Protocol for the Pilot Study of Group Video Yogic Breathing App in Breast Cancer Survivors.

INTRODUCTION: Breast cancer remains a leading cause of cancer deaths; however, recent improvements in treatment have improved survivorship. As a result of this improvement, more individuals are living with the long-term side effects of cancer treatment. Therefore, methods that incorporate lifestyle and mind-body approaches are becoming increasingly used in the patient treatment pathway. METHODS: In this study, PranaScience Institute will develop and test a group video mobile application for Yogic Breathing (YB). YB is shown to reduce symptomatic conditions associated with several conditions including breast cancer. For this initial feasibility study, PranaScience will collaborate with the Medical University of South Carolina to implement the study app-based program in breast cancer survivors. This research is aimed to understand if the YB could be delivered via an app, if participants are able to practice it satisfactorily, and if there is any symptom relief by the YB practice. In the control group, participants will be directed to the Attention Control (AC) feature of the app, which guides users to focus on a mindfulness activity not involving YB. Participants will be randomly assigned to the YB or AC study plan (N = 20 per group). Breast cancer survivors who have completed radiation therapy within last 2 months will be recruited for this study and provided access to the app for a 12-weeks program. The study app will record total practice times. Virtual visits by a study yoga instructor during group video sessions will measure participant compliance with proper technique. Feasibility will be examined by evaluating intervention delivery factors and resource needs. Acceptability of using the mobile study app to support symptom management will be evaluated using a satisfaction and system usability scale. Behavioral survey measures will help guide effect sizes and power calculations for the next larger-scale study. Biomarkers in the saliva (tumor suppressors, cytokines), and fingernails (cortisol, differential proteomics) will be measured at baseline and end of study at 12 weeks. DISCUSSION: All findings from this pilot study will be synthesized to refine the mobile study app in preparation for large-scale evaluation in Phase II involving all-study site participants with cancer. ClinicalTrials.gov Identifier NCT05161260.

Final Analysis of a Phase 2 Trial of Once Weekly Hypofractionated Whole Breast Irradiation for Early-Stage Breast Cancer.

PURPOSE: We hypothesize that 5-fraction once weekly hypofractionated (WH) whole breast irradiation (WBI) would be safe and effective after breast-conserving surgery for medically underserved patients with breast cancer. We report the protocol-specified primary endpoint of in-breast tumor recurrence (IBTR) at 5 years. METHODS AND MATERIALS: After provided informed consent, patients were treated with WH-WBI after breast-conserving surgery were followed prospectively on an institutional review board-approved protocol. Women included in this study had stage 0-II breast cancer treated with negative surgical margins and met prespecified criteria for being underserved. WH-WBI was 28.5 or 30 Gy delivered to the whole breast with no elective coverage of lymph nodes. The primary endpoint was IBTR at 5 years. Secondary endpoints were distant disease-free survival, recurrence-free survival, overall survival, adverse events, and cosmesis. RESULTS: One hundred fifty-eight patients received WH-WBI on protocol from 2010 to 2015. Median follow-up was 5.5 years (range, 0.2-10.0 years). Stage distribution was 22% ductal carcinoma in situ, 68% invasive pN0, and 10% invasive pN1. Twenty-eight percent of patients had grade 3 tumors, 10% were estrogen receptor negative, and 24% required adjuvant chemotherapy. There were 6 IBTR events. The 5-, 7-, and 10-year risks of IBTR for all patients were 2.7% (95% confidence interval [CI], 0.89-6.34), 4.7% (95% CI, 1.4-11.0) and 7.2% (95% CI, 2.4-15.8), respectively. The 5-, 7-, and 10-year rates of distant disease-free survival were 96.4%, 96.4%, and 86.4%; the recurrence-free survival rates were 95.8%, 93.6%, and 80.7%; and the overall survival rates were 96.7%, 88.6%, and 76.7%, respectively. Improvement in IBTR-free time was seen in ductal carcinoma in situ, lobular histology, low-grade tumors, T1 stage, Her2-negative tumors, and receipt of a radiation boost to the lumpectomy bed. CONCLUSIONS: Postoperative WH-WBI has favorable disease-specific outcomes that are comparable to those seen with conventional and moderately hypofractionated radiation techniques. WH-WBI could improve access to care for underserved patients with stage 0-II breast cancer.

