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BACKGROUND: Diabetes is a well-established risk factor for many cancers, but its relationship with lung cancer incidence remains unclear. In this study, we aimed to assess if diabetes is independently associated with lung cancer risk and histology subtype among participants in a screening study. METHODS: In a retrospective cohort study using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) study, we assessed the association of self-reported diabetes with lung cancer incidence using Poisson regression while adjusting for other established risk factors in the PLCOM2012, a validated lung cancer prediction model. The adjusted association of diabetes and lung cancer cell type was evaluated using nominal regression. Stratified analyses were also conducted according to sex, smoking history, and body mass index categories. RESULTS: Overall, 140,395 participants were included in our analysis. Diabetes was not significantly associated with lung cancer incidence [incidence rate ratio (IRR): 1.03, 95% confidence interval (CI): 0.91–1.17]. Similarly, stratified analyses also did not show significant associations between diabetes and lung cancer risk (all P values >0.05). We found no significant difference in the distribution of lung cancer histology in participants with vs. without diabetes (P=0.30). CONCLUSIONS: Diabetes was not an independent risk factor for lung cancer in a large cohort of PLCO participants. We did not observe differences in histology according to diabetes status. These results suggest that patients with diabetes do not need more aggressive lung cancer screening. Future research including more detailed metabolic parameters may further elucidate the relationship between metabolic disease and lung cancer risk.

Objective Obese and overweight body mass index (BMI) categories have been associated with increased immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors (ICIs); however, the impact of being overweight in conjunction with related metabolic syndrome-associated factors on irAEs have not been investigated. We aimed to evaluate the impact of overweight and obese BMI according to metabolic disease burden on the development of irAEs. Design and methods We conducted a retrospective observational study of patients receiving ICIs at a cancer center. Our main study outcome was development of ≥grade 2 (moderate) irAEs. Our main predictor was weight/metabolic disease risk category: (1) normal weight (BMI 18.5–24.9 kg/m2)/low metabolic risk (2)/low metabolic risk, and (4) overweight/high metabolic risk. Results Of 411 patients in our cohort, 374 were eligible for analysis. Overall, 111 (30%) patients developed ≥grade 2 irAEs. In Cox analysis, overweight/low metabolic risk was significantly associated with ≥grade 2 irAEs (hazard ratio (HR): 2.0, 95% confidence interval (95% CI): 1.2–3.4) when compared to normal weight/low metabolic risk, while overweight/high metabolic risk (HR: 1.3, 95% CI: 0.7–2.2) and normal weight/high metabolic risk (HR: 1.5, 95% CI: 0.7–3.0) were not. Conclusions Overweight patients with fewer metabolic comorbidities were at increased risk for irAEs. This study provides an important insight that BMI should be evaluated in the context of associated metabolic comorbidities in assessing risk of irAE development and ICI immune response.

Purpose: Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8+ T-cell activity and improves clinical activity of immune checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors.Methods:We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients versus BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05. ResultsOf 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; [1.54-5.03]; p=0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; [0.09, 0.62]; P=0.0031). Conclusions:Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.

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.

Non-small cell lung cancer (NSCLC) patients frequently have major comorbidities but there is scarce data regarding the impact of these conditions on management strategies. We used simulation modeling to compare different treatments for stage I NSCLC for patients with common major comorbidities.We used data on NSCLC patinet outcomes and quality of life from: (1) the Surveillance Epidemiology and End Results (SEER) database linked to Medicare claims; (2) Kaiser Permanente Southern California electronic health records; and (3) SEER-Medical Health Outcomes Survey to parameterize a novel simulation model of management and outcomes for stage I NSCLC. Relative efficacy of treatment modalities (lobectomy, segmentectomy, wedge resection and stereotactic body radiotherapy [SBRT]) was collected from existing literature and combined using evidence synthesis methods. We then simulated multiple randomized trials comparing these treatments in a variety of scenarios, estimating quality adjusted life expectancy (QALE) according to age, tumor size, histologic subtype, and comorbidity status.Lobectomy and segmentectomy yielded the greatest QALE gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex and age; wedge resection was among the optimal strategies for women aged 80-84 with tumors 0-2 cm in size. SBRT was included in some optimal strategies for patients aged 80-84 with multimorbidity.In simulated comparative trials of four common treatments for stage I NSCLC, aggressive surgical management was typically associated with the greatest projected QALE gains despite the presence of comorbidities, although less aggressive strategies were predicted to be non-inferior in some older comorbid patient groups.

Background Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) are increasingly common malignancies and tend to have favorable long‐term prognoses. Somatostatin analogues (SSA) are a first‐line treatment for many NETs. Short‐term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. Aim In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. Methods and Results Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991‐2016), we identified patients age 65+ with no prior DM diagnosis and a GEP‐NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ 2 tests to compare SSA‐treated and SSA‐untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP‐NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95‐1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. Conclusion DM was very common in GEP‐NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA‐treated and SSA‐untreated GEP‐NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

e18723 Background: Lung cancer is the leading cause of cancer death in the United States, with > 85% classified as non-small cell lung cancer (NSCLC). Diabetes mellitus (DM) is a common comorbidity in patients with NSCLC. While surgery is the standard of care for early-stage NSCLC, patients who have DM with end organ damage are considered medically inoperable according to treatment guidelines and whether this influences NSCLC treatment and outcomes is unclear. This study aimed to investigate treatment patterns and outcomes among patients with early-stage NSCLC and DM. Methods: Using the Surveillance, Epidemiology, and End Results database linked to Medicare (2000-2016), we identified patients ≥65 years old with Stage I-IIIA NSCLC treated with lobectomy, limited resection (wedge resection and segmentectomy), or no surgery. DM and complications at the time of NSCLC diagnosis were ascertained through published claims-based algorithms. Patients were categorized as having no DM, DM without severe complications (DM-c), or DM with ≥1 severe complication (i.e., end-organ damage, DM+c). We used multinomial logistic regression to assess if DM was associated with treatment. Association of DM with overall survival (OS) and lung cancer-specific survival (LCSS) was analyzed with Cox regression stratified by treatment type. These analyses controlled for demographics, comorbidities, and NSCLC histology and stage. Results: Of 60,300 patients analyzed, 45,270 (75%) had no DM, 6,873 (12%) had DM-c and 7,887 (13%) had DM+c. More patients with DM+c (N = 4,508[57%]), did not receive surgery vs. patients with DM-c (N = 3,771[55%]) and without DM (N = 23,289[51%]). DM was associated with lower odds of receiving lobectomy vs. no surgery in adjusted analysis (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.83-0.93 for DM-c, and OR: 0.91; 95% CI: 0.86-0.97 for DM+c vs. no DM), but not for limited resection vs. no surgery (OR: 0.92; 95% CI: 0.83-1.02 for DM-c and OR: 0.91; 95% CI: 0.92-1.11 for DM+c vs. no DM). Cox regression showed that in patients with lobectomy and limited resection, compared to no DM, DM+c was associated with worse OS (hazard ratio [HR]: 1.21; 95% CI: 1.15 to 1.27 [lobectomy]; HR: 1.17; 95% CI: 1.07-1.28 [limited resection]), but not LCSS (HR: 1.06; 95% CI: 0.99-1.14 [lobectomy]; HR: 1.02; 95% CI: 0.90-1.17 [limited resection]). Among patients who received no surgery, DM+c patients had both worse LCSS (HR: 1.05; 95% CI: 1.00-1.09 and OS (HR: 1.12; 95% CI: 1.08-1.16) vs. no DM. DM-c was not associated with worse LCSS or OS for all treatment categories. Conclusions: Patients with Stage I-IIIA NSCLC and DM+c were less likely to undergo surgery and had worse OS but not LCSS if they underwent full or limited resection, while they had worse OS and LCSS if they did not have surgery. These findings suggest that patients with DM with end-organ damage benefit from more aggressive NSCLC treatment, but research is needed to determine optimal treatments in these patients.

