tbuckley/cabot-search huggingface dataset:
Trends of survival based on race and ethnicity in gastrointestinal tract neuroendocrine tumor.
Authors: Suleyman Yasin Goksu, Muhammad Shaalan Beg, Nina Niu Sanford, Benjamin David Fangman, Sarah Herrman, Busra Bacik Goksu, Udit Verma, Aravind Sanjeevaiah, Amy Little Jones, Radhika Kainthla, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2020)

607 Background: There is paucity of data about racial/ethnic disparities in gastrointestinal tract neuroendocrine tumors (GiNET). We aimed to study the race/ethnic differences in disease characteristics and survival in GiNET. Methods: We analyzed the SEER database to identify cases with non-pancreatic GiNET between 2004 and 2015. We evaluated trends in incidence and outcomes between Hispanic, non-Hispanic/non-Black (NH/NB) and non-Hispanic Black (NHB). Kaplan-Meier method and cox regression model were performed for overall survival (OS) after adjusting for stage, grade, gender, race/ethnicity, and surgery. Results: 25,826 cases were included, 12.7% were Hispanic, 18.5% NHB and 68.8% NH/NB; males comprised 46.8%, 50.5%, 41.9%, respectively (p &lt; 0.001). The overall incidence of GiNET increased two-folds in the ten years. The highest increase in incidence was observed in appendiceal NET followed by small intestine NET, and this increase was observed mostly among Hispanic population. NH/NB cases were older ( &gt; 65 years) (31.3% vs. 23.3% vs. 23.5%; p &lt; 0.001) and presented with metastatic disease (17.8% vs. 12.7%, 12.0%; p &lt; 0.001). On multivariate analysis Hispanic population had significantly better OS than NH/NB and NHB (HR: 1.25 95% CI: 1.14-1.37 and HR: 1.15 95% CI: 1.033-1.28, respectively). For stage-4 low- and intermediate-grade GiNET, OS was better if surgery was performed (p &lt; 0.001), and this trend was most pronounced among Hispanic as compared to NH/NB (HR 1.35, 95% CI 1.07-7.71). Conclusions: The incidence of GiNET had increased two-fold in the last ten years with the highest increase in Hispanic. However, Hispanic had significantly better overall survival than NH/NB and NHB population.[Table: see text]
Mesoporous polydopamine with built-in plasmonic core: Traceable and NIR triggered delivery of functional proteins
Authors: Di Wu, Jiajing Zhou, Xiaohong Chen, Yonghao Chen, Shuai Hou, Hehe Qian, Lifeng Zhang, Guping Tang, Zhong Chen, Yuan Ping, Wenjun Fang, Hongwei Duan
Journal: Biomaterials (2020)
Efficacy and safety of nab-paclitaxel plus S-1(nab-P/S-1) versus nab-paclitaxel plus gemcitabine (nab-P/Gem) for first-line chemotherapy in advanced pancreatic ductal adenocarcinoma (aPDAC): A randomized study.
Authors: Yuan Zong, Zhi Peng, Xicheng Wang, Lin Shen, Jun Zhou
Journal: Journal of Clinical Oncology (2020)

