bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration and feasibility of symptom burden assessment and early palliative care into an adolescent and young adult leukemia clinic.
Authors: Wang Amy Yuan , Hoehn Karen Sarah , Hanson Collin , Monick Sarah , Hlubocky Fay J. , McNeer Jennifer Lynn , Henderson Tara O. , Stock Wendy , Daugherty Christopher
Published: June 2021

10052

Background: Patients (pts) diagnosed with hematologic malignancies during adolescence & young adulthood (AYA) are a uniquely challenging population who are understood to have robust supportive care needs. Here, we describe their symptom burdens and the feasibility of integrating palliative care into an outpatient, multi-disciplinary AYA leukemia clinic at an academic medical center. Methods: Palliative care was introduced into the AYA clinic in 8/2020 to provide symptom-focused care. Pre-existing clinic services included psychologists, pharmacists, and social workers. All established pts receiving routine follow up were referred by the oncology team to the Supportive Care team, which provided same-day palliative care consultation in the same clinic space with a telehealth option and as needed follow-up. To describe baseline symptom burdens, a random cross-sectional sample of pts completed a multi-domain symptom assessment (SA) using validated self-report instruments including physical (Edmonton Symptom Assessment Scale [ESAS]); emotional (Brief Symptom Inventory-18 [BSI-18]); financial (FACIT-COST); cognitive (Childhood Cancer Survivor Study – Neurocognitive Questionnaire); spiritual (FACIT -Spiritual Well-being Scale); and quality of life (QOL) (FACT-General) measures. All pts have a diagnosis of acute or chronic leukemia and were on active treatment or in survivorship. Results: Over 6 months, 30 pts (median age 29 years at assessment, range 18-45 years) received symptom-focused palliative care over 16 combined clinics with 81 total encounters averaging 5 pts (range 1-8) per clinic. 47% were female. No pts declined palliative care. Pts received on average 2.7 follow up visits (range 1-6), with 50% of encounters resulting in adjustments to medical management. Common issues addressed included pain, muscle cramps, neuropathy, anxiety, insomnia, depression, nausea, and non-pharmacological symptom control remedies. Of 46 pts, 31 (67%) completed the SA (median age 30 years at assessment, range 18-43 years); 48% were female; 84% were on treatment. 100% of pts reported fatigue, and 48% reported > = 1 severe symptom (range 0-7) based on the ESAS with “poor feeling of well-being” as the most common (23%). 45% met criteria for BSI-18 emotional distress, and 45% reported some neurocognitive impairment. Emotional distress (p < 0.01), financial toxicity (p = 0.03), low spiritual well-being (p < 0.01), and presence of pain, nausea, or depression (p < 0.05) were all associated with lower QOL. Conclusions: AYA pts with leukemia undergoing treatment and in survivorship experience high symptom burden with poor QOL. It is feasible to both assess symptom burden and provide early palliative care focused on symptom management in an outpatient, multi-disciplinary clinic setting.
Lessons from COVID-19, challenges of remote learning for childhood cancer survivors.
Authors: Ruble Kathy , Carey Lisa , Pare-Blagoev Juliana , Milla Kimberly , Henegan Sydney , Cork Katrina , Thornton Clifton , Jacobson Lisa
Published: June 2021

10054

Background: More than half of childhood cancer survivors (survivors) will have neurocognitive deficits that impact schooling, most commonly reflecting attention and executive dysfunction. Schools are legally bound (IDEA, 2004) to support eligible students with Individualized Education Program (IEP) informed instruction and related services (e.g. assistive technology, speech-language, physical, or occupational therapy) to foster academic success. However, these service provision were not designed under the constraints of remote learning. The COVID19 shift to remote learning is likely to extend beyond the pandemic especially for medically fragile students. This quality improvement project describes challenges for survivors during remote learning and recently developed related patient education materials. Methods: Interviews with families were used to identify themes around challenges during remote learning, which informed development of a 29-question survey disseminated via flyer in local oncology clinics and social media posts by local childhood cancer organizations in Fall 2020. Results: The survey was completed by 67 parents describing their affected child (mean age= 8.6 years; 60% male; 78% White, 12% Black, 95% non-Hispanic). Most children (74%) had completed therapy (43% for leukemia, 18% for brain tumor; 39% other). The majority (86%) attended public school and 37% received special education or related services: speech-language (26%), occupational (23%), and physical (14%) therapies, and vision services (3%). Fully remote learning was reported for 73%, in-person 4%, and hybrid learning for 14%. The majority (57%) reported observing greater difficulty with attention and focus during RL, indicating difficulty occurred about half of the time during related services therapies, class and/or small group video instruction. Technology-related challenges included difficulty navigating online instruction/equipment (28%), reading difficulty (16%), and difficulty seeing materials/lack of vision supports (18%). Findings did not differ based on treatment or IEP status (p>0.50). Few (14%) reported their school team discussed assistive technology options for online learning. Parents indicated the most helpful supports for addressing challenges included speech-to-text tools, screen readers, and audio books. Parents reported their oncology team was helpful in making referrals to neuropsychology and therapies and completing documentation necessary to secure supports. Conclusions: Childhood cancer survivors, irrespective of diagnosis or IEP status, report challenges with remote learning. Families find a lack of information or special accommodations as roadblocks to success. Oncology providers were identified as valued resources, so educational materials ( https://tinyurl.com/nxbhj5or ) were developed for oncology teams to share with families.
Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.
Authors: Sharifi Nima , Kruse Megan Lynn , McManus Jeffrey , Chung Yoon-Mi , Wei Wei , Bazeley Peter , Nakamura Fumihiko , Hardaway Aimalie , Downs Kelley Erinn , Chandarlapaty Sarat , Thomas Mathew , Moore Halle C. F. , Budd George Thomas , Tang Wai Hong Wilson , Hazen Stanley L. , Bernstein Aaron , Nik-Zainal Serena , Abraham Jame
Published: June 2021