The COVID-19 crisis placed a pause on surgical management of nonemergency cases of pheochromocytoma, and it was essential for endocrinologists to provide both resourceful and safe care. At the Mount Sinai Hospital in New York City during the peak of the pandemic, we encountered 3 patients with pheochromocytoma and mild symptoms that were medically managed for a prolonged period of time (7-18 weeks) prior to adrenalectomy. Patients were monitored biweekly via telemedicine, and antihypertensive medications were adjusted according to signs, symptoms, and adrenergic profiles. These cases demonstrate that prolonged medical management prior to surgery is feasible and effective in pheochromocytoma patients with mild symptoms and well-controlled blood pressures.

Background While the concept of oligometastatic disease is increasingly recognized as a distinct clinical disease state, the concept of oligoprogression is less well-characterized. Oligoprogression may be particularly relevant in the context of immune checkpoint inhibitors (CPI) given the underlying mechanism of action and insights regarding acquired resistance. In this study, we sought to characterize the incidence of oligoprogression in patients on CPI and explore the impact of local therapy. Materials and Methods We performed a retrospective analysis of all patients with advanced solid tumors (excluding glioblastoma multiforme) who received a PD-1, PD-L1, or CTLA-4 inhibitor at a single institution between 2011 and 2017. Oligoprogression was defined as progression at ≤3 metastatic lesions outside of the brain after achieving at least stable disease on CPI for 3 months. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. Results Among 425 patients treated with CPI, 390 had advanced primary solid tumors outside of the central nervous system. 321 of these patients were evaluable for response, among whom 102 achieved at least stable disease. Oligoprogression was observed in 4.1% of the entire cohort and 15.7% of patients achieving at least stable disease on CPI. Among 16 patients experiencing oligoprogression, 15 received local therapy to the oligoprogressive lesions, many of whom continued CPI. At a median follow-up of 25.8 months, the median PFS for patients with oligoprogression after local therapy was 15.4 months. Conclusions Oligoprogression occurs in a subset of patients after an initial response to CPI. However, patients receiving local therapy to oligoprogressive sites may experience durable disease control. Further study is warranted. Microabstract Oligoprogression was observed in 4.1% of the entire cohort of patients on immune checkpoint inhibitors in this study and 15.7% of patients achieving at least stable disease. Among 16 patients experiencing oligoprogression, 15 received local therapy. At a median follow-up of 25.8 months, the median progression-free survival for patients with oligoprogression after local therapy was 15.4 months and zero patients had died. Oligoprogression occurs in a subset of patients after an initial response to CPI and local therapy to oligoprogressive sites may result in durable disease control.

Immune checkpoint inhibitors (ICIs) treat cancer by augmenting patients’ (pts) immune responses against cancer. The immune activation from ICIs is associated with immune-related adverse events. Inflammation has a known association with hyperglycemia (HG) and insulin resistance. Little is known about the prevalence of post-ICI HG (pIHG) beyond autoimmune diabetes (DM). We hypothesized that: (1)Pts with pIHG are more likely to have steroid exposure, pre-existing DM, and obesity (body mass index ≥30kg/m2); (2)A subset of pts have pIHG that cannot be explained by autoimmune DM or steroid use. We analyzed a cohort of 411 cancer pts on ICIs between 2011 and 2017 at our institution. We included pts who had ≥3 post-ICI glucose measurements. We defined pIHG as a random glucose >200mg/dL from ICI initiation up to 6 months after cessation. We recorded DM diagnosis and steroid exposure as documented in the medical record. We compared pts with and without pIHG using the Fisher’s exact test. 385 pts had post-ICI glucose data. 105 (27.3%) had pIHG. Compared to those without pIHG, pIHG pts were more likely to be male (71% vs. 59%, p=0.04), to have pre-existing DM (54% vs. 10%, p In conclusion, pIHG occurred in over a quarter of pts. Risk factors for pIHG included pre-existing DM and obesity. The majority of new pIHG was related to steroid use. However, a subset of pts had new HG that may be related to ICI therapy, suggesting that ICIs may have a role in immune-related insulin resistance. Disclosure A. Leiter: None. E. Carroll: None. D.C. Brooks: None. J. Ben Shimol: None. E. Eisenberg: None. M. Galsky: Advisory Panel; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Merck & Co., Inc., Pfizer Inc. E. Gallagher: Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Funding National Cancer Institute (P30CA196521, K08CA190770)

Objective: Hypophysitis is an increasingly recognized adverse effect of immune checkpoint inhibitor (ICI) therapy for malignancy. However, the mechanisms through which ICIs induce hypophysitis are largely unknown. We aim to describe 2 cases of ICI-mediated hypophysitis and perform autoantibody profiling on serial samples from these patients to determine if common autoantibodies could be identified. Methods: We describe 2 cases of patients with metastatic urothelial cancer who received ICI therapy and subsequently developed severe fatigue, prompting a hormonal workup consistent with hypopituitarism. Patient 1 received the ICI ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) and patient 2 received the ICI pembrolizumab (anti-programmed cell death protein 1). Both patients had serial seromic immune biomarker profiling using high-density protein arrays before and after developing hypophysitis. Once a common autoantibody was found, zinc finger CCHC-type containing 8 (ZCCHC8), we used immunohistochemistry to assess its presence in pituitary tissue. Results: Of a limited number of increased autoantibodies detected, those to ZCCHC8 were the only common antibodies to increase at least 3-fold post-hypophysitis in both patients. Using immunohistochemistry staining, we show for the first time that ZCCHC8 is expressed in pituitary gland tissue. Conclusion: Seromic profiling identified a common autoantibody, ZCCHC8, in 2 patients who developed hypophysitis on ICI therapy, and other serial autoantibody increases in each patient. These findings warrant validation in other cohorts to determine if the response is to self or tumor antigen, and may reveal novel insights into pituitary gland physiology and the pathogenesis of ICI-mediated hypophysitis.

