bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between caregiver burden and psychological distress among stem cell transplant (SCT) recipients prior to transplant.
Authors: Topping Carlisle , Nelson Ashley , Jacobs Jamie M. , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej 
Published: May 2020

12120 Background: SCT is a potentially curative therapy for patients with hematologic malignancies that involves prolonged hospitalization, intensive follow-up, and a considerable risk of morbidity and mortality. Family and friends caring for SCT recipients experience substantial caregiving burden as they prepare for SCT. Previous research demonstrates caregiver distress is highest pre-transplant and is comparable to or higher than patient-reported distress. However, the extent of this distress and its relationship to certain domains of quality of life (QOL) and caregiving burden is currently unknown. Methods: We conducted a secondary analysis of cross-sectional data from two supportive care studies focused on caregivers of SCT recipients. Caregivers completed the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology QOL questionnaire to assess their psychological distress and QOL prior to SCT. Scores >8 on the HADS anxiety and depression subscales indicated clinically significant symptoms. We selected eight domains from the CareGiver Oncology QOL questionnaire including social support, physical wellbeing, self-efficacy, coping, leisure time, financial stability, private life concerns, and caregiving burden. Multivariate regression models adjusted for age, sex, caregiver relationship, and SCT type were used to examine associations between these domains and caregivers’ anxiety and depression symptoms. Results: A total of 193 caregivers (age M= 57 years, 70% female, 52% allogeneic transplant) were enrolled with a majority caring for their spouse (80%), parent (8%) or child (5%). Overall 47% and 16% of caregivers reported clinically significant anxiety and depression symptoms, respectively. Low social support, physical well-being, coping and leisure time as well as high caregiver burden, private life concerns and financial distress were associated with both caregiver anxiety and depression symptoms (p < .05). Low self-efficacy was associated with higher anxiety symptoms (p < .05). Conclusions: Caregivers of SCT recipients experience substantial anxiety and depression symptoms prior to SCT. Impairments across multiple QOL domains are associated with caregiver’s psychological distress. Psychosocial interventions designed to improve coping, reduce caregiving burden, and enhance QOL are needed for caregivers prior to transplant.
Tumor/normal genomic profiling in patients with metastatic solid tumors identifies pathogenic germline variants of therapeutic importance.
Authors: Cobain Erin Frances , Jacobs Michelle , Wu Yi-Mi , Robinson Dan R. , Vats Pankaj , Chugh Rashmi , Talpaz Moshe , Stoffel Elena Martinez , Chinnaiyan Arul 
Published: May 2020

1501 Background: Tumor molecular profiling via next-generation sequencing (NGS) is routinely utilized to direct patients toward clinical trials of targeted therapeutics. NGS testing of paired tumor/normal samples identifies incidental pathogenic germline variants (PGVs), having potential implications for patients and their families. Methods: From 2011-2018, 1,015 patients with metastatic, refractory solid tumors underwent targeted (1700 genes) exome and transcriptome sequencing of matched tumor/normal samples through the Michigan Oncology Sequencing program. Identified PGVs that conferred increased cancer risk or were associated with certain autosomal recessive conditions were reported to the treating oncologist. Chart reviews were conducted every 3 months to assess whether PGV identification impacted treatment decision making. Results: 169 PGVs were identified in 160 unique patients (15.8% of cohort). 69 PGVs (41%) harbored a clear somatic second hit event in the tumor. PGVs associated with defects in double-strand DNA repair ( BRCA1, BRCA2, ATM, PALB2, BRIP1) or DNA mismatch repair ( MLH1, MSH2 and PMS2) were identified in 49 patients (5% of cohort, 31% of patients with PGVs), 37 of which had not previously been identified. 14 PGVs in DNA double-strand repair and 7 PGVs in DNA mismatch repair were identified in cancer types not commonly associated with hereditary breast ovarian cancer or Lynch syndromes, including cancers of unknown primary origin and sarcomas. 7 patients received a PARP inhibitor (PARPi), 3 patients received an immune checkpoint inhibitor (ICI) and 1 patient received both PARPi and ICI therapy on the basis of a PGV in DNA repair. 6 patients achieved clinical benefit, defined as time on treatment ≥ 6 months. A patient with cancer of unknown primary origin and PGV in MSH2 achieved exceptional response to ICI therapy, with complete response ongoing and lasting 23 months. Conclusions: Targeted NGS of matched tumor/normal samples identified PGVs in about 1 in every 6 patients with metastatic solid tumors. Approximately 40% of PGVs are associated with a somatic second hit in the tumor, supporting their role in tumor pathogenesis. Unexpected PGVs with therapeutic implications are identified in patients with diverse cancer types, providing opportunities to use targeted therapies with potential for significant clinical benefit. Given this finding, testing for PGVs in DNA repair genes should be considered in all patients with metastatic solid tumor malignancies.
Results from MAGENTA: A national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk.
Authors: Swisher Elizabeth M. , Rayes Nadine , Bowen Deborah , Peterson Christine B , Coffin Tara , Norquist Barbara , Gavin Kathleen , Polinsky Deborah , Crase Jamie , Bakkum-Gamez Jamie Nadine , Blank Stephanie V. , Munsell Mark F , Nebgen Denise R , Pradeep Harsha , Law Sherman , Olopade Olufunmilayo I. , Zhou Alicia , Levine Douglas A. , D'Andrea Alan D. , Lu Karen H. 
Published: May 2020

