tbuckley/cabot-search huggingface dataset:
Immunogenicity of pembrolizumab (pembro) in patients (pts) with advanced melanoma (MEL) and non-small cell lung cancer (NSCLC): Pooled results from KEYNOTE-001, 002, 006, and 010.
Authors: Marianne van Vugt, Rik de Greef, Tomoko Freshwater, Eric Mangin, Frank van Aarle, Anna Kondic
Journal: Journal of Clinical Oncology (2016)

3063 Background: Monoclonal antibodies (mAb) can evoke immunogenicity, leading to production of antidrug antibodies (ADA). Pembro, a humanized mAb against PD-1, has demonstrated efficacy in NSCLC and MEL. Results from NSCLC cohorts of KEYNOTE-001 (NCT01295827) and KEYNOTE-010 (NCT01905657) and from MEL cohorts of KEYNOTE-001, KEYNOTE-002 (NCT01704287), and KEYNOTE-006 (NCT01866319) are presented. Methods: Samples were analyzed for antipembro antibodies using electrochemiluminescence immunoassay methodology following a standard 3-tiered assay approach consisting of screening, confirmatory, and antibody titer assessment. Screening positives were tested in a confirmatory assay checking specificity of signal for pembro. In confirmed positive samples Ab titer, neutralizing capacity, drug exposure, efficacy, and AEs were assessed. The immunogenicity approach classified ADA samples as positive, negative, or inconclusive. Overall immunogenicity incidence was defined as proportion of treatment-emergent (TE) positive pts to the number of evaluable pts with a confirmed TE, non–TE-positive or negative immunogenicity status. Negative immunogenicity status was confirmed if ADA results of the pretreatment and postdose samples were negative in the confirmatory assay, and the pembro concentration was below the drug tolerance level in the last postdose sample. Results: Across cohorts, 2910 pts provided 11,886 pretreatment and posttreatment serum samples. Overall, 2632 pts (n = 1535 MEL, n = 1097 NSCLC) were included in the immunogenicity analysis. False-positive rates were 2.7% and 2.8% with Intertek and PPD assays, respectively. Of the 1087 (41%) evaluable pts, 19 (1.7%) had a TE-positive ADA, 10 (0.9%) were non–TE-positive, and 1058 (97.3%) had negative immunogenicity status. Initial results indicate a higher incidence rate in NSCLC vs MEL (2.5% vs 0.7%). In pts with a TE-positive ADA, no impact of antipembro antibodies on drug exposure, safety, or efficacy was observed. Conclusions: Pembro has a low potential to elicit the formation of ADA, and if ADA formation occurs, it has been shown to have no clinically relevant impact. Clinical trial information: NCT01295827, NCT01905657, NCT01704287, NCT01866319.
A phase II randomized, double-blind trial of a polyvalent vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian (EOC), fallopian tube, or peritoneal cancer who are in second or third complete remission.
Authors: Paul Sabbatini, Lee-may Chen, Joseph A. Lucci, Kian Behbakht, Nicola M. Spirtos, Carolyn Muller, Benedict B. Benigno, Matthew A. Powell, Emily Berry, Krishnansu Sujata Tewari, Parviz Hanjani, Wei Deng, Heather A. Lankes, Carol Aghajanian
Journal: Journal of Clinical Oncology (2016)