717 Background: Nab-P/Gem significantly improved survival compared with gem in patients (pts) with metastatic PDAC, but the ORR was limited to 23% with increased myelosuppression. Two phase II trials demonstrated high ORR of 50.0-53.1% with nab-P/S-1 and showed less hematologic toxicity. Methods: A randomized (1:1) phase II trial was conducted. Eligibility required treatment-naïve pts with unresectable PDAC. Pts received nab-P 125mg/m 2 on day 1 + S-1 80-120mg orally per day on day 1-7 every 2 weeks or nab-P 125mg/m 2 + Gem 1000mg/m 2 on days 1,8 every 3 weeks. With an increase of ORR from 25% to 50%, 100 pts were required for 90% power at a two-sided significance level of 0.05. We enrolled 40 pts for a pilot study. Primary endpoints were ORR and 6-month PFS rate. Secondary endpoints were ORR of primary lesion, DCR, PFS, OS and safety. Results: 40 pts were enrolled between 06/2018 and 06/2019, including locally advanced (27.5%) and metastatic (72.5%) PDACs. 42.5% were male and the median age was 61 (range, 36-75) years old. The median duration of treatment was 2.3 months in nab-P/S-1 (n = 20) and 2.7 months in nab-P/Gem (n = 20). In the intention-to-treat (ITT) population, the ORR and DCR were 35.0% vs 25.0% ( P= 0.49) and 70.0% vs 70.0%, respectively.The ORR of primary lesion was 30.0% vs 25.0% ( P= 0.72). In the evaluable pts (nab-P/S-1 n = 18, nab-P/Gem n = 18), the ORR, DCR and the ORR of primary lesion were 38.9% vs 27.8%, 77.8% vs 77.8% and 35.3% vs 29.4%, respectively.With the median follow-up of 5.0 (range 0.3-11.4) months, the median PFS and 6-month PFS rate was 6.3 vs 5.7 months and 56.1% vs 36.2%( P= 0.61) for nab-P/S-1 and nab-P/Gem, respectively. The median OS have not reached. Grade 3/4 toxicities occurred in 30.0% nab-P/S-1 and 30.0% nab-P/Gem: leukopenia/neutropenia(15.0% vs 25.0%), febrile neutropenia (0 vs 5.0%), rash (0 vs 5.0%) and diarrhea (10.0% vs 0). Conclusions: Compared with nab-P/Gem, nab-P/S-1 had higher ORR, ORR of primary lesion and longer PFS without significant difference. Nab-P/S-1 developed a trend towards less hematologic toxicity. Follow up for survival is ongoing. Clinical trial information: 03636308.
Clinicopathological features and treatment outcomes of young patients with gastric and esophageal cancers.
Authors: Lauren Amanda Beck, Lucy Xiaolu Ma, Osvaldo Espin-Garcia, Chihiro Suzuki, Di Maria Jiang, Geoffrey Liu, Eric Xueyu Chen, Jennifer J. Knox, Rebecca Wong, Savtaj Singh Brar, Carol Jane Swallow, Jonathan Yeung, Gail Elizabeth Darling, James Conner, Elena Elimova, Raymond Woo-Jun Jang
Journal: Journal of Clinical Oncology (2020)

e16577 Background: Gastric and esophageal (GE) cancers most commonly occur in older adults in their 60’s.However, there are inconsistent reports about prognosis in adolescent and young adult (AYA) pts, and treatment patterns and outcomes in this population have not been well characterized. Methods: A retrospective analysis was performed for AYA (age 18-40 years) pts with histologic diagnosis of GE cancers who presented to Princess Margaret Cancer Centre from 2008 to 2016. The Kaplan-Meier method was used to analyze progression free (PFS) and overall survival (OS). Results: We identified 57 AYA GE cancer pts (30 gastric, 27 esophageal). Baseline features included: median age 35 years, 51% female (70% in gastric, 30% in esophageal), 82% with Eastern Cooperative Oncology Group performance status 0-1, 82% Charlson Comorbidity Index 0, 54% stage IV. For gastric pts, 53% had diffuse subtype and 47% had signet ring adenocarcinoma. Most had negative family history (77%). Curative intent and palliative treatment was used in 23 (40%) and 34 pts (60%) respectively. In curative pts, 48% had neoadjuvant therapy, 52% had upfront surgery. Of pts who underwent curative resection, 62% had pT3/T4 and 38% had pN2/N3 disease; 5-year OS rate was 37% (95% CI 20-67). Of the palliative pts, 91% received systemic therapy. First-line regimen included triplet (81%) and doublet chemotherapy (13%), administered for a median of 6 cycles. Median PFS was 7.4 months. Second- and third-line treatments were administered in 14 and 3 pts respectively, 1 pt was treated beyond third-line. Median OS in palliative pts was 12.1 months (95% CI 8-21.3). Conclusions: Our gastric AYA pts had increased female predominance and diffuse histology. Many AYA pts had advanced GE cancer at diagnosis, with over half of pts presenting with metastatic disease. In both the curative and palliative setting, AYA pts did not appear to have better survival outcomes despite having few comorbidities, suggesting they may have more aggressive biology.
Usefulness and applicability of next generation sequencing in neuroendocrine neoplasms.
Authors: Sorrapong Manyanont, Kyle Winter, Nikolaos Trikalinos
Journal: Journal of Clinical Oncology (2020)

