tbuckley/cabot-search huggingface dataset:
Clinical predictors of efficacy for immune checkpoint inhibition in lung cancer patients.
Authors: Shijia Zhang, Daniel Fellows Pease, Shilvi Joshi, Yucai Wang, Manish Patel
Journal: Journal of Clinical Oncology (2019)

e20600 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of advanced NSCLC and SCLC. The populations in clinical trials generally were composed of patients (pts) with excellent performance status (PS), a minimal number of prior lines of therapy, and no history of (h/o) autoimmune disease (AD). The aim of this retrospective study was to investigate the predictors of survival in less fit and more heavily pretreated lung cancer pts at our institution. Methods: Medical records of lung cancer pts who started single-agent ICI from 2015 to 2018 were reviewed for data collection. Progression-free survival (PFS) and overall survival (OS) were compared by age, PS, smoking, PD-L1 expression, brain metastasis, prior lines of systemic therapy, h/o AD, and immune-related adverse events (irAE). Results: We included 150 pts who received at least 1 dose of nivolumab, pembrolizumab, or atezolizumab (median age 66, range 36-92, 56% female, 89% NSCLC, 97% stage 4, 13% never smoker, 34% ECOG ≥ 2, 37% ≥ 2 prior lines of therapy, 29% developed irAE). The overall response rate was 30% and clinical benefit rate 51% (3% CR, 27% PR, 21% SD). The median PFS was 3.7 months (m) overall and 12.3 m for those with ≥ 4 cycles of therapy. The median OS was 12.4 m overall and 26.0 m for those with ≥ 4 cycles. The median PFS and OS were not significantly different by age, PS, smoking, PD-L1, brain metastasis, prior lines of therapy, or h/o AD. The median OS was longer for pts with ECOG 0-1 than those ≥ 2 (14.6 vs 7.5 m, p &lt; .001). The median PFS and OS for pts with irAE were longer compared to those without irAE (12.3 vs 2.6 m, p &lt; .001 for PFS and 28.9 vs 9.1 m, p = .001 for OS). Multiple Cox regression analysis identified ECOG 0-1 (HR 0.54, p = .007) and irAE (HR 0.48, p = .003) to be independently associated with improved OS. 27 pts (18%) required steroids for irAE. There were no treatment-related deaths. Of 11 pts with h/o AD, only 1 experienced disease flare. Conclusions: The clinical benefit of ICIs persists in older or heavily pretreated pts. ECOG 0-1 and incident irAE predicted for improved survival. Survival for pts with ECOG ≥ 2 is very limited, suggesting ICIs should be used judiciously in this group. Therapy was well tolerated, with a low risk for flare of previous autoimmune disease.
Markers of melanoma progression in the blood serum structure.
Authors: Alla I. Shikhlyarova, Oleg I. Kit, Olga N. Shatokhina, Amira A. Akhmedova, Yury Valentinovich Przhedetskiy, Viktoria V. Pozdnyakova, Olga V. Khokhlova, Viktoria Przhedetskaya, E. P. Lysenko, Anna S. Goncharova, Anastasia I. Zhadobina, Galina V. Zhukova
Journal: Journal of Clinical Oncology (2019)