Immune checkpoint inhibitors (ICI), such as monoclonal antibodies to cytotoxic T lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and PD ligand 1 (PD-L1) are recognized as effective cancer-directed therapies. Yet, ICI-induced activation of the immune system results in immune-related adverse events (irAEs) affecting many organs, including the thyroid. Separately, Vitamin D (Vit D) deficiency has been associated with increased risk of autoimmune thyroid disease. We hypothesized that patients who were Vit D deficient at the time of initiating ICI therapy would be more likely to develop thyroid irAEs. We retrospectively collected data for 411 patients who received ICIs at our institution between January 2011 and April 2017. We then identified 91 of these patients who had 25-OH Vit D levels obtained; 2 were excluded from analysis due to previous thyroidectomy. We recorded demographics, cancer type, Vit D level closest to the start date of ICI therapy, and thyroid irAEs. Patients were categorized as Vit D deficient (

Introduction: Cushing’s Disease (CD) in pregnancy is a rare, but serious disease that adversely impacts maternal and fetal outcomes. As the sole use of metyrapone in the management of CD has been rarely reported, we describe our experience using it to treat a pregnant patient with pre-existing CD. Clinical Case: The patient is a 29-year-old woman with a history of hypertension (HTN), who was diagnosed with CD a year prior to becoming pregnant based on elevated urinary free cortisol (UFC) 209 ug/24h (Reference Range (RR) 6 - 42), positive 1 mg dexamethasone suppression test, elevated ACTH 61 pg/mL (RR 0-46). and an 8 x 8 x 8 mm pituitary adenoma on magnetic resonance imaging (MRI). She underwent trans-sphenoidal adenoma resection 3 months prior to becoming pregnant; however, was found to have persistent disease based on a repeat MRI showing a residual 8 x 8 x 9 mm adenoma extending into the cavernous sinus and UFC 290 ug/24h. The patient discovered 6 weeks later that she was pregnant. She was referred to endocrinology at 12 weeks’ gestation, where she was experiencing easy bruising and taking labetalol 400 mg twice daily for HTN. UFC was 768 ug/24h and midnight salivary cortisols were 0.175 and 0.625 ug/dL (RR

Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p 5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m2, and 27.5 ± 5.5 kg/m2 at 72 weeks (p

Hypophysitis is a well-recognized immune-related adverse event that occurs in approximately 16% of patients treated with immune checkpoint inhibitors (ICIs), particularly the anti-cytotoxic T-lymphocyte associated antigen (CTLA4) monoclonal antibody, ipilimumab. While the synthesis and secretion of some anterior pituitary hormones may recover, central adrenal insufficiency is thought to be permanent. A 26-year old male with metastatic renal cell carcinoma was started on treatment with the anti-programmed cell death 1 (PD-1) monoclonal antibody nivolumab. His pre-treatment TSH was 3.27 (0.34-5.60 µIU/mL). Six weeks after his first dose of nivolumab he developed biochemical hyperthyroidism: TSH 0.04µIU/mL, FT4 2.1 (0.80-1.50 ng/dL), without symptoms. He continued treatment with nivolumab, and 11 weeks after the first dose he remained hyperthyroid (TSH undetectable, FT4 2.65 (0.80-1.50 ng/dL)). He was then started on ipilimumab in addition to nivolumab for 4 cycles. A baseline random serum cortisol drawn at 1:30pm was 15.0 (6.7 - 22.6 µg/dL). Five weeks after starting combined ICI therapy he developed sudden onset of severe fatigue, and reported feeling unable to get out of bed. Random serum cortisol was 2.0µg/dL at 1pm, and further pituitary hormone evaluation was performed: ACTH 16 (7.2-63.3 pg/mL), prolactin 47.2 (2.6-13.1ng/mL), LH 3.47 (1.2-8.6 mIU/mL), FSH 14.6 (1.3-19.3 mIU/mL), TSH 1.91, FT4 0.85, testosterone 545.46 (300-1080ng/dL). Thyroid autoantibodies (anti-TPO, thyroglobulin, TSH receptor) were normal. A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1mg/kg. A brain MRI reported no pituitary abnormalities. 48 hours after starting prednisone his symptoms resolved. He remained on prednisone 20mg daily for 4 weeks, and continued treatment with the ICI’s. His pituitary labs were repeated (3pm) - ACTH 5, cortisol 4.0, TSH 1.6, FT4 0.99, Testosterone 119, LH 3.63, FSH 18.4, IGF1 195 (155-432 ng/dL). His dose of prednisone was reduced to 5mg once daily. He continued to be monitored regularly by endocrinology with follow up testing of hormone levels. Four months after the initial presentation his testosterone level improved to 973.4, but his cortisol remained low. After five months his random serum cortisol (1pm) increased to 11.0, and testosterone was 901.5. The prednisone was cautiously discontinued with close monitoring for symptoms and hormone levels. He remained asymptomatic after discontinuation of prednisone, and after two months off glucocorticoid replacement his ACTH was 24.1 and cortisol was 13.0. This case demonstrates that central adrenal insufficiency can recover in patients who develop hypophysitis from ICI therapy. Close follow up and repeated measurement of pituitary hormones may identify more patients with hypothalamic-pituitary-adrenal axis recovery.

Background: Immune-related adverse events (irAEs) have been frequently described with the growing use of immune checkpoint inhibitors (ICI) in cancer treatment. While many autoimmune diseases are known to be more prevalent in certain racial groups, it is unknown if there are racial disparities in the rate of irAEs. Clinical trials reporting irAEs thus far have not explored their distribution in underrepresented minorities. It is important to study irAEs in racially diverse populations to better understand which patients are more likely to be impacted. Hypothesis: We sought to describe the demographics of a diverse cohort of patients treated with ICIs, as well as the racial distribution of irAEs. We hypothesized that there would be a significant difference among self-reported races experiencing ICI-related endocrine diseases. Methods: IRB approval was obtained to identify 411 oncology patients who were treated with ICIs between January 2011 and April 2017 from an EMR-based data repository. We collected data on age, gender, BMI, comorbidities, and median follow up time, which were further stratified according to self-identified race (White, Black, Hispanic, Asian, Other/Unknown). Endocrine adverse events were recorded according to race and were defined as events that were ≥ Grade 2 according to the Common Terminology Criteria for Adverse Events. We used the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables in the comparative analyses. Results: Of 411 patients treated with ICIs, 53.3% were White, 10.2% were Black, 10.5% were Hispanic, 7.5% were Asian, and 18.5% were Other/Unknown. The mean age was 65.3 years (67.8 in Whites, 63.7 in Blacks, 62.2 in Hispanics, 60.5 in Asians, 62.8 in Other/Unknown; p=0.0012). 38.4% were Female and 61.6% were Male. Mean BMI was 25.9 kg/m2. 10.9% of all patients had pre-existing autoimmune disease (White: 11.0%, Black: 9.5%, Hispanic: 11.6%, Asian: 0, Other/Unknown: 15.8%; p=0.164). 7.3% of all patients had pre-existing thyroid disease (White: 6.9%, Black: 7.1%, Hispanic: 7.0%, Asian: 0, Other/Unknown: 11.8%; p=0.311). Mean follow up period was 8.7 months. 54 (13.1%) patients experienced any endocrine adverse effect without a statistically significant difference among racial groups (White: 16.0%, Black: 16.7%, Hispanic: 11.6%, Asian: 6.5%, Other/Unknown: 6.6%; p=0.189). 14.8% developed hypophysitis, 70.4% developed thyroid disease, 13.0% developed adrenal insufficiency, and 1.9% developed diabetes. Conclusions: Self-reported race was not associated with the development of ICI-related endocrinopathies in a diverse group of oncology patients. Further studies are needed to continue to characterize the populations experiencing immune-related endocrine complications in ICI therapy.

