bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
Authors: O'Shaughnessy Joyce , Woeckel Achim , Pistilli Barbara , Hegg Roberto , Vahdat Linda T. , Vuina Dragica , Asad ZVK Parisa(Fatemeh) , Smith Timothy W , Kim Julia , Krop Ian 
Published: June 2022

1055 Background: ALP (α-selective PI3K inhibitor and degrader) + FUL was FDA approved and reflected in the NCCN guidelines in 2019 for pts with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) ABC with PIK3CA mutations following progression on or after endocrine-based therapy (ET). The Phase III SOLAR-1 trial excluded prior FUL, and data on ALP + FUL after FUL are limited. As cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET (including FUL) is the standard in the first line (1L) or second line (2L) for pts with HR+/HER2− ABC, more data on ALP + FUL post-FUL are needed. Here we report patterns and clinical outcomes on RW use of ALP + FUL in pts with HR+/HER2– ABC with prior FUL exposure. Methods: This retrospective study used de-identified electronic health record data from the ConcertAI Patient360 Breast Cancer data product sourced from US oncology centers. Adults with HR+/HER2− ABC treated with ALP + FUL (index tx) who received prior FUL (monotherapy or in combination) in the metastatic setting were included; pts with a PIK3CA negative test on or prior to the index were excluded. Pts were followed until date of death or last activity. RW progression-free survival (rwPFS), defined as first documented progression/death from ALP + FUL start date, was assessed. Results: This analysis included 157 pts (median age, 63 y [57-71 y]) who received ALP + FUL from 2019 to 2021, with 11.5% pts in 1L, 17.8% in 2L, 26.8% in third line (3L), and 43.9% in fourth line and beyond (4L+). Prior FUL tx included CDK4/6i + FUL (74.5%), FUL alone (33.8%), and non-CDK4/6i + FUL (21.0%). In pts who received ALP + FUL in 1L (n = 18), prior FUL exposure was in the same line without documented progression. In the metastatic setting, 28.0% of pts received > 1 FUL-containing regimen and/or 72.0% received prior chemotherapy (CT). At the median duration of follow-up (8.7 mo [4.1-12.5 mo]), the median rwPFS was 5.7 mo (4.0-7.3 mo) in the overall population. The median rwPFS was also analyzed by line of therapy (Table). In pts with CDK4/6i + FUL as immediate prior therapy (n = 39), the median rwPFS was 6.2 mo (3.0-9.1 mo); 79.5% of these pts received ALP in ≤ 3L. At the time of analysis, 107 pts (68.2%) had discontinued ALP + FUL; the median time to discontinuation was 4.7 mo (3.7-6.1 mo). Following discontinuation of ALP + FUL, CT was the most common subsequent therapy (33.8%). Conclusions: This analysis on RW data from early years of ALP access in the US shows clinical benefit of ALP + FUL in pts with HR+/HER2− ABC with PIK3CA mutation even when exposed to prior FUL, confirming the oncogenic dependence of the tumor on the PIK3CA mutation. [Table: see text]
LVEF decline in relation to body composition among women treated for breast cancer: WF-97415.
Authors: Reding Kerryn , O'Connell Nathaniel S. , Cheng Richard , Nguyen Johnny , Ladd Amy , Jordan Jennifer , Ky Bonnie , Vasbinder Alexi , Zaha Vlad , Lucas Alexander , Calhoun Tonya , Hackney Mary Helen , Bellissimo Moriah , D'Agostino Ralph , Lesser Glenn Jay , Hundley W. Gregory 
Published: June 2022

