were completed with delay(s), and 8 (14.8%) were not fully completed. Although the PEH cohort had significantly higher rates of delayed and undelivered fractions, the proportion of delayed or incomplete courses was not significantly different from the comparison group of non-PEH, particularly for courses with 10 or fewer fractions. Reasons for missed appointments for PEH were variable. CONCLUSIONS: This is the first publication describing adherence to radiation therapy in PEH. Our data suggest that PEH are as likely as non-PEH to complete a course of radiation therapy, albeit with more treatment interruptions. When treatment courses of >10 fractions are expected, PEH may benefit from more hypofractionated regimens, provided they have equivalent clinical efficacy to longer regimens. Documenting reasons for missed appointments will be essential to further understanding the needs of PEH. This study serves as a foundation for further analysis regarding homelessness and radiation therapy.

Secondary malignancy following stereotactic radiosurgery for benign neurologic disease: A cohort study and review of the literature.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.

Combining multiparametric MRI with receptor information to optimize prediction of pathologic response to neoadjuvant therapy in breast cancer: preliminary results.

Pathologic complete response following neoadjuvant therapy (NAT) is used as a short-term surrogate marker of eventual outcome in patients with breast cancer. Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained before and after the first cycle of NAT ([Formula: see text]), in conjunction with receptor status, may improve the predictive accuracy of tumor response to NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent diffusion coefficient and efflux rate constant, with receptor status in a logistic ridge-regression model. The area under the curve (AUC) and Brier score of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99) and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly support the hypothesis that our proposed model outperforms the other models that we investigated (namely, models without either receptor information or voxel-level information). The contribution of the receptor information was manifested by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These data indicate that combining multiparametric MRI with hormone receptor status has a high likelihood of improved prediction of pathologic response to NAT in breast cancer.

Utilization of hypofractionated radiotherapy in treatment of glioblastoma multiforme in elderly patients not receiving adjuvant chemoradiotherapy: A National Cancer Database Analysis.

To assess the utilization and outcomes of adjuvant monotherapy with hypofractionated radiation (RT) among elderly patients not receiving traditional adjuvant chemoradiotherapy (cRT) for glioblastoma multiforme (GBM). A retrospective analysis using the National Cancer Data Base with GBM patients aged 65 years or older treated between 2005 and 2012 was conducted. Patients who underwent hypofractionated RT (40 Gy), conventional RT (60 Gy), chemotherapy, or best supportive care alone were included. Statistical methods included logistic regression for utilization and Cox regression for survival analysis. A total of 9556 patients were analyzed. On multivariate analysis (compared to those receiving conventional RT), patients more likely to be treated with hypofractionated RT were older (75-84 years old OR 2.05; p < 0.01 and ≥ 85 years old OR 3.32; p < 0.01), with a Charlson/Deyo score of 2 or higher (OR 1.80; p = 0.05), from communities > 50 miles from their treatment facility (50-100 miles OR 8.03; p < 0.01 and > 100 miles OR 7.16; p < 0.01), treated at an Academic/Research facility (OR 2.85; p = 0.04), and diagnosed between 2011 and 2012 (OR 4.15; p < 0.01). On Cox regression, hypofractionated RT (HR 0.65; p < 0.01), conventional RT (HR 0.60; p < 0.01), and chemotherapy alone (HR 0.69; p < 0.01) were all associated with decreased risk of death compared to no adjuvant therapy. Among patients receiving adjuvant treatment, utilization of hypofractionated RT increased from 7 to 19% during the study period. Among elderly patients with GBM not receiving cRT, the utilization of adjuvant monotherapy with hypofractionated RT has increased over time. Retrospective evidence suggests it may be better than best supportive care alone and as good as conventionally fractionated RT alone.

IL-6 variant is associated with metastasis in breast cancer patients.