Background As immune checkpoint inhibitor (ICI) therapies (PD(L)1 and CTLA-4 inhibitors) are increasingly used for treating malignancy, immune-related adverse events (irAEs) are being encountered by clinicians more frequently. Obesity is a pro-inflammatory metabolic state that has been associated with a higher risk of developing autoimmune disease, but its role in irAEs in patients treated with ICIs is not well characterized. Hypothesis We hypothesized that patients on ICI therapy who were overweight or obese would be more likely to have a grade 2 or greater irAE compared to normal or underweight patients. Methods We retrospectively collected clinical data for 398 cancer patients with baseline body mass index (BMI) data who received ICIs between January 2011 and April 2017 at our institution. Patients were categorized as having lower BMI (low or normal weight

Background: Ruxolitinib is a JAK1/2 inhibitor that is FDA approved to treat certain myeloproliferative neoplasms (MPNs), including myelofibrosis (MF) and polycythemia vera (PV). The JAK family kinases are targeted in cancers due to their role in cytokine receptor signal transduction, and are also key intermediates in growth hormone, leptin and prolactin receptor signaling. Clinical trials have reported that ruxolitinib treatment was associated with weight gain, but other metabolic consequences remain unknown. Aim: We aimed to determine the metabolic consequences of JAK1/2 inhibition with ruxolitinib in patients with MPN in the clinical setting. Methods: IRB approval was obtained, and we identified patients from an electronic medical record (EMR) based database who began treatment with ruxolitinib for MPN from December 2011 to December 2016. Data collected from EMRs included age, gender, weight, height, systolic and diastolic blood pressure (SBP, DBP), medications, co-morbidities, random serum glucose, and lipid profile. We compared parameters from baseline (prior to initiating ruxolitinib) to 72±8 weeks after starting treatment. Baseline and 72 week data were compared using the Wilcoxon signed rank test. Results: 129 patients were initially identified, of which 71 had data available for weight, and at least one other metabolic parameter of interest at baseline and 72 weeks. Patient characteristics were as follows: 49.3% male; mean age at initiation of treatment was 64.6±SD11.1 years; indications for treatment were MF (77%), PV(17%), other MPNs (6%). Mean baseline weight was 73.6±16.9kg, and was 78.3±8.9kg at 72 weeks (n=71, p30) at baseline were: 3%, 43%, 41%, and 13%, respectively; at 72 weeks it was 1%, 40%, 34%, and 28%, respectively (p=0.002). At 72 weeks,19% moved up a BMI class from baseline. Next, we investigated the effect of ruxolitinib treatment on BP and glucose concentrations. SBP was 124±15 mmHg at baseline and 129±18 mmHg at 72 weeks, (p=0.042, n=71). DBP was not different between baseline and 72 weeks. Glucose at baseline was 99±28mg/dL and 101±29mg/dL at 72 weeks (p=0.015, n=59). There was no change in the percent of patients with hyperglycemia (glucose ≥200mg/dL) or on treatment for diabetes at baseline (13.6%) and 72 weeks (13.6%). An insufficient number of patients had lipid data available for analysis. Conclusions: Systemic JAK1/2 inhibition was associated with weight gain, the development of obesity, and increased SBP in this cohort of patients. As pharmacological JAK1 and 2 inhibitors are developed and more widely used, it is important to gain a greater understanding of their long-term metabolic consequences.

Objective We describe a patient who presented with thyroid storm and severe gastrointestinal bleed (GIB) and aim to highlight the unique challenges in management. Case A 57-year-old man with a history of psoriasis presented to an outside hospital with palpitations, shortness of breath and diarrhea. Vitals included temperature 98.2F, blood pressure 127/77 mmHg, heart rate 142 bpm with an EKG confirming new onset atrial fibrillation with rapid ventricular rate. Labs included TSH 0.000 mIU/mL (0.35 - 5.50) with a free T4 5.42 ng/dL (0.61 - 1.12). The patient was started on a beta blocker and methimazole (MMI) 10 mg and transferred to our institution for possible cardioversion. Additional labs included Hgb 10.6 g/dL (14-18), platelets 84 K/cm (130-400), ALT 32 U/L (0-45), AST 67 U/L (0-41), ALP 289 U/L (30-115), TBr 5.1 mg/dL (0.2-1.2) and Dbr 4 mg/dL (0-0.2). Echocardiogram confirmed an ejection fraction of 35% and chest radiograph revealed bilateral pleural effusions and pulmonary edema. In preparation for cardioversion, a heparin drip was started resulting in hematemesis, melena and a repeat Hgb of 7.9 g/dL. The patient was intubated, transfused with pRBC’s and started on pantoprazole and octreotide. Endoscopy revealed multiple actively bleeding gastric ulcers treated with clipping. Endocrinology was consulted; the patient was diagnosed with thyroid storm (Burch-Wartofsky ≥ 70 based on known clinical parameters) and treated with an esmolol drip and dexamethasone 1 mg q6h. Due to concern for an active GIB, cholestyramine and SSKI/Lugols were held whereas the dose of MMI was not increased due to worsening transaminitis, doubling of DBr, and downtrending of free T4. After stabilization of the GIB, the patient was extubated with significant clinical improvement. He was discharged on MMI 10 mg and metoprolol tartrate 50 mg BID. Follow-up labs confirmed the diagnosis of Graves’ with TPO 346 IU/mL (0-34), anti-thyroglobulin Ab 31.4 IU/mL (0-0.9) and a TSH-receptor antibody of 15.97 (0-1.75). Thyroid ultrasound revealed heterogenous enlarged gland with no nodules. Conclusion Thyroid storm, a rare but life threatening endocrine emergency is treated by targeting thyroid hormone synthesis, release, conversion to its active form and effects. Active GIB complicates treatment of thyroid storm. First, SSKI/Lugol’s has been shown to be caustic to the GI lining and has been reported to induce a GIB during the treatment of thyroid storm. Second, cholestyramine and steroids have also been associated with an increased risk of GIB. The case was further complicated by worsening transaminitis and hyperbilirubinemia which prevented uptitration of MMI. Despite being limited in treatment options, the patient’s free T4 and clinical symptoms improved on an esmolol drip, dexamethasone and low dose MMI. Our case demonstrates that thyrotoxicosis can be managed despite the treatment limitations posed by an active GIB.

