tbuckley/cabot-search huggingface dataset:
Genomic landscape of non-small cell lung cancer (NSCLC) with methylthioadenosine phosphorylase (<i>MTAP</i>) deletion.
Authors: Stephen L. Graziano, Dean C. Pavlick, Ethan Sokol, Shakti H. Ramkissoon, Eric Allan Severson, Richard S.P. Huang, Douglas A. Mata, Brennan Decker, Kimberly McGregor, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2021)

9116 Background: NSCLC remains a major cause of cancer-associated mortality despite major advancements in treatments. In addition to immune checkpoint inhibitors (ICPI), new strategies for clinically advanced NSCLC now include the development of new synthetic lethality targets focused on protein arginine methyl transferases such as PRMT5 that exploit the impact of tumor cell genomic loss of MTAP. Methods: 29,379 advanced/metastatic NSCLC cases underwent hybrid-capture based comprehensive genomic profiling to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 tumor cell expression was determined by DAKO 22C3 immunohistochemistry (IHC); low positive was a tumor proportion score (TPS) 1-49% and high positive was a TPS ≥50%. Results: 3,928 NSCLC exhibited MTAP homozygous loss. Cases had the following subtypes: adenocarcinoma (59%), squamous cell ca (22%), NSCLC NOS (16%), and large cell neuroendocrine, sarcomatoid, adenosquamous ca (all 1%). GA/tumor were similar when CDKN2A/B losses associated with 9p21 co-deletion with MTAP loss are excluded. Significant differences in currently targetable GA included KRAS G12C higher in MTAP-intact NSCLC (P =.0003) and EGFR short variant mutations higher in MTAP-deleted NSCLC (P &lt;.0001). MTAP-intact NSCLC had higher frequencies of GAs in TP53 (P &lt;.0001) and RB1 and a lower frequency of SMARCA4 (P &lt;.0001). GAs frequencies in ERBB2, MET, ALK, ROS1 and NTRK1 were similar. Biomarkers for potential ICPI efficacy were higher in MTAP-intact including TMB ≥10mut/Mb (P =.0002) and low and high PD-L1 IHC staining (P =.01). Biomarkers potentially predictive of ICPI resistance ( STK11 and KEAP1) were similar in both groups. Conclusions: MTAP loss occurs in 13% of NSCLC, supporting the development of novel targeted therapies designed to exploit PRMT5 hyper-dependence in these tumors. MTAP loss in NSCLC is accompanied by differences in targeted and ICPI options for these patients which may impact future combination strategies. Further study of anti-PRMT5 drugs that are enabled by MTAP loss in NSCLC appears warranted.[Table: see text]
A pilot study to prevent burnout in junior oncology doctors during the COVID-19 pandemic in a tertiary U.K. center.
Authors: Alfred Chung Pui So, Sarah Hunter, Karen Chan, Anne Sagar Rigg, Sue Smith, Raselle Miller, Kiruthikah Thillai
Journal: Journal of Clinical Oncology (2021)