10503

Background: Genetic factors that contribute to endogenous estrogen synthesis and postmenopausal breast cancer risk are unknown. We set out to test the hypothesis that homozygous inheritance of the common 1245A→C missense-encoding polymorphism in HSD3B1, which is common (8-10%) in White populations, functionally adrenal permissive and increases synthesis of the aromatase substrate, androstenedione, is associated with postmenopausal estrogen receptor-positive breast cancer. Methods: A prospective single institution study of postmenopausal estrogen receptor-driven breast cancer for determination of HSD3B1 genotype, circulating steroid concentrations, and adrenal-permissive genotype frequency compared with the genotype frequency in the general population and in estrogen receptor-negative breast cancer. Validation was performed in 2 breast cancer genomic studies with estrogen receptor documentation. The primary outcome is the adrenal-permissive genotype frequency in postmenopausal estrogen receptor-positive breast cancer and the general population. Genotype comparisons were also done with postmenopausal estrogen receptor-negative breast cancer and the association with circulating adrenal androgen concentrations determined. Results: The prospective and validation studies had 199 and 1628 women, respectively. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 9.6% (429/4451) in the general population [p = 0.0077]. The adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using the Cambridge and TCGA genomic datasets together: 14.4% (56/389) compared with 6.0% (9/149) for estrogen receptor-negative breast cancer (p = 0.007) and the general population (p = 0.005). Circulating androstenedione concentration was significantly higher for women with the adrenal-permissive genotype compared with the other genotypes (p = 0.03). Conclusions: The adrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer and have broad implications for risk stratification, prevention, potential biomarkers for hormonal therapy response and possibly other clinical outcomes related to estrogen physiology in postmenopausal women.
Correlation between work productivity loss (WPL) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) domains from the MONALEESA-7 (ML-7) trial of premenopausal women with HR+/HER2- advanced breast cancer (ABC).
Authors: Tripathy Debu , Curteis Tristan , Hurvitz Sara A. , Yardley Denise A. , Franke Fabio , Kanakasetty Govind Babu , Wheatley-Price Paul , Im Young-Hyuck , Pencheva Radost , Chandiwana David , Pathak Purnima , Lanoue Brad , Harbeck Nadia
Published: June 2021

1051

Background: The international, randomized, double-blind, placebo-controlled, Phase III ML-7 trial (NCT02278120) assessed ribociclib + endocrine therapy (ET) vs ET alone in premenopausal women with HR+/HER2– ABC. To our knowledge, the relationship between WPL and domains of the EORTC QLQ-C30 and the tumor-specific module for breast cancer (QLQ-BR23) has not been explored in ABC. In this post hoc analysis (data cutoff, November 30, 2018) of all patients (pts) enrolled in ML-7, we assessed the correlation between the WPL component of the Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire and domains of the EORTC QLQ-C30/BR23. Methods: We analyzed EORTC and WPAI:GH data from all pts enrolled in ML-7 who were employed at any point during the trial (N = 329 of 672 total pts). Domains of the EORTC QLQ-C30 and QLQ-BR23 that had the greatest correlation (pairwise Pearson correlation) with WPL were prioritized for analysis. Separate univariable mixed-model repeated-measures regression models were fitted for each domain, with WPL as the dependent variable and each EORTC domain as a single fixed-effect covariate. Linear and quadratic relationships were considered. Model selection was based on the Akaike information criterion (AIC). Results: Linear models were favored over quadratic models. WPL was negatively correlated with global health status (GHS) and the physical, role, social, and emotional functioning domains and was positively correlated with the fatigue and pain domains of the QLQ-C30 ( P <.001; Table). The coefficients indicated the estimated mean change in WPL was associated with a 1-unit increase in each QLQ-C30 domain. For example, a 10-point increase in GHS was associated with an estimated mean decrease of 7.8% (95% CI, 7.1%-8.5%) in WPL. Conclusions: Greater WPL was associated with higher levels of fatigue and pain and with lower levels of overall quality of life and physical, role, social, and emotional functioning among pts with HR+/HER2− ABC in ML-7. Further investigation of the correlation with QLQ-BR23 and multivariable analysis could determine which EORTC domains and items independently drive these findings. Clinical trial information: NCT02278120 .[Table: see text]
Limitations of direct-to-consumer (DTC) genetic testing for hereditary breast and ovarian cancer.
Authors: Desai Neelam Vijay , Barrows Elizabeth Dominic , Nielsen Sarah M. , Hatchell Kathryn E. , Esplin Edward D. , Tung Nadine M. , Isaacs Claudine
Published: June 2021