1506 Background: Hereditary breast and ovarian cancer (HBOC) is preventable when genetic risk is identified. We aimed to test whether pre and/or post-test genetic counseling is needed to optimally deliver online accessible genetic testing. Methods: MAGENTA (Making GENetic Testing Accessible) is a four-arm non-inferiority trial evaluating electronic genetic education and results delivery alone or combined with pre-test only, or post-test only telephone genetic counseling compared to mandatory pre- and post-test counseling (control arm) in women at risk of HBOC (NCT02993068). Regardless of assigned arm, all subjects with a pathogenic mutation received post-test telephone counseling. All subjects were enrolled electronically as part of either a family history cohort (FHC) or a cascade cohort (CC, known familial mutation). The primary outcome was cancer risk distress at 3 months and the trial was powered for the FHC. Secondary outcomes included completion of testing (i.e., received results), anxiety, depression, quality of life, and decisional regret, all measured by standardized scales. Results: Enrollment is complete and a total of 3,822 participants were randomized, 3,111 in FHC and 711 in CC. Participants were enrolled from all 50 states, but most were white/non-Hispanic (88%). Among participants that completed genetic testing, 173 (7.2%) had a mutation in a breast or ovarian cancer gene, with 114 (5.7%) of FHC and 59 (14.2%) of CC. In the primary intention-to-treat analysis of FHC, each of the three experimental arms was non-inferior to the control arm for distress at 3 months (p < 0.025/3 = 0.0083). In the CC, no and pre-test only counseling were also non-inferior (p < 0.025/3 = 0.0083). Distress was lowest in the arm with neither pre nor post-test counseling. Overall, 318 (18%) participants had very high distress at three month follow-up, and this rate was not significantly different across arms. Anxiety, depression and decisional regret did not have statistically significant differences across arms at follow-up. Test completion was highest in the no counseling arm (86.4%) and lowest in the control arm (60.6%). Conclusions: Electronic genetic education and results release without genetic counseling was non-inferior with regard to patient distress and was associated with higher test completion and lower distress. These results support use of a genetic testing paradigm providing individualized genetic counseling only for patients with positive test results. Clinical trial information: NCT02993068.
Smoking cessation (SC) and lung cancer (LC) outcomes: A survival benefit for recent-quitters? A pooled analysis of 34,649 International Lung Cancer Consortium (ILCCO) patients.
Authors: Fares Aline Fusco , Jiang Mei , Yang Ping , Christiani David C. , Chen Chu , Brennan Paul , Zhang Jie , Schwartz Ann G. , Landi Maria Teresa , Shiraishi Kouya , Ryan Brid M , Shen Hongbing , Schabath Matthew B. , Adonina Garcia , Shete Sanjay , Le Marchand Loic , Cox Angela , Hung Rayjean , Xu Wei , Liu Geoffrey 
Published: May 2020

