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Background Limited knowledge exists on the incidence, treatment patterns, and long-term outcomes of Langerhans cell sarcoma (LCS) in the United States. Patients and Methods We performed a retrospective study of LCS patients diagnosed between 2001 and 2014 using the Surveillance, Epidemiology, and End Results (SEER) and National Cancer Data Base (NCDB) databases. Incidence was calculated from SEER, and treatment patterns and outcomes were calculated from NCDB. Results A total of 25 and 52 cases of LCS were reported to SEER and NCDB, respectively. The overall incidence of the disease was 0.2 per 10,000,000 and did not differ by race (P = .56) or sex (P = .33). The median age at diagnosis was 62 (range, 19-90) years. Of the 52 patients from NCDB, 20 (39%) received chemotherapy as first-line therapy, 24 (46%) received surgery, and 15 (29%) received radiotherapy. The 1-year overall survival (OS) rate was 62%, and the median OS was 19 months. After censoring the patients with bone marrow and reticuloendothelial system involvement, no significant difference in OS was noted between the patients who were managed with or without surgery (P = .75). Postsurgical radiation or chemotherapy were not associated with improvement in median OS (P = .25). Patients who were managed with radiotherapy had a better OS compared to those who received no radiotherapy (P = .03). Conclusion This dual-national registry study shows that LCS is extremely rare and has a poor prognosis. Radiotherapy may offer a survival advantage to patients with locoregional disease without bone marrow and reticuloendothelial system involvement.

The management of patients with advanced-stage hepatocellular carcinoma (HCC) has changed dramatically over the past year. Partial hepatectomy, liver transplantation, ablation, radiation therapy, and embolization procedures remain important interventions for localized HCC, whereas systemic therapy is the cornerstone of therapy for patients with extrahepatic disease. Since 2017, several agents, including regorafenib, lenvatinib, cabozantinib, ramucirumab, nivolumab, and pembrolizumab, have been approved or are likely approved as first- and second-line therapies by Food and Drug Administration (FDA) for systemic treatment of advanced-stage HCC. In this chapter, we overview the molecular mechanisms underlying HCC and how improved understanding of these pathways has helped the development of targeted therapies. We also discuss the value of these molecular-targeted therapeutic agents, safety profile, and their impact on personalization of HCC therapy.

Abstract Importance: The benefit of routine screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in patients with cancer before cancer-directed therapies is unclear. Herein, we characterize the outcomes of a cohort of cancer patients diagnosed with Coronavirus Disease 2019 (COVID-19) by routine screening in comparison with those diagnosed based on clinical suspicion or exposure history (non-routine screening). Objective: To describe and compare the outcomes of cancer patients diagnosed with COVID-19 on routine screening vs. non-routine screening at a multi-site tertiary cancer center. To identify risk factors for COVID-19-related hospital admission. Design: A multi-site prospective observational study was conducted between March 18 and July 31, 2020. Setting: Three major and 5 satellite campuses of the Mayo Clinic Cancer Center. Participants: Adult patients diagnosed with active cancer within the past five years and confirmed SARS-CoV-2 infection were included. Primary Outcomes and Measures: Clinical and laboratory data were assessed as independent variables. The primary outcome was COVID-19-related hospital admission. Secondary outcomes included intensive care unit (ICU) admissions and all-cause mortality. Results: Between March 18 and July 31, 2020, 5452 patients underwent routine screening in the outpatient setting, 44 (0.81%) were diagnosed with COVID-19. Routine screening detected additional 19 patients from inpatient and pre-procedural settings; 161 patients were diagnosed with COVID-19 based on non-routine screening. The median age of the entire cohort at diagnosis was 54 years, and 95 patients (42.2%) were female. COVID-19 related-hospitalization rate (17.5% vs. 26.7%, p=0.14), ICU admission (1.6% vs. 5.6%, p=0.19), and mortality (4.8% vs. 3.7%, p=0.72) were not significantly different between routine screening and non-routine screening groups. In the multivariable analysis, age ≥ 60 years (odds ratio: 4.4, p=0.023) and an absolute lymphocyte count ≤1.4 × 109/L (odds ratio: 9.2, p=0.002) were independent predictors of COVID-19-related hospital admission. Conclusions and Relevance: The COVID-19 positivity rate was low based on routine screening. Comparing the outcome with the non-routine screening cohort, there was no significant difference. These results led to an important practice change at our cancer center. We currently follow a testing strategy based on symptoms, exposure, risk factors, and clinical judgment. Citation Format: Zhuoer Xie, Antoine N. Saliba, Jithma Abeykoon, Umair Majeed, Daniel Almquist, Julia Wiedmeier-Nutor, Evandro Bezerra, Xavier Andrade-Gonzalez, Ashley Hickman, Karl Sorenson, Sagar Rakshit, Christopher Wee, Sri Tella, Anuhya Kommalapati, Nadine Abdallah, Joshua Pritchett, Mariza De Andrade, Dipesh Uprety, Andrew Badley, Joleen Hubbard, Naseema Gangat, Carrie A. Thompson, Thomas Witzig, Robert R. McWilliams, Konstantinos Leventakos, Thorvardur R. Halfdanarson. Outcomes of COVID-19 in patients with cancer: Results of a prospective observational comparison of routine screening strategy versus testing based on clinical suspicion [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S06-03.

