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Describe fracture risk assessment practices among physicians treating osteoporosis in a real-life setting.This is a retrospective cohort study in a tertiary academic center. Inclusion criteria involved adults (aged ≥18 years) who received minimum adequate therapy (bisphosphates, raloxifene, or denosumab ≥ 3 years or teriparatide ≥ 18 months). Of 1,814 charts randomly selected and reviewed, 274 patients met the inclusion criteria. Risk stratification tools included fragility fractures, Dual-energy X-ray Absorptiometry (DXA), and fracture risk assessment using the FRAX tool. Fracture risk assessment was performed before therapy initiation (N= 274) and at the time of institution of the drug holiday (N=119). High-risk patients were defined as the presence of a fragility fracture, T-score ≤-2.5, or a high-risk score by FRAX calculation. FRAX scores were independently calculated by the research team for comparison and assessment purposes.Before initiation of therapy (N=274) versus upon starting a drug holiday (DH; N=119), 29.9% versus 3.4% had a history of fragility fractures (P0.001), 58.8% versus 67.2% had a DXA scan performed (P0.05), 10.5% versus 10.9% of physicians calculated a FRAX score (P0.05), and 71.5% versus 66.4% were considered at high risk and eligible for therapy. A DXA scan was performed after DH in 40.2% of these patients and at least once in 95.3% of the entire cohort.The reporting of FRAX score in DXA scan reports may significantly increase its utilization in fracture risk assessment. We recommend comprehensive fracture risk assessment utilizing history of prevalent osteoporosis fractures, DXA assessment, and FRAX scoring.

Published literature on physicians' preferences and sequential treatment patterns of osteoporosis therapy is scarce.A retrospective cohort study of patients who received bisphosphonates, denosumab, and/or raloxifene for at least 3 consecutive years or teriparatide for at least 18 months for osteoporosis. Data collection spanned 10 years, from October 2007 to September 2016, at a tertiary care center in the United States.In total, 12 885 patients were identified on the basis of receiving at least 1 treatment at any point in time; 1814 patients were randomly reviewed, and 274 patients met the inclusion criteria. The mean age was 68.8 ± 10.7 years, and women represented 90.9% of all the cases. Primary care physicians and rheumatologists constituted 65.7% and 22.6% of the prescribers, respectively. Before instituting a drug holiday, alendronate was the most common initial treatment (percentage, mean duration ± standard deviation in years: 69%, 5.4 ± 2.4 years) followed by ibandronate (9.5%, 4.9 ± 2.1 years) and raloxifene (9.1%, 5.2 ± 1.6 years). Denosumab was the most common second course of treatment, accounting for 29.3% of 82 patients who were subsequently prescribed another therapy, followed by alendronate (24.4%) and zoledronate (20.7%). Among patients who were placed on a drug holiday and eventually restarted on osteoporosis therapy, denosumab was the most common treatment instituted (n = 21), accounting for 40% of the total patients, followed by alendronate (32%) and zoledronate (16%). There was a progressive decline in osteoporosis therapy over the duration of the study.Alendronate was the most common initial therapy. Denosumab was the most common second course of treatment prescribed.

Context Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies. Objective This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials. Methods A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019). Results A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients with hormonal overproduction. More patients in the late cohort had stage IV disease compared to the early cohort (36.8% vs 23.1%; P Conclusion ACC clinical outcomes improved over the past 2 decades as more patients had complete resection or received more lines of systemic therapy.

Background After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy. Methods In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias. Results Of the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09–0.42; P P = 0.021) and for OS 0.25 (0.09–0.69; P = 0.007). Conclusions Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.

BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

BACKGROUND: Adrenocortical carcinoma (ACC) in an aggressive malignancy with suboptimal response to frontline chemotherapy and without established second line treatment. cMET activation is associated with ACC resistance to chemotherapy. Cabozantinib is a multi-kinase inhibitor that targets the VEGFR, c-MET, AXL, and RET receptors. We report interim data about using cabozantinib in ACC through a prospective phase II clinical trial. Methods: This is an investigator-initiated, open label clinical trial to evaluate the efficacy and safety of cabozantinib in patients with unresectable/metastatic ACC (ClinicalTrials.gov Identifier: NCT03370718). The primary objective is 4-month progression-free survival rate (PFS4). Participants are ≥ 18 years old with histologically confirmed ACC. Subjects who used mitotane within 6 months of consent must have mitotane serum level of < 2 mg/L. Cabozantinib starting dose is 60 mg daily with possible dose reductions. Subjects stopped treatment at time of disease progression, death, or occurrence of severe adverse events. Objective tumor responses were assessed per RECIST v.1.1 criteria. Adverse effects were graded per CTCAE v.4.03 Results: At time of data cut off (Oct 28, 2019), we screened 16 patients for enrollment. Ten patients (3 females) received cabozantinib out of whom 5 had history of mitotane use. Nine patients were eligible for response evaluation, defined as having at least one follow up imaging. One patient was taken off study after one week due to hypertensive crisis. Median age at time of diagnosis was 45 years (range 32 - 72). Five patients had hormonally active ACC. Median number of prior lines of systemic therapy was 2 (range 0 -5). Median duration of cabozantinib therapy was 6.6 months (range 0.7 -11.3). Eight patients (80%) were without evidence of progression at 4 months (achieved study endpoint). At time of data cut off, 1 patient had partial response (53% reduction over 8.8 months and ongoing), 3 patients had stable disease, and 5 patients had progressive disease. Nine patients were alive with disease and one patient died (not drug related). Grade 3/4 clinical adverse events included thromboembolic events (3 patients), severe hypertension (1 patient), intracranial hemorrhage secondary to hypertensive crisis (1 patient), weight loss (1 patient), and abdominal pain (1 patient). Grade 3/4 laboratory adverse events included increased AST (2 patient), increased ALT (1 patient), increased GGT, increased amylase (1 patient), increased lipase (1 patient) and hyponatremia (1 patient). Conclusions: In this interim analysis of phase II study, majority of subjects reached the study primary endpoint (PFS4). These data are in favor of continuing study accrual to assess magnitude of response to therapy and safety profile in ACC. Aggressive blood pressure management and close monitoring of liver enzymes are crucial to ensure the safety of study subjects.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC.