10515

Background: With the advent of DTC genetic testing, individuals have access to genetic testing without input from a healthcare professional. DTC testing now exists for the 3 Ashkenazi Jewish (AJ) BRCA1/2 founder variants. DTC testing may provide false reassurance to individuals that they do not carry a pathogenic or likely pathogenic variant (PLPV) in BRCA1/2 or other cancer-risk genes. Methods: Multi-panel genetic testing was performed in 348,692 individuals for a clinical indication of hereditary breast/ovarian cancer (Clinical cohort) and 7,636 self-referred ostensibly healthy individuals (Healthy cohort) by a clinical testing laboratory. The primary analysis evaluated PLPVs for Group 1 genes: BRCA1/2 AJ founder variants and Group 2: full sequence BRCA1/2. Secondary analyses assessed PLPVs in Group 3: high-risk breast cancer genes ( BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53), Group 4: all breast or ovarian cancer-risk genes (Group 3 genes plus ATM, BARD1, BRIP1, truncating CHEK2, EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D) and Group 5: 41 cancer-risk genes; these analyses were limited to participants who tested for all 41 genes. Potentially mosaic variants were excluded. Results: Table illustrates PLPVs found in both cohorts. The BRCA1/2 AJ founder variants account for only ̃11% (1513/13,987) and ̃30% (19/64) of the BRCA PLPVs in the Clinical and Healthy cohorts, respectively. Even among AJ individuals, testing only for the 3 founder variants will miss ̃10% (52/513) of all BRCA1/2 PLPVs. Evaluating only the BRCA AJ founder variants missed a higher percentage of PLPVs in other cancer-risk genes. Conclusions: The 3 BRCA1/2 AJ founder variants analyzed by DTC testing account for a small fraction of PLPVs in cancer-risk genes in the general population, and miss 10% of BRCA PLPVs even among AJ individuals. Greater public education is needed to dispel the misconception that DTC tests are equivalent to clinical assessment and comprehensive genetic testing. PLPVs identified in Clinical and Healthy Cohorts.[Table: see text]
Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.
Authors: Lavery Jessica A , Brown Samantha , Riely Gregory J. , Bedard Philippe L. , Park Ben Ho , Warner Jeremy Lyle , Kehl Kenneth L. , Lepisto Eva M , Rizvi Hira , LeNoue-Newton Michele , McCarthy Caroline G. , Yu Celeste , Kundra Ritika , Mastrogiacomo Brooke , Schultz Nikolaus , Rudolph Julia Elizabeth , Sweeney Shawn , Schrag Deborah , Panageas Katherine ,   AACR GENIE Consortium
Published: June 2021

10535

Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]
Identification and characterization of de novo TP53 mutation carriers in Li-Fraumeni syndrome families: A single institution experience.
Authors: Vera Recio Carlos Christian , Corredor Jessica , Dodd-Eaton Elissa , Gutierrez-Barrera Angelica M. , Daw Najat C. , Arun Banu , Wang Wenyi
Published: June 2021

10538

Background: Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome mainly caused by a deleterious mutation in TP53. An estimated 48% of LFS patients present due to a deleterious de novo mutation (DNM) in TP53. The knowledge of DNM status, DNM or familial mutation (FM), of an LFS patient requires genetic testing of both parents which is often inaccessible, making de novo LFS patients an understudied population. Famdenovo.TP53 is a Mendelian Risk prediction model used to predict DNM status of TP53 mutation carriers based on the cancer-family history and several input genetic parameters, including disease-gene penetrance. The good predictive performance of Famdenovo.TP53 was demonstrated using data collected from four historical US cohorts. We hypothesize that by incorporating penetrance estimates that are specific for different types of cancers diagnosed in family members, we can develop a model with further improved calibration, accuracy and prediction. Methods: We present Famdenovo.CS, which uses cancer-specific penetrance estimates that were derived previously using a Bayesian semi-parametric competing risk model, to calculate the DNM probability. We use our model to analyze 101 families recently collected from the Clinical Cancer Genetic program at MD Anderson Cancer Center (CCG-TP53) that includes 20 families with known DNM status and 81 families with unknown DNM status. We used the concordance index (AUC), observed:expected ratios (OE) and Brier score (BS) to measure our model’s discrimination, calibration and accuracy, respectively. We estimate the proportion of probands that present a DNM and compare DNM to FM carriers in several areas including: cancer types diagnosed, age at diagnosis, number of primary cancers diagnosed, sex, amino acid change caused by mutation in TP53. Results: Famdenovo.CS showed equally good discrimination and calibration performance to Famdenovo.TP53, while improving the overall accuracy, demonstrated by a decrease in the Brier score of -0.09 (95% CI: [-0.02, -0.19]). Of the 101 probands in the CCG-TP53 cohort, we predict 39 to be DNMs and 62 to be FMs. The cancer types and ages of diagnosis observed in FMs and DNMs are similarly distributed. Conclusions: Famdenovo.CS shows improved model accuracy in the CCG cohort. DNMs in TP53 are a prevalent cause of LFS and we did not find differences in the clinical characteristics of DNM and FM carriers. Our model allows for a systematic identification and characterization of TP53 DNM carriers.
TNF-alpha immunosuppressive use and future malignancy risk.
Authors: Driscoll Conor , O'Shea Kaitlyn , Zhang Hui , Rich Jordan , Yang Christopher , Isaacson Dylan , Li Eric , Siddiqui Mohammad , Kundu Roopal , Schaeffer Edward M. , Kundu Shilajit ,   TNF Alpha ASCO 2021
Published: June 2021