Therapeutic options for advanced, unresectable hepatocellular carcinoma (HCC) have changed dramatically over the last 3 years. While surgical resection, orthotropic liver transplantation, and localized therapeutic options such as ablation, radiation therapy, and embolization remain therapeutics of choice in localized disease, systemic therapy is the only option in advanced, metastatic HCC. Since the United States Food and Drug Administration (US FDA) approval of sorafenib in 2008, targeted therapies such as sunitinib, tivantinib, brivanib, erlotinib, and linifanib; monoclonal antibody- bevacizumab showed no meaningful improvement in treatment of HCC. However, with improved understanding on the molecular pathophysiology and tumor heterogeneity of HCC, we have made progress in expanding the therapeutic options in advanced HCC. Targeted therapy with lenvatinib, cabozantinib, and regorafenib; monoclonal antibody ramucirumab; immunotherapies nivolumab and pembrolizumab have demonstrated promising results in the clinical trials. The current work outlines the molecular mechanisms and tumorigenesis of HCC, a detailed discussion of the trial results of the approved therapies in HCC, future perspectives and potential options to overcome the challenges of systemic therapy in HCC.

Fibroblast growth factor receptor (FGFR) inhibitors have shown promising results in terms of objective response rates in phase I/II trials in various malignancies that harbor FGFR genetic aberrations. The class of medications brings in the concept of 'personalized' treatment by targeting susceptible FGFR genetic alterations in some rare but dismal cancers such as cholangiocarcinoma. Despite the fact that FGFR inhibitors are well-tolerated, these drugs are associated with toxicities that are distinct from that of other small-molecule tyrosine kinase inhibitors. These toxicities can result in dose reductions, interruptions, and even drug discontinuation as reported in the clinical trials. The prevention and effective management of the FGFR inhibitor-associated toxicities will allow patients to stay on these medications without the therapy interruptions. The current work is focused on summarizing the available literature on unique FGFR inhibitor-associated toxicities with a special emphasis in managing the unique adverse events.

Background Cancer associated venous thrombo-embolism (VTE) constitutes major cause of mortality and morbidity in patients with hematological malignancies. There is limited data on the incidence and management of VTE in patients receiving chimeric antigen receptor (CAR) T-cell therapy. Methods We performed a single center retrospective study of 148 patients receiving CD19-directed CAR T-cell therapy for aggressive B-cell lymphomas between 05/2015 and 09/2019 to evaluate the incidence and management of known and new VTE phenomenon between day 0-100 after CAR T-cell infusion. Results Prophylaxis with anticoagulation (AC) was utilized in 4% (6/148) of patients between day 0-100 after CAR T-cell infusion. 19% (28/148) had known VTE prior to CAR T-cell infusion and 50% (12/28) of these were still on AC at the time of infusion. Of those on AC for prior VTE at the time of infusion, 50% (6/12) had it held between day 0-100 after CAR T-cell infusion due to low platelet count or risk of bleeding, while the remainder continued without interruption. A new episode of VTE, between day 0-100, occurred in 11% (16/148) of patients. None of these patients had previous known VTE. Of these, 75% (12/16) started therapeutic AC, however 42% (5/12) had AC held before day 100 after CAR T-cell infusion due to low platelet count or risk of bleeding. None of the patients that continued therapeutic AC in the 2 cohorts had a bleeding event. Details of the thrombotic events and management with AC are shown in the table. Conclusions This is the first study to our knowledge that describes in detail the incidence and characteristics of VTE and use of AC in lymphoma patients receiving CAR T-cell therapy. Most patients were managed with AC without complications of recurrent VTE or bleeding.

Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction, and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials.This review summarizes the current understanding and future directions of targeted therapeutic options in the management of advanced cholangiocarcinoma.Advanced cholangiocarcinoma has a dismal prognosis; improved understanding of the molecular pathogenesis and advancements in development of targeted therapy offers hope that we may improve outcomes in this rare, but highly lethal cancer. Among the newly discovered molecular alterations, targeting FGFR2 fusions, IDH1/2 mutations and HER2 receptors hold great promise for improving the future management of cholangiocarcinoma. Immunotherapy in combination with targeted agents and chemotherapy may improve outcomes. In addition, drugs targeting the MEK, EGFR, KRAS, BRAF, and ROS1 pathways and neo-angiogenesis may also provide new horizons in the management of cholangiocarcinoma.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is divided into three types, namely type 1, type 2 (2A, 2B, 2M, 2N), and type 3. We report a case of a 24-year-old Caucasian woman with a rare variety of type 2M VWD. Her von Willebrand factor versus antigen ratio was 0.44 (normal ratio is greater than 0.7) . She was asymptomatic and hence not treated but followed up regularly. VWD is not life-threatening when treated timely.