e21035 Background: Lack of prognostic markers of melanoma to assess its progression, metastasis (MTS), and treatment effectiveness, determines the feasibility of studying biophysical aspects of the transmission of events from cellular to extracellular environment. Receipt and circulation of pathological proteins of melanoma (M) in the blood carries important information, and its trap is the phase transition of biofluids into a solid state. The purpose of the study was to determine markers of melanoma at the supramolecular level in solid-state samples of the blood serum (BS). Methods: 240 samples of BS obtained prior to the surgery from 60 patients with M were studied. The preparations were prepared by the Shatokhina-Shabalin method by creating a closed "analytic cell": dehydration of a BS drop (10 mcL) under a cover glass at 20–24 0 С, humidity 65–70%, for 72 hours. The folding of M proteins was assessed by a polarized light microscopy (Leica DM LS2 microscope, x400-640) using photo and video control and the Morphotest program. Results: The initial stages of M development were characterized by the early appearance of single combined melanoform crystals — anisotropic microspherolites (Mi) embedded in the center of a large anisomorphone (lAM). As M progressed, Mi aggregation with basic lAMs was enhanced. Anisotropy of Mi increased, revealing clear sectors filled with melanin. In the later stages of M growth, melanoform aggregations dominated with point, filamentous, and chained melanin structures. The manifestation of MTS was accompanied by the destruction of the aggregations and the filling of the analytic cell space with numerous Mi. Conclusions: Correspondence of crystallogenesis of M melanomorphic markers in BS in tumor progression allows using the studied supramolecular factors to predict the development of melanoma.
Prevalence and clinicopathological factors of the EGFR mutation status of Vietnamese non-small cell lung cancer patients.
Authors: Khoa Trong Mai, Cam Phuong Pham, LUNG TIEN Nguyen, Quynh Thi Thuy Vo, Nguyen TUAN Anh, Nguyen HUY Binh, NGO Thi Thu Hien, Nguyen Thuan Loi, Tran Dinh Ha
Journal: Journal of Clinical Oncology (2019)

e13120 Background: To determine the epidermal growth factor receptor ( EGFR) mutation status in non-small cell lung cancer (NSCLC) patients in Vietnamese population at Bach Mai Hospital, and relation of different variables to the frequency of EGFR mutations. Methods: The EGFR mutation status of 1451 tissue samples in NSCLC patients and correlation among different variables of age, gender, smoking habit and histology groups were evaluated. Results: A total of EGFR mutation analysis was performed, with an overall mutation rate of 40.7%. The most prevalent categories were in-frame deletions in exon 19 (57.2% of the overall mutations); followed by L858R and L861Q in exon 21 (35.7%); exon 18 (4,6%); double mutation: 2.9%; The T790M mutation in exon 20 represented approximately 2.5%; The pooled prevalence of EGFR mutation was higher in female (60.6%), non-smokers (61.1%), and patients with adenocarcinoma (42.2%). Conclusions: The prevalence of EGFR mutations of NSCLC in Vietnam is higher than that in the West, but comparably equal to that in some Asian countries. It is associated with female sex, non-smoker status, and adenocarcinoma, sample tissue type and age, but not depends on disease stage and tumor sampling.
ABC-06 | A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy.
Authors: Angela Lamarca, Daniel H. Palmer, Harpreet Singh Wasan, Paul J. Ross, Yuk Ting Ma, Arvind Arora, Stephen Falk, Roopinder Gillmore, Jonathan Wadsley, Kinnari Patel, Alan Anthoney, Anthony Maraveyas, Justin S. Waters, Claire Hobbs, Safia Barber, David Ryder, John Ramage, Linda M Davies, John A. Bridgewater, Juan W. Valle
Journal: Journal of Clinical Oncology (2019)

