Search

Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in metastatic castration-resistant prostate cancer (mCRPC). We sought to demonstrate the safety and efficacy of olaparib + radium-223. We conducted a multicenter phase I 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival, and efficacy by homologous recombination repair (HRR) gene status. Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI; 100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLT) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% confidence interval, 27%–80%). Nine patients were evaluable for HRR gene status; 1 had a BRCA2 alteration (rPFS 11.8 months) and 1 had a CDK12 alteration (rPFS 3.1 months). Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase II study.

PURPOSE Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non–muscle-invasive downstaging to < pT2N0. RESULTS Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)–positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 ( P = .3 for association between PD-L1 and < pT2N0). CONCLUSION Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.

Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in metastatic castration-resistant prostate cancer (mCRPC). We sought to demonstrate the safety and efficacy of olaparib + radium-223.We conducted a multicenter phase I 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival, and efficacy by homologous recombination repair (HRR) gene status.Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI; 100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLT) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% confidence interval, 27%–80%). Nine patients were evaluable for HRR gene status; 1 had a BRCA2 alteration (rPFS 11.8 months) and 1 had a CDK12 alteration (rPFS 3.1 months).Olaparib can be safely combined with radium-223 at the RP2D 200 mg orally twice daily with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase II study.

Prostate cancer is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. In the Prostate, Lung, Colorectal, and Ovarian cancer cohort, we calculated the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaire data among 3,517 men and women who provided a blood sample at enrollment. We used these scores in multivariable-adjusted linear regression to validate EDIH and EDIP against relevant circulating biomarkers. In a separate sample of 49,317 men, we used multivariable-adjusted Cox regression to evaluate associations of EDIH and EDIP with prostate cancer (total and subtypes) risk. Participants consuming the most hyperinsulinemic diets (EDIH quintile 5) had significantly higher concentrations of C-peptide, insulin, c-reactive protein, TNFα-R2, and lower adiponectin, than those in quintile 1. Similarly, participants consuming the most proinflammatory diets had significantly higher concentrations of IL6, TNFα-R2, C-peptide, insulin, and lower adiponectin. Men consuming hyperinsulinemic diets were at higher total prostate cancer risk: HRquintile5vs1, 1.11; 95% confidence interval (CI), 1.01–1.23; P trend = 0.03, especially high-grade cancer: HRquintile5vs1, 1.18; 95% CI, 1.02–1.37; P trend = 0.06. The EDIP was not associated with prostate cancer risk. In summary, EDIH and EDIP predicted concentrations of known insulinemic and inflammatory biomarkers, and EDIH further predicted risk of future prostate cancer. Interventions to reduce the adverse role of hyperinsulinemic diets may be a means of prostate cancer prevention.

Supplementary tables

Background Hyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk. Objective To determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality. Design, setting, and participants We prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr. Outcome measurements and statistical analysis Total, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression. Results and limitations During 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35). Conclusions Hyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease. Patient summary Avoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.

Objectives Immune checkpoint inhibitors (ICIs) are being increasingly used across cancer types. Emergency room (ER) and inpatient (IP) care, common in patients with cancer, remain poorly defined in this specific population, and risk factors for such care are unknown. Methods We retrospectively reviewed charts for patients with solid tumors who received >1 ICI dose at 1 of 2 sites from January 1, 2011 to April 28, 2017. Demographics, medical history, cancer diagnosis/therapy/toxicity details, and outcomes were recorded. Descriptive data detailing ER/IP care at the 2 associated hospitals during ICI therapy (from first dose to 3 mo after last dose) were collected. The Fisher exact test and multivariate regression analysis was used to study differences between patients with versus without ER/IP care during ICI treatment. Results Among 345 patients studied, 50% had at least 1 ER visit during ICI treatment and 43% had at least 1 IP admission. Six percent of ER/IP visits eventually required intensive care. A total of 12% of ER/IP visits were associated with suspected or confirmed immune-related adverse events. Predictors of ER care were African-American race (odds ratio [OR]: 3.83, P=0.001), Hispanic ethnicity (OR: 3.12, P=0.007), and coronary artery disease (OR: 2.43, P=0.006). Predictors of IP care were African-American race (OR: 2.38, P=0.024), Hispanic ethnicity (OR: 2.29, P=0.045), chronic kidney disease (OR: 3.89, P=0.006), angiotensin converting enzyme inhibitor/angiotensin receptor blocker medication use (OR: 0.44, P=0.009), and liver metastasis (OR: 2.32, P=0.003). Conclusions Understanding demographic and clinical risk factors for ER/IP care among patients on ICIs can help highlight disparities, prospectively identify high-risk patients, and inform preventive programs aimed at reducing such care.