Histiocytic sarcoma (HS) is an aggressive hematologic malignancy derived from non-dendritic, non-Langerhans histiocytic cells of the monocyte/macrophage system [1]. The diagnosis of HS is made base...

The introduction of bone-modifying agents (BMA) or skeletal protective agents in the mid 1990’s into oncology armamentarium has revolutionized the management of skeletal related events (SREs) in cancer patients with established bone metastases. The health and financial burden of SREs are significantly reduced with the use of adjuvant BMAs.

We present a case of a dialysis-dependent end-stage renal disease patient who originally presented with sepsis and later developed heparin-induced thrombocytopenia-related upper extremity deep venous thrombosis that rapidly progressed to phlegmasia. Argatroban, a direct thrombin inhibitor, was initiated without delay. Argatroban restored the venous patency completely but did not reverse his two gangrenous fingers. The patient finally underwent digital amputation. The management of this uncommon, but life-threatening, situation of upper limb phlegmasia cerulea dolens secondary to heparin-induced thrombocytopenia leading to gangrene is discussed in this case report.

Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC.This is a retrospective study of stage IV NSCLC patients diagnosed between 2004 and 2014 using the National Cancer Data Base (NCDB). We classified the total number of patients treated at facilities into quartiles: quartile 1 (Q1): ≤23; quartile 2 (Q2): 24-36, quartile 3 (Q3): 37-55, and quartile 4 (Q4): ≥56 cases/year. Cox regression was used to assess whether risk of death differed between quartiles after adjusting for demographics, insurance type, Charlson-Deyo score, and type of therapy received.There were 338, 445 patients with stage IV NSCLC treated at 1326 facilities. We included the patients who received any form of therapy in the survival analysis. The unadjusted median overall survival by facility volume was: Q1: 6 months, Q2: 6 months, Q3: 7 months, and Q4: 8 months (p .001). Multivariable analysis showed that facility volume was independent predictor of all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95%CI, 1.04-1.06]; Q2 HR, 1.12 [95%CI, 1.11-1.14]; Q1 HR, 1.11 [95%CI, 1.10-1.12]).Patients who were treated for stage IV NSCLC at highest-volume facilities had less risk of all-cause mortality compared with those who were treated at lower-volume facilities. Although the survival advantage of being treated at highest-volume facilities appeared small, the results of this study suggest differences in cancer care delivery models among various facilities, and may become more relevant in the future era of personalized treatment of stage IV NSCLC.

To determine the association between the number of patients with intra-hepatic cholangiocarcinoma (IHCC) treated annually at a treatment facility (volume) and overall survival (outcome).Patients with IHCC reported to the National Cancer Database (years 2004-2015) were included. We classified facilities by tertiles (T; mean IHCC patients treated/year): T1:2.56; T2: 2.57-5.39 and T3: ≥5.40. Volume-outcome relationship was determined by using Cox regression adjusting for patient demographics, comorbidities, tumor characteristics, insurance type and therapy received.There were 11,344 IHCC patients treated at 1106 facilities. On multivariable analysis, facility volume was independently associated with all-cause mortality (p 0.001). The unadjusted median OS by facility volume was: T1: 5 months (m), T2: 8.1 m, and T3: 13.1 m (p 0.001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 hazard ratio (HR), 1.12 [95% CI, 1.05-1.23]; T1 HR, 1.21 [95% CI, 1.11-1.33]. Patients treated at high-volume centers were more likely to get surgery (34.6 vs 13.1%) and adjuvant therapy.IHCC patients treated at high-volume facilities had a significant improvement in OS and were more likely to receive surgery and adjuvant therapy as compared to that of patients at low-volume facilities.

TO THE EDITOR: Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system that is diagnosed using immunohistochemistry markers, such as CD68, lysozyme, CD4, and CD163, on the tissue biopsies.[1][1] HS can occur in

Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15-20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

Context: Immune checkpoint inhibitors, including anti–programmed cell death protein 1 (PD-1), anti–programmed cell death protein ligand 1 (PD-L1), and anti–cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti–CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. Case Description: We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti–PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient’s symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. Conclusion: To our knowledge, this is the first report of central DI associated with anti–PD-L1 immunotherapy. The patient’s endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality., We report a case of central diabetes insipidus induced by the anti–PD-L1 drug avelumab. The patient was successfully managed by holding the immune checkpoint inhibitor.

Abaloparatide (previously known as BA058) is a synthetic 34-amino acid peptide and novel selective activator of parathyroid hormone receptor 1 (PTHR1) currently under development as a new anabolic agent in the management of osteoporosis. This paper reviews the profile and potential of abaloparatide in the treatment of postmenopausal osteoporosis. This paper is based on clinical trials and a PubMed search. Search terms used were "abaloparatide", "BA058", and "PTHrP". This review outlines the effects of this anabolic PTHR1 activator, which increases bone mineral density in patients at high risk for osteoporosis. The potential adverse effects of abaloparatide are also summarized. Abaloparatide has 41% homology to parathyroid hormone (PTH) (1-34) and 76% homology to parathyroid hormone-related protein (PTHrP) (1-34). The molecule was meticulously selected to retain stability and potent bone anabolic activity, and it has a limited effect on bone resorption (hence, a low calcium-mobilizing potential). Abaloparatide has shown promising results in a reduction of new onset vertebral (approximately 86% reduction) and nonvertebral fractures (approximately 43% reduction). In clinical trials to date, abaloparatide appears to have a good safety and tolerability profile with a significantly lower degree of hypercalcemia compared to that of teriparatide. Based on the clinical trials, the optimum dose of abaloparatide is 80 mcg subcutaneous once daily.