10556 Background: Despite an improvement in survival from breast cancer (BC), many women experience cardiotoxicity. Left ventricular ejection fraction (LVEF) is reduced by an average of 9.7% in women receiving anthracyclines. Obesity and central adiposity at BC diagnosis may influence risk of LVEF decline. We sought to examine associations between body composition and LVEF decline in the UPBEAT (Understanding and Predicting Fatigue, Cardiovascular Decline, and Events After Breast Cancer: WF-97415) study, which was conducted in collaboration with NCI Community Oncology Research Program. Methods: The analytic cohort was comprised of 167 women treated for stage I-III BC with chemotherapy and/or radiation in the UPBEAT prospective study, in whom LVEF was obtained at baseline (pre-treatment) and 3 months. Linear regression was used to examine LVEF decline in relation to 1) waist circumference (WC) and body mass index (BMI) at baseline and 2) changes in WC and BMI during BC treatment. All models were adjusted for age and race. Results: In this cohort (mean [SD] age: 55.7 [10.8] yrs; in whom 75% were white; 19% were Black), the mean (SD) LVEF at baseline was 60.7 (6.7)% with a mean decline of 2.7 (7.2)% from baseline to 3-months. Both WC and BMI at BC diagnosis were associated with LVEF decline during follow-up (Table). For each additional inch in WC, EF decreased by 0.25% points at 3 months (P=0.024); for each additional kg/m2 in BMI, EF decreased by 0.2% points at 3 months (P=0.007). Reduced BMI during treatment was associated with LVEF decline, whereas a change in WC was not. Each kg/m2 reduction in BMI was associated with a 0.4% point decrease in LVEF (p=0.037). Anthracycline use was associated with a 1.89% point decline in LVEF at 3 months versus non-users (p=0.049). After additional adjustment for anthracycline use, baseline WC remained statistically significantly associated with LVEF decline to the same degree. Conclusions: These data show that central adiposity at BC diagnosis is associated with LVEF decline during treatment, even after controlling for anthracyclines. Loss of central adiposity was not associated with LVEF decline, whereas BMI loss during treatment was. This suggests that shifts in body composition during BC treatment, potentially via loss of muscle mass, are important to monitor in patients. Future work should examine how changes in body composition, particularly changes in skeletal muscle and adipose tissue depots, influence cardiac dysfunction in BC patients during treatment. Funding: 2UG1CA189824, R01CA199167, 2UG1CA189828. [Table: see text]
Analysis of genomic alterations in pan-cancer from a large real-world Chinese population.
Authors: Dong Zhouhuan , Gao Jie , Zhu Fengwei , Gai Fei , Su Wenqing , Liang Zhixin , Tian Xiaodong , Shi Huaiyin 
Published: June 2022

10568 Background: Effective targeted therapy sorely depends on comprehensive and precise genomic profiling. Besides, single nucleotide variations (SNVs) and InDels, gene fusions, as drivers and therapeutic targets of great importance, are not yet well characterized in Chinese patients. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues from 1,384 pan-cancer patients were collected and sequenced using next-generation sequencing (NGS) targeting 40 cancer genes including SNV, fusion and assessing copy number variation (CNV) (AmoyDx HANDLE Classic Panel). qPCR and fluorescence in situ hybridization (FISH) were further applied to verify NGS detected fusion genes. Results: 1,384 patients were recruited including 890 lung cancers, 272 colorectal cancers, 174 gastric cancers, and 48 endometrial cancers. The prevalence of fusion genes (5.49%), including ALK-fusion (2.67%), ROS1-fusion (0.94%), RET-fusion (0.72%), NRG1-fusion (0.29%), and NTRK-fusion (0.07%), was nearly double the frequency of previously reported data from East Asians. Prevalence of fusion genes varied in different types of cancers. For instance, ALK (3.7%), ROS1 (1.5%), RET (1.0%) and NRG1 (0.2%) fusions were largely found in patients with non-small cell lung cancer (NSCLC), and were rarely detected in other cancer types. Further analysis of genomic alterations in fusion-positive patients revealed that, TP53 (21%) was the most frequently co-occurred mutated gene with ALK fusion, while RET fusions and ROS1 fusions were rarely accompanied by other mutated genes. In addition, two patients with RBPMS- NRG1 fusion were accompanied by BRAF and RB1 mutations, whereas no co-occurred mutation was found in patients with other partners of NRG1. Patients with inconsistent results of RNA-based NGS and FISH validation fusions are still being followed for treatment and survival, updated data will be available at the time of the presentation. Conclusions: Genomic alterations in real-world Chinese populations have specific characteristics, especially fusion genes. Further characterization of these variants is essential for clinics to guide appropriate targeted therapies.
Characteristics of patients with neuroendocrine tumors in the United States: A study of 392,412 patients.
Authors: Reddy Ravali A. , Liao Cheng-I , Johnson Caitlin Ruth , Tian Chunqiao , Darcy Kathleen M. , Kapp Daniel Stuart , Chan John K 
Published: June 2022