INTRODUCTION: Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases. METHODS: We performed an initial case-control study using Vanderbilt University Medical Center's BioVU, a genomic biobank linked to de-identified electronic medical records in the Synthetic Derivative database, to identify germline SNPs that may predict the development of metastatic disease to any site from any solid tumor including breast cancer. We identified a SNP in IL-6: rs1800795 to be of significance and evaluated this finding using a separate, matched-pair cohort of breast cancer patients with and without metastases from The Ohio State University Wexner Medical Center. RESULTS: The initial study suggested that GG relative to CG at rs1800795 (OR 1.52; 95% CI 1.14-2.02; p = 0.004) was significantly associated with the development of metastases. This association was also observed in the Ohio State University cohort (OR 2.23; 95% CI 1.06-4.71; p = 0.001). There were no significant relationships between rs1800795 status and any patient or tumor characteristics, including estrogen receptor status. CONCLUSIONS: These findings suggest that GG SNP at IL-6: rs1800795 may indicate an increased risk of metastasis of primary breast cancer. Further studies in larger population sets are warranted as advanced screening and prophylactic intervention might be employed in GG carriers.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement.

PURPOSE: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. METHODS AND MATERIALS: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement. RESULTS: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). CONCLUSIONS: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

Multi-institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non-small cell lung tumors.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date. METHODS: Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models. RESULTS: A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis. CONCLUSIONS: The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.

Socioeconomic and Ethnic Disparities in Periocular Cutaneous Malignancies.

Cutaneous malignancies make up the majority of periocular tumors diagnosed and treated by ophthalmologists. In this review, we examine literature regarding ethnic and socioeconomic disparities in incidence and clinical outcomes of the three most common cutaneous periocular tumors: basal cell carcinoma, squamous cell carcinoma, and melanoma. In all three tumor types, the literature shows an increased incidence among two groups: those with lightly pigmented skin and those of higher socioeconomic status. While incidence is high in these groups, clinical outcomes for these patients tend to be good. Those with lower socioeconomic status and ethnic minorities, on the other hand, have a low incidence but are more likely to have poor clinical outcomes. These disparities are likely the result of both biologic and behavioral differences between patients and could provide opportunities for intervention to change risk perception and improve outcomes.

Thicker host tissues moderate light stress in a cnidarian endosymbiont.

The susceptibility of algal-cnidarian holobionts to environmental stress is dependent on attributes of both host and symbiont, but the role of the host is often unclear. We examined the influence of the host on symbiont light stress, comparing the photophysiology of the chlorophyte symbiont Elliptochloris marina in two species of sea anemones in the genus Anthopleura. After 3 months of acclimation in outdoor tanks, polyp photoprotective contraction behavior was similar between the two host species, but photochemical efficiency was 1.5 times higher in A. xanthogrammica than in A. elegantissima. Maximum relative electron transport rates, derived from rapid light curves, were 1.5 times higher in A. xanthogrammica than in A. elegantissima when symbionts were inside intact tissues, but were not significantly different between host species upon removal of outer (epidermis and mesoglea) tissue layers from symbiont-containing gastrodermal cells. Tissues of A. xanthogrammica were 1.8 times thicker than those of A. elegantissima, with outer tissue layers attenuating 1.6 times more light. We found no significant differences in light absorption properties per unit volume of tissue, confirming the direct effect of tissue thickness on light attenuation. The thicker tissues of A. xanthogrammica thus provide a favorable environment for E. marina - a relatively stress-susceptible symbiont - and may explain its higher prevalence and expanded range in A. xanthogrammica along the Pacific coast of North America. Our findings also support a photoprotective role for thicker host tissues in reef corals that has long been thought to influence variability in bleaching susceptibility among coral taxa.

New variant CJD-BSE (mad cow disease). The need for disposable ENT instruments.

This paper outlines the development of Bovine Spongiform Encephalopathy (BSE) in the United Kingdom. The relationship between BSE and new variant Creutzfeldt-Jakob disease (vCJD) is considered and the risks of iatrogenic spread reviewed. The rationale for disposable surgical instruments in adenotonsillectomy to prevent iatrogenic spread is discussed.