e19523 Background: Previous studies have shown a disparity in outcomes of MM between clinical trials and real-world practice. This could be partly due to clinical trial exclusion of patients who need urgent treatment due to high burden of disease or significant illness. In this study, we aim to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS). Methods: We included MM patients reported to National Cancer Data Base (2004-2014). We excluded 2,860 patients with suspected smoldering MM due to initial treatment beyond 120 days. Relative risk of delayed time to systemic therapy was assessed by logistic regression model. Kaplan-Meier method and Cox multivariate analysis were used to evaluate the association between time to therapy and OS. Results: A total of 53, 519 MM patients were included. Median time to systemic therapy in our cohort was 18 days (range 0-120). Of the entire cohort, 24% patients received systemic therapy for MM < 7 days from diagnosis, and 32% received it after 30 days. Factors associated with time to systemic therapy > 30 days were Black race (OR 1.12, CI 1.07-1.16), female sex (OR 1.10, CI 1.06-1.14), lower Charlson comorbidity score (OR 1.36, CI 1.28-1.45), and academic facility (OR 1.18, CI 1.13-1.24). The median OS for patients who initiated therapy > 30 days after diagnosis was longer than those who received it within 7 days (37 vs. 29 month, p < 0.001). Similarly, on multivariate analysis, patients who received treatment > 30 days after diagnosis were found to have a lower mortality as compared to those who initiated treatment < 7 days (HR 0.81, CI 0.79-0.83; Table). Conclusions: In our study, time to initiation of systemic therapy was an independent prognostic factor in MM. This could be related to the high-risk nature of disease of patients treated within a short duration of diagnosis. These findings have implications for future clinical trial design, which should allow for a pragmatic approach toward enrollment of these high-risk patients to improve external validity. [Table: see text]

e16107 Background: Guidelines recommend surgical resection of primary tumor in stages 1-3 RCC. TTS refers to the time frame from the initial diagnosis to surgical resection of primary tumor. Shorter TTS has shown OS benefit in breast, head and neck cancers whereas longer TSS was shown to be acceptable in colon cancer. However, no such data exists for RCC. Using National Cancer Data Base (NCDB), we sought to determine the factors associated with TTS and its effect on OS. Methods: Patients with RCC who underwent partial or total nephrectomy were included, excluding those received neoadjuvant therapy. Logistic regression model was utilized to evaluate relative risk of delayed TTS. OS in association with TTS was estimated using the Kaplan-Meier method and Cox multivariate analysis (MVA). Results: A total of 60,198 RCC patients met the inclusion criteria. In contrast to a prior study that showed a median TTS of 41 days our study showed a median TTS of 35 days. We dichotomized the TTS as ≤ 35 days or ≥ 36 days. On MVA, TSS ≥ 36 days had significantly better OS (HR: 0.95 [CI:0.92-0.99], p < 0.01). Factors associated with TSS ≥ 36 days were race, insurance, higher Charlson score, lower grade, and getting managed at academic facilities and Pacific region (p < 0.01) (Table). Conclusions: A longer TTS with RCC is understandably associated with greater comorbidity, and non-private insurance, but questionably so in race, ethnicity, and facility related factors. However, given that TTS ≥ 36 days was not associated with higher risk of death, it may indicate that a reasonable delay could be pursued in certain cases for more accurate preoperative evaluation. [Table: see text]

e18108 Background: Early integration of PC has shown to improve quality of life and survival in some solid malignancies. In this study we sought to analyze the PC utilization in mRCC patients. Methods: Patients with mRCC reported to NCDB between 2004 & 2015 were extracted and we included the patients who died of mRCC. We classified the patients into three cohorts based on their length of survival ( < 6, 6-24, and > 24 months) to account for disease severity. Using SPSS, we performed multivariable logistic regression to determine the patient and institutional factors determining the PC use. Results: A total of 29,296 patients were analyzed. Overall, 20% (n = 5737) of the patients received PC. Among these, 7%,17%,7%, 53%, and 12% received pain management PC; palliative chemotherapy, surgery, radiation and combination therapies, respectively. On cox multivariate analysis, among patients that survived < 6 months, receipt of PC was associated with better overall survival (OS) [HR: 0.91 (CI:0.87-0.95), p < 0.01]. Patients who received PC were more likely to be of White race, non-Hispanic origin, treated at non-academic facilities, and had higher educational background (p < 0.01) (Table). Patients living in East, Central, and Mountain regions had higher odds of receiving PC than those in the Pacific coast. The odds of receiving PC were significantly higher in patients who survived for < 6 months as compared to that of > 24 months (23 vs 13%, p < 0.01). Conclusions: We noticed a significantly better OS in mRCC patients who received PC. Despite the benefits in OS and guidelines advocating the PC use, the overall PC utilization in mRCC is markedly low and plagued by race, facility type and geographic region. [Table: see text]