Background: Obesity has been associated with worse outcomes in patients with clinically localized urothelial cancer. However, this impact has not been evaluated in metastatic disease. Objective: To assess the impact of obesity on outcomes of patients with metastatic urothelial cancer. Methods: Data from 537 patients were aggregated from eight phase II and phase III clinical trials investigating first-line cisplatin-based combination therapy in metastatic urothelial cancer. Chemotherapy regimen, adverse events, treatment response, and survival outcomes were compared across body mass index (BMI) and body surface area (BSA) categories. Results: BMI was classified according to WHO criteria (30 obese). BSA was classified as either below or greater than or equal to (average for this cohort (1.87 m2 for males and 1.66 m2 for females). There was no significant difference in number of chemotherapy cycles, adverse events, and response rate or survival outcomes (overall and progression-free) across BMI and BSA categories. There was no significant difference in adverse events across BMI categories, but the incidences of embolic events and renal failure were higher in patients with an average or higher BSA than those with a lower than average BSA (6.6% vs. 3.1% for renal failure p = 0.06; 5.9% vs. 2.7% for renal failure, p = 0.07). There was no significant difference in response rate or survival outcomes (overall and progression-free) amongst BMI and BSA categories. Conclusions: Obese patients with metastatic urothelial cancer on cisplatin-based therapies have similar response rates, survival outcomes, and tolerability of cisplatin-based therapy to non-obese patients.

INTRODUCTION: In early March 2020, COVID-19 spread in New York City This paper shows trends of rising cases of DKA associated with a worsening COVID-19 pandemic in New York City With the potential for such a large number of DKA patients, our institution found a need for revised glycemic management protocol We discuss how a multidisciplinary team designed a protocol to care for patients with COVID-19 infection and DKA METHODS: Five of The Mount Sinai Health System's EDs are on a shared electronic health record system (Epic Systems, Verona, WI) Deidentified visit data extracted for routine quality review was made available for analysis We looked at total visits and select visit diagnoses related to DKA through March, April and May 2019 and compared those counts to the same period in 2020 Our protocol was developed by stakeholders in a multidisciplinary hospital team We focused on the basic tenets of DKA management: insulin therapy, fluid resuscitation, and electrolyte repletion RESULTS: A total of 93,218 visits were recorded across the five EDs from March 1-May 31, 2019 During that period there were 106 diagnoses of DKA made in the EDs (0 114% of visits) Across the same period in 2020 there were 59,009 visits, and 214 diagnoses of DKA (0 363% of visits) This coincides with the height of the Sars-CoV-2 pandemic in New York City To address this surge, our protocol decreased the frequency of fingerstick monitoring, with changes to insulin dosing allowing admission to non-ICU beds We transitioned from a provider-driven protocol to a nurse-driven protocol to avoid treatment delays due to order placement Insulin infusion rate charts were created to provide nurses guidance on dosing modifications To minimize ARDS risk, our protocol's fluid replacement recommendations lowered resuscitation and replacement rate volumes, adjusting based on provider reassessment Lab values were monitored every 3-4 hours CONCLUSIONS: There is a correlation between the rise of the Sars-CoV-2 pandemic in New York City and a net rise in patients diagnosed with diabetic ketoacidosis We believe our DKA protocol will facilitate safe and effective management of patients with COVID-19 and DKA, reducing the healthcare burden associated with protocols that necessitate frequent treatment modifications and ICU-level care

e15097 Background: Improved immunotherapy (IO) outcomes have been observed among non-small cell lung cancer patients with a current or former smoking history. This is thought to be a consequence of increased immunogenic mutation burden among smoking-related cancers. We set out to explore the association between smoking status and immunotherapy outcomes in lung and other smoking-associated cancers. Methods: This was a retrospective analysis of 200 consecutive patients with advanced, smoking-associated solid tumor types, treated with single-agent anti-PD1/PDL1 therapy at a single center between July 2014 and February 2018. The primary outcome was overall survival from date of IO initiation. The secondary outcome was overall response, defined as radiographic complete response or partial response, by RECIST 1.1 criteria. The primary predictor was smoking status (former/current smoker vs. never smoker). The primary and secondary outcomes were analyzed using multivariable Cox proportional hazards models and multivariable logistic regression models, respectively. Models were adjusted for age and sex, and stratified by cancer type. Results: The majority of patients were male (64%) with a history of smoking (72%); the average age was 67.1 ± 11.4 years. Cancer types represented were: non-small cell lung cancer (NSCLC, N = 81), hepatocellular carcinoma (HCC, N = 41), urothelial carcinoma (BLCA, N = 39), head and neck squamous cell carcinoma (HNSC, N = 21), and renal cell carcinoma (RCC, N = 18). Over a median follow-up of 11.3 months (range 0.5-53.2), there were 96 deaths and 27% of evaluable patients achieved radiographic response. Response was not evaluable in 27 patients. In multivariable regression analysis, smoking status was not significantly associated with overall survival nor overall response in any cancer type examined (Table). Conclusions: Smoking status was not associated with outcomes in our cohort of IO-treated patients with smoking-associated cancers, though sample size was limited. [Table: see text]

e15109 Background: Regulatory T cells play a key role in protecting kidney cells from ischemic injury. Immune checkpoint inhibitors (ICIs) may increase the risk of acute kidney injury via inhibition of regulatory T cells [1, 2]. Prospective clinical trials have largely excluded patients with chronic kidney disease (CKD); thus, we have limited knowledge of the safety and efficacy of ICI in these patients. Herein, we hypothesize that patients with CKD receiving ICIs have worse clinical outcomes. Methods: This single-institution retrospective cohort study included adult patients with solid tumors who were treated with ICIs at The Mount Sinai Hospital between 2011 and 2017. Clinical endpoints [response to treatment, progression of disease (POD) on treatment, mortality] were compared between patients with and without CKD using multivariate logistic regression. Odds ratios were controlled for demographics, primary tumor type, presence of cardiovascular comorbidities, smoking status, incidence of renal adverse events, and a composite of stage of illness with indication for treatment [localized—neoadjuvant, localized—adjuvant, regionally advanced, metastatic disease]. Data were analyzed using R version 3.5.1 with the following packages: readr, dplyr, broom, lubridate, tableone. Results: 420 patients met inclusion criteria: 399 patients without CKD and 21 patients with CKD. Cohorts are well matched for demographics, smoking status, stage/indication for treatment. The CKD cohort has a higher proportion of patients with urothelial cancer compared to patients without CKD (33% vs 11%) as well as a higher proportion of patients with HTN (81% vs 53%), HF (14% vs 3%), and DM (48% vs 21%). There was no statistical difference in odds of response to treatment [OR 0.76, 95% CI 0.26-2.23], POD [OR 0.42, 95% CI 0.15-1.17], or mortality [OR 2.05, 95% CI 0.71-5.96] between the CKD and non-CKD cohort. Conclusions: The data suggest the presence of CKD is not associated with worse clinical outcomes in cancer patients treated with ICIs. As a small retrospective study, the conclusions are hypothesis-generating but support continued use of immunotherapy in CKD in clinical practice and the inclusion of patients with CKD in immunotherapy clinical trials to further clarify safety and efficacy. [Table: see text]