1512 Background: Tobacco smoking profoundly impacts LC risk; however, data are limited as to what extent SC prior to diagnosis impacts LC overall survival (OS) and lung cancer specific survival (LCSS). LC screening offers a possible teachable moment, but there is uncertainty of SC benefits after a lifetime of smoking. We use the ILCCO database to answer if SC prior to LC dx is associated with better OS and LCSS, considering time since smoking cessation (TSSC). Methods: Using individual data, analysis was performed on 17 ILCCO studies with available TSSC to estimate survival using univariable analysis and models of stage-adjusted and cumulative smoking-adjusted multivariable analysis. Adjusted Hazard Ratios (aHR) from Cox models, cubic spline smooth curves and Kaplan-Meier curves were created. Sensitivity analysis was performed for TSSC and LCSS on 13 studies. Results: Of 34649 patients, 14322 (41%) were current smokers 14273 (41%) ex-smokers and 6054 (18%) never smokers at diagnosis. We confirmed that ex-smokers (aHR 0.88 CI 0.86-0.91) and never smokers (aHR 0.76 CI 0.73-0.8) improved OS compared to current smokers. Amongst ex-smokers, < 2y TSSC (aHR 0.88 CI 0.82-0.94), 2-5y TSSC (aHR 0.83 CI 0.77-0.90) and > 5y TSSC (aHR 0.8 CI 0.76-0.84) had improved OS compared to CS. Sensitivity analysis showed a trend towards improved LCSS survival for < 2y TSSC (aHR 0.95 CI 0.86-1.05) and 2-5y TSSC (aHR 0.93 CI 0.83-1.04), whereas > 5y TSSC significantly improved LCSS by 15% (aHR 0.85 CI 0.78-0.92). To mimic the LC screening participants, in analysis of > 30 pack-years individuals, associations were strikingly strong: < 2y TSSC had improved OS by 14% (aHR 0.86 CI 0.80-0.93); 2-5y TSSC by 17% (aHR 0.83 CI 0.76-0.90); and > 5 TSSC by 22% (aHR 0.78 CI 0.74-0.83), compared to current smokers; for < 30 packs-years, a trend towards better OS was observed for < 2y TSSC (aHR 0.95 CI 0.92-1.02) and 2-5y TSSC (aHR 0.86 CI 0.74-1.01), whereas > 5y TSSC improved OS by 23% (aHR 0.77 CI 0.72-0.82). Conclusions: Among ex-smokers, the risk of overall death was reduced by 12% on < 2y TSSC, 17% on 2-5y TSSC and 20% > 5y TSSC, whereas for LCSS, the benefit was significant only for > 5y TSCC, compared to current smokers at time of diagnosis. Here we demonstrate that convincing screening participants to quit smoking at any point of their trajectory, even just prior to dx such as < 2y TSSC, improved OS, and LCSS benefit was present beyond 5y of quitting. These relationships are independent of pack-years, age, across all stages and other prognostic variables.
Genetic counseling referrals after next generation sequencing testing.
Authors: Gonzalez Rafael , Ryan Emma , Watson Catherine , Broadwater Gloria , Kauff Noah D. , Havrilesky Laura J , Berchuck Andrew , Strickler John H. , Castellar Edgardo , Menendez Carolyn S. , Green Michelle , Strickland Kyle C , Previs Rebecca A. 
Published: May 2020

1515 Background: Next generation sequencing (NGS) testing of tumor tissue or blood is performed to identify ‘actionable’ mutations that might guide patient care. NGS testing might incidentally identify germline mutations associated with cancer syndromes. No distinction is made between germline and somatic alterations on NGS reports, thus confirmatory germline testing is required. In this quality improvement (QI) initiative, we evaluated the frequency of referrals to genetic counseling (GC) for patients with potentially heritable germline mutations identified through NGS testing. Methods: We generated a list of high-risk mutations (HRMs) which merit GC referral based on NCCN guidelines. NGS test results for 3,400 consecutive patients with solid tumor malignancies were reviewed by the molecular tumor board from 1/2014-9/2019 and were screened for pathogenic HRMs. Basic demographic, oncologic, and GC data were retrospectively abstracted for each patient. The outcomes of interest were the frequency of HRMs identified through NGS testing, the proportion of patients subsequently referred to GC, and the proportion of patients ultimately diagnosed with a hereditary cancer syndrome. Results: 472 individual patients (14%) had NGS testing with one or more HRM identified; 465 patients were evaluable which corresponded to 519 HRMs that were included in the analysis (Table). Malignancies included were gastrointestinal 199 (42.8%), lung 83 (17.8%), genitourinary/renal 56 (12.0%), breast 49 (10.5%), gynecologic 35 (7.5%), and other 43 (9.2%). 75 (16.1%) patients had germline testing prior to NGS testing. Of those patients without prior germline genetic testing, 62 (15.9%) were referred to GC, and 19 (4.9%) patients were diagnosed with a hereditary cancer syndrome. Conclusions: Tumor NGS testing identifies HRMs that may represent an undiagnosed heritable germline mutation. Providers ordering NGS tests should review results for HRMs, refer to GC when appropriate, and offer confirmatory germline testing for patients and their families. [Table: see text]
Deep learning to identify high-risk smokers for lung cancer screening from chest radiographs.
Authors: Raghu Vineet , Mayrhofer Thomas , Aerts Hugo , Hoffmann Udo , Lu Michael T 
Published: May 2020