Financial Toxicity in Women With Breast Cancer Receiving Radiation Therapy: Final Results of a Prospective Observational Study.

PURPOSE: We sought to quantify financial toxicity (FT) present in a prospective cohort of women with breast cancer (BC) receiving radiation therapy (RT), identify predictors of FT, correlate FT with health-related quality of life (QoL), and determine whether duration of RT is associated with FT. METHODS AND MATERIALS: Consecutive patients with stage I-III BC completed Functional Assessment of Cancer Therapy-G7 (FACT-G7), a tailored FT questionnaire, and Comprehensive Score for Financial Toxicity (COST) scoring within 1 month of RT completion. Lower scores on FACT-G7 (range, 0-28) and COST (range, 0-44) indicate worse QoL and FT. Group comparisons were performed with a 2-sample t test and χ2 tests for continuous and categorical variables, respectively. Pearson correlation was used to associate COST with FACT-G7. Linear and multiple regression were used to evaluate predictors of COST. RESULTS: One hundred eight enrolled patients were eligible for analysis with completed COST scores, including 56, 42, and 10 patients treated with long-, intermediate-, and short-course RT. Mean COST score was 28.6 and mean FACT-G7 was 18.4. Among patients treated with intermediate- and long-course RT (n = 98), marital status (higher COST associated with married status relative to other), medication cost (higher COST for no significant medication costs relative to significant medication costs), employment type (lower COST associated with disabled status or unemployed, higher COST with retired status relative to working), and surgery type (higher COST for lumpectomy relative to mastectomy) were significantly associated with COST score by multivariable analysis (all P values < .05). RT length group was not associated with COST (P = .79). COST and FACT-G7 were strongly correlated for the overall cohort (P < .0001). CONCLUSIONS: In this prospective study of women with BC receiving RT, distinct factors including surgery type were significantly associated with FT. FT was strongly correlated with health-related QoL. Increased characterization of the relationship between FT and health-related QoL for women with BC receiving RT and defining clinical predictors of FT may help guide future studies investigating optimal targeted interventions for patients with BC at high risk for FT.

Development of a Financial Toxicity Screening Tool for Radiation Oncology: A Secondary Analysis of a Pilot Prospective Patient-Reported Outcomes Study.

PURPOSE: Financial toxicity is highly prevalent in oncology. Early identification of at-risk patients is essential because financial toxicity is associated with inferior outcomes. Validated general oncology screening tools are cumbersome and not specific to challenges related to radiation therapy, such as daily treatments. In the population of radiation oncology patients, no standardized, validated, rapid screening tool exists. We sought to develop a rapid, no-cost, and reliable financial-toxicity screening tool for clinical radiation oncology. METHODS AND MATERIALS: We retrospectively analyzed data from a prospective survey study conducted at a large referral center with a heterogeneous population. Before treatment, a 25-item modified comprehensive survey for financial toxicity incorporating subjective and objective patient-reported measures was administered to identify factors linked to the risk of developing financial toxicity, which was defined as radiation therapy resulting in any of the following: loss of income, job, or spouse or difficulty paying for meals, housing, or transportation. We applied a logistic regression model with a stepwise, backward model selection procedure. Estimated probabilities of experiencing financial toxicity were computed using the inverse-logit transformation of the sum of patient-specific predictor values multiplied by the coefficients of the selected logistic regression model. The Youden index was used to determine a reasonable risk threshold. RESULTS: A total of 157 patients completed the questionnaire, and 34 (22%) were assessed as experiencing financial toxicity. The model retained 3 factors: age, money owed, and copayment-related worries. It resulted in a concordance statistic of 0.85, developed with a risk threshold of 18% (Youden index, 0.59). This model conferred a sensitivity of 89%, specificity of 70%, positive predictive value of 44%, and negative predictive value of 96%. CONCLUSIONS: Our proposed financial-toxicity screen is rapid, free, sensitive, and specific, and in this study, it identified early-onset, patient-reported financial toxicity after radiation therapy with just 3 simple variables: age, money owed, and copayment-related concerns. Future research steps should include a validation cohort and identification of interventions to mitigate financial toxicity.