5517 Background: Phase I data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression versus OPT-821 alone in patients with EOC in second or third clinical complete remission (cCR) following chemotherapy. Secondary objectives were overall survival (OS), safety and immunogenicity. Methods: Patients were randomized (1:1) to receive OPT-821 + vaccine conjugate subcutaneously at weeks 1, 2, 3, 7, 11 and then every 12 weeks (total 11) Dose delay or reduction was not permitted. Patients were removed for pre-defined DLT. Randomized patients were evaluated for efficacy. Results: Between 2010 and 2013 171 patients were randomized; 170 treated. Most received 2 prior regimens (68%), had serous carcinoma (85%), stage 3 disease at diagnosis (77%), and no bevacizumab (67%). 54% received > 6 cycles treatment [median 6 in each arm (p = 0.33)]. 77% of patients discontinued due to progression, 4% due to toxicity, and 1 due to MDS. Maximum toxicity was grade 5 (n = 1, unrelated), grade 4 MDS and depression (n=2, unlikely), grade 3 GI disorders + others (n = 20, 4 related). Most common lesser adverse events were injection site reactions (84%) and fever (19%). (+) immunogenicity is defined as 1:40 or two fold increase. Estimated hazard ratio for PFS of vaccine conjugate + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At followup of 34 months, median OS for OPT-821 is 47 months and not reached for vaccine conjugate + OPT-821. Conclusions: Vaccination with this polyvalent construct was modestly immunogenic and does not prolong PFS when compared to OPT-821 alone. The secondary OS endpoint requires additional followup. The second and third remission cohort is a feasible and well defined population to explore innovative consolidation or maintenance approaches. Clinical trial information: NCT00857545.Predefined definition (+) for immunogenicity (patients with pre and post titers n = 148). GLOBO-H GM2 MUC1-TN MUC 1 TF IGG IGM IGG IGM IGG IGM IGG IGM IGG IGM 7% 21% 8% 26% 32% 40% 45% 49% 13% 22%
Optimal method of identifying individuals eligible for lung cancer screening: Comparing methods of eliciting and recording smoking history.
Authors: Hannah Boman, Abbie Begnaud
Journal: Journal of Clinical Oncology (2018)

e18595 Background: Although smoking history is classically quantified as pack-years (packages of cigarettes per day smoked times the number of years smoked), there is no standard for eliciting this history. More importantly, eligibility for lung cancer screening (LCS) is based on a concrete threshold for smoking history (30 pack-years). Electronic health record (EHR) is frequently lacking this quantitative measurement of smoking history, creating a barrier to timely identification of patients eligible for potentially life-saving LCS. Methods: We performed detailed telephone interview to collect a “gold standard” smoking history. Patients undergoing LCS at our institution were invited to participate in telephone interview. Data Collection – An interviewer called participants to collect the detailed smoking history. Chart review was used to collect smoking history data from multiple sources: a) electronic health record (EHR) social history section; b) the LCS exam order; and c) patient questionnaire administered at the time of LCS exam. Results: We invited 150 patients to participate. Thirteen opted out or declined. Telephone interviews were conducted to obtain a quantitative gold standard smoking history in pack-years. These results were compared to EHR report. Mean and median pack-year smoking history values were similar for each method (interview, EHR, LCS, PRQ). Most patients did not have complete data set (either unable to reach via telephone, or incomplete EHR history). Pack-year value as reported by provider ordering LCS exam is most similar to patient-reported values on risk questionnaire. Conclusions: Obtaining a smoking history that is detailed and accurate can be time consuming. However, in most cases a quick estimate obtained by a provider is adequate to determine LCS eligibility, based on current guidelines. Nevertheless, EHR smoking history is frequently incomplete to estimate pack-year history. Thus, prompting providers to conduct an abbreviated smoking history for patients who may be eligible (based on age and smoking status) may be adequate to identify most eligible persons.
P03.07 A Care Pathway for personalized healthcare
Authors: F Brienen, S Bossmann, R Smeenk, A Gijtenbeek, S Mulder, M ter Laan
Journal: Neuro-Oncology (2018)

The diagnosis of a brain tumor can be devastating and stressful. Not just for the patient but also for their relatives. The healthcare system can be incredibly confusing and complex due to the multitude of appointments, a wide range of specialists, disabling neurological deficits, difficulty accessing services and a lack of information. Each patient goes through a personal process of diagnosis, medical treatment and palliative care. To address these problems, we developed an App-based system that clarifies the patients individual care pathway. Both, patients and caregivers are able to connect via a secure digital environment in one joint care process. The Care Pathway provides an personalized overview of all appointments, examinations and treatments on a timeline. The app is linked with the patient’s electronic medical record to always guarantee an up-to-date, personal and relevant timeline. Another great advantage is that this app allows clinicians to easily extract data regarding outcome measures. In the app, all information about the care of a patient is bundled. They will only receive the information that is relevant at that certain moment in time. Consequently, they keep a grip on their own care process and are better prepared for what is to come. Therefore, patient will be more able to make decisions regarding their treatment.
Phase I/II study of laser interstitial thermotherapy (LITT) combined with checkpoint inhibitor for recurrent glioblastoma (rGBM).
Authors: Andrew E. Sloan, Lisa R. Rogers, Mitchell Machtay
Journal: Journal of Clinical Oncology (2018)