11015 Background: Burnout is a syndrome defined by emotional exhaustion, depersonalisation and loss of personal accomplishment. It is a growing concern amongst doctors, particularly in oncology, who face the added stress of delivering life changing results to patients and managing end of life care. This has potential for negatively impacting mental health, job satisfaction and ultimately patient care. This has been compounded by the COVID-19 pandemic and the uncertainty around complex oncological treatment decisions, longer working hours, redeployment, and constant changes to working patterns to meet the evolving clinical need. In response to this, a novel wellbeing intervention was designed by the educational lead consultant and psychologists to prevent burnout during the pandemic. Methods: Junior doctors working at a single UK cancer centre during the COVID-19 pandemic were invited to attend weekly 30 minute wellbeing sessions facilitated by a clinical psychologist throughout their oncology placement (average 4-6 months). Sessions had an average attendance of 3-6 doctors and began with a 5 minute breathing and relaxation exercise followed by a mixture of clinical debriefing, reflective practice, and mindfulness strategies. Trainees were invited to have individual sessions if required. Surveys based on the 14 point Warwick Edinburgh Well Being Scale (WEMWBS) were conducted at the start and end of placement. Additional qualitative feedback was collated. Results: Throughout a 6 month period, 10 doctors participated in this study. Baseline WEMWBS scores revealed average mental wellbeing (n = 8), high mental wellbeing (n = 1) and probable depression (n = 1). Median baseline WEMWBS score was 52(41-62). Median number of sessions attended was 11(3-14). Post intervention, there was no significant deterioration in baseline WEMWBS score (mean change +2.2; p= 0.34). When doctors were asked about their optimism for the future, there was a significant increase by +0.4 points ( p= 0.037). With respect to participant feedback, 100% were either ‘satisfied’ (n = 1) or ’very satisfied’ (n = 9) with the group facilitation and 100% found the group sessions either ‘helpful’ (n = 7) or ‘very helpful’ (n = 3). Trainee feedback described the benefits of reflecting in a structured and safe environment, breathing exercises, and learning mindfulness strategies. Conclusions: Burnout is a serious concern amongst junior oncologists and is rising as a result of COVID-19. We present a novel intervention that promoted psychological flexibility and importantly maintained mental wellbeing throughout the pandemic. Further studies are planned to develop evidence based interventions to tackle this important issue.
Python-based preprocessing for applying machine learning in breast cancer metastasis prediction.
Authors: Yousri A. Rostom, Salah-Eldin Abd-El-Moneim, Nevine Makram Labib, Samia Gharib, Marwa Shaker, Nayera Mahmoud
Journal: Journal of Clinical Oncology (2021)

e13558 Background: Artificial intelligence (AI) and machine learning (ML) have outstanding contributions in oncology. One of the applications is the early detection of breast cancer. Recently, several ML and data mining techniques have been used for both detection and classification of breast cancer cases. It is found that about 25% of breast cancer cases have an aggressive cancer at diagnosis time, with metastatic spread. The absence or presence of metastatic spread largely determines the patient’s survival. Hence, early detection is very important for reducing cancer mortality rates Methods: This study aims at applying ML and data mining, using AI techniques, for exploring and preprocessing breast cancer dataset, before building the ML classification Model for breast cancer metastasis prediction. The model will be implemented for mass screening, to prioritize patients who are more likely to develop metastases. A dataset of breast cancer cases was provided by the Oncology and Nuclear Medicine Department, Faculty of Medicine, Alexandria University. It contains clinical records of 5236 patients, diagnosed with breast cancer. ML libraries in Python programming language was used to explore the dataset and determine ratio of missing data, define data types, redundant data, and specify class label and predictors that to be used for the classification model. Results: In this work, the results showed that missing data ratio in some columns exceeds 90%, there are redundant features to be eliminated, data type conversion and feature reduction should be applied to prepare the data. Conclusions: Based on the previous findings, it is recommended to use ML preprocessing python libraries to prepare the dataset before building ML classification model of breast cancer metastasis prediction.
Integrating gut microbiome and host immune markers to understand the pathogenesis of <i>Clostridioides difficile</i> infection
Authors: Shanlin Ke, Nira R. Pollock, Xu-Wen Wang, Xinhua Chen, Kaitlyn Daugherty, Qianyun Lin, Hua Xu, Kevin W. Garey, Anne J. Gonzales-Luna, Ciarán P. Kelly, Yang-Yu Liu
Journal: Gut Microbes (2021)

