tbuckley/cabot-search huggingface dataset:
Clinical activity of ONC201 in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Mark N. Stein, Howard Kaufman, Cyril Benes, Martin Stogniew, Wolfgang Oster, Joshua E. Allen, Bruce George Haffty, Joseph R. Bertino
Journal: Journal of Clinical Oncology (2016)

e16514 Background: Proteasome inhibitors that induce the integrated stress response are effective in preclinical models of hormone-refractory prostate cancer and have induced objective responses in prostate cancer patients in early phase clinical trials. ONC201 is a PERK-independent small molecule inducer of the integrated stress response that has compelling efficacy in preclinical advanced cancer models. In vitro sensitivity profiling has determined that prostate cancer is one of the most sensitive tumor types to ONC201 among solid tumors and that the drug is effective in hormone-refractory cancer cells. In addition, ONC201 shows excellent tolerability and can be given orally with infrequent dosing regimens. Methods: A phase I dose escalation trial recently established 625mg of ONC201 administered orally every three weeks (one cycle) as the recommended phase II dose. Metastatic castration-resistant prostate cancer patients were enriched in a dose expansion cohort based on the preclinical sensitivity profile of ONC201 in solid tumors. Results: Of the 28 patients in the phase I, 5 prostate cancer patients (age range 62-90) received 625mg ONC201 every three weeks; currently, 4 patients have recieved at least 2 cycles. One patient previously treated with sipuleucel-t, abiraterone, enzalutamide, and docetaxel exhibited stable disease after initiation of ONC201 therapy and remained on study for 6 months. A second patient previously treated with sipuleucel-t, abiraterone, enzalutamide, had a 25% decline in PSA after 2 cycles of ONC201 and remains on study after 4 cycles with radiographically stable disease. A third patient exhibited a mixed response, with overall stable disease after 4 cycles. A fourth patient had progression after 2 cycles and the fifth patient is in the first cycle of treatment. No drug related toxicity > grade 1 was observed. Conclusions: These results suggest that ONC201 is clinically active in prostate cancer patients and that investigation of more frequent dosing and/or combination therapy is warranted and enabled by its safety and pharmacokinetic/pharmacodynamic profile. Clinical trial information: NCT02324621.
Does PSA 10-20 impact pathologic progression and secondary treatments in men with Gleason 6 on biopsy? Implications for active surveillance in intermediate risk patients.
Authors: Fernando Caumont, John Burns, Sydney Akapame, John Paul Flores, Christopher R. Porter
Journal: Journal of Clinical Oncology (2018)

e17081 Background: PSA of 10-20 often excludes men from Active Surveillance (AS). These men are considered intermediate risk (IR) even with Gleason (Gl) 6 prostate cancer (PCa) on biopsy. Radical treatment is often chosen, due to concerns for occult pathology and the possibility of secondary treatments if curative treatment is delayed. Using the National Cancer Database (NCDB) we evaluated rates of pathologic progression (PP) and secondary treatments for IR PCa defined by PSA alone compared to low risk (LR). Methods: We reviewed NCDB (2010-2013) for men ≤75 y/o with non-metastatic PCa stage ≤ cT2a, Gl ≤3+3 PCa, and PSA < 20, who underwent radical prostatectomy (RP). We stratified men into LR (NCCN LR criteria) and IR PCa (NCCN LR criteria except PSA 10-20). Our primary endpoint was PP at RP, defined as positive margins, pathologic upgrading to ≥3+4, or upstaging to ≥pT3a. Secondary endpoint was rate of secondary treatments defined as radiation therapy (RT) or hormonal therapy (HT). Multivariate logistic regression evaluated factors contributing to PP and need for secondary treatment, including age, race, clinical stage, facility type, insurance, Charlson comorbidity index, year of diagnosis, geographic location, neighborhood income. Results: Our cohort included 61,330 LR and 5,430 IR patients. Median PSA for each was 4.8 and 12.2, respectively. Rates of PP were significantly higher in IR men undergoing RP, 54.5% vs. 47.2% LR, p < 0.001. Positive margins (p < 0.001), pathologic Gl ≥ 3+4, (p < 0.001), and stage ≥3 PCa (p < 0.001) were all significantly higher in the IR vs. LR cohort, Table 1. Rates of secondary treatments were significantly higher in the IR cohort (OR = 2.45). Secondary treatment was uncommon for both cohorts (4.5% IR vs. 1.7% LR). Conclusions: Risk of PP and need for secondary treatment is significantly higher in those with IR PCa defined by PSA alone vs. LR patients at RP. When considering AS for patients with Gl 6 and PSA 10-20, the increased risk of PP and the increased risk of secondary treatments must be discussed. Table 1 PP (%) LR IR LR IR Positive Margin 11.5 15.9 ≥ pT3 8.1 14.3 Gleason ≥ 3+4 40.6 48.5 Any PP 47.2 54.5 Secondary Treatment (%) LR IR RT 0.9 2.2 HT 0.8 2.3
The epidemiology of carcinoid tumors of small and large intestine in USA: A national inpatient sample analysis (2009-2014).
Authors: Nauman S Siddiqui, Zubair Khan, Basmah Khalil, Wasif M. Saif
Journal: Journal of Clinical Oncology (2018)