10558

Background: Tumor Necrosis Factor Alpha (TNF-a) inhibitors suppress the immune system in patients with systemic inflammatory conditions. Long term data assessing future cancer risk for these patients is not known. We assessed long term risk of malignancy in patients with Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Psoriasis [PS], and Ankylosing Spondylitis [AS], who were or were not exposed to a TNF-a inhibitor. Methods: This was a retrospective, cohort study conducted using electronic medical record data for patients with complete demographic and treatment data at Northwestern Medicine from years 1998 to 2020 (RA: n = 10763; IBD: n = 12106; PS: n = 1920; AS: n = 5103). Inverse Probability of Treatment Weighting (IPTW) was used to balance the distributions of age, race, gender, smoking status, and follow-up time across exposure groups within each inflammatory condition type. Relative risk (RR) of malignancy based on TNF-a exposure was assessed using logistic regression. Results: 2583 (24.0%) of RA, 2185 (18.0%) of IBD, 1811 (94.3%) of PS, 572 (11.2%) of AS patients had TNF-a exposure. Median follow-up for patients was 43 months. The RR for any cancer was higher for patients exposed to a TNF-a agent with rheumatoid arthritis (RR 1.121 (95% CI 1.02-1.23, p = 0.015) and psoriasis (RR 1.763 (95% CI 1.32-2.37, p < 0.001). The relative risk of any cancer was lower in patients exposed to a TNF-a agent with IBD (RR 0.858 (95% CI 0.78-0.94, p = 0.001). No significant difference in relative risk associated with TNF-a exposure was detected with ankylosing spondylitis (RR 0.929 (95% CI 0.8-1.08, p = 0.344). Conclusions: Patients with RA or PS and TNF-a exposure had higher RR of overall malignancy. Patients with IBD and TNF-a exposure had lower risk of overall malignancy. TNF-a immunosuppression may alter cancer risk differently based on the disease states for which it is being used. This information is critical when counseling patients on long term risk and screening strategies when considering TNF-a inhibition.
Young patients with cancer related to modifiable behaviors in the United States: What can we learn from them?
Authors: Chan John , Caesar Michelle Ann P. , Chan Chloe , Richardson Michael , Kapp Daniel Stuart , Francoeur Alex Andrea , Liao Cheng-I
Published: June 2021

10560

Background: We proposed to examine trends in modifiable behaviorally related cancers among younger men and women in the United States. Methods: Alcohol-associated cancers, HPV-associated, obesity-associated, physical inactivity-associated, and tobacco-associated were defined using ICD-O-3 site codes. From 2001 and 2017, registry data were obtained from the United States Cancer Statistics database. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate the trends of associated cancers expressed per 100,000. Results: Of the young women (ages 20-49 years) the incidence of cancers in 2017 associated with alcohol, smoking and obesity were 89/100,000, 43/100,000 and 64/100,000 respectively. Based on analysis of trends of women from 2001 to 2017, obesity, physical inactivity and alcohol related cancers increased with an annual percent change (APC 2.31%, 1.67%, 0.46%, p < 0.001). Using a projection model, in Hispanic women, obesity related cancers will become the highest incidence cancers by 2035, surpassing alcohol and physical inactivity. Of the young men (ages 20-49 years) the incidence of cancers in 2017 associated with alcohol, obesity, and tobacco were 23/100,000, 36/100,000 and 44/100,000 respectively. On trends analysis, obesity, physical inactivity, and alcohol related cancers have increased (APC 2.0%, 1.65%, 0.17%, p < 0.001, p < 0.001, p = 0.044), whereas tobacco-related cancers are decreasing with an APC of -0.44% (p < 0.001). When examining different regions, the highest APC for obesity and physical inactivity related cancers was 2.43% in the Midwest (p < 0.001). Using a prediction model, obesity is predicted to surpass alcohol and physical inactivity related cancers for men 20-49 years old by 2035. Conclusions: In women, most modifiable factors associated with cancer are increasing except in HPV related cancers. In men, these rates of cancer are increasing except in tobacco related cancers. However, rates of obesity related cancers are on the rise in Hispanic women and younger men in southern U.S. regions. Obesity is projected to become the major modifiable factor for many associated cancers.
Rate of incidental germline findings detected by tumor-normal matched sequencing in cancer types lacking hereditary cancer testing guidelines.
Authors: Yap Timothy A. , Ashok Arya , Stoll Jessica , Schwarzbach Anna Ewa , Blackwell Kimberly L. , Li Tianhong , Kang Hyunseok , Garber Judy Ellen , Meric-Bernstam Funda
Published: June 2021