626 Background: Neuroendocrine neoplasms (NENs) are rare tumors that can arise anywhere in the body and treatment options are limited due to their rarity. Knowledge of their mutational status might allow for tumor agnostic treatments or aid in enrollment in clinical trials, especially in the metastatic setting. Methods: Eligible NEN patients on an institutional, IRB approved protocol, who had NGS as standard of care and were treated in the past 24 months were included. Tumors were categorized by location and histologic grade. We explored the actual and theoretical eligibility for tumor agnostic treatments and enrollment in clinical trials as available on clinicaltrials.gov. Results: Between August 2017 and July 2019 a total of 107 patients were eligible. Globally 102 clinical trials included patients with NEN and specific mutations.NGS detected one (1%) case of MSI high and one (1) TRK fusion positive tumor, eligible for checkpoint inhibitor and TRK inhibitor therapy respectively. Moreover, NGS identified 16 (15%) cases of MEN1, 1 (1%) of RET, 2 (2%) of NF1 and 3 (2.8%) of MUTYH, 2 (2%) TSC or TSC2, BRCA in 1(1%). These patients were appropriately referred to genetic counseling. About 51.5% of patients would in theory be eligible for an investigational treatment based on mutations and clinical trial availability. Fifty two of 107 patients (48.5%) would not have been eligible for a clinical trial with reasons varying between no mutations (24%), sample failure (8.4%) or nonactionable mutations (15.9%). Conclusions: NGS can point to clinical trial eligibility and guide genetic counseling and should probably be a standard approach in the evaluation of new metastatic NEN patients.
A phase I study to evaluate the safety and tolerability of AB680 combination therapy in participants with gastrointestinal malignancies.
Authors: Johanna C. Bendell, Gulam Abbas Manji, Shubham Pant, Dominic W. Lai, Jill Colabella, Wade Berry, Melissa Constance Paoloni, William J. Grossman, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2020)

TPS788 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) expresses very high levels of CD73 among tumor types, and CD73 expression level is a known poor prognostic factor in PDAC. Adenosine, a product of AMP breakdown by CD73, is highly immunosuppressive against effector T &amp; NK cells in the tumor microenvironment. AB680 is the first clinical-stage small-molecule CD73 inhibitor, which is highly potent, pharmacodynamically active, and safe in healthy volunteer dose escalation studies. Targeting the adenosine pathway in combination with standard of care regimens may have a more profound effect on activating and inducing sustained anti-tumor immunity. Methods: This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AB680 in combination with AB122 (anti-PD-1 antibody) and standard chemotherapy (nab-paclitaxel [NP] and gemcitabine [Gem]) in participants with first line (1L) mPDAC. In the dose-escalation Ph1 portion, increasing dose levels of AB680 are administered every 2 weeks (Q2W) in combination with AB122 (240 mg Q2W) and NP/Gem (Gem 1000 mg/m2 + NP 125 mg/m2 IV on Days 1, 8, and 15 of each 28-day cycle). Up to 30 participants may be evaluated in Ph1 dose-escalation. In the dose-expansion Ph1b portion, AB680 will be administered at the recommended dose for expansion in combination with AB122 and NP/Gem in up to 40 participants. Adverse events will be graded according to NCI CTCAE 5.0 and antitumor activity assessed using RECIST v1.1. Conclusions: This Ph1/1b study will be the first to target the adenosine axis using a highly potent small-molecule inhibitor of CD73, AB680, in 1L mPDAC in combination with standard of care chemotherapy (NP/Gem) and a PD-1 antibody (AB122). Future results will be shared in upcoming scientific conferences. Clinical trial information: NCT04104672.
Phase Ib/II study of sorafenib (SOR) and pembrolizumab (PEM) in advanced hepatocellular cancer (HCC).
Authors: Rohit Gosain, Sarbajit Mukherjee, Sunyoung S. Lee, Austin Miller, Hans Minderman, Orla Maguire, Junko Matsuzaki, Danielle Casucci, Devalingam Mahalingam, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2020)