4003 Background: Level A evidence supports use of CisGem as first-line chemotherapy for ABC; no robust evidence is available for second-line chemotherapy. Methods: Pts diagnosed with ABC with disease progression after prior CisGem were randomised (1:1) to either ASC+mFOLFOX or ASC. Randomisation was stratified by serum albumin levels ( &lt; 35 vs ≥35 g/L), platinum sensitivity (determined from first-line CisGem) and disease extent (locally advanced vs metastatic). Pts with ECOG PS0-1, adequate haematological, renal and liver function, and adequate biliary drainage were eligible. Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 pts delivering 148 events were required (80% power; 5% two-sided alpha) for a hypothesised hazard ratio (HR) of 0.63. Assumed median survival for ASC was 4 months. Results: 162 pts (81 in each arm) were randomised (27 March ‘14 - 04 Jan ‘18); median age 65 yrs (range 26-84); sex: 80 (49%) male, 82 (51%) female; primary site: intrahepatic 72 (44%), extrahepatic 45 (28%), gallbladder 34 (21%) and ampullary 11 (7%). Baseline characteristics were balanced between arms except platinum sensitivity (ASC+mFOLFOX 27 pts (33%); ASC 34 pts (42%)). After 150 OS events, the adjusted HR was 0.69 (95% CI 0.50-0.97; p = 0.031; ASC+mFOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+mFOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) pts in the ASC+mFOLFOX and ASC arm, respectively; these were balanced between arms except for fatigue and neutropenia (more frequent in ASC+mFOLFOX arm); data cleaning is ongoing. No chemotherapy-related deaths were reported. Conclusion: Survival with ASC was greater than assumed; ASC+mFOLFOX improved OS after progression to CisGem with a clinically meaningful increase in 6m and 12m OS rate. ASC+mFOLFOX should become standard of care in second-line for ABC. Clinical trial information: NCT01926236.
An evaluation of artificial intelligence-based clinical decision supports use in Brazil.
Authors: Hermano Alexandre Lima Rocha, Irene Dankwa-Mullan, Sergio Ferreira Juacaba, Anita Preininger, Winnie Felix, Julie V Thompson, Tiffani Bright, Gretchen Purcell Jackson, Pedro Meneleu
Journal: Journal of Clinical Oncology (2019)

e18081 Background: The Instituto do Câncer do Ceará (ICC), a 160-bed oncology hospital located in Brazil, serves approximately 23,000 patients monthly. In December of 2017, ICC implemented Watson for Oncology (WFO), an artificial intelligence (AI)-based clinical decision-support (CDS) tool to help enhance personalized cancer care. As of December 2018, 903 cases involving mainly breast, prostate and gastric cancers were entered in WFO. The purpose of this study was to investigate how implementation of WFO and use by oncologists affects clinical decision-making and workflow. Methods: 7 oncologists who employed WfO during and after the patients’ first visit were recruited to complete a survey regarding usability, decision-making and workflow. The group consisted of 1 urologist, 3 gastric surgeons, 1 gynecologist, 1 breast surgeon, 1 head-neck surgeon. Survey questions integrated the CDS Five Rights framework. Results: Most oncologists agreed that WFO is easy to understand and provides complete, relevant and actionable information at an appropriate time (Table). Opinions on the impact on treatment decisions varied. 71.4% expressed positive statements (agree or strongly agree) pertaining to the use of WFO. Conclusions: In this study, oncologists felt WFO met 5 Rights expectations for CDS; 57% felt that WFO exceed expectations. Further research is needed to understand how variation in experience affects decision impact. [Table: see text]
Understanding and predicting fatigue, cardiovascular (CV) decline, and events after breast cancer treatment (UPBEAT): A prospective cardio-oncology study.
Authors: Kerryn Reding, Ralph D'Agostino, Glenn Jay Lesser, Heidi D. Klepin, Lynne I. Wagner, Dalane Kitzman, Peter H. Brubaker, Shannon Mihalko, Jennifer Jordan, Nancy E. Avis, Karen Marie Winkfield, Bonnie Ky, Susan Faye Dent, Teresa Crotts, Tonya Calhoun, Kimberly Lane, W. Gregory Hundley
Journal: Journal of Clinical Oncology (2019)

TPS11634 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients,treated with modern cancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and future development of CV events. The comprehensive assessment of factors includes ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, Expanded SPPB), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points, include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO 2 peak via cardiopulmonary exercise test), fatigue (via FACT-F). Eligibility criteria are: age &gt;18 years; ECOG 0-2, able to walk without symptoms; and for BC patients, treatment with chemotherapy. 143 participants are accrued and currently enrolling through ECOG and NCORP sites. Participants will be followed for 9 years with active surveillance of CV events, i.e., heart failure, myocardial infarction, stroke, all-cause and CV death. Clinical trial information: NCT02791581.
A weighted criterion-based approach to value assessment of oncology drugs.
Authors: Doreen Anuli Ezeife, Ellen R. Cusano, Aline Fusco Fares, Mike Sung, Francois Dionne, Craig Mitton, Craig Earle, Kelvin K. Chan, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2019)