Background It remains controversial if radical prostatectomy or definitive radiation therapy produces equivalent outcomes in high‐risk localized prostate cancer. Methods We queried The Surveillance, Epidemiology, and End Results (SEER) database for those who received upfront surgery or who were recommended for surgery but instead received radiation. Inverse probability of treatment weighing was used to adjust for covariate imbalance and the weighted Cox proportional hazards model was used to estimate the effects of treatment groups on survival. A meta‐analysis was performed to pool estimates from published studies. Results Among eligible 62 533 patients, 59 540 had upfront surgery and 2993 patients had upfront radiotherapy. EBRT + BT was associated with a superior cancer‐specific survival (CSS) compared with surgery or EBRT alone (HR, 0.55, 95% CI, 0.3‐1.0; HR, 0.49, 95% CI, 0.24‐0.98, respectively), whereas EBRT was associated with an inferior overall survival (OS) compared with surgery (HR, 1.46, 95% CI, 1.16‐1.8). Radiotherapy (EBRT ± BT) was inferior to surgery by OS (HR, 1.63, 95% CI, 1.13‐2.34) in patients ≤ 65 years, and was superior to surgery by CSS in patients > 65 years (HR, 0.69, 95% CI, 0.49‐0.97). The meta‐analysis showed consistent results. Conclusion EBRT + BT was associated with a significantly better prostate CSS compared with surgery or EBRT. EBRT alone was inferior to surgery by OS., In high‐risk localized prostate cancer, radiotherapy with brachytherapy boost was associated with a longer survival outcome, compared with surgery or radiotherapy without brachytherapy boost.

BackgroundThe role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab. For enrollment in track 2 (reported here), patients with histologically confirmed clear cell aRCC, Karnofsky performance status ≥70%, and life expectancy ≥3 months who had previously progressed after IO (anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)) therapy were eligible. Previous treatment with anti-CTLA-4 therapy plus anti-PD-1/PD-L1 therapy precluded eligibility for enrollment in the nivolumab plus ipilimumab arm. Patients were treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for up to 2 years or until progression, toxicity, or protocol-specified discontinuation. The primary outcome measures were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Secondary outcomes were safety and tolerability up to 2 years. Overall survival (OS) was a tertiary/exploratory endpoint. Overall, 46 patients were included with a median follow-up of 33.8 months. The ORR was 17.4% (95% CI, 7.8 to 31.4) with eight (17.4%) patients achieving partial response. Stable disease was achieved in 19 (41.3%) patients, while 14 (30.4%) had progressive disease. Median DOR (range) was 16.4 (2.1+ to 27.0+) months. The PFS rate at 24 weeks was 43.2%, and median OS was 23.8 (95% CI, 13.2 to not reached) months. Grade 3–4 immune-mediated adverse events were reported in seven (15.2%) patients. No treatment-related deaths were reported. Patients with aRCC treated with nivolumab plus ipilimumab may derive durable clinical benefit after progression on previous IO therapies, including heavily pretreated patients, with a manageable safety profile that was consistent with previously published safety outcomes. These outcomes contribute to the knowledge of optimal sequencing of IO therapies for patients with aRCC with high unmet needs.Trial registration numberNCT02996110.

INTRODUCTION AND OBJECTIVE:The role of CN in the treatment of mRCC has been questioned with the recent approval of novel systemic therapy (ST) agents and the results of the CARMENA trial. Our objec...

INTRODUCTION AND OBJECTIVE:IO/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setti...

Background Radiation necrosis (RN) is a potential complication after radiation therapy for brain tumors. It is hypothesized that VEGF plays an important role in the pathophysiology of RN. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse RN. Methods We retrospectively studied a cohort of 102 patients with renal cell carcinoma and brain metastases seen at The Ohio State University James Cancer Center between January 1, 2011 and April 30, 2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN. Results The cumulative incidence of RN is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, P = .741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 vs 315 days, P = .315). One patient developed RN after stopping cabozantinib. Eight patients developed RN while on cabozantinib, pazopanib, or sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently. Conclusions VEGFR TKIs do not consistently prevent RN. The therapeutic effects of VEGFR TKIs against RN warrant further research.