10572 Background: To evaluate the characteristics and trends amongst patients with neuroendocrine tumors in the United States. Methods: Data was obtained from the United States Cancer Statistics database from 2001 to 2018. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate characteristics and trends of these cancers per 100,000. The age-adjusted incidences were determined based on the standard population in the United States from 2000. Results: Of 392,412 patients with neuroendocrine tumors, 53.1% were identified in women and 46.9% in men. White, Black, Hispanic, Asian/Pacific Islander and unknown race comprised 73.6%, 14.1%, 7.8%, 2.7%, and 1.7% of the patient population respectively. The majority (64.7%) of tumors originated from the digestive system, followed by 24.5% from the respiratory system. In 2018, the incidence of all neuroendocrine tumors was higher in older (70-79 years) patients as compared to younger (< 50 years) ones at 30.17 vs. 2.79/100,000, in women as compared to men at 8.36 vs. 7.77/100,000, and in White patients as compared to Black, Hispanic, and Asian/Pacific Islander patients (10.82, 10.15, 5.08 and 4.80/100,000 respectively). Amongst different types of neuroendocrine tumors, those originating from the digestive system had the highest incidence at 6.72/100,000 in the year 2018 with colon tumors being the most common subtype. On trend analysis, the groups with the highest annual percent increase included: younger (< 50 years) patients increasing at 5.06%, Hispanic patients rising at 6.44%, and appendiceal tumors increasing at 12.89% per year. On intersection analysis, Black patients between the ages of 70-79 had the highest incidence at 33.39/100,000, while younger (< 50 years) Hispanic patients had the largest increase at 6.22% per year. Conclusions: The incidence of neuroendocrine tumors has increased over our study period. The highest incidence was found in older Non-Hispanic Black patients, with younger Hispanic patients having the highest annual percent increase. Further studies are warranted to better characterize the reasons for these trends and disparities amongst minority patients affected by these tumors.
Genetic counselling and testing for breast and ovarian cancer in Asia: A multinational survey of unmet needs.
Authors: Kwong Ava , Tan David Shao Peng , Ryu Jai Min 
Published: June 2022

10586 Background: Enabling equitable access to healthcare services among women remains a challenge in Asia. Differences in the presentation and treatment stage contribute to disparities in cancer outcomes. Genetic testing provides accurate risk assessment to help guide personalised preventative and treatment options. However, there is a critical need for research to further our understanding of barriers in leveraging optimal benefits of genetic testing and counselling (GT&C) to address cancer among women. Methods: A team of multinational experts was assembled to form the Asian Consensus and Recommendations on Genetic Testing and Counselling (ACROSS) Consortium to assess the challenges in adoption of GT&C for patients with breast and ovarian cancer in Asia. Critical publications were identified, and a pre-meeting questionnaire was developed. The questionnaire was refined to align with the objectives over iterations, and final approval was obtained from the steering committee. Survey responses were gathered from oncologists from ten countries across Asia. The expert committee discussed the survey results to highlight (1) current knowledge, attitude, and practices; (2) unmet needs and gaps; and (3) recommendations for addressing critical obstacles. Results: Adoption of GT&C for cancer is low in Asia. Lack of time, resources, and access to genetic counsellors are major difficulties faced. In most cases, the practising oncologists provide pre-test genetic counselling and communicate test results. For breast cancer (BC), most experts preferred germline testing only, with few opting for somatic testing if germline testing was negative. The agreement was lower among the ovarian cancer (OC) experts, with advocates for either germline or somatic testing or both. There was a lack of consensus on clinical criteria for selecting suitable candidates for genetic testing and the use of multiple gene panel germline testing. The need for government-aided subsidies and training programmes was highlighted. Conclusions: Recommendations from the expert panel included (1) development of guidelines and criteria to identify candidates suitable for GT&C; (2) training healthcare professionals with required competencies; (3) improving accessibility and affordability; (4) increased patient education and awareness; and (5) adoption of GT&C into the national healthcare system. The consortium agreed that a multifaceted plan of action combining the expertise of clinicians, scientists, and policymakers is required to facilitate uptake of GT&C in Asia. [Table: see text]
Universal genetic testing versus guideline-directed testing for hereditary cancer syndromes among traditionally underrepresented patients in a community oncology program.
Authors: Jones Jeremy Clifton , Coston Tucker , Kunze Katie , Golafshar Michael A. , Rao Rohit , Wysokinska Ewa Maria , Johnson Elizabeth , Esplin Edward D. , Nussbaum Robert Luke , Heald Brandie , Klint Margaret , Barrus Kathleen , Bekaii-Saab Tanios S. , Dronca Roxana Stefania , Samadder Jewel 
Published: June 2022