1519 Background: Appearance on chest radiography may inform selection of high-risk smokers for lung cancer screening CT, beyond Centers for Medicare & Medicaid Services (CMS) eligibility criteria. Methods: A convolutional neural network (CXR-LC) predicting 12-year incident lung cancer from the chest radiograph image, age, sex, and smoking status (current/former) was developed in 41,856 persons aged 55-74 from the Prostate, Lung, Colorectal & Ovarian trial (PLCO). The final model was tested in held-out smokers from PLCO (n=5,615, 37.9% CMS eligible, 12-year follow-up), and externally in the National Lung Screening Trial (NLST, n=5,493, all CMS eligible, 6-year follow-up). Sensitivity was compared at a fixed screening population size defined by CMS eligibility. Ordinal CXR-LC risk score (low/indeterminate/high/very high) was based on development dataset 12-year probability thresholds (<2%/2-<3.3%/3.3-<8%/≥8%). Results are provided in test datasets only. Results: In the PLCO test dataset, CXR-LC was more sensitive than CMS eligibility at a fixed screening population size (74.9% vs. 63.8%, p=0.01) and missed 30.8% fewer lung cancers. CXR-LC risk groups were associated with incident lung cancer in PLCO test dataset smokers (very high vs. low CXR-LC risk: 12.4 vs 1.1 lung cancers/1,000 person-years) with external testing in NLST (all CMS eligible: 12.7 vs 2.3) (Table). This association was robust to adjustment for radiologist findings and the PLCOm2012 risk score. Conclusions: CXR-LC identified smokers at high risk of incident lung cancer, beyond CMS eligibility. [Table: see text]
Comparing and assessing the reported penetrance of cancer susceptibility genes for breast cancer.
Authors: Yin Kanhua , Braun Danielle , Tiwari Ankur , Wang Jin , Singh Preeti , Zhou Jingan , Parmigiani Giovanni , Hughes Kevin S. 
Published: May 2020

1520 Background: It is critical for oncologists to be aware of unbiased and interpretable cancer risks (i.e., penetrance) in carriers with germline pathogenic variants in cancer susceptibility genes. However, relevant literature is large and varies significantly in study design, patient ascertainment, and types of risk estimates reported. This heterogeneity can cause inconsistent conclusions between studies and create barriers for clinicians to understand and apply them in practice. To further understand the current literature, we assessed penetrance studies associated with non-BRCA breast cancer susceptibility genes based on study design and ascertainment adjustment. Methods: We used a validated natural language processing-based abstract classifier to identify all penetrance studies regarding eleven genes: ATM, BARD1, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11, and TP53. Relevant studies were then manually annotated as “with ascertainment adjustment” if a study was based on: (1) a general population; (2) a pedigree analysis or a family-based study with appropriate ascertainment adjustment; or (3) a hospital-based study or a panel testing analysis with well-matched cases and controls. Results: A total of 49 penetrance studies were identified, with a median of nine studies for each gene (range: 4-16). The case-control study was the dominant study type, accounting for over 80% in five genes, 50% in two genes, and 18% to 43% in the other four genes. The proportion of studies with ascertainment adjustment was generally low (mean: 33%) and varied widely between different genes (7% to 80%). Contradictory breast cancer risks (no increased risk vs. significantly increased risk) were found in eight genes (73%) (Table). The most common ascertainment bias identified was a case-control study with cases (patients) who had a strong family history but using general population controls. Conclusions: Ascertainment bias is common in penetrance studies, but few studies adjust for it appropriately. Clinicians should be aware of this issue, and new methods are warranted to select unbiased risk estimates, synthesize them, and provide the accurate general-population penetrance. [Table: see text]
BRCA testing concordance with national guidelines for patients with breast cancer in community cancer programs.
Authors: Boehmer Leigh , Shivakumar Latha , Weldon Christine B. , Trosman Julia Rachel , Cohen Stephanie A. , Nixon Dawn , Ali-Khan Catts Zohra , Miesfeldt Susan , Wiryaman Stephanie , Tafra Lorraine , Muto Lisa , Fadrowski Natalie , Hulvat Melissa , Pallister Tiana , Shelton Charles Hendrix 
Published: May 2020