399 Background: PSCC is a rare form of exocrine pancreatic malignancy with a dismal prognosis. Using the NCDB, we determined the prognostic factors and survival outcomes of PSCC in the United States. Methods: We performed a retrospective analysis of patients with histologically confirmed PSCC from 2004-2015 using NCDB. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Hazard Ratios were calculated using the Cox-proportional hazard method. Results: Of the 654 cases included in our analysis, 46% were female. Median age at diagnosis was 70 years and did not differ by sex (p = 0.19). The proportion of patients with stage I, II, III and IV diseases were 5%, 18%, 12%, and 54%, respectively (10%, unknown stage). Among these, 23% (35 of 150) of stage I and II disease, 10% (8 of 78) of stage III, and 2% (7 of 353) received surgical resection of the primary tumor. The rate of R0 resection was 74% in stage I and II; 38% in stage III; 29% in stage IV disease. Median OS for the entire cohort was 4 months and was significantly higher in patients who received surgical resection of the primary tumor (17 vs. 4 months, p < 0.001). On stage wise sub-group analysis, stage I-II patients had OS benefit from surgery (21 vs. 5 months, p < 0.001) as opposed to stage III (7 vs. 6 months, p = 0.31) and IV disease (5 vs. 3 months, p = 0.17). Adjuvant chemotherapy had no role in prolonging survival in stage I-II disease (20 vs 24 months, p = 0.6). Stage IV patients treated with chemotherapy had a better median OS than those without (5 vs. 2 months, p < 0.0001). On Cox multivariable analysis, stage IV disease (HR: 1.92 CI: 1.46-2.52, p < 0.001) and advanced patient age (HR: 1.02; CI:1.01-1.03, p < 0.001 were associated with poor OS, whereas OS was not dependent on the sex, race, grade, insurance status, surgery, and chemotherapy. Conclusions: This is the largest registry-based study on PSCC to date. PSCC had a diverse OS varied significantly according to increasing age and stage of the disease at presentation. Surgical resection of primary tumor was associated with improved OS in stages I-II, whereas chemotherapy improved OS in stage IV disease. The results of our study may aid the prognostication of patients and in treatment decision making.

393 Background: Clinicopathological features and the outcomes of patients with fibrolamellar hepatocellular carcinoma (FLHCC) are not clearly defined. Methods: Data were collected by retrospective chart review on 42 patients with FLHCC treated between 1990 and 2017 at the Mayo Clinic. Clinicopathological characteristics, response to treatment, recurrence pattern and survival were analyzed. Results: Of 42 patients (17 males and 25 females; median age at diagnosis 22 years, range 15 to 39), 10 patients (23%) had stage I disease and 32 patients (77%) had stage II to IVB disease. All 10 patients with stage I disease and 21 of 32 patients with stage II-IVB disease underwent resection at presentation. In stage I patient group, 6 patients experienced recurrence with a median time to recurrence of 30.5 months, resulting in a 5 year overall survival (OS) of 86%. Patients with stage II to IVB disease who underwent resection (n=21) at presentation had a median OS of 32.5 months and 5 year OS of 44%. In the upfront surgery group, 71% of the patients experienced recurrent disease. The median OS of patients with unresectable disease (n=11) was 10 months. Systemic therapy was given to 17 patients which included sorafenib, FOLFOX (5-fluorouracil/leucovorin and oxaliplatin), gemcitabine plus oxaliplatin, single agent adriamycin or gemcitabine, capecitabine plus interferon alfa, gemcitabine plus cisplatin, cisplatin plus adriamycin and nivolumab . Sorafenib was given to 9 patients and 4 patients achieved stable disease (SD) with duration ranging from 5 months to 5 years. One programmed cell death receptor positive-1 patient had a durable complete response after 2 months of therapy with nivolumab. Conclusions: In FLHCC, surgical resection was associated with prolonged OS. However, recurrences were common after the surgery. Limited benefit was derived from the systemic treatment. In rare cases, therapy with a checkpoint inhibitor may provide a viable treatment option.

672 Background: Rectal squamous cell carcinoma (RSCC) is a rare form of gastrointestinal malignancy. Using the NCDB, we determined the prognostic factors and survival outcomes of RSCC in the United States. Methods: We identified histologically confirmed cases of RSCC from the National Cancer Data Base (2004-2015). Univariate and multivariable methods were used to assess factors associated with survival. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Results: Of the 5,527 cases included in our analysis, 67% were female. Median age at diagnosis was 61 years and did not differ by sex. The proportion of patients with stage 1, 2, 3 and 4 diseases were 22%, 16%, 20%, and 11%, respectively (30% unknown stage). Among the ones who received surgical resection of primary tumor, 41%, 30%, 20% and 8% are of stages 1, 2, 3 and 4 respectively. The rate of R0 resection was 54%, 63%, 55% and 38% in stage 1, 2, 3 and 4, respectively. The R0 resection rate was much higher in patients who received neoadjuvant chemo or radiation therapy or both (87%, 78%, 74%, and 57% in stages I, 2, 3 and 4, respectively) as compared to that of their counterparts. On stage wise sub-group OS analysis, stage 1-3 patients had OS benefit from surgery (as compared to no-surgery) (145 vs 90 months, p