Trends in Incidence and Mortality Rates of Uterine Cancer in Kentucky.

OBJECTIVES: The objective of this analysis was to gauge how the incidence and mortality of uterine cancer in Kentucky have changed from 1995 through 2017. An assessment of the trends in incidence and mortality across different geographic areas and between different races was also performed. METHODS: Age-adjusted annual incidence and mortality rates for uterine cancer were obtained from the Kentucky Cancer Registry. A meta-regression framework was used to assess changes in incidence and mortality rates during the time frame and to determine differences in these rates between rural versus urban counties, Appalachian versus non-Appalachian counties, and Black versus White women. RESULTS: The incidence of uterine cancer has significantly increased throughout the state of Kentucky since 1995. Uterine cancer incidence was 10% and 22% higher in rural and Appalachian counties, respectively, compared with urban and non-Appalachian counties (P < 0.0001) from 1995 through 2017. In contrast, urban and non-Appalachian women had higher or equivalent age-adjusted mortality from uterine cancer, compared with rural and Appalachian women, respectively. The incidence of uterine cancer was significantly higher in White women compared with Black women from 1995 through 2006, but since 2007, there has been no significant difference in uterine cancer incidence based on race. Black women had higher age-adjusted mortality than White women throughout the entire time period examined. CONCLUSIONS: The incidence of uterine cancer is higher in rural and Appalachian Kentucky, without a corresponding geographic trend in mortality. Uterine cancer mortality is significantly higher in Black women.

Vaginal cuff brachytherapy: do we need to treat to more than a two-centimeter active length?

PURPOSE: American Brachytherapy Society (ABS) guidelines recommend using a 3-5 cm active length (AL) when treating vaginal cuff (VC) in adjuvant setting of endometrial cancer (EC). The purpose of this study was to evaluate local control and toxicity, using an AL of 1 or 2 cm and immobilization with a traditional table-mounted (stand) or patient-mounted (suspenders) device. MATERIAL AND METHODS: Between 2005 and 2019, 247 patients with EC were treated with adjuvant high-dose-rate vaginal cuff (HDR-VC) brachytherapy with or without external beam radiation (EBRT). Treatment was prescribed to a 0.5 cm depth, with an AL of 1 or 2 cm, using stand or suspenders. VC boost after EBRT was typically administered with 2 fractions of 5.5 Gy, while VC brachytherapy alone was typically applied with 3 fractions of 7 Gy or 5 fractions of 5.5 Gy. RESULTS: The combination of suspender immobilization and an AL of 2 cm (n = 126, 51%) resulted in 5-year local control of 100%. An AL of 2 cm compared to 1 cm correlated with better local control (99.1% vs. 88.5%, p = 0.0479). Regarding immobilization, suspenders correlated with improved local control compared to stand (100% vs. 86.7%, p = 0.0038). Immobilization technique was significantly correlated with AL (p < 0.0001). Only 5 (2.0%) patients experienced grade ≥ 3 toxicity, all of whom received EBRT. CONCLUSIONS: In the present series, an AL of 2 cm provided excellent local control, while 1 cm was inadequate. Suspender immobilization was a practical alternative to stand immobilization in HDR brachytherapy of the vaginal cuff.

Role of adjuvant chemotherapy in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with surgery and post-operative radiotherapy.

