Assessing the Financial Toxicity of Radiation Oncology Patients Using the Validated Comprehensive Score for Financial Toxicity as a Patient-Reported Outcome.

PURPOSE: The financial burden of cancer care may significantly affect patient quality of life and clinical outcomes. However, the financial effect of radiation therapy on patients remains difficult to characterize, in part owing to the lack of standardized methods to measure patient distress related to treatment costs. Here, we assessed financial burden in the radiation oncology population by applying the Comprehensive Score for Financial Toxicity (COST), a patient-reported outcome measure, which has been validated in medical oncology patients.   METHODS AND MATERIALS: Consecutive patients from a single academic radiation oncology clinic were recruited. Participants completed the 11-item COST-Functional Assessment of Chronic Illness Therapy questionnaire, with total possible scores ranging from 0 to 44. Scores were collected along with data regarding patient demographics, insurance, diagnosis, and treatment. Univariate and multivariate analyses were performed to identify factors associated with higher financial burden as measured by COST. RESULTS: A total of 167 patients completed the COST questionnaire. Lower COST scores indicated higher financial toxicity. The population's mean COST score was 21.9 (95% confidence interval, 20.5-23.3). Fifteen percent of participants reported grade 2 to 3 COST toxicity, corresponding to a moderate or severe effect on quality of life. Use of concurrent or previous systemic therapy was significantly associated with lower COST scores on univariate analysis (P = .03), but not significant on multivariate analysis. A subset analysis of posttreatment follow-up patients identified rural residence and recent completion of radiation therapy as significant correlates of worse COST scores on univariate analysis, and rural residence remained independently associated on multivariate analysis (P = .017). CONCLUSIONS:  COST effectively identified a significant number of radiation oncology patients experiencing financial toxicity, indicating its prevalence in this population. A correlate of financial toxicity in this population is the use of systemic therapy. Of those who have completed radiation therapy, rural residence was independently associated with worse financial toxicity.

The Impact of Radiotherapy Facility Volume on the Survival and Guideline Concordance of Patients With Muscle-invasive Bladder Cancer Receiving Bladder-preservation Therapy.

OBJECTIVES: Higher facility surgical volume predicts for improved outcomes in patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy. We investigated the association between facility radiotherapy (RT) case volume and overall survival (OS) for patients with MIBC who received bladder-preserving RT, and the relationship with adherence to National Comprehensive Cancer Network (NCCN) guidelines for bladder preservation. METHODS: The National Cancer Database was used to identify patients diagnosed with nonmetastatic MIBC from 2004 to 2015 and received RT at the reporting center. Facility case volume was defined as the total MIBC patients treated with RT during the period. Facilities were stratified into high-volume facility (HVF) or low-volume facility at the 80th percentile of RT case volume. OS was assessed using Kaplan-Meier analysis. Rates of compliance with NCCN guidelines regarding the use of transurethral resection of the bladder tumor before RT, planned use of concurrent chemotherapy, and total RT dose were compared. Cox proportional hazard model was used to evaluate predictors of OS. RESULTS: There were 7562 patients included. No differences in age, Charlson-Deyo score, T stage, or node-positive rates were observed between groups. HVFs exhibited greater compliance with NCCN guidelines for bladder preservation (P<0.0001). Treatment at an HVF was associated with the improved OS for all patients (P=0.001) and for the subset of patients receiving NCCN-recommended RT doses (P=0.0081). Volume was an independent predictor of OS (P=0.002). CONCLUSIONS: Treatment at an HVF is associated with improved OS and greater guideline-concordant management among patients with MIBC.

First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma.

PURPOSE: Standard treatment for glioblastoma (GBM) includes surgery, radiation therapy (RT), and temozolomide (TMZ), yielding a median overall survival (OS) of approximately 14 months. Preclinical models suggest that pharmacologic ascorbate (P-AscH-) enhances RT/TMZ antitumor effect in GBM. We evaluated the safety of adding P-AscH- to standard RT/TMZ therapy. PATIENTS AND METHODS: This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH-) and an adjuvant (ADJ) phase (post RT/TMZ/P-AscH- phase). Eight P-AscH- dose cohorts were evaluated in the RT phase until targeted plasma ascorbate levels were achieved (≥20 mmol/L). In the ADJ phase, P-AscH- doses were escalated in each subject at each cycle until plasma concentrations were ≥20 mmol/L. P-AscH- was infused 3 times weekly during the RT phase and 2 times weekly during the ADJ phase continuing for six cycles or until disease progression. Adverse events were quantified by CTCAE (v4.03). RESULTS: Eleven subjects were evaluable. No dose-limiting toxicities occurred. Observed toxicities were consistent with historical controls. Adverse events related to study drug were dry mouth and chills. Targeted ascorbate plasma levels of 20 mmol/L were achieved in the 87.5 g cohort; diminishing returns were realized in higher dose cohorts. Median progression-free survival (PFS) was 9.4 months and median OS was 18 months. In subjects with undetectable MGMT promoter methylation (n = 8), median PFS was 10 months and median OS was 23 months. CONCLUSIONS: P-AscH-/RT/TMZ is safe with promising clinical outcomes warranting further investigation.

Weekly cisplatin chemotherapy dosing versus triweekly chemotherapy with concurrent radiation for head and neck squamous cell carcinoma.

BACKGROUND: Triweekly high-dose cisplatin (100 mg/m2 ) with concurrent radiation therapy is the current standard of care in the definitive or appropriate postoperative setting in head and neck squamous cell carcinoma (HNSCC). We compared triweekly 100 mg/m2 with alternative weekly 40 mg/m2 and weekly <40 mg/m2 cisplatin regimens. METHODS: From 2011 to 2016, 163 patients received concurrent cisplatin and intensity-modulated radiotherapy for locally advanced HNSCC. Primary endpoints were overall survival (OS) and progression-free survival. RESULTS: Cisplatin weekly <40 mg/m2 showed inferior OS outcomes when compared to weekly 40 mg/m2 (P = 0.084) and triweekly 100 mg/m2 (P = 0.04) regimens. CONCLUSION: Our study displayed inferior outcomes with weekly cisplatin doses under 40 mg/m2 , suggesting the inferiority of low-dose weekly chemotherapy and the need for ongoing randomized trials to further explore 40 vs 100 mg/m2 chemotherapy regimens.

CASTLE Thyroid Tumor: A Case Report and Literature Review.

Carcinoma showing thymus-like differentiation is a rare tumor of the thyroid gland, which is structurally similar to thymic tissue. Overall, it has a favorable prognosis. Radiotherapy has been shown to be an effective local treatment, but there have been reports of distant recurrence. It has been suggested that adding chemotherapy may decrease the risk of recurrence. Here, we present a case report of a patient with a large tumor and extrathyroidal extension. The patient was treated with surgery, radiotherapy, and cisplatin with acceptable toxicity. The patient is free of locally recurrent or distant disease at 3 years.

SIRT6 minor allele genotype is associated with >5-year decrease in lifespan in an aged cohort.

Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value  = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death.

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PURPOSE: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). METHODS AND MATERIALS: A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. RESULTS: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. CONCLUSION: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.