TPS2074 Background: Glioblastoma (GBM) has a survival of only 3-5 months at recurrence.. Salvage chemotherapy has been largely ineffective with PFS-6 rates of 10-15%. Bevacizumab's impact on OS is modest at best.. Thus, there is a pressing need for minimally invasive, approaches to debulk rGBM such as laser interstitial thermotherapy (LITT). Methods: Rationale for treating rGBM with LITT: Laser interstitial thermotherapy (LITT) is a minimally invasive technique for ablating tumors percutaneously using thermal radiation which has demonstrated efficacy in several non CNS tumors. Subsequent studies reproduced the efficacy of LITT for glioma demonstrating that survival was consistently related to tumor volume and a minimal dose threshold. This suggested the possibility of an abscopal effect mediated by unmasking of tumor antigens by LITT as has been previously demonstrated for ionizing radiation (radiotherapy). Rationale for Immunotherapy for rGBM: GBM patients are known to have elevated levels of immunosuppressive cells such as Treg, M2 macrophages and MDSC, both in the tumor as well as in the systemic circulation. Rationale: Immunotherapy targeting co-inhibitory checkpoints such as CTLA-4 and PD-1 have proven highly effective for some solid tumors. The first trial targeting CTLA + PD-1 in rGBM demonstrated evidence of safety. Interestingly, targeting PD-1 concurrent with RT appeared to be synergistic and was effective in preclinical models. However, patients with rGBM have typically received maximum tolerated radiotherapy and are thus not candidates for additional RT off trial. We hypothesize that thermal radiation delivered using LITT technology interferes with tumor microenvironment, minimizing immunosuppression and re-introducing tumor neoantigens. The primary objective of this phase II trial is to estimate radiological response to LITT + pembrolizumab and compare this to that observed for LITT alone. Each patient will undergo a stereotactic biopsy followed by 200 mg pembrolizumab at various times before or after LITT. Secondary endpoints include a putative serum biomarker for GBM. Here we present the concept and the outcomes of the first patients in the study. Clinical trial information: NCT 03277638.
Prognostic prediction of pemetrexed-platinum chemotherapeutic regimen for NSCLC by serum metabolomics.
Authors: Jie Wang, Yanhua Tian, Zhijie Wang, Hua Bai, Jianchun Duan
Journal: Journal of Clinical Oncology (2017)

e20603 Background: Pemetrexed-platinum chemotherapeutic doublet has become a standard schedule as the first-line treatment for advanced non-squamous NSCLC due to its promising efficacy and a favorable toxicity profile. However, chemotherapy resistance inevitably limits the therapeutic effect of this preferred chemotherapeutic regimen, especially for these intrinsically resistant patients. Development of predictive biomarkers to identify those patients who can benefit from this pemetrexed-based regimen has great significance for personalized chemotherapy. Methods: Total 354 patients who were diagnosed with inoperable stage IIIB or IV lung adenocarcinoma (LADC), assigned to receive pemetrexed-platinum doublet chemotherapy as the first-line treatment were enrolled into this prospective study, including 251 cases diagnosed ahead as training set for predictive model establishment and the subsequently diagnosed 103 cases into validation set. Ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS) analytical platform were applied to perform the metabolic profiling studies of pre-treatment serum samples. Results: In the training set, eight potential biomarkers, comprising of hypotaurine, taurine, choline, betaine, dimethylglycine, uridine, dodecanoylcarnitine and L-palmitoylcarnitine, were discovered to be differentially expressed between the patients in disease progressive group (PD, n = 53) and disease control group (including CR, PR and SD, n = 198). In the validation set (PD vs non-PD: 23 vs 80), targeted quantitative analysis of these metabolic biomarkers revealed similar levels as that observed in the training set. Logistic regression model was accordingly established based on this eight-metabolic biomarker panel, to discriminate patients who might benefit from this chemotherapy regimen with over 90% accuracy. Conclusions: This prospective study identified blood-based biomarker panel by metabonomics analysis could predict the clinical outcome of pemetrexed-platinum chemotherapy prior to treatment for LADC patients, which needed to be validated by clinical trials of large samples.
TCT-623 12 months outcomes of a Non-inferiority Randomized Clinical Trial comparing the efficacy and safety of Angiolite vs Xience in patients with PCI indication
Authors: Jose Moreu Burgos, Armando Perez de Prado, Bruno Garcia, Raul Moreno, Jose Diaz, Eduardo Pinar Bermudez
Journal: Journal of the American College of Cardiology (2018)
Abstract 14177: Prognostic Value of Normal Regadenoson Stress Cardiovascular Magnetic Resonance Myocardial Perfusion Imaging
Authors: Benjamin H Freed, Nicole M Bhave, Akhil Narang, Peter Czobor, Victor Mor-Avi, Emily R Zaran, Kristen M Turner, Kevin P Cavanaugh, Sonal Chandra, Sara M Tanaka, Michael H Davidson, Roberto M Lang, Amit R Patel
Journal: Circulation (2013)