Clostridioides difficile (C. difficile) infection is the most common cause of healthcare–associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of C. difficile infection (CDI) pathogenesis is crucial for disease diagnosis, treatment, and prevention. Here, we characterized gut microbial compositions and a broad panel of innate and adaptive immunological markers in 243 well-characterized human subjects (including 187 subjects with both microbiota and immune marker data), who were divided into four phenotype groups: CDI, Asymptomatic Carriage, Non-CDI Diarrhea, and Control. We found that the interactions between gut microbiota and host immune markers are very sensitive to the status of C. difficile colonization and infection. We demonstrated that incorporating both gut microbiome and host immune marker data into classification models can better distinguish CDI from other groups than can either type of data alone. Our classification models display robust diagnostic performance to differentiate CDI from Asymptomatic carriage (AUC~0.916), Non-CDI Diarrhea (AUC~0.917), or Non-CDI that combines all other three groups (AUC~0.929). Finally, we performed symbolic classification using selected features to derive simple mathematic formulas that explicitly quantify the interactions between the gut microbiome and host immune markers. These findings support the potential roles of gut microbiota and host immune markers in the pathogenesis of CDI. Our study provides new insights for a microbiome-immune marker-derived signature to diagnose CDI and design therapeutic strategies for CDI.
Abstract 13876: Novel Safe and Effective Role for Subcutaneous-ICDs in Patients With Hypertrophic Cardiomyopathy
Authors: Nathaniel Steiger, Austin Burrows, Ethan J Rowin, Christopher Madias, Mark S Link, Barry J Maron, Martin S Maron
Journal: Circulation (2019)

Introduction: The transvenous (TV) implantable cardioverter defibrillator (ICD) is effective for preventing sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). The effica...
Social disparities in Southeastern Brazil and the burden of cervical cancer.
Authors: Sabina B. Aleixo, Jose Zago Pulido, Narelle Parmanhane, Luciana Sogame
Journal: Journal of Clinical Oncology (2021)

e18511 Background: Cervical cancer (CC) is the fourth most common malignancy in women worldwide and around 85% of the cases currently diagnosed are in underdeveloped countries. According to the National Cancer Institute of Brazil (INCA), in the year 2021, 16.590 new cases are expected with an estimated risk of 15.43 cases per 100,000 women and unfortunately numbers are not decreasing. Low socioeconomic status is been known to be associated with inferior cancer survival. Although Brazil’s publicly funded Unified Health System (SUS) increased access to health care, the universal access is still a problem. Brazil is a country of continental dimensions with widespread regional and social inequalities. The CC differs enormously by regions in the Brazilian country. Here, we use a population-based cancer registry to explore sociodemographic characteristics and CC in Southeastern Brazil. Methods: We collected retrospective data of patients with CC registered in the regional cancer reference center from the south of Espirito Santo (ES) the Hospital Evangélico de Cachoeiro de Itapemirim (HECI). We used the brazilian Health Information System - SISRHC from 2010 to 2017. Characteristics such as educational level (years of study), age, race, type of health insurance for treatment (SUS or private) and disease stage at diagnosis were recorded. Results: Among 3272 women diagnosed with cancer in the period analyzed, 286 had a diagnosis of CC.The educational level of 44,61% was less than 9 years, 16,43% between 10 and 12 years and 3,15% more than 12 years (36,01% without information).Mean age at diagnosis was 49 years, and 50 % were younger than 50 years. As for race, 50% of the women self-declared as non-white and 40,91% as white (9,09% without information), and 89,9% were treated by SUS and 10,1% treated by private health system. The distribution of CC stages at diagnosis was 0 (13,99%), I (15,03%), II (23,08%), III (18,53%) and IV (3,5%). Stage status was missing for 35,87% of CC cases. Conclusions: The majority of the women in the study where non-white, had low education level , used public health system (SUS) for treatment and had advanced disease. We also found that Brazilian SISRHC needs more attention to be a reliable cancer source data. These findings reinforce that social determinants affects access to diagnosis and treatment of CC patients in Southeastern Brazil. Future health awareness and preventive interventions must target less-educated communities to reduce delays in seeking medical care for cancer.
Incidence of asymptomatic COVID-19 positivity in cancer patients and effects on therapy.
Authors: Nicole Ross, Elizabeth A. Handorf, Caitlin R. Meeker, Giana Chen, Donald Baldwin, Namrata Vijayvergia
Journal: Journal of Clinical Oncology (2021)