e15157 Background: Immune checkpoint inhibitors (ICIs) are widely adopted for multiple indications across various malignancies. Despite the surge in their use, what occurs at radiographic progression (rPOD) remains poorly characterized. Herein, we describe patients at our institution that experienced rPOD on ICIs. Methods: We retrospectively reviewed charts of patients (pts) with solid tumors that received at least 2 doses of ICI at our institution from 12/01/2010 to 04/25/2017. Patients’ demographic data, medical history, ICI course, and outcomes were recorded. Characteristics at rPOD included change in tumor size by metastatic site, symptoms, and hospital utilization. Additionally, we characterized outcomes of pts who continued ICIs after rPOD. Fisher’s exact test was performed to identify potential clinical predictors of hospitalization at rPOD. Results: Of the 361 evaluable pts, 238 experienced rPOD. In this cohort, the most common primary sites of disease are: genitourinary (24%), thoracic (24%), skin (21%), and hepatobiliary (15%). At rPOD, 71 (30%) patients were hospitalized within 30 days, with infection (27%) and pain (18%) being the most common reasons. Median survival of pts with hospitalization was 2 months (mos; 95% CI: 0-4), compared to 10 months (95% CI: 8-12) for those not hospitalized (p

e15142 Background: Immune checkpoint inhibitors (ICIs) are increasingly utilized across cancer types. Risk factors for emergency room (ER) and inpatient (IP) care in this patient (pt) population remain poorly defined. Methods: We retrospectively reviewed charts for pts with (w/) advanced solid tumors who received more than 1 ICI dose at Mount Sinai from 1/1/11 – 4/28/17. Demographics, medical history, cancer diagnosis and therapy (tx) details, and outcomes were recorded. Descriptive data detailing ER/IP care during ICI tx (from first dose to 3 months after last dose) were collected. Fisher’s exact test and multivariable regression analyses were used to study differences between pts w/ versus w/out ER/IP care during ICI tx. Significance level was set at 0.05 for all tests. Results: 345 patients met the inclusion criteria for this study. Mean age was 64 years. Common tumor types were non-small cell lung cancer (n = 87), melanoma (n = 78), hepatocellular carcinoma (n = 53), and urothelial carcinoma (n = 38). 83% of patients had metastatic disease. Median duration of ICI tx was 2 months. During ICI tx, 50% received ER care and 43% received IP care, resulting in 369 total episodes of ER and/or IP care. 12% of episodes were attributed to ICI toxicity; 6% required intensive care. Median time to ER/IP care was 111 days. Median IP length of stay was 2 days. Several factors were found to be significant predictors of risk for ER or IP care on multivariable analysis (Table). African-American race and Hispanic ethnicity were each predictive of increased risk for both ER and IP care. Conclusions: ER/IP care is common among pts w/ advanced solid tumors on ICI tx. Understanding demographic and clinical risk factors can help prospectively identify higher-risk pts to inform preventive programs aimed at reducing such care. [Table: see text]

e15160 Background: Development (DV) of immune-related adverse events (IRAEs) to immune checkpoint inhibitor (ICI) have been associated (asso/) with (w/) favorable treatment (tx) response, but heterogeneity in clinical presentation remains a concern. We aim to characterize the type, timing, and risk factors asso/ w/ IRAE DV in ICI-treated solid tumor (ST) patients (pts). Methods: The characteristics (char), tx course, and clinical outcomes of ST pts who received at least 2 ICI doses at our institution from 1/1/2011 to 4/29/2017 were reviewed. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test and multivariable regression analyses (MVA) were performed to study the differences between pts w/ versus without (w/o) IRAE. Results: Of the 344 pts identified, 111 pts (32%) had IRAE(s) w/ 145 total events (GR 1: 31%, GR 2: 57%, GR 3: 12%), of which 45% required systemic steroids (SS), 27% lead to ICI discontinuation (DC), and 17% lead to hospitalization (HP, Table). Median time to any IRAE was 12 weeks (w, range 1-149.5w). The most common IRAEs were endocrine (30%), gastrointestinal (GI, 28%), and skin (24%) related. On univariable analysis, antibiotic use, melanoma, and combination ICI use were asso/ w/ IRAE DV; melanoma remained significant on MRA (odds ratio, OR: 3.58 [1.68, 7.64], p = 0.0010). Pts w/ IRAE had higher disease control rate (complete/partial response + stable disease) than pts w/o IRAE (OR: 2.20 [1.29, 3.75], p = 0.0038). Conclusions: Our real-world data showed higher IRAE incidence when compared to those reported in trials, although no GR 4/5 IRAEs occurred. Melanoma was asso/ w/ IRAE DV on MRA, possibly due to the type, dose, and combination of ICIs. These findings warrant further investigation to better identify those at the highest risk to develop clinically significant IRAE. [Table: see text]

Purpose Clinical trials are critical to informing cancer care but often are hampered by slow accrual and lack of generalizability because of poor geographic accessibility. We tested the feasibility of replacing onsite study visits with telemedicine visits in a prospective clinical trial. Methods Castration-naïve patients with prostate cancer and a rising serum prostate-specific antigen after definitive local therapy were eligible. Patients were required to have a single onsite visit for enrollment. Study treatment consisted of oral metformin 850 mg daily for 1 month followed by 850 mg twice daily for 5 months. Telehealth video visits (televisits) were conducted monthly by using a Health Insurance Portability and Accountability Act–compliant smartphone application. The primary objective was to determine the feasibility of telemedicine-enabled study visits. Secondary objectives were defining safety, anticancer activity, quality of life, and patient satisfaction. Results Fifteen patients with a median age of 68 years (range, 57 to 83 years) and median one-way driving time to the study center of 71 minutes (range, 12 to 147 minutes) were enrolled. The patients completed 84 eligible televisits (completion rate, 100%; 95% CI, 0.80 to 1). Diarrhea was the most common adverse event but was limited to grade 1 in severity; a single patient experienced grade ≥ 3 adverse events. Seven patients (46.7%; 95% CI, 24.8% to 69.9%) had a ≤ 20% increase in prostate-specific antigen relative to baseline. Patients agreed or strongly agreed that they would participate in a telemedicine-enabled clinical trial in the future. Conclusion To our knowledge, this interventional oncology clinical trial is the first to be conducted through telemedicine. Telemedicine-enabled trials are feasible and may overcome geographic barriers to trial participation. Metformin was generally well tolerated but associated with modest anticancer activity.