Background: Although regadenoson has been extensively studied in patients undergoing nuclear myocardial perfusion imaging (MPI), its use with cardiovascular magnetic resonance (CMR) for stress-MPI ...
Burden of chemotherapy-induced febrile neutropenia in paediatric oncology in developing countries: The Children's Hospital Lahore Pakistan experience.
Authors: Alia Ahmad
Journal: Journal of Clinical Oncology (2017)

e22021 Background: The Oncology Department Of The Children’s Hospital Lahore is a 60 bedded unit providing free treatment to over 1000 new childhood cancer cases each year.The aim of this prospective study was to analyze the burden of chemotherapy induced FN and to assess the leading risk factors . Methods: Prospective review of 100 patients with FN admitted in July to August 2016 was done. Data regarding their age, sex, and clinical features, baseline CBC, course of therapy, hospital stay and understanding of caregivers regarding FN analyzed. Results: Total 100 patients with age ranging from &lt; 1 to 15 years (67% &lt; 5 yrs) were included.M: F Ratio was 1.7:1, 72% of cases had ALL and 28% with solid tumors. 28% had last chemotherapy received in 72 hours, 30% in last week and rest in more than a week time 36% had respiratory tract infections, 18% gastrointestinal infections, 20% mucositis, 10% no focus found and rest 16% had other manifestations Only 2 % presented in &lt; one hour of start of symptoms, 27% &lt; 24 Hours, 61% in &lt; 5 Days and 10% &gt; 5 days duration of symptoms. 45% had Hb &lt; 8 gm%, 33% had platelets &lt; 50000, and 54% had WBC &lt; 1000 and 63% had ANC &lt;100 (p-Value = 0.003- Hospital Stay). 29% presented with first episode while 51 % had 3 or more FN episodes.28% cases stayed 1 hour distance from CHL while 72% had to travel &gt; 1-5 hrs to reach the primary treatment center. 66% received paracetamol at home, 17 had oral antibiotics while 17% had no treatment before reached PTC. Only19% caregivers had adequate awareness regarding FN, 72% had some understanding while 9% had no knowledge about FN (p-value = 0.000). 40% had social issues, 41% were unaware while 13% showed negligence in seeking treatment .46% stayed for 5 days and 48% for more than 5 days. 21% patients had increased doses of oral chemotherapy not adjusted timely according to CBC. Conclusions: Health educationof caregivers and health professionals is of utmost importance to prevent and manage FN effectively. Need of capacity building in pediatric oncology in low income countries along with sustainable social support is essential for provision of standard childhood cancer care and implementation of effective infection control measures.
Implementation of an oral chemotherapy adherence tracking program at a medically underserved comprehensive community cancer center.
Authors: Abhinav Binod Chandra, Mary Sweigart, Angelic Alvarez, Vivek Kumar
Journal: Journal of Clinical Oncology (2018)