Background DNA damage response (DDR) genomic alterations may play an important role in clinical outcomes of patients with urothelial cancer (UC). However, data on the prognostic role of DDR gene alterations in patients with advanced UC remain unclear. Materials and Methods We retrospectively collected data of three independent patient cohorts with relapsed or advanced UC including 81 and 91 patients from four institutions who underwent FoundationOne genomic sequencing as well as 129 patients selected from The Cancer Genome Atlas bladder cohort. Fisher's exact test was used to determine differences of mutation frequency among the three cohorts. Logistic regression analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI). Overall survival (OS) was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% CI. Results DDR genomic alterations were present in 76.5% (62/81), 40.7% (37/91), and 51.2% (66/129) of the three cohorts. ATM alterations consistently correlated with significantly shorter OS, whereas other DDR alterations (excluding ATM) were associated with better prognosis. In 152 patients treated with platinum pooled from the three cohorts, the prognostic value of alterations in ATM as compared with other predefined DDR genes was substantially different (ATM: adjusted HR [HR], 2.03; 95% CI, 1.03–4; p = .04; other DDR: adjusted HR, 0.49; 95% CI, 0.31–0.8; p = .003). Conclusions Genomic alterations in ATM and other DDR genes may have opposite prognostic value in relapsed and/or advanced UC. ATM may have a complex role in UC progression. Implications for Practice Somatic mutations of DNA damage response (DDR) genes are frequently found in urothelial cancer and appear to play an important role in tumorigenesis, progression, treatment response, and outcomes. In a set of DDR genes, ATM alterations were associated with worse survival, while other alterations were associated with better survival in advanced urothelial cancer. The results of this study suggest a complex role of ATM in tumor progression and call for further studies to determine the underlying mechanisms and biomarker clinical utility.

Prostate cancer is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. In the Prostate, Lung, Colorectal, and Ovarian cancer cohort, we calculated the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaire data among 3,517 men and women who provided a blood sample at enrollment. We used these scores in multivariable-adjusted linear regression to validate EDIH and EDIP against relevant circulating biomarkers. In a separate sample of 49,317 men, we used multivariable-adjusted Cox regression to evaluate associations of EDIH and EDIP with prostate cancer (total and subtypes) risk. Participants consuming the most hyperinsulinemic diets (EDIH quintile 5) had significantly higher concentrations of C-peptide, insulin, c-reactive protein, TNFα-R2, and lower adiponectin, than those in quintile 1. Similarly, participants consuming the most proinflammatory diets had significantly higher concentrations of IL6, TNFα-R2, C-peptide, insulin, and lower adiponectin. Men consuming hyperinsulinemic diets were at higher total prostate cancer risk: HRquintile5vs1, 1.11; 95% confidence interval (CI), 1.01–1.23; P trend = 0.03, especially high-grade cancer: HRquintile5vs1, 1.18; 95% CI, 1.02–1.37; P trend = 0.06. The EDIP was not associated with prostate cancer risk. In summary, EDIH and EDIP predicted concentrations of known insulinemic and inflammatory biomarkers, and EDIH further predicted risk of future prostate cancer. Interventions to reduce the adverse role of hyperinsulinemic diets may be a means of prostate cancer prevention.

Background: Evidence-based practice in geriatric oncology is growing, and national initiatives have focused on expanding cancer care and research to improve health outcomes of older adults. However, there are still gaps between knowledge and practice for older adults with cancer. Methods: The Cancer and Aging Resiliency (CARE) clinic is a multidisciplinary approach for implementing geriatric-driven health care for older adults with cancer. The CARE clinic was developed as a direct response to recommendations targeting key multifactorial geriatric health conditions (e.g. falls, nutritional deficits, sensory loss, cognitive impairment, frailty, multiple chronic conditions, and functional status). We review the influence of these factors across the cancer care trajectory, including at screening, diagnosis, and treatment and discuss ways in which these conditions may be targeted to improve cancer care in older adults. Results: The CARE clinic was implemented at The Ohio State University Comprehensive Cancer Center (OSUCCC) and targets modifiable risk factors affecting outcomes in older adults with cancer: weight loss, polypharmacy, physical impairments, social support, and mood symptoms. The multidisciplinary team at the CARE clinic discusses and delivers a comprehensive set of recommendations, all in one clinic visit, to minimize burden on the patient and the caregiver. The CARE clinic is part of a set of initiatives that feature education of future leaders in geriatric oncology, survivorship care for an aging population, and outcomes research. Conclusions: Older adults with cancer have a unique set of needs that need to be taken into account throughout their cancer care. The CARE clinic model is an important example of an approach that may combat these difficulties and lead to better outcomes among older adults with cancer.