e16188 Background: Carcinoid tumors (CTs) are the most common type of neuroendocrine tumor. About two-thirds of all carcinoid tumors appear in the gastrointestinal system, particularly in the intestine. The aim of this analysis is to define epidemiology of CTs of intestine in hospitalized US population. Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of benign and malignant CTs of both small (SI) and large intestine (LI) as primary or secondary diagnosis via ICD 9 codes during the period from 2009-2014. Results: From 2009 to 2014, there were total 46602 discharges of CTs of intestine. Out of these, there were 20246 discharges of malignant CTs of SI (43.4%), 7161 discharges of benign CTs of SI (15.4%), 12710 discharges of malignant CTs of LI (27.3%) and 6484 discharges of benign CTs of LI (13.9%). Most of the patients with malignant and benign CTs of SI were of age above 50, 86.2% & 84.3% respectively. They were mostly insured by Medicare, 50.5% & 52.1% respectively. There was slight male predominance, and more routine discharges for this group. The patients with malignant CTs of SI were more likely to develop Carcinoid Syndrome (CS) than benign CTs of SI (12.9% Vs 4.6%, P = < 0.001). The odds of having diabetes and complications, smoking, alcoholism and obesity were more in benign CTs of SI than malignant CTs of SI. More patients with malignant CTs of LI were of age above 50 than benign CTs of LI (74.8% Vs 57.7%, P = < 0.001). Most of these patients were privately insured with female predominance. Patients with malignant CTs of LI were discharged more to skilled nursing facilities (9.6% Vs 4.8%, P = < 0.001) and requiring home health care (16.4% Vs 8.6%, P = < 0.001) than benign CTs of LI. The patients with malignant CTs of LI were more likely to develop CS than benign CTs of LI (6.9% Vs 2.1%, P = < 0.001). Conclusions: The malignant CTs of SI are the most common out of all CTs of intestine. Interestingly there was male predominance in CTs of SI and female predominance in CTs of LI. The different insurance status of CTs of SI and LI is suggestive of different social etiological factors. In comparison with other tumors, Malignant CTs of LI were associated with worse outcomes.
TCT-41 Acute and Six-month Outcomes of a Novel Self-expanding Transcatheter Heart Valve
Authors: Ulrich Schäfer, Lenard Conradi, Volkmar Falk, Stefan Verheye, Francesco Maisano, Holger Thiele, Martin Landt, Michael Haude, Stephan Baldus, Stephan Kische, Hendrik Treede, Pim Tonino, Hüseyin Ince
Journal: Journal of the American College of Cardiology (2018)
Patterns of disease progression in advanced non-small cell lung cancer patients treated with PD-1 inhibitors.
Authors: Angel Qin, Gregory Peter Kalemkerian, Bryan J. Schneider, Khaled Aref Hassan, Kemp Bailey Cease, Lili Zhao, Edus H. Warren, Nithya Ramnath
Journal: Journal of Clinical Oncology (2017)

