tbuckley/cabot-search huggingface dataset:
Development of an automated and sensitive microfluidic device for circulating tumor cell (CTC) analysis and single cell capturing.
Authors: Priya Gogoi, Saedeh Sepehri, Michael A. Gorin, Kalyan Handique, Yixin Wang, Kenneth J. Pienta
Journal: Journal of Clinical Oncology (2016)

e23031 Background: Current technologies for the analysis of circulating tumor cells (CTCs) are hindered by sub-optimal sensitivity and specificity as well as the incorporation of clinically relevant biomarkers. We have developed and validated a novel technology to capture and characterize CTCs from whole blood samples. Methods: The Celsee PREP uses a microfluidic chip which has 56,320 individual capturing chambers. Based on differences in size and deformability of cells, each chamber ensures that smaller blood cells escape while larger CTCs are trapped and isolated in the chambers. Coupled with the Celsee ANALYZER, the system automates the entire process from sample preparation to image analysis. Results: In a study of 18 blood samples from patients with metastatic prostate cancer, the CTC capturing efficiency of the Celsee system was higher than with the CellSearch technology (94% vs. 61%). The Celsee platform also enabled downstream characterization of captured cells with immunocytochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). Captured CTCs can be retrieved from the microfluidic chip, further purified with anti-CD45 magnetic beads. This procedure reduced the leukocyte background to about 100 cells from a starting volume of 4 ml of blood. The CTC preparation from the Celsee system can then either be lysed for subsequent molecular analysis (such as RT-PCR, NGS) or readily partitioned into single cells. Conclusions: The integrated Celsee system represents a promising CTC technology for single cell capturing and subsequent downstream molecular characterization.
Prevalence of Burnout Among Physicians
Authors: Lisa S. Rotenstein, Matthew Torre, Marco A. Ramos, Rachael C. Rosales, Constance Guille, Srijan Sen, Douglas A. Mata
Journal: JAMA (2018)

Burnout is a self-reported job-related syndrome increasingly recognized as a critical factor affecting physicians and their patients. An accurate estimate of burnout prevalence among physicians would have important health policy implications, but the overall prevalence is unknown.To characterize the methods used to assess burnout and provide an estimate of the prevalence of physician burnout.Systematic search of EMBASE, ERIC, MEDLINE/PubMed, psycARTICLES, and psycINFO for studies on the prevalence of burnout in practicing physicians (ie, excluding physicians in training) published before June 1, 2018.Burnout prevalence and study characteristics were extracted independently by 3 investigators. Although meta-analytic pooling was planned, variation in study designs and burnout ascertainment methods, as well as statistical heterogeneity, made quantitative pooling inappropriate. Therefore, studies were summarized descriptively and assessed qualitatively.Point or period prevalence of burnout assessed by questionnaire.Burnout prevalence data were extracted from 182 studies involving 109 628 individuals in 45 countries published between 1991 and 2018. In all, 85.7% (156/182) of studies used a version of the Maslach Burnout Inventory (MBI) to assess burnout. Studies variably reported prevalence estimates of overall burnout or burnout subcomponents: 67.0% (122/182) on overall burnout, 72.0% (131/182) on emotional exhaustion, 68.1% (124/182) on depersonalization, and 63.2% (115/182) on low personal accomplishment. Studies used at least 142 unique definitions for meeting overall burnout or burnout subscale criteria, indicating substantial disagreement in the literature on what constituted burnout. Studies variably defined burnout based on predefined cutoff scores or sample quantiles and used markedly different cutoff definitions. Among studies using instruments based on the MBI, there were at least 47 distinct definitions of overall burnout prevalence and 29, 26, and 26 definitions of emotional exhaustion, depersonalization, and low personal accomplishment prevalence, respectively. Overall burnout prevalence ranged from 0% to 80.5%. Emotional exhaustion, depersonalization, and low personal accomplishment prevalence ranged from 0% to 86.2%, 0% to 89.9%, and 0% to 87.1%, respectively. Because of inconsistencies in definitions of and assessment methods for burnout across studies, associations between burnout and sex, age, geography, time, specialty, and depressive symptoms could not be reliably determined.In this systematic review, there was substantial variability in prevalence estimates of burnout among practicing physicians and marked variation in burnout definitions, assessment methods, and study quality. These findings preclude definitive conclusions about the prevalence of burnout and highlight the importance of developing a consensus definition of burnout and of standardizing measurement tools to assess the effects of chronic occupational stress on physicians.
Treatment pattern differences across the United States and EU5 among patients with ovarian cancer.
Authors: Chitra Karki, Ripsi Patel, Samantha Martino, Valerie Wriede, Bijal Shah-Manek
Journal: Journal of Clinical Oncology (2018)