Background: Older adults with hematologic malignancies have inferior survival outcomes due to multiple factors including under-treatment, drug toxicity, treatment discontinuation and concerns of frailty. However, aging is heterogeneous and chronological age is a poor indicator of underlying health. Standardizing the approach to identify frailty is an unmet need in malignant hematology. We have established a multi-disciplinary clinical model designed to identify frailty and develop personalized treatment based on objective measures of health. We have standardized a geriatric assessment (GA) model to identify vulnerability, frailty and geriatric syndromes. Here we report, the largest cohort to date, of older adults with hematologic malignancies (HM) depicting geriatric deficits and interventions with long-term clinical outcomes. Methods: From Feb 2016 to October 2019, 311 older adults with HM were evaluated in our multi-disciplinary Cancer and Aging Resiliency (CARE) clinic. The CARE clinic is a 7-member team prescriptively evaluating the following domains: pharmacy, audiology, psychosocial needs, nutrition, physical functioning, and cognition. Geriatric syndromes were documented by CARE physician. Referral to CARE clinic is recommended for patients 60 years of age or older but all referrals are accepted independent of age. Data was abstracted by retrospective chart review. Descriptive statistics for patient characteristics, frailty measures, and prescribed interventions in each of the GA domains were provided. Univariable and multivariable Cox models were fit to associate clinical factors with OS. OS by Rockwood Clinical Frailty Scale and deficits in activities of daily living (ADLs) was evaluated by Kaplan-Meier method. Correlation between number of geriatric syndromes, clinical frailty score, and deficits in ADLs and instrumental ADLs (IADLs) was also assessed. Results: Over the 42-month study period, 311 older adults with HM with a median age of 75.9 years were evaluated in CARE clinic. Key demographic features and the frequency of specific frailty measures are outlined in table 1.Geriatric interventions were common with 59% requiring 1-2 interventions and 34% requiring 3+ interventions. In univariable analysis, any degree of frailty by Clinical Frailty Scale (Hazard Ratio [HR]: 2.63, 95% Confidence Interval [CI]: 1.43-4.82, p Discussion: The Clinical Frailty Scale is predictive of OS among older adults with HM. GA-directed intervention is warranted in the vast majority of older adults with HM. In univariable analysis, Clinical Frailty Scale, increasing age, anemia, high risk HM, and increasing geriatric syndromes are associated with inferior OS. In multivariable analysis, age, anemia, and high risk HM remain significant. Nutrition and physical function are key modifiable risk factors predictive of inferior OS. Prospective studies focusing on geriatric interventions are warranted in this population with an emphasis on modifiable risk factors. This demonstrated prognostic significance of both geriatric assessments and interventions in older adults with HM should give way to future improvements in OS, quality of life, and treatment tolerability through GA-directed intervention. Disclosures No relevant conflicts of interest to declare.

Background Evidence-based practice in geriatric oncology is growing, and national initiatives have focused on expanding cancer care and research to improve health outcomes for older adults. However, there are still gaps between knowledge and practice for older adults with cancer. Main text Here we provide a detailed methodology of geriatric oncology care delivery within a single institution. The Cancer and Aging Resiliency (CARE) clinic is a multidisciplinary approach for implementing geriatric-driven health care for older adults with cancer. The CARE clinic was developed as a direct response to recommendations targeting key multifactorial geriatric health conditions (e.g. falls, nutritional deficits, sensory loss, cognitive impairment, frailty, multiple chronic conditions, and functional status). The multidisciplinary team assesses and delivers a comprehensive set of recommendations, all in one clinic visit, to minimize burden on the patient and the caregiver. The CARE clinic consultative model is a novel approach integrating cancer subspecialties with geriatric oncology healthcare delivery. Conclusions Older adults with cancer have unique needs that are independent of routine oncology care. The CARE clinic model provides specific assessments and interventions to improve health outcomes among older adults with cancer.