TPS596 Background: SOR has been the backbone of advanced HCC therapy with poor outcome. Anti-PD-1 therapy is approved as a second-line treatment option in HCC due to its promising efficacy and safety. Our preclinical work showed that SOR is immunomodulatory and may be synergistic when combined with anti-PD-1 therapy. Guided by this data, we initiated this multicenter study of SOR and PEM in advanced HCC patients (pts). Methods: Pts who have Child-Pugh Class A, ECOG PS of 0/1, biopsy-proven measurable HCC that is unresectable or metastatic, are included. Pts must not receive either SOR or anti-PD-1 therapy before. A total of 27 pts will be enrolled from 2 sites. Pts must have the following lab values: ANC ≥ 1,500/ mc; Hgb ≥ 8.5 g/dL; Plts ≥75,000/ mcL; serum total bilirubin ≤ 2.0 mg/dL; AST/ALT ≤ 5 X ULN; serum creatinine ≤ 1.5 X ULN. Pts with active hep B must be on antiviral therapy. Pts would be on a 4-week run-in of SOR alone at 400mg BID to ensure tolerability and stable dose (minimum 200 BID) before beginning PEM 200mg IV q3 weeks. Both drugs would be administered until progression or unacceptable toxicity with response assessment q6 weeks by RECIST 1.1 criteria. Primary endpoint: response rate. Secondary endpoints: safety, overall survival, and progression-free survival. Correlative Endpoints: Pre-treatment levels of immunosuppressive cells and the functional activity of effector T cells would be compared to post-treatment blood and tumor samples. The first 6 pts who completed 4 weeks of SOR-only treatment and began the combination therapy (addition of PEM at a fixed dose of 200 mg Q3W) would comprise the safety lead-in. Pts who withdrew before initiation of combination therapy (for reasons other than DLT) would be replaced. Dose-Limiting toxicity was defined as any ≥ grade 3 clinically significant toxicity, which is deemed possibly treatment-related and occurs within the first cycle of combination therapy. Toxicity would be assessed by NCI CTCAEV4.0. Status: First patient enrollment on 12/19/2017. On 11/28/2018, our 6th patient completed the SOR lead-in phase and began combination treatment with SOR and PEM. As of Sept 12, 2019, thirteen pts have enrolled, and 9 pts have received combination treatment. Support: Merck. Clinical trial information: NCT03211416.
Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR
Authors: Giancarlo Fatobene, Vanderson Rocha, Andrew St. Martin, Mehdi Hamadani, Stephen Robinson, Asad Bashey, Ariane Boumendil, Claudio Brunstein, Luca Castagna, Alida Dominietto, Hervé Finel, Yves Chalandon, Chantal Kenzey, Mohamed Kharfan-Dabaja, Hélène Labussière-Wallet, Jose M. Moraleda, Rocco Pastano, Miguel-Angel Perales, Hanadi Rafii El Ayoubi, Annalisa Ruggeri, Anna Sureda, Fernanda Volt, Ibrahim Yakoub-Agha, Mei-Jie Zhang, Eliane Gluckman, Silvia Montoto, Mary Eapen
Journal: Journal of Clinical Oncology (2020)

PURPOSE To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation. PATIENTS AND METHODS We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide. RESULTS Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P &lt; .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively). CONCLUSION When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.
Efficacy and toxicities of immune checkpoint inhibitors (ICIs) in advanced melanoma: A single institution experience.
Authors: Karim Welaya, Andrea M. Baran, Manidhar Reddy Lekkala, Deepak M. Sahasrabudhe
Journal: Journal of Clinical Oncology (2020)