BACKGROUND: The optimal treatment of patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown. OBJECTIVE: To compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without chemotherapy in this group of patients. METHODS: Patients diagnosed between January 2004 and January 2016 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant concurrent chemotherapy were identified in the National Cancer Database. Overall survival was assessed with Kaplan-Meier curves. A Cox model was constructed to evaluate survival after controlling for confounding variables. A logistic regression model was used to reveal predictors of chemotherapy use. RESULTS: A total of 2173 patients were included. The receipt of chemotherapy was associated with an increased 5-year overall survival from 67.6% to 75.6% (p=0.0313). This association trended toward statistical significance on multivariate analysis (adjusted HR (aHR) 0.80; 95% CI 0.63 to 1.01; p=0.0653). Other factors associated with improved survival were undergoing a lymphadenectomy, absence of lymphovascular space invasion, younger age, smaller tumor size, non-black race, and absence of comorbidities. Patients who underwent brachytherapy, had lymphovascular space invasion, were younger, were diagnosed in the more recent years, and were treated in higher volume centers were more likely to receive adjuvant chemotherapy. CONCLUSION: Adjuvant chemotherapy and radiation therapy were associated with an increase in survival in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma compared with those treated with adjuvant radiotherapy alone.

A Phase II Trial of Once Weekly Hypofractionated Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: To report an interim analysis of a phase II trial of once weekly, hypofractionated breast irradiation (WH-WBI) following breast conserving surgery (BCS). METHODS: Patients had stage 0-II breast cancer treated with breast BCS with negative margins. WH-WBI was 28.5 or 30Gy delivered to the whole breast using tangential beams with no elective coverage of lymph nodes. The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were distant disease-free survival (DDFS), recurrence free survival (RFS), overall survival (OS), adverse events and cosmesis. RESULTS: From 2011 to 2015, 158 patients received WH-WBI. Median follow up was 4.4 years (range 0.2-8.1). Stage distribution was DCIS 22%; invasive pN0 68%; invasive pN1 10%. 80 patients received 30 Gy and 78 received 28.5 Gy with median follow up times of 5.6 and 3.7 years, respectively. There were 5 IBTR events, all in the 30 Gy group. The 5- and 7- year risks of IBRT for all patients were 2.2% (95% CI 0.6-5.8) and 6.0% (95% CI 1.1-17.2), respectively. The 7-year rates of DDFS, RFS, and OS were 96.3%, 91.5% and 89.8%, respectively. Improvement in IBTR-free time was seen in DCIS, lobular histology, low grade tumors, Her2 negative tumors and 28.5 Gy dose (all p < 0.0001). CONCLUSIONS: Disease-specific outcomes after WH-WBI are favorable and parallel those seen with conventional radiation techniques for stage 0-II breast cancer.

The impact of brachytherapy boost and radiotherapy treatment duration on survival in patients with vaginal cancer treated with definitive chemoradiation.

PURPOSE: Vaginal cancer is a rare tumor that is optimally treated with a combination of chemotherapy (CHT) and radiation therapy. Because of the rarity of this cancer, the benefit of a brachytherapy boost (BT) and the relevance of radiotherapy time to treatment completion (TTC) are unclear. METHODS: Patients diagnosed between 2004 and 2015 with non-metastatic vaginal cancer treated with definitive CHT and external beam radiotherapy with or without BT but with no surgery were identified in the National Cancer Database. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. A Cox model using a penalized spline function was constructed to evaluate how the length of radiation therapy correlated with OS among patients receiving BT. RESULTS: A total of 1094 patients who met the inclusion criteria were identified. The utilization of BT was associated with improved 5-year OS (62.9% vs. 49.3%, p = 0.0126) on propensity score-weighted analyses. TTC of 63 days or less was associated with improved 5-year OS (67.8% vs. 54.5%, p = 0.0031) in patients who underwent BT. Other factors associated with improved OS in patients who received CHT, external beam radiotherapy, and BT were younger age, absent comorbidity score, and negative lymph nodes. CONCLUSIONS: A brachytherapy boost and shorter TTC were associated with a survival benefit in a cohort of patients with non-metastatic vaginal cancer treated with definitive chemoradiotherapy.