e17516 Background: The standard treatment approach for ovarian cancer (OC) is a combination of a platinum compound and a taxane, with combination drug therapy reportedly being more effective in the initial treatment of OC compared to monotherapy. The objective of this study was to examine the current treatment patterns for ovarian cancer patients in the US and 5 European countries (EU5) (France, Germany, Italy, Spain, UK) using real world data from Ipsos' Global Oncology Monitor. Methods: A multi-country, multi-center retrospective medical chart-review of OC patients was conducted by cancer-treating physicians in the US and EU5 between Jul 2016-Jun 2017. Physicians randomly selected patient charts currently on an anti-cancer regimen and abstracted data on patient demographics, disease status, treatment patterns, and biomarker status. Only patients who were diagnosed with Stage III-IV OC were included in the analyses. Results: A total of n = 1,371 (US) and n = 729 (EU5) patients were included in this analysis. The mean (SD) age of the patients included was 61.75 years (SD = 12.64) and 65.31 years (SD = 9.51) in the US and EU5 respectively. About 51% of the US patients were on Medicare/Medicaid; average expected length for current treatment regimen were similar in both US and EU5 (5.0 months vs 4.9 months). Overall, carboplatin with paclitaxel, a platinum compound, was both the most common regimen (40% US, 27% EU5) and the most common 1st line regimen (57% US, 48%EU). Among those with a 2nd line regimen in the US, Pegylated Liposomal Doxorubicin (17%) was the most common regimen compared to Bevacizumab (18%) in the EU5. Similarly, for the 3rd line regimen, Bevacizumab (18%) was the most common in the US and Carboplatin with Gemcitabine (22%) in the EU5. Conclusions: Approximately half of all patients received Carboplatin in combination with Paclitaxel as first line therapy, while regimens such as Carboplatin monotherapy and Gemcitabine were used less frequently in the US and EU5. This study provides an important baseline assessment of current treatment patterns in the US and EU5 and opportunity to assess treatment outcomes among patients on monotherapy vs. combination therapy.
All-cause mortality among people with HIV released from an integrated system of jails and prisons in Connecticut, USA, 2007–14: a retrospective observational cohort study
Authors: Kelsey B Loeliger, Frederick L Altice, Maria M Ciarleglio, Katherine M Rich, Divya K Chandra, Colleen Gallagher, Mayur M Desai, Jaimie P Meyer
Journal: The Lancet HIV (2018)
Patient attitudes toward oncofertility care in male cancer patients receiving targeted and immune therapies.
Authors: Katy K. Tsai, Puneet Kamal, Joris Ramstein, Alain Patrick Algazi, Adil Daud, James F Smith
Journal: Journal of Clinical Oncology (2017)

e21593 Background: Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) have resulted in durable response for many cancer patients. The impact of these agents on future fertility are not well described, and patients are often committed to long-term treatment without adequate oncofertility counseling. We sought to better characterize patient attitudes toward oncofertility and challenges faced by male cancer patients undergoing treatment with TKI or ICI. Methods: Men receiving TKI/ICI at the UCSF Helen Diller Family Comprehensive Cancer Center were retrospectively identified. Eligible men had received at least one dose of TKI/ICI. Detailed questionnaires addressing cancer history, possible effects of treatment on fertility, and obstacles to fertility preservation were completed. Results: Between January 2013 to September 2016, 51 men with a mean age of 46 years (SD 12, range 21-72), 65% white, completed questionnaires. Most (61%) were CML patients, with 12% RCC, 10% GIST, 6% melanoma, and NET, oligodendroglioma, and HCC comprising remaining histologies. 96% were treated with TKI, and 4% with ICI. At the time of diagnosis, 35% of patients indicated a desire to father future children, and 53% believed that cancer treatment might affect their fertility. Despite this, 45% were not asked whether having children was important to them, and 47% did not receive information from any provider on their oncology care team about the possible risks of TKI/ICI to future fertility. The majority of patients felt there was inadequate discussion of how treatment might affect testosterone levels (73%) and their ability to father a child (53%), yet only 14% recalled adequate referrals to a fertility specialist. Conclusions: These data demonstrate that male cancer patients perceive treatment-related infertility risks as important, yet have few opportunities to discuss these concerns with providers. Care plans to address oncofertility needs, especially as TKI/ICI are increasingly used in multiple cancer types, are needed as part of the diagnosis, treatment, and follow up of these patients. Larger retrospective and prospective studies are ongoing to further characterize this patient cohort.
ctDNA detection of EGFR mutations in NSCLC patients using TargetSelector.
Authors: Frans Beerkens, Chul Kim, Syed P. Hasan, Deepa Suresh Subramaniam, Stephen V. Liu, Lyle Arnold, Cecile Rose T. Vibat, Veena M. Singh, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2017)