59 Background: Historically, the prognosis of advanced melanoma has been poor. Recent landmark studies (KEYNOTE-006, CheckMate 066, CheckMate 037 and CheckMate 067) have shown significant improvement in outcomes of patients with advanced melanoma treated with ICIs. In a single institution retrospective study, we evaluated the efficacy and toxicities of ICIs in patients with advanced melanoma treated in real-world clinical practice. Methods: We included patients who received pembrolizumab (PEMBRO), nivolumab (NIVO), or ipilimumab plus nivolumab (IPI/NIVO) at the University of Rochester Medical Center from June 2015 to December 2018. Patient- and cancer-related characteristics were collected and compared between treatment groups. Outcomes including duration of treatment, response rates, and adverse events (AEs) were captured. Progression free survival (PFS) and overall survival (OS) were summarized using the Kaplan-Meier method. Results: We included 89 patients (55 received PEMBRO, 20 received NIVO, and 14 received IPI/NIVO); median age at ICI initiation was 68 years (range, 28-92) and 29% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥2. Forty-five patients (51%) had ≥2 co-morbidities. Nine patients (10%) had autoimmune diseases prior to initiating ICIs and 34 patients (38%) had brain metastasis. ICIs were given as first line in 71 patients (80%). Compared to those who received PEMBRO or NIVO, patients who received IPI/NIVO were younger (median age was 61 vs.71 vs. 70, p=0.003) and had better ECOG PS (ECOG PS ≥2 was 0% vs. 40% vs. 33%, p=0.007). Table shows the outcomes for the three groups. Conclusions: Patients with advanced melanoma treated with ICIs derived similar response rates to those seen in published landmark studies. However, median OS was shorter (range was 38 months to not reached in published studies). [Table: see text]
Abstract MP06: Everyday Discrimination And Mental Stress-induced Myocardial Ischemia In Young Women Post-mi
Authors: Izraelle I McKinnon, Amit J Shah, Bruno B Lima, Kasra Moazzami, An Young, Samaah Sullivan, Zakaria Almuwaqqat, lisa elon, Paolo Raggi, Arshed A QUYYUMI, Viola Vaccarino, Tene T Lewis
Journal: Circulation (2020)

Objectives: Mental stress-induced myocardial ischemia (MSIMI) is a transient myocardial ischemic response to mental stress. Women are about two times more likely to develop MSIMI compared to men, which could potentially explain their worse morbidity and mortality after myocardial infarction (MI). We sought to examine the associations between experiences of everyday discrimination, as a gender-related stressor, and both MSIMI and conventional (exercise/pharmacologic)-induced myocardial ischemia among young survivors of MI. Hypothesis: Reports of everyday discrimination are associated with a higher prevalence of MSIMI, but not conventional ischemia in those with recent MI; furthermore, this relationship is stronger among young women compared to men. Methods: We studied 295 post-MI patients (145 women, 150 men) aged 25-61 years. Participants underwent single-photon emission computed tomography (SPECT) perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores of myocardial segments were summed, with the summed difference score between stress and rest scores used to determine the presence of ischemia under both stress conditions. The Everyday Discrimination Scale (EDS) was assessed via questionnaire and used to measure exposure to experiences of discrimination (possible range 1-4). Results: EDS scores ranged from 1-3.8 (mean 1.7; SD 0.6). After adjustment for sociodemographic and cardiovascular risk factors, indicators of MI severity and symptoms of depression, each one point increase in average exposure to everyday discrimination (more frequent exposure) was associated with a doubling of odds of MSIMI (OR=2.46 [1.21 – 5.00]), but was not associated with exercise/pharmacological-induced ischemia (OR=0.75 [0.41 – 1.36]). These results were more robust among women, who demonstrated a nearly four-fold increase in odds of MSIMI with each one-point increase in average discrimination score compared to a two-fold increase among men, however there was no evidence of interaction by gender. Conclusion: Among young post-MI patients, experiences of everyday discrimination were positively associated with risk of MSIMI, but not associated with conventional stress ischemia. The risk of MSIMI tended to be greater among women than men, potentially implicating discrimination in triggering a physiological response to which women are particularly vulnerable.