The effect of omission of adjuvant radiotherapy after neoadjuvant chemotherapy and breast conserving surgery with a pathologic complete response.

OBJECTIVE(S): Neoadjuvant chemotherapy (NAC) is a standard of care for locally advanced breast cancers. Adjuvant radiotherapy (RT) after NAC is an area of active research. We hypothesize overall survival (OS) is not altered by omitting RT in women with a pathologic complete response (pCR) to NAC after breast conserving survery (BCS). METHODS: Patients from the National Cancer Database who underwent NAC, BCS, and had a pCR were included. Inflammatory disease, <6 months follow up, and unknown variables were excluded. Descriptive statistics characterized the retained cohort. Logistic regression analyzed the influence of variables on the rate of RT omission. Cox proportional hazard modeling analyzed the influence of prognostic variables on OS. RESULTS: Of 5383 women included, 364 (7%) omitted RT. 5-year OS was 94.1% with RT, 93% without. RT omission was most likely in women >70yo (adjusted OR2.4, 95%CI 1.58-3.65, p < .0001;reference 40-49 yo), Hispanic (AOR 1.73, 95%CI 1.19-2.52, p = .0044; reference non-Hispanic), ≥20 miles from treatment facility (20-49 miles; AOR 1.45, 95%CI 1.09-1.93, p = .0109: >50 miles; AOR 2.02, 95%CI 1.42-2.87, p < .0001;reference 0-19 miles), grade 1 (AOR 4.29, 95%CI 2.16-8.51, p < .0001; reference grade 3), and clinical T4 disease (AOR 3.17, 95%CI 1.74-5.79, p = .0002; reference T0/1). Women ≥60yo (60-69: AHR 2.33, 95%CI 1.41-3.83, p = .0009:70+:AHR 2.4, 95%CI 1.24-4.62, p = .0092; reference 40-49) and with N1 and N3 disease (N1: AHR 1.67, 95% CI 2.28-3.24, p = .0034; N3: AHR3.37,95%CI2.01-5.65,p < .0001) showed increased death. Triple-positive (AHR 0.18, 95%CI 0.07-0.43, p = .0002) and HER2+ patients (AHR 0.44, 95%CI 0.30-0.64, p < .0001) had improved OS compared to triple-negative disease. No survival difference was seen with omission of RT (log-rank test: p = .1783; Cox model AHR 1.33, 95%CI 0.76-2.31, p = .3181). CONCLUSION: Women ≥70, of Hispanic origin, living ≥20 miles from treatment facility, and grade 1 disease were more likely to omit RT. HER2+ patients had favorable OS, while older age and N3 disease were negative prognostic factors. Omitting RT after a pCR to NAC and BCS was not found to affect OS.

Patient-Reported Outcomes and Cosmesis After Once-Weekly Hypofractionated Breast Irradiation in Medically Underserved Patients.

PURPOSE: To evaluate patient-reported outcomes (PROs) and cosmesis from a phase 2 trial of once-weekly hypofractionated breast irradiation (WH-WBI) after breast-conserving surgery (BCS). METHODS AND MATERIALS: Patients had stage 0-II breast cancer treated with BCS and negative margins. WH-WBI was 28.5 to 30 Gy in 5 weekly fractions of 5.7 to 6 Gy delivered with or without a boost. PROs were collected for 3 years after treatment using the Breast Cancer Treatment Outcome Scale (BCTOS) and European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23). Physicians rated cosmetic outcome with the Global Cosmesis Score. Longitudinal growth models were used to assess changes in BCTOS across time, and baseline values and changes between time points were correlated with patient and treatment factors. RESULTS: From 2011 to 2015, 158 women received WH-WBI, and 148 were eligible for analysis after a median follow-up of 39.3 months. Adverse changes (P < .001) in global BCTOS score and breast pain and arm function subscores were observed 6 months after radiation therapy, followed by improvement to near-baseline values at years 1 and 3. Adverse changes in BCTOS cosmetic subscore were also detected at 6 months (P < .001), with no significant improvement at 1 (P = .385) and 3 (P = .644) years. No effect was detected for longitudinal changes in BCTOS scoring for age, body mass index, diabetes, smoking, breast volume, tumor size, seroma volume, dosimetric factors, dose, boost, or systemic therapy. Physician-rated cosmesis at 3 years was excellent/good in 89% and fair/poor in 11%. CONCLUSIONS: WH-WBI was associated with transient worsening in arm function and breast pain but persistent adverse changes in cosmetic PROs that were typically mild or moderate in severity. Physician-rated cosmetic outcomes were acceptable.