482 Background: Despite the widespread use of immune checkpoint inhibitors (ICIs), patterns of disease progression (POD) are poorly characterized. We aim to define these characteristics in patients (pts) with advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) treated with ICIs. Methods: We retrospectively reviewed charts of pts with advanced UC and RCC who received at least 2 ICI doses at our institution from 12/1/10 – 10/31/18. Demographics, medical history, ICI course, toxicity, and outcomes were recorded. Characteristics at the time of radiographic POD including location of metastases (mets), symptoms (sx), and hospitalization details were collected. Fisher’s exact test was used to study differences in pts with and without hospitalization at POD. Results: Of the 71 pts identified (UC N=53; RCC N=18), 59 pts had POD. At POD, 19 (32.2%) pts had new sites of disease involvement, while the remaining pts (N=40, 67.8%) had progression only at previously known sites of disease. Fourty-six (78.0%) pts had sx at POD: 1 sx (N=19, 32.2%), 2 sx (N=13, 22.0%), 3+ sx (N=14, 23.7%). Pain was the most common sx at POD (N=32, 54.2%), followed by loss of energy (N=18, 30.5%), and loss of appetite (N=14, 23.7%). Twenty-five (42.4%) pts were hospitalized at POD, most commonly for sepsis (N=8, 32%). No clinical factors were identified to predict for pts being hospitalized at POD. Conclusions: In our review of GU cancer patients on ICIs, a large proportion of pts reported clinical sx at POD, pain being the most frequent. Furthermore, a substantial number of pts were hospitalized at POD, most commonly for sepsis. Thus, further studies are warranted to confirm these findings, and potentially identify strategies to optimize patients’ quality-of-life and reduce rates of hospitalizations at the time of POD on ICIs.

480 Background: Immune related adverse events (IRAEs) with immune checkpoint inhibitor (ICI) therapy are well recognized, but predictors for IRAEs are not well defined. We aim to characterize the type, timing, and clinical risk factors associated with (w/) IRAEs in ICI-treated, advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) patients (pts). Methods: We retrospectively reviewed charts of pts w/ advanced UC and RCC who received at least 2 ICI doses at our institution from 1/1/10 to 10/31/18. Patient baseline characteristics, treatment course, and clinical outcomes were collected. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test was used to study the differences between pts w/ versus without IRAE. Results: Of the 71 pts identified (UC n = 53; RCC n = 18), 27 pts (38%) developed IRAEs with 42 total events (38% GR1, 60% GR2, and 2% GR≥3) [table]. The majority of pts with dermatitis (70%) also developed a secondary, systemic IRAE(s). Systemic steroid (SS) was required in 17 events. The median time to any IRAE was 17.5 weeks (w, range 1-93). ECOG ≤ 1 predicted IRAE development (p < 0.05). No other characteristics (demographics, co-morbidities, metastatic sites, ICI type, line of therapy, and duration of ICI > 12w) were associated with IRAE. Conclusions: In our study, good function status is associated with the development of IRAE. Time to IRAE ranged from immediately to 93w after initiating ICI. Clinical validation with additional datasets will be needed to confirm these findings. [Table: see text]

BACKGROUND Enzalutamide and abiraterone are new androgen-axis disrupting treatments for metastatic castration resistant prostate cancer (mCRPC). We examined response and outcomes of enzalutamide-treated mCRPC patients in the real-world context of prior treatments of abiraterone and/or docetaxel. METHODS We conducted a seven-institution retrospective study of mCRPC patients treated with enzalutamide between January 2009 and February 2014. We compared baseline characteristics, PSA declines, PSA progression-free survival (PSA-PFS), duration on enzalutamide, and overall survival (OS) across subgroups defined by prior abiraterone and/or docetaxel. RESULTS Of 310 patients who received enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79 (25%) received prior abiraterone, 30 (10%) received prior docetaxel, and 165 (53%) received both prior abiraterone and prior docetaxel. Within these groups, respectively, ≥30% PSA decline was achieved among 67%, 28%, 43%, and 24% of patients; PSA-PFS was 5.5 (95% CI 4.2–9.1), 4.0 (3.2–4.8), 4.1 (2.9–5.4), and 2.8 (2.5–3.2) months; median duration of enzalutamide was 9.1 (7.3-not reached), 4.7 (3.7–7.7), 5.4 (3.8–8.4), and 3.9 (3.0–4.6) months. Median OS was reached only for patients who received both prior abiraterone and docetaxel and was 12.2 months (95% CI 10.7–16.5). 12-month OS was 78% (59%–100%), 64% (45%–90%), 77% (61%–97%), and 51% (41%–62%). Of 70 patients who failed to achieve any PSA decline on prior abiraterone, 19 (27%) achieved ≥30% PSA decline with subsequent enzalutamide. CONCLUSIONS The activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.

Studies show decreased risk of breast cancer recurrence and improved survival with statin use, but data on racial disparities regarding breast cancer prognosis and statin use are lacking. Our objective was to investigate if racial disparities in breast cancer prognosis can be partially explained by differences in pre-diagnosis statin use. Patients were identified from a prospective, multicenter study examining the effects of metabolic factors on breast cancer prognosis in Black and White women. Statin use, prognosis (as measured by Nottingham Prognostic Index), anthropometric, tumor, and socio-demographic characteristics were examined. Five hundred eighty-seven women (487 White, 100 Black) with newly diagnosed primary invasive breast cancer were recruited. Obesity was more prevalent in Black women than White women (47 vs 19%, p

Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, we found that the mean survival time was significantly shortened for patients whose GBMs had both EGFR amplification and miR-34a deletion. Expression of miR-34a was significantly lower in GBM samples compared with normal brain tissue. Forced expression of miR-34a in GBM cells decreased their ability to migrate and profoundly decreased their levels of cyclin-A1, -B1, -D1, and -D3, as well as cyclin-dependent kinase and increased expression of cyclin kinase inhibitor proteins (p21, p27). Also, human GBM cells (U251) stable overexpressing mir-34a formed smaller tumors when growing as xenografts in immunodeficient mice compared with wild-type U251 GBM cells. Furthermore, the protein expression of EGFR decreased in the cells with forced overexpression of miR-34a. Additional studies showed that mir-34a targeted Yin Yang-1 (YY1) and YY1 is a transcription factor that can stimulate the expression of EGFR. Thus, our data suggest that miR-34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell-cycle proteins and EGFR. Moreover, we discovered for the first time that both deletion of miR-34a and amplification of EGFR were associated with significantly decreased overall survival of GBM patients.

Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells. We demonstrate that PAP is strongly expressed in PCa bone metastases in 7/7 patients, while prostate-specific antigen (PSA) is only weakly expressed. The human PCa cell line VCaP secretes PAP and induces an osteoblastic reaction in bone similar to that seen in human PCa bone metastases. Coculture of MC3T3 mouse preosteoblast cells with VCaP cells induces MC3T3 cell growth and differentiation as measured by alkaline phosphatase secretion, and this effect is inhibited by addition of the PAP-inhibitor, l-tartrate. Taken together, these data indicate that PAP is expressed in PCa bone metastases and may play a causal role in the osteoblastic phase of the disease.

Over the past decade, the treatment of metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of antiangiogenic therapies. Five drugs are now approved by the US Food and Drug Administration and other regulatory agencies, directed at the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling axis: four orally bioavailable small molecule multikinase inhibitors with activity against VEGFR (sorafenib, sunitinib, pazopanib, and axitinib) and an intravenously administered monoclonal antibody that binds the VEGF ligand (bevacizumab). These regulatory approvals were largely based on improvements in time-to-event end points (eg, progressionfree survival) compared with placebo or control and were all based on trials completed in the metastatic setting. Consistent with an oncologic drug-development paradigm that has existed for>50 yr, after establishing the safety and efficacy of VEGFR-targeted agents in metastatic RCC, these drugs are now being studied in earlier clinical disease states in the hope of achieving an even greater impact on the natural history of the disease. In fact, a large number of randomized trials evaluating adjuvant VEGFR kinase inhibitors and collectively enrolling >7000 patients have been are ongoing or have completed accrual (Table 1). In this context, several critical questions emerge: Based on theirmechanism of action, is it reasonable to expect that the perioperative application of VEGFR-targeted therapies will increase the likelihood of cure in patients with clinically localized disease (or at least significantly delay recurrence)?What are the relative risks and benefits of application of these therapies in the neoadjuvant setting versus the adjuvant setting? What is the optimal antiangiogenic drug and duration of treatment in the perioperative setting? And

Background or aims: Lack of clinical trial awareness is a known obstacle to clinical trial enrollment. We sought to define the prevalence of clinical trial awareness in the US population, determine characteristics associated with increased trial awareness, and explore potential disparities in trial awareness. Methods: We utilized data from the Health Information National Trends Survey from 2008 and 2012. Logistic regression was utilized to assess predictors of clinical trial awareness, particularly sociodemographic variables and information-seeking preferences. Trial awareness and information-seeking preferences were compared in patient subgroups and between the two time periods. Results: Clinical trial awareness increased from 68% to 74% between 2008 and 2012. In the 2012 dataset, higher education level (odds ratio: 3.52, 95% confidence interval: 2.16–5.74), higher yearly income category (odds ratio: 1.84, 95% confidence interval: 1.17–2.89), and Internet use (odds ratio: 2.13, 95% confidence interval: 1.52–3.00) were significantly associated with clinical trial awareness. Hispanic ethnicity (odds ratio: 0.41, 95% confidence interval: 0.25–0.68) was significantly associated with decreased awareness. Clinical trial awareness increased in African-American/Blacks (Δ10.6%) and Hispanics (Δ10.7%) between 2008 and 2012, as did Internet use in both subgroups (Δ14.2%, Δ18.1%, respectively). Conclusion: Overall clinical trial awareness has increased between 2008 and 2012, although a large subset of the population still lacks general awareness of clinical trials. Racial and ethnic disparities in trial awareness exist, although disparities may be decreasing among the Black population. These findings may help target educational efforts and inform approaches to increasing trial awareness.

243 Background: Clinical trials are critical to informing cancer care but are hampered by slow accrual and suboptimal generalizability, both contributed to by poor geographic accessibility. We previously reported that > 50% of the US population resides > 1 hour from the nearest PCa clinical trial site (Galsky, JAMA Int Med, 2015). We sought to test the feasibility of replacing on-site study visits with telemedicine visits in a prospective clinical trial. Methods: Castration-naïve non-metastatic pts with PCa and a rising PSA after local therapy were eligible. Pts required a single on-site visit for enrollment. Treatment consisted of metformin 850 mg QD x 1 month followed by 850 mg BID x 5 months. Telemedicine visits were conducted monthly using a HIPAA-compliant smartphone application. The primary objective was to determine feasibility defined as completion of all eligible telemedicine visits by > 2/3 enrolled pts; pts were ineligible for future telemedicine visits if treatment discontinued early for toxicity or disease progression. Secondary objectives included safety, % patients with ≤ 20% PSA rise at 6 months, quality of life, and patient satisfaction. Results: 15 pts were enrolled, median age 68 (range, 57, 83), one-way driving time 1.3 hours (range, 0.2-2.8), Gleason score 7 (range, 6, 9), and pre-study PSA 4.1 (range, 0.52, 31.7). The 6 month course of metformin was completed by 11/15 (73%) pts; 2 discontinued early due to rising PSA, 1 due to adverse event (AE), and 1 remains on study. Excluding 1 pt still on study, 14/14 (100%; 95% CI 76, 100) pts completed all 78 eligible telemedicine visits. The most common AEs were diarrhea (grade 1 = 60%) and fatigue (grade 1 = 20%); 1 pt experienced grade ≥ 3 AE (dehydration). The 6-month PSA was ≤ 20% baseline in 1 pt; median % PSA change at last televisit was +52.8% (range, -3.0, +318.8). Quality of life and pt satisfaction will be reported at the meeting. Conclusions: To our knowledge, this is the first ever interventional oncology clinical trial conducted via telemedicine. Telemedicine-enabled trials are feasible and may overcome barriers to trial participation. Metformin was generally well tolerated but associated with minimal anti-PCa activity as measured by PSA. Clinical trial information: NCT02376166.

Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct.

Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma.

Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells. We demonstrate that PAP is strongly expressed in PCa bone metastases in 7/7 patients, while prostate-specific antigen (PSA) is only weakly expressed. The human PCa cell line VCaP secretes PAP and induces an osteoblastic reaction in bone similar to that seen in human PCa bone metastases. Coculture of MC3T3 mouse preosteoblast cells with VCaP cells induces MC3T3 cell growth and differentiation as measured by alkaline phosphatase secretion, and this effect is inhibited by addition of the PAP-inhibitor, l-tartrate. Taken together, these data indicate that PAP is expressed in PCa bone metastases and may play a causal role in the osteoblastic phase of the disease.