Background: Langerhans cell sarcoma (LCS) is a rare malignant neoplasm of Langerhans cells characterized by multi-organ involvement and an aggressive clinical course.Given the rarity of the disease, the true epidemiological data on LCS are lacking, and most of our knowledge is obtained from institutional case series. In this study, we utilized two national databases- the Surveillance, Epidemiology, and End Results (SEER) Program database (https://seer.cancer.gov/) and National Cancer Data Base (NCDB) to study the incidence, clinical presentation, and outcomes of LCS. Methods: We calculated LCS incidence (cases/10, 000, 000 individuals) from SEER database using SEER*Stat (v 8.3.4; https://seer.cancer.gov/seerstat/) statistical software. SEER is a population-based registry program of the United States National Cancer Institute that covers approximately 28% of the population. We identified LCS cases that were confirmed histologically using International Classification of Diseases for Oncology edition 3 (ICD-0-3) histology code 9756/3 from SEER 18 (2000-2014) registry. As the disease was mandatory reportable only after 2001, we included cases that were diagnosed after 2001 in the analysis. Demographic patterns, clinical presentation, and overall survival (OS) were calculated utilizing the patient level data from the NCDB Participant User File. NCDB is a joint program by the American College of Surgeons and American Cancer Society that represents approximately 70% of newly diagnosed cancer cases in the nation. All patients aged > 18 years with a diagnosis LCS (ICD-0-3 Code 9756/3) from 2004 to 2015 were included. To ensure accuracy of follow-up, we excluded the patients that were not treated at the same facility of diagnosis from survival analysis. Results: A total of 25 cases of LCS were reported to SEER between 2000 and 2014. The overall incidence of the disease was 0.2 per 10,000,000 [95% CI:0.1-0.3] and was similar among males and females (p=0.33). The incidence of the disease did not differ significantly among different races (whites, blacks and other races) (p=0.56). Between 2004 and 2015, 52 patients with newly diagnosed LCS were identified from NCDB and 60% were males. The median age of diagnosis was 62 (range, 19-90 years). The most common sites of the presentation were connective tissue (29%; n=15), reticuloendothelial system (RES) and hematopoietic system (25%; n=13), skin (19%, n=10), gastrointestinal (10%, n=5), bones and joints (8%, n=4), brain (2%, n=1) and breast (2%, n=1). Site specific details were missing in 27% (n=14) of cases. Out of the 52 patients, twenty patients (39%) received chemotherapy as first-line therapy, while 24 (46%) received surgery and 15 (29%) received radiation therapy. After a median follow up of 18 (range, 1-144) months, 27 patients (52%) had died. The one- year survival rate was 62%, and the median OS was 19 months (Fig. 1A). We also calculated the 1-year disease-specific survival and OS using SEER database, and was 74% and 63%, respectively. After censoring the patients with hematopoietic and RES involvement, the patients who were managed with radiation therapy (median dose 3960 cGy, range 750-6400) had a better OS as compared to those who received no radiation therapy (p=0.03, Fig. 1B). On the contrary, after excluding the patients with hematopoietic and RES as primary site, no significant difference in OS was noted between the patients who were managed with and without surgery (17 vs 21 months; p = 0.75; Fig. 1C). In addition, post-surgical radiation or chemotherapy had no significant benefit in median OS (p=0.25). Among patients with hematopoietic and RES involvement, there was no association between OS and receipt of chemotherapy (p = 0.16; Fig. 1D); however, the number of patients who received chemotherapy was small (n=6). Conclusion: This dual-national registry study shows that LCS is extremely rare, and has a poor prognosis. Although the data regarding optimal management of LCS are limited, our study demonstrates that radiation therapy may offer survival advantage in patients without hematopoietic and RES involvement. Disclosures No relevant conflicts of interest to declare.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, with ~21,000 estimated new cases in 2018. Prior retrospective studies have suggested an increased risk of second primary malignancies (SPMs) in CLL patients. Population-based studies on the risk of SPMs in CLL are limited, especially in the last decade with improvements in prognostic and therapeutic tools over the last decade. As the survival of CLL patient improves, it may lead to more survivors who are at risk of developing SPMs. In this study, we sought to evaluate the risk of development of SPMs among CLL patients diagnosed from 2000-2014. Methods: We used the SEER 18 registries for the calculation of risk of SPMs and included CLL cases that were confirmed histologically between 2000-2014 (https://seer.cancer.gov/). SPMs diagnosed within 2 months of primary CLL diagnosis were excluded. Time to SPM was calculated by subtracting second malignancy survival/follow-up time from CLL survival/follow-up time. The SEER*Stat Multiple Primary-SIR tool was used to calculate SIRs for secondary malignancies by comparing these patients' subsequent cancer experience with the number of cancers that would be expected based on incidence rates for the general U.S. population. These analyses were adjusted for age, gender, race, and year of CLL diagnosis. Multivariate logistic regression was performed to identify factors associated with development of SPM. Results: The study cohort included 46,164 patients with CLL. After a median follow up of 50 months (range 1-179), 5220 (11.3%) patients developed a total of 5,738 subsequent malignancies. As compared to that of general population, CLL patients had a higher risk of developing SPMs (SIR: 1.40 [95%CI:1.37-1.44]) and the risk was much higher for hematologic malignancies (SIR: 2.63 [95%CI:2.47-2.80]) as compared to solid organ malignancies (SIR: 1.25 [95%CI: 1.22-1.29]). In addition to known common SPMs in CLL (lymphoma, melanoma, lung cancer, and prostate cancer), there was an elevated risk of developing acute lymphoblastic leukemia (SIR 5.43), chronic myeloid leukemia (SIR 2.18), thyroid cancer (SIR 2.09), and kidney cancer (SIR 1.70) (Table). Out of the 5220 patients who developed SPMs, 437 (8.3%) patients developed two subsequent second primary malignancies, and 81 (1.5%) patients developed > 2 subsequent primary cancers, which was significantly more than the endemic rate (SIR, 1.40; p On logistic regression, males had higher odds of developing SPMs than females (OR: 1.46 [95% CI: 1.38-1.56], p Conclusion: In this large population-based study, CLL patients had an elevated risk of developing second primary hematologic and solid malignancies. The specific types of SPMs were varied, ranging from common ones such as lymphoma, lung cancer, prostate cancer, to uncommon ones such as thyroid cancer, kidney cancer, and chronic myeloid leukemia. The patients who were diagnosed after 2007 had a lower risk of developing SPMs as compared to those diagnosed before. There is a need for studies evaluating immunological repertoire of CLL and its impact on development of SPMs. Knowledge of these SPMs may help physicians with their early detection. Disclosures No relevant conflicts of interest to declare.