e20607 Background: The PD-1 inhibitors nivolumab and pembrolizumab are approved for the treatment of advanced non-small cell lung cancer (NSCLC), but little is known about patterns of disease progression when these agents fail. Understanding patterns of failure is key to developing strategies to improve duration of response to these agents. Methods: We gathered clinical and radiographic data on patients treated at the University of Michigan and the Ann Arbor VA for advanced NSCLC with standard-dose nivolumab (n = 68) or pembrolizumab (n = 23) after progression on platinum-based chemotherapy. Sites of disease progression were described as local (within the same lobe as primary disease), nodal (thoracic), or distant. Results: 91 patients were evaluable, of whom 56 (61.5%) had progression of disease after an average duration of therapy of 3.2 months (95%CI, 2.6-3.8). 10 (17.9%) patients had progression at local sites alone, 3 (5.4%) at nodal sites alone, 12 (21.4%) at distant sites alone, and 31 (55.4%) at a combination of sites. Overall, 41 (73.2%) had progression at distant sites. There was no statistically significant difference in clinical factors ( i.e. age, histology, comorbidity index) between progressors vs. non-progressors or distant-progressors vs. non-distant progressors. Of 37 patients who had prior radiation, 17 (45.9%) had progression at an irradiated site, with patients who had local and/or nodal progression more likely to have received radiation at site of progression (p = 0.01). The most common distant sites of progression were liver (13), bone (10), and brain (9). Conclusions: The most common site of disease progression was distant, with the liver being the most commonly involved site. This may be due to the immunotolerogenic environment of the liver, which is characterized by high IL-10 concentration and propagation of suppressive regulatory T cells, which can dampen activation of cytotoxic T cells. Prior irradiation did not seem to prevent disease progression. Our preliminary analysis suggests that the efficacy of checkpoint inhibitors is hindered in immune-privileged sites. Strategies to overcome immune tolerance should be investigated to improve duration of response to these agents.
Abstract P306: Participation in Cardiac Rehabilitation and Survival After Mitral or Aortic Valve Surgery
Authors: Quinn R Pack, Brian D Lahr, Ray W Squires, Francisco Lopez-Jimenez, Kevin Greason, Hector Michelena, Kashish Goel, Randal J Thomas
Journal: Circulation (2016)

Background: Cardiac rehabilitation (CR) improves functional capacity after heart valve surgery (HVS), but no survival benefit has yet been described. We hypothesized that attendance at CR after HVS would be associated with improved long-term survival. Methods: In 2013, we surveyed all patients (or a close family member if the patient was deceased) who had isolated HVS between 2006 through 2010 at the Mayo Clinic to assess if they attended CR after their HVS. We assessed survey reliability among local patients by comparing self-reported vs. medical-record verified CR attendance with the kappa statistic. We then performed a propensity-adjusted landmark mortality analysis through October 2014 for the association between CR attendance and long-term all-cause mortality conditional upon surviving the first year after HVS. Results: Survey response rate was 40% (573/1420), with responders more likely to be older, have longer hospitalizations, more aortic valve disease, but have better survival than non-responders. Among local patients, there was “substantial” agreement between reported attendance and medical-record verified CR attendance (agreement at 84%, kappa = 0.62.) A total of 547 patients (age 70 yrs., 62% male, 59% aortic valve surgery) with valid survey responses were included in the propensity analysis, of whom 296 (54.1%) attended CR. There were 100 deaths during a median follow-up of 5.4 years. For all patients, the propensity-adjusted model suggested no impact of CR on mortality (HR 1.03, 95% CI, 0.66 to 1.62). When stratified by procedure type, results suggested a potentially favorable, but non-significant, effect among patients with mitral valve surgery (HR 0.49, 95% CI 0.15 to 1.56), but not among patients with aortic valve surgery (HR 1.00, 95% CI 0.61 to 1.64.) Conclusions: Important improvements in functional capacity from CR have been previously reported after HVS, but, contrary to our hypothesis, we found that CR does not provide long-term survival benefits after HVS. These findings need additional confirmation to better clarify any mortality impact that may exist for CR following HVS, particularly among patients undergoing mitral valve surgery.
Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors.
Authors: Garth S Herbert, Julia M. Greene, John S. Berry, Doreen O Jackson, Timothy J. Vreeland, Diane F. Hale, Erica J Schneble, Pauline Nichol, Sook Yin, Xianzhong Yu, Thomas Wagner, George Earl Peoples
Journal: Journal of Clinical Oncology (2016)