6627 Background: The rising cost of anti-cancer therapy has motivated recent efforts to quantify the overall value of new cancer treatments. Multi-criteria decision analysis offers a novel approach to establish an explicit framework to evaluate new cancer treatments. Methods: We recruited a diverse multi-stakeholder group who identified and weighted key criteria to establish the Drug Assessment Framework (DAF). Strength of evidence (SOE) modifiers deducted points for lower quality evidence. Through one-on-one meetings with stakeholders, face and content validity of the DAF were established in an iterative process. Construct validity assessed the degree to which DAF scores were associated with the pan-Canadian oncology drug review (pCODR) funding decisions and European Society for Medical Oncology Magnitude of Clinical Benefit score (ESMO-MCBS, version 1.1). Sensitivity analyses were performed on the final results. Results: The final validated DAF includes ten criteria: overall survival, progression-free survival, response rate, quality-of-life, toxicity, unmet need, equity, feasibility, disease severity and caregiver well-being. The first five clinical benefit criteria represent 64% of the total weight. DAF scores range from 0 to 300, reflecting both the expected impact of the drug and the quality of the supporting evidence. When the DAF was retrospectively applied to the last 60 drugs (in blinded fashion) reviewed by pCODR (2015-2018), the mean total DAF score was 94 (range, 18-179). Drugs with positive pCODR funding recommendation had higher DAF scores than drugs not recommended for reimbursement (103 vs. 63, t-test p = 0.0007). Funded drugs had fewer SOE points deducted than those that were not funded (median 0 vs. 24 points deducted, Wilcoxon p = 0.03). The correlation coefficient for DAF and ESMO-MCBS was 0.37 (95% CI, 0.10 to 0.59). Sensitivity analyses that varied the subjective criteria either positively or negatively did not change the results. Conclusions: Using a structured and explicit approach, a criterion-based valuation framework was designed and validated. The DAF can provide a transparent and consistent method to value and prioritize cancer drugs, in order to facilitate the delivery of affordable cancer care.
All-Cause and Cause-Specific Mortality Risks Associated With Alopecia Areata
Authors: Solam Lee, Young Bin Lee, Beom Jun Kim, Sejin Bae, Won-Soo Lee
Journal: JAMA Dermatology (2019)

Alopecia areata is associated with diverse systemic and psychiatric diseases. However, whether all-cause and cause-specific mortality in patients with alopecia areata differs from that of the general population remains unclear.To investigate all-cause and cause-specific mortality risk in patients with alopecia areata.Using the National Health Insurance Service database and National Death Registry of Korea, a retrospective cohort study of participants identified in 2006, with investigation of mortality until 2016, was carried out. Patients with alopecia areata with at least 3 documented visits to a dermatologist with an International Statistical Classification of Diseases (tenth revision) code of L63 during 2002 to 2006 were included. For comparison, 1:10 age- and sex-matched controls without documented visits with a code of L63 until 2016 were included.Patients with alopecia areata and controls without alopecia areata.The study population was followed from January 1, 2007, for a period of 10 years to estimate all- and cause-specific mortality.The study comprised 73 107 patients with alopecia areata and 731 070 age- and sex-matched controls. Of these, 6023 were patients with alopecia totalis/universalis. No differences in all-cause mortality risk between the cohorts were found (HR, 0.97; 95% CI, 0.87-1.09). However, mortality associated with intentional self-harm/psychiatric diseases was greater in patients than in participants in the control group (HR, 1.21; 95% CI, 1.04-1.41). Adult patients aged 35 years or younger (HR, 1.68; 95% CI, 1.32-2.12) and those with alopecia totalis/universalis (HR, 1.85; 95% CI, 1.25-2.75) were particularly affected. Mortality associated with lung cancer was greater in patients with alopecia totalis/universalis (HR, 2.16; 95% CI, 1.41-3.33). However, mortality associated with diabetes mellitus was significantly lower in patients with alopecia areata (HR, 0.53; 95% CI, 0.36-0.79).Patients with alopecia areata have a higher risk of mortality associated with self-harm, psychiatric diseases, and smoking-associated malignant diseases including lung cancer. For better outcomes, clinicians should appropriately treat patients to ensure emotional and psychological well-being.
“Complete” Remission in Chronic Lymphocytic Leukemia (CLL) Is Strongly Affected by the Use of CT Scanning: Results from a Prospective Randomized Trial of Fludarabine Plus Cyclophosphamide (Flu/Cy) with or without Genasense (Oblimersen) in Patients with Relapsed or Refractory Disease.
Authors: Peter Maslak, James Caravelli, Asher Alban Chanan-Khan
Journal: Blood (2006)
Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3).
Authors: David J. Kwiatkowski, Valerie W. Rusch, Jamie E. Chaft, Bruce E. Johnson, Alan Nicholas, Ignacio Ivan Wistuba, Robert Merritt, Jay M. Lee, Paul A. Bunn, Yan Tang, See-Chun Phan, Saiama Naheed Waqar, Alexander Patterson, Eric B. Haura, Eric M. Toloza, Karen L. Reckamp, Dan Raz, Katja Schulze, Ann Johnson, David Paul Carbone
Journal: Journal of Clinical Oncology (2019)