10582

Background: Up to 10% of all cancers are associated with hereditary cancer syndromes; however, guidelines for germline testing are currently limited to patients and families with specific cancer types (ovarian, breast, prostate, pancreatic, etc.). Although germline alterations have been shown in genes associated with cancers such as bile-duct, head & neck, brain, bladder, esophageal, and lung cancers, genetic testing is not routinely offered (PMID: 28873162). In such cancers, a guidelines-based approach may fail to detect cancer risk variants found by tumor-normal (T/N) matched sequencing. Here, we report the prevalence of incidental germline findings in patients with the aforementioned 6 cancer types and highlight frequently mutated genes by cancer type. Methods: We retrospectively analyzed next-generation sequencing data from de-identified records of 19,630 patients tested using Tempus|xT T/N matched assay. Incidental germline findings (i.e., single nucleotide variants and small insertions/deletions) detected in 50 hereditary cancer genes were determined for: bile duct (n = 466), head & neck (n = 673), esophageal (n = 395), brain (n = 1,391), bladder (n = 810), and lung (n = 5,544), where n = total patients. For comparison, we also included 4 cancer types that frequently undergo germline testing: ovarian (n = 2,042), breast (n = 3,542), prostate (n = 2,146), and pancreatic (n = 2,621). Results: We detected incidental pathogenic/likely pathogenic germline variants (P/LPV) in 6.5% (601/9,279) of patients diagnosed with the 6 selected cancer types lacking hereditary cancer testing guidelines. The highest prevalence of P/LPV was identified in patients with bladder (8%), brain (6.9%), and lung (6.5%) cancers. Frequently mutated genes (Table) include ATM (n = 62), BRCA2 (n = 60), BRCA1 (n = 33), APC (n = 27), and CHEK2 (n = 21). Of note, the Ashkenazi Jewish variant (p.I1307K) was the most frequent mutation in APC. For cancer types where patients frequently undergo germline testing, the rates of incidental germline findings in descending order were ovarian (15%), breast (12%), prostate (9.4%), and pancreatic (8.5%) cancers. Conclusions: In addition to enhanced variant calling, T/N matched sequencing may identify germline variants missed by a guidelines-based approach to testing. The identification of such germline findings may have clinical implications for the patient, as well as at-risk family members, thereby resulting in the opportunity for genetic counseling and risk-stratified intervention.[Table: see text]
An evaluation of gender discrepancies in genetic referrals for BRCA testing for indicated malignancies.
Authors: Smith Wesley , Smith Kayla , Sessions William , Evins Connor , Baker Michael , Blumer Mary
Published: June 2021

10584

Background: Tumor suppressing genes BRCA1 and BRCA2 were discovered in 1990 and 1994, respectively, with mutations linked to hereditary breast-ovarian cancer syndromes (HBOCs). The discovery of these mutations has led to screening of at-risk patient populations and their family members. Women with BRCA1 or BRCA2 mutations are generally recommended to have prophylactic bilateral mastectomies and oophorectomies to decrease their future risk of cancer. While the initial discovery mostly focused on cancers in women, research has shown that BRCA mutations increase the risk of other cancers such as prostate cancer and pancreatic cancer, that also affect men. Previous research suggests that men are three times less likely to receive genetic testing in cancer driven by a 10:1 disparity in HBOC genetic testing. This was thought to be due to the lack of information on the importance of HBOC testing along with social roles in health. We wanted to evaluate the magnitude of the potential gender gap in BRCA testing in men compared to women. Methods: This was an IRB-approved, single center retrospective study to evaluate the rate of referrals to genetics for BRCA testing. Eligible patients had a personal history of cancer meeting criteria for BRCA testing per NCCN recommendations. Chart review was performed for patients with ovarian cancer, female breast cancer 45 years and younger, female triple negative breast cancer 60 years and younger, metastatic prostate cancer, all male breast cancer that have made an office visit since 2017, and pancreatic cancer since 2019. Rates of referral for genetic testing was the primary outcome and the groups were compared via the Chi-Square test. Results: 1,320 patients were included in the study, of which 664 were men and 656 were women. 128/664 (19.3%) of men were referred to genetics for screening compared to 527/656 (80.3%) for women ( p <.001). Additionally, 42/128 (32.8%) men who were referred for screening did not complete genetic screening compared to 72/527 (13.7%) women ( p <.001). A total of 62/541 (11.5%) patients who completed screening had either a BRCA1 or BRCA2 mutation. Conclusions: In our study, men were referred for BRCA testing significantly less than women for primary cancers, despite recommendation from the NCCN. In addition, men were also more than twice as likely not to complete genetic screening even if referred. The integration of genetics and oncology will continue to grow as personalized medicine continues to drive more treatment options. Closing this gender gap is important not only for familial screening purposes but also for treatment implications as patients with germline BRCA mutations are eligible for poly ADP ribose polymerase (PARP) inhibitors (e.g. olaparib) in both metastatic prostate cancer and pancreatic cancer. Further quality improvement initiatives are needed in order to close this gap by increasing education of the importance of BRCA testing in men.
Compliance with germline testing in pancreatic cancer in a rural tertiary care hospital.
Authors: Travaline Catherine , Elliott Leighton Andrew , Ramdin Nadia N. , Vadakara Joseph
Published: June 2021