Background: Early integration of Palliative Care (PC) have shown to improve survival in some solid malignancies such as lung and colon cancers. In this study we sought to analyze the PC utilization in acute myeloid leukemia (AML) patients. Methods: Using the National Cancer Data Base (NCDB) Participant User File, we extracted patient-level data of patients with AML reported between 2004 to 2015.Patients who received pain management and/or other palliative procedures were considered as PC utilizers. After excluding the cases with acute promyelocytic leukemia t (15, 17) (given its excellent prognosis), we classified the AML into three groups- AML with genetic abnormalities, therapy related AML and AML with dysplasia. Other co-variates included in the analysis were age, sex, race, origin, Charlson-Deyo comorbidity score, insurance status, household income, educational status, facility type (academic vs non-academic) and year of diagnosis. Multivariate logistic regression was performed to identify the predictors of palliative care utilization. Statistical analysis was done using PC SPSS v24.0. Results: Of 102,778 patients, 3.4% (n=3504) received PC as initial treatment. PC utilization increased significantly from 2004-2006 to 2013-2015 (2.5% vs 3.9%, p < 0.001). Individuals of non-Hispanic origin (as compared to that of Hispanics) are more likely to receive PC as compared to that of non-Hispanics. (3.5 vs 1.8%, p Conclusions: We noticed a differential utilization of palliative care based on the histological subtype of AML. The lesser utilization of PC in AML with certain genetic abnormalities may be attributed to their better overall survival outcomes. Though we noticed an increased trend in PC utilization over the past decade, the overall PC utilization in AML is markedly low and plagued by origin and socio-economic status. Disclosures No relevant conflicts of interest to declare.

Thyrotoxic hypokalemic periodic paralysis (TPP) is a condition characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. We describe two cases of thyrotoxic periodic paralysis who presented to our hospital with potassium values of 1.3 MeQ/l and 1.2 MeQ/l, respectively. Surprisingly, the two patients had no documented past medical history. Based on the clinical features of high heart rate, palpitations (seen in both the patients), and exophthalmos (seen in one patient), thyrotoxic periodic paralysis was suspected. A thorough laboratory workup confirmed the diagnosis of thyrotoxicosis. Beta blockers were initiated promptly, along with intravenous potassium chloride, and the patients eventually improved symptomatically. These patients were eventually diagnosed with Graves’ disease and were placed on methimazole, which prevented further attacks. Thyroid periodic paralysis (TPP) is a rare clinical manifestation of hyperthyroidism. Patients present with sudden onset paralysis associated with severe hypokalemia. The presence of paralysis and hypokalemia in a patient who has a history of hyperthyroidism should prompt the physician about thyrotoxic periodic paralysis. A high index of suspicion, prompt diagnosis, and management of the condition can prevent severe complications, such as cardiac arrhythmias.

9524Background: Therapeutic advances altered the course of MMel in the last decade. The therapeutic and survival disparities of MMel were evaluated based on hospital volume using the National Cance...

e16118Background: IHCC is a rare cancer with poor OS. The purpose of this study is to determine the association between the number of patients with IHCC treated annually at a treatment facility (vo...