3089 Background: Tumor vaccines use various strategies to generate immune responses, commonly targeting specific and purported tumor-associated antigens instead of antigens unique to a patient’s tumor. We developed a process by which dendritic cells (DC) are exposed to a patient’s particular tumor antigens, creating a patient-specific DC vaccine in 48 hours. Here we describe initial results with the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine. Methods: This open label phase I/IIa trial includes patients with solid tumors of any stage, ECOG < 1, and > 4 months of life expectancy. Using as little as 1mg of tumor and 120ml blood from which DC are isolated, a personalized vaccine is created using a particle loading system. The primary vaccination series consists of four vaccines administered intradermally 1 month apart, and is followed by optional boosters every 3 months. Patients are followed per standard of care, and imaging results are centrally evaluated. Endpoints include vaccine safety and tumor response according to RECIST criteria. Results: To date 19 pts have been enrolled with 12 different tumor types. The median age is 57 (range 20 - 74). 18/19 had advanced-stage disease (stage III/IV). Median follow-up was 6.4 months (range 2.0 - 20.2). Most adverse events were mild, with no toxicities > grade 2. Of 17 patients with residual and measurable disease, 10 (58.8%) demonstrated clinical benefit consisting of 3 complete responses, 3 partial responses, and 4 with stable disease. Two patients treated in the adjuvant setting remain disease-free after 9 and 20 months. Conclusions: The TLPLDC vaccine is a scalable technology that generates a personalized DC vaccine in 48 hours, and requires less autologous tumor tissue and fewer DCs than previous DC vaccines. The vaccine is safe, with primarily grade 0/1 toxicities. Furthermore, it resulted in a 35% objective response rate in a variety of tumor histologies, warranting further study in larger trials.
What are the expectations and preferences of patients with ovarian cancer to a maintenance therapy? A NOGGO/GCIG/ENGOT-ov22 survey (Expression IV) in 2101 patients.
Authors: Irena Rohr, Maren Keller, Radoslav Chekerov, Gülten Oskay-Özcelik, Rolf Richter, Michaela Heinrich, Cagatay Taskiran, Florence Joly, Pia Wolfrum-Ristau, Andreja Gornjec, Ignace Vergote, Patrick Achimas, Domenica Lorusso, Johanna Unelma Maenpaa, Jalid Sehouli
Journal: Journal of Clinical Oncology (2017)

e17096 Background: The primary aim of the survey was to investigate the expectations of European patients about maintenance therapy. Methods: A 24-item questionnaire was provided to ovarian cancer patients via internet or paper-version in9 European countries (Austria, Belgium, France, Germany, Italy, Romania, Slovenia, Finland and Turkey). Data was captured about demographics, tumor stage and therapy after first line and/ or recurrent disease and particularly about preferences of administration and expectations concerning a maintenance therapy. Results: Overall, 2101 questionnaires of ovarian cancer patients were evaluated. Over 63% of the patients were between 51 and 70 years (range 18-90). The majority of the patients were FIGO stage III at their primary diagnosis. 96% of the patients had a surgery and 93% received a chemotherapy. 38% of respondents had recurrent disease. 45% of the patients had already heard of and 29% received maintenance therapy. 85% of the patients heard about maintenance therapy from the doctor and 10% from other patients and 9% read about it on the internet. The four most disturbing side effects of maintenance therapy were polyneuropathy (37%), nausea (36%), loss of hair (34%) and vomiting (34%). The main objective of maintenance treatment for all patients was to increase the chances of cure (73%), followed by an improvement in the quality of life (47%) and the delay of tumor growth (37%). Many patients are willing to take a maintenance therapy until tumor progression (38%). 39% of the patients would prefer an oral administration and 29% do not have any preference for any specific administration. When we performed cross country sub-analysis between patients with primary diagnosis and relapse, or sub-analysis between patients who are actually receiving maintenance therapy or not, we observed no significant differences of expectations to a maintenance therapy. Conclusions: There is an urgent need for more information regarding side effects and treatment goals of maintenance therapy to avoid misunderstandings by the patient. This information may increase patient’s compliance for maintenance therapy in ovarian cancer.
Abstract 16645: Atorvastatin Reduces Ascending Aortic Plaque Volume on CT in HIV: Correlation With Coronary Plaque Volume and Serum Oxidized LDL
Authors: Michael T Lu, Balint Szilveszter, Kathleen V Fitch, Udo Hoffmann, Steven K Grinspoon, Janet Lo
Journal: Circulation (2016)

Introduction: HIV is associated with excess aortic inflammation and serum oxidized LDL (oxLDL); oxLDL is associated with atherosclerosis. Hypothesis: Atorvastatin reduces ascending aortic plaque vo...
TCT-644 Use of New Thienopyridines in Patients with Coronary Artery Disease Treated with Percutaneous Coronary Interventions in Argentina. Results From A “Real World” Multicenter Registry
Authors: Alfredo Rodriguez Granillo, Carlos Haiek, Miguel Larribau, Carlos Fernandez Pereira, Juan Mieres, Ricardo Sarmiento, YingBing Pan, Ming Zheng, Antonio Pocovi, Alfredo Rodriguez
Journal: Journal of the American College of Cardiology (2018)
A phase Ib study evaluating the safety and tolerability of durvalumab in combination with eribulin in patients with HER2-negative metastatic breast cancer and recurrent ovarian cancer.
Authors: Chrystal Ann Landry, Jeannette Marcelle Guziel, Meng Ru, Charles L. Shapiro, Julie Fasano, Aarti Sonia Bhardwaj, Hanna Irie, Nina Bhardwaj, Amy Tiersten
Journal: Journal of Clinical Oncology (2018)