Personalized cell therapy targeting tumor antigens with expanded tumor-infiltrating lymphocytes (TILs) has shown great promise in metastatic melanoma (MM) since the 90s. However, MM was first-in line to benefit from the wave of checkpoint inhibitors (CPI), which shifted the focus of immunotherapy almost fully to immune CPI. Still, the majority of patients fail to benefit from CPI treatment, raising the intriguing question on how TIL therapy may fit into the changing landscape of melanoma treatment. We took advantage of data from a unique cohort of patients with MM treated with T-cell therapy in consecutive clinical trials at our institution across the last 10 years. Based on detailed data on patient characteristics, pre-TIL and post-TIL treatments and long-term follow-up, we were able to address the important issue of how TIL therapy can be positioned in the current CPI era. We found that previous progression on anticytotoxic T-lymphocyte-associated protein 4 do not seem to harm neither rate nor duration of response to TIL therapy. Importantly, even in the hard-to-treat population of patients who progressed on antiprogrammed cell death protein 1 (anti-PD-1), an objective response rate of 32% was achieved, including durable responses. Yet, median progression-free survival was reduced in this anti-PD-1 refractory population. Trial registration number: ClinicalTrials.gov ID: NCT00937625, NCT02379195 and NCT02354690.

Objective:We present a series of three cases of hypertriglyceridemia-induced acute pancreatitis with concurrent diabetic ketoacidosis (DKA) as first presentation of type 2 diabetes mellitus in adult patients. This triad has been described in previous literature; however, it is extremely rare in previously undiagnosed diabetic patients. We discuss the potential mechanism, diagnosis, management strategies, and prognosis in these cases.Methods:Three patients with no known history of diabetes mellitus or hyperlipidemia presented with diabetic ketoacidosis, elevated serum triglycerides, and typical symptoms of acute pancreatitis. Diagnosis was confirmed with abdominal computed tomography (CT) scan, and all three patients were managed in intensive care units, received aggressive fluid repletion, intravenous insulin, and lipid-lowering agents.Results:Two patients had uneventful recovery with rapid resolving hyperglycemia and hypertriglyceridemia. One patient had severe complication of acute kidney injury, sepsis, and acute respiratory distress syndrome, requiring temporary continuous veno-veno hemodialysis, antibiotic treatment, and transient intubation. All patients were discharged on subcutaneous insulin and lipid-lowering agents. They remained symptom-free during follow-ups.Conclusion: The triad of DKA with concurrent hypertriglyceridemia-induced acute pancreatitis occurs in approximately 4% of DKA cases. However, it is extremely rare as first presentation of diabetes in adult patients. A prompt diagnosis is challenging, although crucial for appropriate management. CT scan and lipid panel should be performed to confirm diagnosis when there is clinical suspicion or no improvement after treatment of DKA. Management mainly consist of intravenous fluids, continuous insulin infusion, and lipid-lowering agents. Plasmapheresis with success has been reported in previous literature; however, it was not necessary in our cases.Abbreviations:ABGarterial blood gasAPacute pancreatitisCTcomputed tomographyDKAdiabetic ketoacidosis