Cervical cancer incidence and mortality rates in Kentucky.

OBJECTIVES: The goal of this study was to assess how the incidence and mortality of cervical cancer in Kentucky has changed from 1995 through 2017. Additionally, trends in incidence and mortality across different geographic areas and between different races were evaluated. METHODS: Age-adjusted annual incidence and mortality rates for cervical cancer were collected from the Kentucky Cancer Registry (KCR). A quadratic fit model was used to evaluate changes in the incidence and mortality over time and to compare differences in cervical cancer incidence and mortality by: 1) rural versus urban counties, 2) Appalachian versus non-Appalachian counties, and 3) black versus white women. RESULTS: Overall, the incidence of cervical cancer has significantly decreased throughout Kentucky since 1995. When comparing different geographic regions, the incidence was 14% and 23% higher in rural and Appalachian counties, respectively, compared to urban and non-Appalachian counties (p < 0.0001) throughout the study period. The incidence of cervical cancer was significantly higher in black women compared to white women from 1995 through 2007, but since 2008 there has been no significant difference in cervical cancer incidence based on race. Similar to incidence rates, mortality from cervical cancer was 29% higher in Appalachia (p = 0.0004) throughout the studied time period. Black women had higher age-adjusted mortality than white women until 2012, but since that time there has not been a significant difference in cervical cancer mortality based on race. CONCLUSIONS: Women residing in rural and Appalachian Kentucky have higher cervical cancer incidence and mortality rates.

Evaluating patterns of utilization of gene signature panels and impact on treatment patterns in patients with ductal carcinoma in situ of the breast.

BACKGROUND: Broad patterns of use of the gene signature panel Oncotype DX DCIS and its large-scale impact on postoperative administration of radiation therapy in women with ductal carcinoma in situ of the breast remain unclear. This study sought to evaluate the patterns of use of this gene signature panel in women with ductal carcinoma in situ and the impact of these tools on postoperative radiation therapy administration. METHODS: The National Cancer Database was queried for women with ductal carcinoma in situ treated with breast-conserving therapy who had information regarding whether a gene signature panel was performed between 2010 and 2015. Demographic characteristics, the characteristics of their ductal carcinoma in situ, and whether they received postoperative radiation therapy were compared among patients who did have a gene signature panel performed and those who did not. Patterns of radiation therapy administration were also evaluated based on the recurrence risk score by the gene signature panel. RESULTS: Gene signature panel use increased over time, with a sharp increase in utilization occurring in 2015 (8.0% in 2015 vs 4.4% in 2014, P < .001). Patients with estrogen receptor-positive ductal carcinoma in situ were somewhat more likely to have a gene signature panel ordered (3.9% estrogen receptor positive vs 1.7% estrogen receptor negative, P < .001), as were patients with lower-grade ductal carcinoma in situ (4.5% grade I/II vs 3.1% grade III, P < .001). Gene signature panel utilization was associated with a decrease in the administration of postoperative radiation therapy (48.6% gene signature panel vs 83.4% no gene signature panel, P < .001). Among patients in whom a gene signature panel was performed, postoperative radiation therapy was administered in 81.9%, 72.0%, and 35.9% of patients with high-, intermediate-, and low-recurrence scores, respectively. CONCLUSION: Gene signature panel use in patients with ductal carcinoma in situ has increased over time and is more commonly used in women with lower-risk, clinicopathologic features to determine the magnitude of benefit afforded by radiation therapy. Gene signature panel use is associated with decreased rates of postoperative radiation therapy administration, particularly among patients with scores suggesting a low rate of recurrence.

Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence matter?

PURPOSE/OBJECTIVES: We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG. MATERIALS/METHODS: After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed. Patients from this group who had received BEV were also identified. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were analyzed as study endpoints. Date of recurrence was defined as the date of radiographic evidence of progressive/recurrent disease. Kaplan-Meier curves were generated utilizing a log-rank test with a p-value ≤ 0.05 considered significant to compare treatment sequences in terms of survival outcomes. RESULTS: A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT. Patient characteristics were as follows: median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months. For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only). In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively. In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75). CONCLUSIONS: The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.

Patients Undergoing Radiation Therapy Are at Risk of Financial Toxicity: A Patient-based Prospective Survey Study.

PURPOSE: Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, currently, no financial toxicity screening tools have been validated for use in radiation oncology. METHODS AND MATERIALS: Physician surveys were used to gauge provider understanding of treatment costs and their willingness to adopt the use of financial toxicity screening tools. Post-treatment patient surveys were used to investigate the covariates of treatment-induced financial risk. RESULTS: Of the 210 radiation oncologists who completed our survey, 53% reported being "very concerned" with treatment-related costs negatively affecting their patients, and 80% believed that a financial toxicity screening tool would be useful in practice. An analysis of patient surveys using logistic regression found age and cancer site to be the most important variables associated with financial toxicity. Thirty-four patients (22%) experienced financial toxicity related to treatment. The financial toxicities experienced were loss of job (28%), loss of income (24%), difficulty paying their rent or mortgage (20%), difficulty paying for transportation (15%), and difficulty paying for meals (13%). CONCLUSIONS: Financial toxicity is an important measure for patients and providers and is experienced by approximately one quarter of patients. Further studies to improve models to predict financial toxicity and how financial toxicity is related to patient outcomes and quality of life are warranted.

Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases.

PURPOSE: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. METHODS AND MATERIALS: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The ClinicalTrials.gov registration number is NCT01703507. RESULTS: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively. CONCLUSIONS: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted.

Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. MATERIALS/METHODS: In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). RESULTS: Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was 1.9×10/L in patients receiving Radium alone, versus 2.3×10/L in patients receiving concurrent therapy (P=0.77). Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone, versus 1.8 g/L in patients receiving concurrent therapy (P=0.31). Mean change from initial platelet count to nadir was 52.3×10 cells/L in patients receiving Radium alone versus 70.6×10 cells/L in patients receiving concurrent therapy (P=0.39). Individual blood counts for each measured laboratory are included in the supplemental data. PSA was stable or decreased in 22% of patients receiving Radium alone versus 35% of patients receiving combination treatment (P=0.24). CONCLUSIONS: Concurrent administration of Radium-223 and next-generation antiandrogen therapies appears to be well tolerated with similar toxicities to standard administration of Radium-223 alone. This particular cohort of patients represents a high-risk, heavily pretreated group of patients with advanced metastatic disease and significant marrow burden. Despite these risk factors, hematologic toxicity was modest and was in the range expected for this risk group based on previous trials. To date, this is the first study investigating the toxicity of combination treatment. Further studies investigating the safety and efficacy of combination treatments are warranted.

Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.

OBJECTIVES: To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). METHODS: A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography-derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. RESULTS: A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (<225 g) was associated with a significantly longer median OS than was a TGA≥225 g (17.2 vs. 9.7 mo, P=0.01). CONCLUSIONS: Yttrium-90 microsphere brachytherapy provided favorable survival times in patients with unresectable liver metastases from uveal melanoma. Metabolic tumor volume and TGA are predictive functional tumor parameters, which may aid patient selection and risk stratification.