e23037 Background: EGFR mutations are the most frequent targetable genomic alterations in non-small cell lung cancer (NSCLC) patients (pts). While tissue biopsy remains the standard for assessing of EGFR mutation status, it is invasive and not always feasible. Liquid biopsy is a minimally invasive alternative. Biocept’s proprietary TargetSelector system evaluates circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood. We aimed to clinically validate the accuracy of EGFR-specific TargetSelector in NSCLC pts. Methods: At three time points (T0: baseline before TKI, T1: during EGFR-TKI therapy, T2: after progression), blood samples were collected in Biocept OncoCEE BCT validated to preserve DNA up to 8 days. These samples were interrogated for three EGFR mutations: exon 19 deletions (Del 19), L858R, and T790M. The objectives are to assess detection sensitivity of liquid biopsy using EGFR mutation status vs the tissue as gold standard and to evaluate whether the detection sensitivity changes with EGFR-TKI therapy. Results: A total of 53 study pts were enrolled (male, 21; female, 32). The mean age was 70.6 (range: 46 – 90). Most pts had stage IV disease (43, 81.1%) and lung adenocarcinoma (48, 90.6%). 26 (49.1%) pts had EGFR mutations in tumor tissue: Del 19, 13; L858R, 8; T790M, 6; other, 8. Detection sensitivity for sensitizing EGFR mutations (Del 19 and L858R) at T0, T1, and T2 was 60.0% (6/10), 33.3% (5/15), and 33.3% (1/3), respectively. There was no statistical difference in CTC counts between activating EGFR mutation-positive and -negative pts (mean CTC count: 10.5 vs 20.1; p = 0.11 by two-sided t-test). Detection sensitivity for T790M was 33.3% (2/6) and 5 of 6 pts were receiving T790M directed therapy (3, rociletinib; 2, osimertinib) at the time of blood draw. Two pts – one patient before initiation of EGFR-TKI and the other during treatment with erlotinib – were found to have T790M mutations only in blood and not in tissue. Conclusions: Activating EGFR mutation detection may decrease during the course of TKI therapy, possibly due to treatment response. Further research with an expanded sample size and serial collections are needed to evaluate this finding, and to investigate possible implications of the presence of T790M only in blood.
Observational study of the efficacy of nivolumab (Nivo) as 2+ line treatment and quality of life (QoL) in advanced refractory non-small cell lung cancer (NSCLC) patients: Interim analysis.
Authors: Konstantin K Laktionov, Alla L Arzumanyan, Larisa V Bolotina, Valeriy Vladimirovich Breder, Natalia N Buevich, Anastasia Danilova, Elena A Filippova, Anna Kornietskaya, Mikhail M Kramchaninov, Eugenia K Kushniruk, Dilorom Hamidovna Latipova, Daria A Lipatova, Fedor Vladimirovich Moiseenko, Tatiana P Nikitina, Sergey Orlov, Rashida Orlova, Svetlana Protsenko, Ksenia A Sarantseva, Daniil Stroyakovskiy, Tatyana I Ionova
Journal: Journal of Clinical Oncology (2017)