10599

Background: Pancreatic cancer is the 7th most common cause of cancer death worldwide and is projected to be the second leading cause of cancer death in the next decade. Personalized care is becoming more of a reality with pharmacological regimens targeting specific genetic mutations. In March 2019, the National Comprehensive Cancer Network (NCCN) guidelines were updated to recommend germline testing (GT) in all patients with pancreatic adenocarcinoma (PDAC) considering 1 in 10 may have a germline mutation (GM). The goal of this study was to quantify compliance with these recently updated guidelines. Methods: The electronic medical records and survivorship data of all patients diagnosed with PDAC between January 1, 2017 and October 1, 2020 were reviewed. April 1, 2019 was used as the transition point (TP) for guideline updates. Descriptive statistics for all variables were determined. The rate of ordered referrals to genetic counseling (GC), as well as completion rate, was calculated. Results: A total of 304 patients were diagnosed with PDAC during the study period (223 prior to the TP). A total of 54 patients were referred for GC and 41 had GT ordered. The rate of GC referrals ordered after the TP was significantly higher than before the TP (22/81, 26.6% vs. 32/223, 14.4%; p-value 0.010). Almost 60% of patients who had genetic evaluation had private insurance. The patients who completed GT were significantly more likely to have a documented family history of cancer (61.0% vs 4.2%; p-value <.0001Patients who completed GT had more problems on their problem list (median 10 vs 7, p = 0.001). The median overall survival (OS) for all patients in the study was 7.8 months (95% CI: 6.3-9.8). Conclusions: Overall compliance with the updated NCCN guidelines significantly improved; however, it was below 25%. This study showed that there may be some lingering bias toward GT in PDAC solely for those who have a family history of cancer. Although patients with stage IV PDAC have poor outcomes, GT may still improve surveillance for family members. The approval of olaparib in patients with BRCA1/2 mutations based on the POLO trial is likely to increase provider compliance as it provides a viable maintenance strategy in these patients. Patient complexity was unlikely to affect GT rate. Assessment of provider awareness was outside the scope of this study. There is need for continued advocacy for awareness and implementation of guidelines that highlight the importance of germline evaluation on prevention, surveillance, and treatment in pancreatic adenocarcinoma.
Real-world quality of life (QoL) in black, indigenous and people of color (BIPOC) treated with palbociclib (PAL) and endocrine therapy for hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): A subgroup analysis from POLARIS.
Authors: Rocque Gabrielle Betty , Blum Joanne Lorraine , Montero Aldemar , Karuturi Meghan Sri , Manning Kenneth , Shabazz Lloyd , Gallagher Christopher , Zuberi Lara , Cappelleri Joseph C , Drucker Marc , Wang Yao , Tripathy Debu
Published: June 2021

1071

Background: Racial disparities in breast cancer incidence, mortality, and care are well documented. PAL plus endocrine therapy is indicated for patients (pts) with HR+/HER2− ABC. Findings from the PALOMA clinical trials have shown that pts receiving PAL maintained stable QoL; however, limited QoL data are available from real-world settings for BIPOC receiving PAL. Methods: POLARIS is a noninterventional, prospective, primarily US-based study in pts with HR+/HER2– ABC receiving PAL. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline, monthly for the first 3 mo of treatment (Tx) with PAL, and then every 3 mo. In this interim analysis, we report Tx patterns and QoL assessments at baseline and at 6 mo and 12 mo in BIPOC from POLARIS. Results: Of 1280 pts treated with PAL as November 10, 2020, 233 were included in the BIPOC subgroup of whom 159 (68.2%) completed PAL Tx for ≥6 mo and 112 (48.1%) for ≥12 mo. In the BIPOC cohort, 59.2% of pts were black, 35.2% Hispanic, 3.4% American Indian or Alaskan native, 2.1% Pacific Islander. PAL in combination with letrozole/anastrozole was received by 116 pts, 94 received PAL plus fulvestrant, 13 received PAL plus exemestane, and 10 received PAL plus another Tx; 175 pts (75.1%) received PAL as first-line Tx. Mean EORTC QLQ-C30 global health QoL and functional scales scores remained stable over the first 12 mo of PAL Tx, without any changes at or above the 10-point threshold considered clinically meaningful, and were similar to those previously reported in an earlier analysis of the entire POLARIS population (Table and Rocque et al SABCS 2019). Symptom scales scores, including nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea, also remained stable over 12 mo. Conclusions: In this subgroup analysis, PAL had no significant adverse impact on QOL in BIPOC with HR+/HER2– ABC, consistent with previous findings from the total POLARIS study population. Pfizer (NCT03280303). Clinical trial information: NCT03280303 .[Table: see text]
A phase Ib study of TQB2450 plus anlotinib in patients with advanced triple-negative breast cancer.
Authors: Wang Jiayu , Xu Binghe , Sun Tao , Ouyang Quchang , Han Yiqun , Li Qing , Zhang Pin , Ma Fei , Luo Yang , Fan Ying , Cai Ruigang , Li Qiao , Lan Bo , Mo Hongnan , Wang Jiani , Li Yiqun
Published: June 2021