TPS3116 Background: Recent studies have revealed only modest responses to single-agent immune checkpoint blockade in metastatic breast cancer (MBC) and recurrent ovarian cancer (ROC) patients as compared to other more immunogenic tumors. Methods to improve response employing the rational combination of cytotoxic chemotherapy with immunotherapies have shown promise. Eribulin (E), a novel microtubule inhibitor, is an effective single-agent chemotherapy in metastatic breast cancer with promising results observed in ovarian cancer patients. Preclinical studies have shown that E may induce intratumoral vascular remodeling through novel anti-vascular activity. It is hypothesized that the combination of E with durvalumab (D), a PD-L1 inhibitor, will result in increased T cell infiltration and activation leading to improved systemic and tumor site immune responses. Methods: This is a single center Phase Ib study to evaluate the safety, dose-limiting toxicity (DLT) rate, and the recommended phase II combination dose of E with D. Patients must have metastatic HER-2 negative MBC or ROC, adequate organ function, no prior treatment with E or anti-PD-1/PD-L1, and a history of prior metastatic therapy with no more than 5 prior lines. A 3+3 dose-escalation design is employed to evaluate 3 dose levels of E given by intravenous (IV) injection. The starting dose is 1.1mg/m2 with dose escalation to 1.4mg/m2 on day 1 and day 8 of a 21-day cycle. In the event that multiple DLTs are observed at the initial dose level, a dose de-escalation to 0.7 mg/m2 will be utilized. A fixed dose of D (1.12g by IV) is given on day 1 of each cycle. Secondary objectives include preliminary evaluation of anti-tumor activity as measured by objective response rate, progression-free survival, and overall survival. Responses will be assessed per iRECIST every 9 weeks. Patients will be treated until unacceptable toxicity or disease progression. Optional blood samples will be collected at various time points for quantification and characterization of immune responses and evaluation for potential biomarkers of response. We estimate accrual of 6-12 patients. Clinical trial information: NCT03430518.
Experience with FOLFIRINOX regimen in patients over 65 years old diagnosed with pancreatic adenocarcinoma: Efficacy and safety data.
Authors: Jessica Ribeiro Gomes, Jessica Sayuri Tsukamoto, Matheus Bongers Alessandretti, Renata D'Alpino D'Alpino
Journal: Journal of Clinical Oncology (2016)

e21534 Background: Despite being the standard first-line therapy for patients with advanced pancreatic cancer and good performance status (PS), there are no data regarding efficacy and safety of FOLFIRINOX regimen in the elderly population. We aim to evaluate our experience with FOLFIRINOX in patients ≥ 65 years old. Methods: Patients diagnosed with either unresectable or metastatic pancreatic adenocarcinoma and treated at Centro Oncológico Antonio Ermírio de Moraes (Brazil) from March 2011 to January 2016 were reviewed. Eligible patients were ≥ 65 years old at diagnosis, had ECOG PS of 0 or 1, and had received at least one cycle of FOLFIRINOX regimen. Results: A total of 50 patients were included in the analysis. Median age was 71 (range 65-83); 66% were male. FOLFIRINOX was the first-line therapy in 92% and median number of cycles was 10 (range 1-23). Median progression-free survival (PFS) and overall survival (OS) were 18.7 (95% CI 13,9-23,4), and 28.3 months (95% CI 25,2-31,3), respectively. There was no OS difference between patients aged 65-70 and those > 70 (p = 0,64). All patients received dose-attenuated FOLFIRINOX at the beginning of treatment, with dose reduction or escalation according to tolerability. Toxicity report was available in 35 patients. About 48.6% of the individuals received G-CSF prophylaxis. Median dose reduction during treatment was 33% for 5-fluorouracil (0-80%), 28% for irinotecan (0-100%), and 28% for oxaliplatin (0-80%). Grade 1/2 toxicities included diarrhea (60%), nausea (51,4%), fatigue (11,4%) and neuropathy (5,7%). Grade 3 toxicities were diarrhea (14,3%), nausea (2,8%), fatigue (11,4%), and neuropathy (5,7%). Only one patient developed grade 4 toxicity (neutropenia). Febrile neutropenia was diagnosed in 8.5% of the patients. Chemotherapy was discontinued after 2 cycles in one patient due to coronary spasm. No deaths were attributed to chemotherapy. Conclusions: In our experience, dose-attenuated FOLFIRINOX is a well-tolerated regimen in the elderly population, and should also be considered a reasonable first-line therapy for those patients with good PS.