e13506 Background: As the coronavirus disease 2019 (COVID-19) pandemic threatens the delivery of cancer care, challenges to providing safe and quality care persist. Screening measures including SARS-CoV-2 polymerase-chain reaction (CovPCR) testing prior to invasive procedures, therapy administration, were instituted to address risk of spread from asymptomatic (AS) pts. Studies have documented poor outcomes with COVID-19 in cancer pts with rate of AS COVID-19 ranging from 0.6%- 8%. (Liang et.al, 2020; Al-Shamsi, et.al, 2020, Shah et.al. 2020). In the general population, rates of AS cases was estimated to be 17% (Byambasuren, O., 2020). This study aimed to examine the incidence and characteristics of AS COVID -19 in cancer pts, and determine its effect on cancer care delivery at a tertiary care center. Methods: With IRB approval, a retrospective chart review was conducted on cancer pts undergoing CoVPCR screening. Pts were considered AS if they had no recent fever (≥100.5 °F), cough, headache, loss of taste/smell, shortness of breath, diarrhea, or high risk exposure. This analysis compared cases (positive CoVPCR) identified by screening of AS pts to control (negative CoVPCR) pts (matched by planned procedure type and month of screening). Each COVID case was matched to 2 negative controls on month and planned procedure type. Patient characteristics and outcomes were compared between cases and controls using conditional logistic regression or Mantel-Haenszel tests. Results: Between 03/2020 and 09/2020, 4143 AS pts underwent CovPCR testing and 75 were chosen for analysis (25 cases; 50 controls). The incidence of AS COVID-19 in cancer pts was 0.6% (25/4143). Median age was lower in the cases (64 vs 70y, p = 0.04). Gender, race, primary cancer diagnosis, and co-morbidity distribution was similar between cases and controls. Of the cases, 10 pts (40%) never underwent the planned oncologic intervention while 11 (44%) had a delay related to the positive CoVPCR (2 pts had no intervention planned). Only 1 pt (2%) in control arm didn’t undergo the planned procedure. The mean duration of delay was 18 days (range 0-49 days, SD 16.72) in cases versus Zero days in control. Four (16.7%) cases developed symptoms within 14 days of positive CoVPCR testing but the PCR value did not predict this conversion. Conclusions: Incidence of AS COVID in our cancer pts was significantly lower than general population. Active screening delayed oncologic care but with institution of safety measures like separate treatment rooms and scheduling procedures at the end of the day have ensured safe and prompt cancer care delivery during the pandemic. Future research needs will address incorporating vaccination status into the screening algorithm to limit widespread CoVPCR screening, thus improving care delivery and cost effectiveness.
Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial
Authors: A.A. Hamid, H.-C. Huang, V. Wang, Y.-H. Chen, F. Feng, R. Den, G. Attard, E.M. Van Allen, P.T. Tran, D.E. Spratt, R. Dittamore, E. Davicioni, G. Liu, R. DiPaola, M.A. Carducci, C.J. Sweeney
Journal: Annals of Oncology (2021)

The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined.Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC.The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015).This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.
Influence of parent age and gender on anticipation in familial B-cell malignancies
Authors: D. T. Alexandrescu, K. Brown, J. P. Dutcher, P. H. Wiernik
Journal: Journal of Clinical Oncology (2006)

7553 Background: Anticipation (A) occurs when a disease manifests at an earlier age or with increased severity in the next generation. Dependence of A on parent age and sex has not been previously investigated in B-cell malignancies. Methods: 144 pairs [45 mixed Hodgkin’s/non-Hodgkin’s (HD/NHL) and NHL/HD, 44 NHL, 24 HD and 31 CLL] were analyzed retrospectively for presence of anticipation in overall, paternal (PT) and maternal transmission (MT). 90 pairs belong to our familial hematological malignancies database, and 54 were pooled from the literature. A among diseases, as well as PT and MT were compared by t-test. Parent age at conception was correlated with A by Pearson correlation (PC). Results: Age at conception was similar among all malignancies, and overall anticipation varied between −18.93 and −26.61 yr, with no significant difference among diseases, except between CLL and mixed HD/NHL-NHL/HD (−18.93 vs. −26.61 yr, mean difference −7.68 yr, p = 0.03, 95% CI −14.74 to −0.62). A significant PC between the parent age at conception and A was found for all malignancies, with the exception of borderline significance in the case of mixed HD/NHL-NHL/HD MT. No difference in overall A was observed between PT and MT, except for HD (−27.25 vs. −14.25 yr, mean difference −13.00 years, P = 0.02, 95% CI −23.68 to −2.32). However, higher PCs were observed with PT than MT for all diseases (Table). Conclusions: A is present in all familial B-cell malignancies analyzed and it correlates with parent age of conception. Although mean absolute A was more prominent with PT than MT only in the case of HD, all diseases showed a tendency towards a higher PC with PT. Although less prominent than with neurological disease, this phenomenon points towards a germline inheritance of B-cell malignancies and a common genetic basis for HD and NHL. [Table: see text] No significant financial relationships to disclose.
Socioeconomic status variables contribute to the disparities in female triple negative breast cancer outcome in the United States, 2011-2015: A population study based on NCI Surveillance, Epidemiology and End Results (SEER) database.
Authors: Zikun Wang, Yi Dong, Zheyu Lu, Zhongxue Chen
Journal: Journal of Clinical Oncology (2021)