8503 Background: Small pilot studies (e.g., N Engl J Med. 2018;378:1976) have shown that preoperative immune checkpoint inhibitor therapy may be of benefit in early-stage NSCLC. This large multicenter trial assesses the benefit of neoadjuvant treatment with atezolizumab (atezo; NCT02927301). Methods: Patients (pts) with stages IB to selected IIIB resectable NSCLC receive 2 cycles of atezo 1200 mg (days 1, 22) then undergo resection (day 40 ± 10). Primary tumor +/- node biopsies and blood samples are obtained before atezo and at surgery for biomarker studies. The primary endpoint is major pathological response (MPR), defined as ≤ 10% viable tumor cells in the resection specimen. Secondary endpoints include safety and correlation of response with PD-L1 expression, tumor mutation burden (TMB) and gene expression signatures. Results: For this interim efficacy analysis (5 Sep 2018 data cut), we report on the first 101 of 180 planned pts: 47 males, median age, 64 y; all ECOG PS 0-1; 23 current and 68 former smokers; 66 non-squamous NSCLC; clinical stages IB/IIA/IIB/IIIA/IIIB n = 11/16/28/39/7. There were 2 treatment-unrelated Gr 5 AEs (cardiac death post surgical resection; death due to disease progression), 29 Gr 3-4 AEs (6 [6%] treatment related). 90 pts had surgery. Excluding 8 pts who had driver mutations (7 EGFR, 1 ALK, no MPR), MPR rate was 15/82 (18%, 95% CI 11%-28%), 4 pts had pathological complete response (pCR). By RECIST, 6/82 pts had PR, 72 had SD and 4 had PD. Two of 26 (8%) PD-L1− (TC0 and IC0, clone SP142) and 10 of 35 (29%) PD-L1+ had MPR ( P= 0.055). Five of 44 (11%) TPS &lt; 50 (PD-L1 clone 22C3) and 7 of 20 (35%) TPS &gt; 50 had MPR ( P= 0.040). Exome sequencing data was available for 47/101 pts. Median TMB was 10.4 (range, 1.5-46.5) mutations per Mb and was not different in those with MPR compared with those without MPR. Further analysis of TMB, mutation signatures, and gene expression profiling is ongoing. Conclusions: Atezo in the neoadjuvant setting was well tolerated, and pCR and MPR rates are encouraging in this large multicenter trial. Efficacy interim analysis passed its futility boundary, and study enrollment continues. Safety, efficacy results and ongoing correlative analyses will be presented. Clinical trial information: NCT02927301.