Introduction: Type 1 diabetes mellitus (T1DM) is a known immune related adverse event (irAE) following treatment with Programmed Death 1 (PD-1) immune checkpoint inhibitors with reported 0.9% incidence. Little is known about such irAEs in individuals with HIV treated with PD-1 inhibitors. Case: A 48-year-old man with HIV on HAART, diagnosed with Hodgkin’s lymphoma, initiated PD-1 inhibitor nivolumab. After 6 months, he reported polydipsia and polyuria. Labs revealed glucose 764 mg/dl and A1c 7.1%. Low C-peptide and elevated GAD-65 antibody levels confirmed T1DM, and he started insulin therapy. Nivolumab continued for 12 more months. Despite discontinuation of nivolumab, he remains on insulin therapy. Discussion: While A1c may reflect average glycemia, it alone cannot distinguish T2DM from T1DM progression. C-peptide and autoantibodies for T1DM must be included when screening patients on PD-1 inhibitors. Patients with HIV have higher autoantibody titers in active disease states or following HAART initiation, as seen in immune reconstitution. Moreover, in vitro PD-1 inhibition elevates HIV cell proliferation and immune hyperactivity. The challenge in patients with HIV on HAART and PD-1 inhibitors is unraveling whether autoantibody generation resulting in T1DM is potentiated by pre-existing HIV on HAART and/or provoked by immune response to PD-1 inhibition. Conclusion: Clinicians treating patients with immune checkpoint inhibitors should maintain a high index of suspicion for development of autoimmune disorders. Literature on the use of PD-1 inhibitors in HIV patients is limited and warrants further investigation. To our knowledge, this is the first reported case of T1DM following PD-1 inhibition in a patient with HIV on HAART therapy. Such patients are predisposed to immune reconstitution, and response to PD-1 inhibition may potentiate risk for autoimmune complications. Therefore, higher clinical suspicion for irAEs is merited in patients with HIV on PD-1 inhibitors. Disclosure M.S. Hughes: None. S. Bedrose: None. M. Vasudevan: None. M. Marcelli: None.

s Objectives: Cardiogenic ascites has been well described regarding its pathophysiology and fluid characteristics in prior literatures. However, ascites in patients with cardiac cirrhosis has not been characterized as a separate entity despite its unique pathophysiology and clinical aspects. This study aims to describe the fluid profile of ascites of cardiac cirrhosis and explore the utility of ascitic fluid protein (AFP) to predict concurrent cardiac cirrhosis.We retrospectively selected and reviewed samples from the patients with cardiogenic ascites with and without concurrent cardiac cirrhosis. Epidemiologic characters, serum laboratory values, and fluid characteristics were directly compared between the groups.We analyzed 20 samples of ascitic fluid from the patients of cardiac cirrhosis and compared with 48 samples of non-cirrhotic cardiac ascites. The AFP was significantly lower in patients with cardiac cirrhosis (3.66g/dl) as compared to non-cirrhotic patients (4.31g/dl, p .01); while there was no difference in serum-ascites albumin gradient (1.48g/dl vs. 1.47g/dl, p = .95). AFP equal to or less than 4.3g/dl predicted cirrhosis with a sensitivity of 95% and negative likelihood ratio of 0.10; the corresponding ROC curve of AFP has an AUC of 0.777, higher than AUC of other noninvasive prediction models.We presented the first fluid characterization of ascites in patients with cardiac cirrhosis. AFP was significantly lower than that from non-cirrhotic cardiac ascites, likely secondary to decreased serum protein level. AFP equal to or less than 4.3g/dl could be utilized to screen for concurrent cardiac cirrhosis with high sensitivity in patients with cardiogenic ascites without other predisposing factors for liver injury.

e16518 Background: This study aimed to identify predictors of time to castration-resistance prostate cancer (tCRPC) from initial diagnosis of metastatic prostate cancer (mPC) and develop a prognostic score in the underserved population of an inner-city tertiary care hospital. Methods: We retrospectively reviewed charts of 278 men diagnosed with mPC between 2001 and 2015, of which 155 patients were analyzed. Socio-demographic, clinical and pathologic factors were ascertained at the time of diagnosis. Kaplan-Meier and cox regression analyses were done to explore correlates tCRPC. Crude (HR) and adjusted (aHR) hazard ratios with 95% confidence intervals (CI) were obtained. Results: Over a median follow-up of 46 months (95% CI 23-69), 73.5% of men developed castration-resistance. Median tCRPC was 16 months (95% CI 12.5-19.5). All patients received medical or surgical castration at the time of diagnosis. Significant correlates of short tCRPC included: prostate specific antigen >20 ng/mL (HR 2.56, 95% CI 1.25-5.23, P=0.010), core involvement >50% (HR 2.11, 95% CI 1.43-3.11, P240 U/L (HR 2.42, 95% CI 1.62-3.61, P200 U/L (HR 1.68, 95% CI 1.16-2.43, P=0.006) and neutrophil-lymphocyte ratio >2.4 (HR 1.50, 95% CI 1.03-2.20, P=0.035). In multivariate model, core involvement >50% (aHR 2.99, 95% CI 1.79-5.01, P240 U/L (aHR 2.08, 95% CI 1.13-3.84, P=0.019) and LDH >200 U/L (aHR 1.71, 95% CI 1.02-2.86, P=0.043) independently predicted short tCRPC and each factor decreased tCRPC by almost 50%. Mean prognostic score (PS), based on 1 point for each independent predictor (scale 0-3), was 1.23 (SD 0.91) and significantly predicted short tCRPC (P50%), high ALP (>240 U/L) and high LDH (>200 U/L) significantly predicts tCRPC in men with mPC. Prospective studies are warranted to further validate this score. [Table: see text]