6521 Background: Cancer disparities pertinent to socioeconomic status (SES) still exist in the American healthcare system. How SES variables impact the outcome of triple negative breast cancer (TNBC) needs identification. Methods: We enrolled 22,434 women diagnosed with invasive TNBC in 2011 – 2015 from the SEER 18 program. The primary outcome was to identify SES risk factors for TNBC cause specific survival (TNBCCSS)and overall survival (OS) via the Cox Proportional Hazard Regression Model. SES information was collected: race, insurance status, marital status, and percentage of families with incomes below the poverty level and adults with less than high school graduate (&lt;HSG) in a county of the patient’s residency; all analyses were also adjusted for clinicopathological characteristics. We categorized rates of poverty and &lt;HSG as quartiles. Results: 18,578 (82.8%) women were insured or insured/ no specifics (NS), and 3,360 (15.0%) received Medicaid upon TNBC diagnosis; only 496 (2.2%) patients were uninsured. The TNBCCSS rates of insured, insured/ NS, Medicaid, and uninsured cohorts were 86.6%, 83.6%, 77.4% and 73.2%, respectively. In multivariable adjusted analyses, the TNBC cause specific mortality risk of patients who were uninsured or receiving Medicaid was significantly higher than that of women who were insured (Hazard ratio [HR] = 1.60, 95% confidence interval [CI]: 1.34-1.92 and HR = 1.29, 95% CI: 1.18-1.41, respectively). Women residing in a county with a high poverty rate (the 3rd quartile [rate of 11.1 – &lt;14.3%]) had significantly worse TNBC cause specific mortality risk as compared to women with residency of the lowest poverty rate (HR = 1.25, 95% CI: 1.10-1.41). Single and widowed cohorts had better HR of TNBCCSS compared with the married population (HR = 0.86, 95% CI: 0.79-0.95 and HR = 0.82, 95% CI: 0.73-0.93, respectively). Notably, we observed a synergistic effect among race, insurance status and TNBC OS: black women receiving Medicaid had significantly lower HR compared with their non-Hispanic white counterparts (HR = 0.86, 95% CI: 0.74-0.98). Rate of &lt;HSG was marginally correlated with the TNBCCSS. Conclusions: SES variables contribute to the disparities in TNBC survival. TNBC cause specific mortality risk of patients without insurance or with Medicaid at the time of TNBC diagnosis is 60% and 29% higher compared with insured women (Table). Race and insurance status act synergistically upon TNBC OS.[Table: see text]
Recommendations for including or reviewing patient reported outcome endpoints in grant applications
Authors: Claire Snyder, Alexandra Gilbert, David Moher, Derek Kyte, Ellie Daniels, Madeleine King, Melanie Calvert, Ronald C Chen, Michael Brundage
Journal: BMJ (2021)

Patient reported outcomes are increasingly included in research studies to provide the patient perspective. Grant applicants and grant reviewers require guidance on the key information that should be included in funding applications to demonstrate rigorous methods for patient reported outcomes. This paper provides prioritised practical recommendations from an international consortium of experts on patient reported outcomes to inform grant applicants in preparing their research strategies and grant reviewers in evaluating applications.