1074

Background: TQB2450 is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib is an antiangiogenic small molecule, multi-target tyrosine kinase inhibitor that has improved clinical outcomes in various solid tumors. This phase 1b study aims to evaluate the safety and efficacy of TQB2450 plus anlotinib for patients with advanced triple-negative breast cancer (TNBC) after the failure of standard therapy. Methods: This ongoing study included a dose-escalation phase and an expansion phase. Advanced TNBC patients with prior anthracyclines and/or taxanes treatment and failed at least first-line therapy were enrolled. In the dose-escalation phase, eligible patients received anlotinib (8mg, 10mg, and 12mg, qd, days 1-14; 21 days per cycle) plus TQB2450 (1200mg, day 1; 21 days per cycle) following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to ≥2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase, eligible patients were enrolled into the expansion cohort. The primary endpoint was objective response rate (ORR), and the secondary endpoints were overall survival (OS), disease control rate (DCR), progression-free survival (PFS), and safety. Results: Between May 29, 2019, and December 31, 2020, in the dose-escalation phase, three patients receiving 10mg anlotinib plus 1200mg TQB2450 had no DLTs in the first cycle, neither did three patients with 12mg anlotinib plus TQB2450. Next, 28 patients with advanced TNBC received 12 mg anlotinib plus TQB2450 in the expansion phase. Finally, a total of 34 patients were included with median age of 49.5 (32-70) and median prior lines of 2 (1-6). Numbers of patients with prior platinum therapy: 16, prior anthracycline therapy: 32. The ORR was 26.47% (9/34) and DCR was 82.35% (28/34). The median PFS was 8.57 months. Seventeen patients experienced grade 3 treatment-related AEs (TRAEs). Most frequently occurring (>5%) grade 3 TRAEs were QT interval prolongation (17.65%), hypertension (14.71%), diarrhea (8.82%), hand-foot syndrome (HFS) (8.82%), and hypertriglyceridemia (5.88%). Conclusions: TQB2450 plus anlotinib showed an acceptable safety profile with promising activity for previously anthracyclines and/or taxanes-treated advanced TNBC patients. Clinical trial information: NCT03855358 .[Table: see text]
Control arm heterogeneity in trials for unselected advanced triple-negative breast cancer (aTNBC).
Authors: Gala Kinisha , Kalucha Ankit , Martinet Samuel , Goel Anushri , Narisetty Kalpana Devi , Larvol Bruno , Punie Kevin
Published: June 2021

1082

Background: Primary endpoints of clinical trials frequently include subgroup-analyses. Several solid cancers such as aTNBC are heterogeneous, which can lead to unpredictable control arm performance impairing accurate assumptions for sample size calculations. We explore the value of a comprehensive clinical trial results repository in assessing control arm heterogeneity with aTNBC as the pilot. Methods: We identified P2/3 trials reporting median overall survival (mOS) and/or median progression-free survival (mPFS) in unselected aTNBC through a systematic search of PubMed, clinical trials databases and conference proceedings. Trial arms with sample sizes ≤25 or evaluating drugs no longer in development were excluded. Due to inconsistency among PD-L1 assays, PD-L1 subgroup analyses were not assessed separately. The primary aim was a descriptive analysis of control arm mOS and mPFS across all randomized trials in first line (1L) aTNBC. Secondary aims were to investigate time-to-event outcomes in control arms in later lines and to assess time-trends in aTNBC experimental and control arm outcomes. Results: We included 33 trials published between June 2013-Feb 2021. The mOS of control arms in 1L was 18.7mo (range 12.6-22.8) across 5 trials with single agent (nab-) paclitaxel [(n)P], and 18.1mo (similar range) for 7 trials including combination regimens (Table). The mPFS of control arms in 1L was 4.9mo (range 3.8-5.6) across 5 trials with single-agent (n)P, and 5.6mo (range 3.8-6.1) across 8 trials including combination regimens. Control arm mOS was 13.1mo (range 9.4-17.4) for 3 trials in first and second line (1/2L) and 8.7mo (range 6.7-10.8) across 5 trials in 2L and beyond. R2 for the mOS best-fit lines across control and experimental arms over time was 0.09, 0.01 and 0.04 for 1L, 1/2L and 2L and beyond, respectively. Conclusions: Median time-to-event outcomes of control arms in 1L aTNBC show considerable heterogeneity, even among trials with comparable regimens and large sample sizes. Disregarding important prognostic factors at stratification can lead to imbalances between arms, which may jeopardize accurate sample size calculations, trial results and interpretation. Optimizing stratification and assumptions for power calculations is of utmost importance in aTNBC and beyond. A digitized trial results repository with precisely defined patient populations and treatment settings could improve accuracy of assumptions during clinical trial design.[Table: see text]
COVID-19 and medical education: Rethinking student assessment—The Virtual Observational Standard Clinical Examination.
Authors: Abal Mariana , Gil Deza Lourdes , Gil Deza Ernesto , Dragosky Marta , Acuna Claudia Lorena , Marin Ordoñez Alba , Montiel Monica , Tognelli Flavio A , Smolje Leonel , Gonzalez Cesar , Brandon Maximiliano , Garcia Gerardi Carlos , Martin Reinas Gaston , Jaunarena María del Huerto , Gercovich Natasha , Rivarola Edgardo G. J. , Morgenfeld Eduardo L. , Gercovich Felipe G. ,   IOHM-USAL-ECOE-2020
Published: June 2021