e14593 Background: Therapy with immune checkpoint inhibitors (ICI) changed the paradigm of treatment in many solid tumors including NSCLC. Recently several ICI were approved for NSCLC second and first line. By now data on Nivo benefits/risks in NSCLC is quite limited. The aim of this study was to evaluate clinical and patient-reported outcomes on Nivo in second plus line within the expanded access program in NSCLC. We report interim analysis on response rates, safety and QoL. Methods: Adult pts with advanced refractory NSCLC received Nivo 3 mg/kg q2w. Tumor response was assessed using RECIST v. 1.1., adverse events (AEs) with NCI CTCAE v3.0. and QoL by RAND SF-36. Group comparisons were made using Wilcoxon test. Results: From July of 2015 to January of 2017, 157 pts were enrolled in 7 centers in RF. Median follow-up time was 14 weeks. Clinical characteristics: 66% – males; median age – 62 (29−80); ECOG PS 0-1/2-3 – 81%/19%; former/current smokers – 73%; non squamous NSCLC – 64%; ≥2 lines of previous systemic treatment – 51%. We observed 1.5 increase of Integral QoL index in 53% of pts at 4 weeks; significant improvement was observed for emotional functioning (33.3 vs 50.0; p &lt; 0.05). Efficacy was evaluated in 56 pts: PR – 6/56, SD – 35/56, PD – 15/56. Clinical improvement was noticed in 36 pts. Early deaths from cancer occurred in 9 pts; early deaths not related to cancer – 2 pts. 18 pts discontinued Nivo prematurely ( &lt; 8 weeks) because of rapid clinical worsening. 72 pts were not evaluated for response on cut-off. More pts with quick worsening as compared with responders were with non squamous NSCLC (75% vs 50%) and had brain mets (20% vs 0%). Among responders 33% were with PS &gt; 1 and were &gt; 65 y.o; pts in this group had no brain mets. AEs were registered in 40 pts (median of Nivo treatment – 6 weeks); among them 11 with grade 3-4 AEs. Conclusions: Early data from this study supports thata large number of pts benefits fromNivo treatment. Nivo is well tolerated by this population, with 7% of grade 3 or 4 toxicities. Nivo treatment is accompanied with significant QoL improvement in 53% pts.
Comparison of legacy quality of life measures with the electronic quality of life measuring system (NIH PROMIS) in glioblastoma patients.
Authors: Tobias Walbert, Lonnie Schultz, Aarushi Suneja
Journal: Journal of Clinical Oncology (2018)

e18823 Background: Health-related quality of life (QoL) and patient reported outcomes are an essential component of patient-care and research. The National Institute of Health sponsored electronic Patient-Reported Outcomes Measurement Information System (PROMIS) is well established in multiple cancers but not in the setting of Glioblastoma (GBM), the most common and aggressive primary brain tumor. The aim of this study was to analyze the feasibility of utilizing the computer adaptive PROMIS questionnaire in GBM patients and to compare it to the European Organization for Research and Treatment of Cancer core instrument (EORTC-QLQ-C30) and the brain tumor specific EORTC QLQ-BN20 questionnaire (EORTC-BN20). Methods: Newly diagnosed patients with GBM were enrolled to assess feasibility. The PROMIS modules were selected to reflect the quality of life domains assessed in the EORTC- QLQ-C30 and EORTC-BN20 questionnaires. PROMIS modules selected included the modules for anxiety, depression, fatigue, physical function, sleep disturbance, sleep-related impairment, social satisfaction role, applied cognitive ability and global health. Descriptive analysis was performed. Results: 43 patients with GBM, WHO Grade IV (60% male, 91% Caucasian, 7% African American, 2% Asian) were recruited from the Hermelin Brain Tumor Clinic and completed the surveys at home or during clinic visits. 63% of patients completed a survey prior to radiation and 77% after radiation treatment. The average number of computer adapted PROMIS questions ranged from 4.07 to 5.8 (4-12 questions). The median times to complete the EORTC-QLQ-C30 and the EORTC-BN20 surveys were 4.77 (range = 2.05-18.6) and 2.63 (range = 1.17- 24.83) minutes respectively. For the PROMIS instruments except global health, the median times to complete different modules ranged from 0.6- 1 minute (range = 0.15-7.77). For global health, the median time was 2.35 minutes (range = 1.02-21.12). Median time to complete all PROMIS questions was 8.62 minutes (range = 0.92-30.08). Conclusions: Electronic assessment of QoL is feasible. The wide range of time requirements suggests that it is not a feasible tool for all patients.
Rebiopsy status among non-small cell lung cancer patients after Icotinib therapy in China.
Authors: Hanping Wang, Li Zhang, Xiaoyan Si, Xiaotong Zhang, Mengzhao Wang
Journal: Journal of Clinical Oncology (2018)