e18873 Background: The field of oncology has witnessed a significant increase in the number of oral antineoplastic agents over the last several years and their utilization is expected to grow. Several deficiencies in procedures for safe management and monitoring of oral chemotherapy regimens remain unaddressed. Rates of adherence to oral antineoplastic agents have varied in literature and not widely studied. There is paucity of data on impact of oral chemotherapy adherence to patient outcomes or emergency room visits. Methods: Baseline oral chemotherapy adherence was tracked in new oral treatment plans. This was supplemented with education of staff to run reports and increase chemotherapy tracking with special focus on education and follow ups. Over 9 month period, the oral chemotherapy tracking process was implemented with the goal of 80% tracking being achieved. Emergency room (ER) visits were calculated on patients having active oral chemotherapy care plans during a 3-month period before and after implementation of the program. Results: Reporting metric for compliance with oral tracking showed improvement from 5% completed reports to 84% completed reports over 9 months. The goal set to achieve 80% tracking was reached. The program was successfully implemented from January 2017 – September 2017. Prior to implementation of the program, over a 3-month period, 55 patients were receiving active oral chemotherapy care, with 56 encounters of ER visits by 30 patients related to their cancer. After successful implementation of the program and with consistent 80% chemotherapy tracking in place, we analyzed data for another 3 month period. During this 3-month period, 108 patients were receiving active oral chemotherapy, with 31 encounters of ER visits by 17 patients for their cancer. Conclusions: Implementation of a tracking program for oral chemotherapy led to 72% reduction in emergency room visits by patients on oral chemotherapy care plans. We were successfully able to implement an oral chemotherapy adherence tracking program in a medically underserved comprehensive community cancer program. A prospective study can further validate the findings of this study.
Incidence of solid tumors or lymphoma in patients with polycythemia vera: Data from the REVEAL study.
Authors: Anas Al-Janadi, Kamal Patel, Nashat Y. Gabrail, Thomas H. Cartwright, Muhammad-Ali A. Zaydan, David A. Garcia, Philomena Colucci, Shreekant Parasuraman, Dilan Paranagama, Brady Stein
Journal: Journal of Clinical Oncology (2018)

e19029 Background: Polycythemia vera (PV), a myeloproliferative neoplasm characterized by hematopoietic cell proliferation, is associated with risk of leukemic transformation, but published data on the risk of developing solid tumors or lymphoma in the US are limited. REVEAL (NCT02252159) is an ongoing observational study of patients (pts) with PV in the US. We describe the incidence of solid tumors and lymphoma in pts with PV enrolled in REVEAL. Methods: Pts aged ≥18 y with PV were enrolled and followed in accordance with their usual care for ≤36 mo. Standardized incidence ratios (SIR) relative to the National Program of Cancer Registries (2010-2014) were calculated for selected malignancies diagnosed after PV. Results: Of 2485 evaluable pts enrolled in REVEAL, 170 were diagnosed with a malignancy prior to PV diagnosis; the most common were breast (1.5%), prostate (1.3%), colorectal (0.8%), and melanoma (0.8%). At data cutoff (May 18, 2017), 159 of 2315 evaluable pts (6.9%) without a history of cancer before PV diagnosis developed cancer after PV diagnosis; the most common were nonmelanoma skin cancer (NMSC), prostate, and colorectal cancers. Median time to cancer diagnoses ranged from 1-7 y after PV diagnosis (Table). Compared with an unselected population, breast cancer was twice as frequent in women with PV (SIR, 2.0) and prostate cancer was 4 times more frequent in men with PV (SIR, 4.5). Colorectal cancer incidence was lower than the background rate (SIR, 0.79). Thirty pts (1.3%) reported transformation to leukemia, myelofibrosis (MF), or myelodysplastic syndromes (MDS). Conclusions: This analysis confirms previously published data that pts with PV have a higher incidence of breast and prostate cancers relative to the general population. Updated data as of the May 2018 cutoff will be presented. Clinical trial information: NCT02252159.Incidence of Malignancies After PV Diagnosis Malignancy Total (N = 2315a), n (%) Median Time From PV Diagnosis to Malignancy (range), ya NMSC 48 (2.1) 7.3 (0.0-26.6) Prostate 28 (2.2)b 6.0 (0.0-28.0) Colorectal 12 (0.5) 1.2 (0.0-15.6) Breast 10 (0.9)c 2.6 (0.1-12.2) Lymphoma 7 (0.3) 5.1 (0.0-13.9) Transformations (MF, MDS, or leukemia) 30 (1.3) 8.6 (1.0-27.4) aOnly in those pts with new malignances. bMen, n = 1260. cWomen, n = 1055.