11005

Background: The COVID-19 pandemic introduced new challenges for medical education. In particular, student assessment posed some of the most urging questions. How do we evaluate practical skills when our universities are on lockdown and our hospitals are working on a shortage of personnel? Is it possible to evaluate these skills via online means, mitigating the effects in students’ career development? This paper presents an online evaluation experience implemented at Instituto Oncológico Henry Moore-Universidad del Salvador, Buenos Aires in the postgraduate program of Clinical Oncology. The Virtual Observational Standard Clinical Examination (V-OSCE) is a technology-based adaptation of the Observational Standard Clinical Examination (OSCE) (JCO 34 (15), Abstract e18150, 2017) implemented in previous years. Methods: The V-OSCE took place in November 14, 2020 and consisted on a half-day evaluation during which students rotated through 8 stations (Table). The exam ran on three platforms: Blackboard Collaborate for the interactive elements of all stations; University online campus (Moodle platform) for student questionnaires, and Google Forms for the evaluators’ assessment of each student. Students and evaluators participated in various training sessions, and were given a month to practice before the exam. All interactions were recorded and an anonymous survey on students’ experience and opinions was conducted after the exam. Results: A total of 25 postgraduate Oncology students participated in the V-OSCE. 24 students (96%) completed all stations on time with minimum or no network connection issues. Student opinions: 24 students completed the exam experience anonymous survey; 23 found the exam tech-friendly and valued the practice time provided. When asked to score the exam in a scale of 1 to 10: 80% of the students ranked the exam with 9 or 10; and 20%, with 7 or 8. Conclusions: A) It is feasible to design new ways to assess medical students via online means. B) The experience of an OSCE can be translated to an online environment with minimum technological requirements. C) The COVID-19 pandemic effects are extensive, with serious implications in medical education. However, it has proved to be an opportunity to rethink our educational practices, design innovative formative experiences, and assess new skills that will remain significant even long after the pandemic has ended.[Table: see text]
Where are the women and underrepresented minorities in medicine? Race/ethnicity and gender representation in oncology journals’ editorial boards.
Authors: Patel Shruti Rajesh , Riano Ivy , Geiger Gabriella , Pimienta Jacqueline , Abuali Inas , Ai Angela , Ramirez Roggio Adriana , Dhawan Natasha , Dizman Nazli , Salinas Alexandra Lizette , Duma Narjust
Published: June 2021

11007

Background: The proportion of women & underrepresented groups in medicine (URM) in the field of hematology and oncology remains low, particularly in academic leadership positions. Editorial board appointments allow physicians to have a substantial impact on the nature of the published scholarly work and serve as a platform for academic opportunities. We aimed to assess gender and race/ethnicity representation in editorial board positions in hematology and oncology journals. Methods: Editorial leadership board members from 60 journals from oncology, hematology, radiation oncology, and surgical oncology were reviewed, 54 journals were included in the analysis. Gender and race/ethnicity were determined based on publicly available data for editor-in-chief (EiC) and second-in-command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. Results: A total of 793 editorial board members are included in the analysis. 72.6 % were men and 27.4 % were women. 71.3% of editorial leadership were non-Hispanic white with Asian editorial board members representing the second largest majority at 23.3%. The editorial position was significantly different among men and women (p = 0.038) with women filling only 15.9% (10/63) of the EiC positions. Of these 10 women, the racial breakdown was 90% white and 10% Asian. In the prevalence odds ratio (pOR), women were about half as likely to be in the EiC position compared with men [pOR: 0.47, 95%CI (0.23, 0.95, p = 0.03)]. Women represented 28.4% (207/730) of SiC editorial positions. White editors had the highest representation at 71.0% in the SiC editorial positions, followed by Asian editors at 16.0%. Notable differences were seen in gender proportions between journal specialties (p = 0.001); with surgical oncology and hematology having the lowest female representation at 11.9% and 22.7%, respectively. Conclusions: Women and UIM are markedly underrepresented in leadership roles on Editorial Boards in hematology and oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero which is a sign of unconscious attitudes that may exclude women and minorities from certain positions. It is imperative that we work to move towards a more diverse and inclusive editorial board to ensure critical perspectives are heard and scientific discovery is fostered.[Table: see text]