Older adults with cancer have comorbidities that require medical management and confounders of chemotherapy and supportive medications exacerbate polypharmacy. A multidisciplinary team model was created to address these needs within the Cancer Aging and Resiliency (CARE) clinic. To reconcile medications for accuracy, compliance, side effects, and effectiveness, a pharmacist-led audit includes identification of potential therapeutic duplications, drug-drug interactions, or potential medication inappropriateness identified using Beers criteria. A pharmacist led review of patient’s prescriptions can identify drug therapy problems (DTP) and result in safer medication management. METHODS: A retrospective review of pharmacy specific interventions was conducted using CARE Clinic patient data from February 2016 to October 2019 evaluating data from n=259 patients. RESULTS: A preliminary analysis of n=137 patients who had received medication reconciliation were included. The mean number of medications per patient was 13.1 ± 5.7 and 457 DTP were identified leading to 523 medication related interventions. There was an average of 3.3 DTP per patient. The most common types of DTP included medication reconciliation (n=137, 30.0%), potentially inappropriate medication (PIM) (n=74, 16.2%), administration/technique (n=35, 7.7%), and drug-drug interaction (n=28, 6.1%). The most frequent types of interventions involved education to the patient (n=166, 31.7%), medication reconciliation (n=137, 26.2%), medication discontinuation (n=84, 16.1%), patient to discuss further with physician (n=39, 7.5%), and medication initiated (n=35, 6.7%). Updated results involving approximately 259 patients will be presented. CONCLUSION: Comprehensive medication review within a multidisciplinary setting for the management of older adults with cancer can reduce polypharmacy and inappropriate medication use.

INTRODUCTION Radiation necrosis (RN) is a potential complication after radiation therapy to primary brain tumors and brain metastases. The pathophysiology of RN is not well understood but it is hypothesized that vascular endothelial growth factor (VEGF) plays an important role. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse cerebral radiation necrosis METHODS We retrospectively studied a cohort of 102 patients with renal cell carcinoma (RCC) and brain metastases seen at The Ohio State University James Cancer Center between 01/01/2011 and 04/30/2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN. RESULTS The cumulative incidence of RN in our cohort is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, p= 0.741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 versus 315 days, p=0.315). One patient developed RN after stopping cabozantinib. Three other patients developed RN while on cabozantinib. Two patients developed RN while on pazopanib, and 3 patients developed RN while on sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently. CONCLUSIONS VEGFR TKIs do not consistently prevent or reverse cerebral radiation necrosis and do not seem to have the efficacy that bevacizumab has against RN.

Background: Some cancer patients with thromboembolism require dual treatment of VEGFR TKIs and factor Xa inhibitors (direct or indirect), which may contribute to increased bleeding risks. However, the safety of such combination treatment has not been well characterized in the literature or national guidelines. Methods: This is a single center retrospective study, where we identified metastatic cancer patients (renal cancer, colorectal cancer, sarcoma, etc) who received concurrent VEGFR TKIs (pazopanib, sunitinib, sorafenib, axitinib, regorafenib, vandetanib, lenvatinib or cabozantinib) and Xa inhibitors (low-molecular weight heparin [LMWH] or direct oral anticoagulants [DOACs] including rivaroxaban or apixaban) at the Ohio State University Medical Center. We assessed bleeding risks of dual therapies vs. factor Xa inhibitors alone, using the same patients as self controls. We reviewed medical charts of all identified patients for clinically significant bleeding events (defined as combined major bleeding and clinically relevant non-major bleeding by the International Society of Thrombosis and Haemostasis criteria). The Cox proportional hazard model was used to compare the differences of time to first clinically significant bleeding event between the groups of concurrent use and anticoagulant use only. Results: A total of 86 patients (26 females and 60 males) were included: 78 Caucasians, 6 African Americans, and 2 others. 81 patients had concurrent TKI and LMWH treatment; 20 patients had concurrent TKI and DOACs; and 85 patients have had been on factor Xa inhibitor alone (LMWH or DOACs) at some point. Some patients had been on both LMWH and DOACs at different time periods. Overall, there were 29 clinically significant bleeding events (including 8 major bleeding) during concurrent treatment and 17 events (4 major bleeding) during factor Xa inhibitor alone over a median follow up of 63 days (52 days for concurrent treatment and 99 days for Xa inhibitor alone). In this self-control study, concurrent treatment was associated with a statistically higher risk of clinically significant bleeding events (HR, 2.84; 95% CI, 1.43-5.64, P < 0.01), which reached 37% patient population in the first 3 months, while the bleeding associated with factor Xa inhibitor alone seemed spaced out at the entire length of anticoagulation (8% by 6 months). Similar trend was found in the analysis of patient group of concurrent TKI and LMWH vs. LMWH alone (HR, 1.96; 95% CI, 0.95-4.02, P = 0.067), although significance was not reached likely due to insufficient power. Sample size was inadequate for meaningful comparison between concurrent VEGFR TKI and DOAC vs. DOAC alone. Conclusions: Concurrent treatment of VEGFR TKI and factor Xa inhibitors is associated with a significantly increased bleeding risks when compared with factor Xa inhibitors alone in patients with metastatic cancer. Disclosures No relevant conflicts of interest to declare.