1526 Background: Current National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment state that testing for highly penetrant breast/ovarian cancer genes is clinically indicated for women with early onset (≤ 45 years) or metastatic HER-2 negative breast cancer. A recent Association of Community Cancer Centers (ACCC) survey (N = 95) showed that > 80% of respondents reported ≤ 50% testing rate of patients with breast cancer who met guidelines. Given this disconnect, ACCC partnered with 15 community cancer programs to assess practice gaps and support interventions to improve access to genetic counseling (GC)/testing. Methods: Pre-intervention data from 9/15 partner programs for women diagnosed with stages 0-III breast cancer between 01/01/2017 and 06/30/2019 was collected. De-identified variables included: family history documentation, GC appointment/test results, and timing of results relative to treatment decisions. Results: There were 2691 women with stages 0-III breast cancer. Forty-eight percent (1284/2691) had a documented high-risk family history, 57% (729/1284) of whom had a GC appointment. This was a significantly higher rate of GC compared to the 23% (181/778) of women with no family history and 6% (35/629) of women with no documentation of family history (p < 0.0001). Patients ≤ 45 years old attended a GC appointment 72% (199/278) of the time and 49% (135/278) had genetic test results, with 84% (113/135) receiving results before surgery. For women with test results available before surgery, 37% (119/322) had breast conserving surgery, compared to 60% (144/240) with test results disclosed post-operatively (p < 0.0001). Conclusions: Genetic testing is underutilized in a community cohort of women with breast cancer. Further analysis is needed to understand the impact genetic test results have on surgical decisions. Opportunities exist to improve current rates of appropriate GC/testing. ACCC will share results of quality improvement projects to illuminate which strategies hold promise in reducing the hereditary breast cancer GC/testing practice gap.
A single-institution and commercial laboratory database analysis of BRIP1-associated cancer risks.
Authors: Whitaker Kristen Danielle , Bernhisel Ryan , Kidd John , Hughes Elisha , Rosenthal Eric Thomas , Hall Michael J. 
Published: May 2020

1538 Background: BRIP1/ FANCJ participates in DNA replication and repair via interactions with BRCA1 and possibly MLH1. Previous studies have reported that pathogenic variants (PV) in BRIP1 are associated with an ~2-fold increase in risk for ovarian cancer (OC) and triple-negative breast cancer (TNBC). Although multigene panel testing for hereditary cancer (CA) has identified BRIP1 PV and uncertain variants (VUS) in patients with diverse CAs including breast (BC), colorectal (CRC) and melanoma (Mel), association with these CA types has not been established. Methods: We examined BRIP1 risks in two independent populations: Fox Chase Cancer Center (FCCC) and Myriad Genetics (MGL). At FCCC, pedigrees of BRIP1 PV ( N= 10) and VUS families ( N= 47) were reviewed. The MGL population included patients referred for testing by multigene panel (9/2013-12/2019) ( N= 586,740). Multivariable logistic regression analysis estimated BRIP1 CA risks as odds ratios (ORs) and 95% confidence intervals (CIs). Models were adjusted for age, sex, ancestry, personal CA history (PHX), and family CA history. Results: In the FCCC cohort, BRIP1 PV carriers ( N= 12) reported PHX of early-onset ( < 50) BC, CRC, and bladder CA. BRIP1 VUS were also identified among several patients with striking PHX and negative panel testing: BC < 40 ( N= 3), bilateral BC ( N= 4), TNBC ( N= 2), CRC < 40 ( N= 3), and a patient with 3 CAs < 40 (CRC, BC, and Mel). All FCCC families with a BRIP1 PV and select VUS families ( N= 6) are seen in the Table. In the MGL population, 0.3% (1,678/586,740) carried a BRIP1 PV. Logistic regression analyses found that female BRIP1 PV carriers have significantly increased risk for OC (OR 2.40, 95% CI 1.93-2.98) and TNBC (OR 1.93, 95% CI 1.52-2.46). Data were insufficient for testing risk of bladder or prostate CA. Findings did not support associations of BRIP1 with CRC, melanoma, endometrial, pancreatic or gastric CA. Conclusions: BRIP1 PV and VUS may be identified in patients with diverse CA histories. These results confirm studies showing that BRIP1 PV are associated with an ~2-fold increased risk of OC and TNBC, but do not support increased risks of CRC, melanoma or endometrial CA in BRIP1 PV carriers. [Table: see text]