e21146 Background: Acquired T790M mutation accounts for 50-60% of TKI resistant mechanism in EGFR mutation (+) NSCLC patients progressed after TKIs. Rebiopsy was recommend in these patients to detect the T790M mutation. Icotinib was a first-generation EGFR TKIs widely used in China. We aimed to investigate the rebiopsy status and the incidence rate of T790M of patients after Icotinib therapy Methods: This was a retrospective study. The target patients were EGFRm+ NSCLC who progressed from Icotinib therapy. The primary endpoint was the rebiopsy rate (number of cases in which rebiopsies were performed successfully/total number of patients progressed from icotinib). The secondary endpoints included the incidence rate of T790M mutation, the differences between first biopsy and rebiopsy, and the details of why rebiopsy not be performed in relevant patients Results: 77 adenocarcinoma patients progressed from icotinib therapy in the past 2 years were evaluated (median age 58 years, range 36 to 81). Tissue rebiopsy was successful in 41 patients (53.2%). Compared with the sampling method at first biopsy, the percutaneous tissue biopsy increased from 51.2% (21/41) to 70.7% (29 /41), while the bronchoscopy biopsy, and surgical rate decreased from 19.5% (8/41) to 14.6% (6/41) and 7.1% (7/41cases) to 7.3% (3/41) respectively. As for the site of biopsy, the primary lung lesions were more common at first biopsy than at rebiopssy (33/41, 80.5% vs 27/41, 65.9%), but metastatic lesions outside the lung were more selected (14/41, 34.1%, includes metastasis in bone, lymph node, and liver et al) at rebiopsy. The incidence rate of T790M was 56.1% (23/41). The reasons for not rebiopsy in 36 patitents included lesions size and/or location unfit for biopsy (16 pts), the positive/negative result of ctDNA (6 pts), patients’ unwillingness (5 pts), too old or severe comorbidity (4 pts), and too ill (5 pts). No severe rebiopsy-associated complications was found Conclusions: The rebiopsy rate was 53.2% in this real-world study. The incidence rate of T790M mutation was 56.1% in these patients after Icotinib therapy. More effort was needed to increase the rebiopsy rate, so that improve the selection of patients who may benefit from third-generation TKIs
Real world treatment patterns and discontinuation of systemic combination therapies in metastatic melanoma.
Authors: Ying Qiu, Zhiyi Li, Jackson Tang, Pavel Atanasov, Syed Mahmood, Kris Grzegorzewski, Lei Chen, Joyce S Chen
Journal: Journal of Clinical Oncology (2017)

e21003 Background: Guidelines for metastatic melanoma (MM) recommend targeted therapy combination (combo) for patients (pts) with BRAF mutation (BRAF+) and immunotherapy for pts irrespective of BRAF status. The study objective was to describe real world characteristics and treatment patterns among mm pts treated with either dabrafenib+trametinib (D+T) or ipilimumab+nivolumab (I+N) combo therapies. Methods: This retrospective observational study utilized Flatiron Health’s electronic health record (EHR) data. Included pts were ≥18 years and treated with either D+T or I+N (post mm diagnosis) from Jan 2013 - Jul 2016. Baseline characteristics, treatment patterns and data on therapy discontinuation were collected from structured data in patient records and unstructured data in physician notes. Non-parametric statistical tests were used in light of sample size limitations. Results: 135 D+T pts and 75 I+N pts were included. Median age was 60 for D+T pts and 64 for I+N pts. 69% of D+T pts were male vs 68% of I+N pts. Most pts were Caucasian (82% for both). Before receiving combo therapy, 100% of D+T pts vs 31% of I+N pts were BRAF+, 38% of D+T pts vs 31% of I+N pts had brain metastasis (mts) (p &gt; .05), 25% of D+T pts vs 16% of I+N pts had high LDH levels (p = .05), and 18% of D+T pts vs 35% of I+N pts reported ECOG = 0 status (p &lt; .01). Median follow-up time was 234 days for D+T pts vs 173 days for I+N pts (p &lt; .01). 64% of D+T pts vs 81% of I+N pts received combo therapy as first line (1L) therapy (p = .02). The 3 and 6 month discontinuation rates were 9% and 24% for D+T 1L pts; 12% and 26% for I+N 1L pts; and 21% and 47% for the subset of I+N 1L BRAF+ pts. 13% of D+T 1L pts vs 28% of I+N 1L pts discontinued treatment over the follow-up period citing toxicity in physician notes (p = .05). Among pts with brain mts, the 3 and 6 month discontinuation rates were 3% and 20% for D+T 1L pts; 24% and 35% for I+N 1L pts; and 33% and 50% for I+N 1L BRAF+ pts. Conclusions: Prior to initiation of combo therapy, D+T pts had more advanced disease: pts were more likely to have brain mts, high LDH level, receive D+T as 2L+ therapy, and less likely to have ECOG = 0 status than I+N pts. I+N 1L pts were more likely to discontinue therapy due to toxicity than D+T 1L pts even with a shorter median follow-up time.