1083Background: Recent randomized trials evaluating the role of surgery in de novo stage 4 BC yielded mixed results indicating that patient/tumor characteristics might influence the survival. We an...

133 Background: Since the advent of Rituximab (R) in 1997, cancer immunotherapy is increasingly used for management of lymphoproliferative disorders. Unexpected cases of PML have been reported in HIV-negative patients in 2005 receiving Rituximab ( R) and subsequently in 2012 and 2014, who received brentuximab vedotin ( B) or ibrutinib ( I), respectively. We sought to compare and contrast clinical characteristics and outcomes of PML in HIV-negative patients who were treated with R, B or I therapy. Methods: Retrospective analysis of the FDA adverse event reporting system (FAERS) and previously published data by our group with confirmed cases of PML associated with R (1997-2008), B and I therapy (2009-2015). Results: PML develops early during the therapy with B and I, compared to that of R group. Confirmation of the diagnosis of PML by MRI in conjunction with JC virus identification in the cerebrospinal fluid or brain biopsy using objective criteria was found only in 40-60% of the cases. Among confirmed cases of R, I, or B-associated PML, mortality was > 90%, usually occurring within weeks to months following diagnostic confirmation. Rare cases of survival were associated with return of immunologic function, including in one case development of an immune reconstitution syndrome. Conclusions: This is the first study that compared the clinical characteristics of PML in R, B and I. PML cases can occur early during the therapy using B and I, while usually occurs late with R. Additional research is needed to quantify the risk factors of PML and to know if this association is causal or incidental. Meanwhile, physicians and patients should be vigilant in detecting and reporting this rare AE to minimize future fatalities [Table: see text]

e20042 Background: INT 0139 study showed that patients who received surgery after neoadjuvant chemoradiation did not have an overall survival (OS) benefit as compared to chemoradiation alone. Moreover, patients who underwent right sided pneumonectomy had non-significantly worse overall survival than chemoradiation alone. Methods: We sought to compare the survival outcomes in patients who received surgery after neoadjuvant chemoradiation based on the surgery type and the laterality of the disease using National Cancer Data Base (2004-15). Kaplan-Meier estimates were used to compare OS between the groups. Results: A total of 2881 and 499 patients had lobectomy and pneumonectomy after neoadjuvant chemoradiation, respectively. We found no difference in median OS in the patients who had left vs right lobectomy (Table). However, 30-, 90-day morality was higher in right lobectomy patients (p = 0.03). Similar trend was seen in the 30-, 90-day mortality and median OS in right and left pneumonectomies (Table). Total number of patients that got right pneumonectomy after neo-adjuvant chemoradiation before and after INT 0139 study (2009) did not change (49% vs 45%, p = 0.33). Conclusions: The short-term mortality was higher in right sided stage IIIA NSCLC patients in our cohort who received surgery irrespective of type of surgery. Interestingly, we did not notice any decrease in pneumonectomy rates since 2009. [Table: see text]

7020 Background: Chimeric antigen receptor T-cell (CAR-T) therapy can lead to durable responses in chemorefractory patients with hematologic malignancies. CAR-T, however, can be associated with neurotoxicity. There is a significant body of literature describing patient-reported concerns with cognition in hematopoietic cell transplant (HCT) recipients, a similar treatment group. However, little is known about subjective cognition in CAR-T patients. This study examined changes in subjective cognition over time in CAR-T recipients and compared their outcomes with allogeneic HCT recipients. Methods: At baseline and 90 days after infusion, participants completed the Everyday Cognition Questionnaire (ECog). The ECog provides scores for total cognition, memory, language, visuospatial abilities, planning, organization, divided attention, and satisfaction with cognition. Comparison data from allogeneic HCT recipients came from a previous observational study. Linear mixed models compared changes in subjective cognition between recipients of CAR-T and allogeneic HCT over time. Models were adjusted by age, marital status, education, and Karnofsky performance status. Results: Participants were 111 CAR-T recipients (mean age 60 years, 37% female) and 190 allogeneic HCT recipients (mean age 53, 42% female). Linear mixed models indicated CAR-T recipients’ subjective cognition didn’t change within the 90 days after infusion (p’s > .05). At baseline, there were no group differences between CAR-T and allogeneic HCT recipients in subjective cognition (p’s > 0.05). Over time, however, subjective cognition between groups differed. Specifically, CAR-T recipients reported stable subjective cognition whereas allogeneic HCT recipients reported worsening total subjective cognition (p = 0.04), memory (p = 0.02), visuospatial abilities (p = 0.01), planning (p = 0.01), and divided attention (p = 0.01). At follow-up, CAR-T recipients reported better total subjective cognition (p < 0.01), memory (p < 0.01), language (p = 0.01), visuospatial abilities (p < 0.01), planning (p < 0.01), and divided attention (p < 0.01) than allogeneic HCT recipients. Conclusions: Despite the neurotoxicity associated with CAR-T, patients can expect to perceive similar subjective cognition at day 90 compared to baseline. Future studies should also evaluate objective cognition in CAR-T recipients.