10588 Background: Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognostication, treatment selection, clinical trial enrollment and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but these leave a significant number of cases missed by guideline-directed testing (incremental PGV). We have previously shown that 50% of patients with PVGs would not have been detected with guideline-based testing alone. In this project, we aimed to determine the feasibility and generalizability of this approach within a more racially/ethnically diverse cohort from a community cancer practice. Methods: We completed a prospective study of proactive germline genetic sequencing among patients with solid tumor malignancies at a community-based oncology practice in downtown Jacksonville, FL between June 2020, and September 2021. The patients were unselected for cancer type, stage, family history, race/ethnicity, and age. PGVs identified using an 84-gene NGS platform were stratified by penetrance. National Comprehensive Cancer Networks (NCCN) guidelines were used to determine incremental PGV rates. Results: 221 patients were enrolled, median age 63.0 years, 21.7% male. 56.6% of patients were white (non-Hispanic), 32.6% were black/African American, 5.4% were Hispanic. 39.8% of patients were commercially insured, 52.4% insured by Medicare/Medicaid and 2.7% uninsured. The cohort was comprised predominantly of breast cancer (61.5%), lung cancer (10.4%) and colon cancer (7.2%) patients. A total of 27 PGVs were identified in 23 patients. We found no significant difference in the rate of PGVs based on race/ethnicity. The overall rate of variants of uncertain significance (VUS) was numerically higher in black/African American patients (61.1%) compared with other ancestry (45%). 13 of 23 (56.5%) patients with detected PGVs did not meet NCCN guidelines for germline genetic screening (incremental PGVs). Conclusions: This prospective study found that universal multi-gene panel testing among patients from a racially/ethnically diverse cohort from a community cancer practice was associated with an increased detection of heritable variants with treatment implications over the predicted yield of targeted testing based on guidelines. This study is the first to evaluate this approach in an exclusively community-based practice. Clinical trial information: NCT04456140.
Germline screening rates and patterns for patients with pancreatic cancer at an academic medical center.
Authors: Coleman DeJuana , Thomas Martha , Le Tri Minh , Kunk Paul Raymond , Reilley Matthew 
Published: June 2022

10590 Background: Current National Comprehensive Cancer Network guidelines recommend germline genetic testing for all pancreatic cancer patients irrespective of family history. Germline testing provides insight on inherited pathogenic variants that may influence care. Approximately 10% of pancreatic adenocarcinoma (PDAC) patients have pathogenic mutations which may have treatment implications and warrant the introduction of targeted therapy approaches. Patients with germline BRCA1/2 or PALB2 mutations have increased sensitivity to platinum chemotherapy and PARP-inhibitor therapies. Germline testing results may have important implications for patients’ family members for earlier targeted screening. A better understanding of the current state of testing is needed to develop systems to improve screening rates. We conducted a retrospective review of clinical practice patterns at an academic cancer center to assess the current uptake. Methods: Patients with pancreatic adenocarcinoma seen at the University of Virginia Health System within the 2021 calendar year were identified. Retrospective review of genetic counseling referral and germline genomic screening for individual patients was performed. Results: 210 patients with pancreatic adenocarcinoma were identified. 39 (19%) PDAC patients had a referral to genetic counseling placed in the electronic medical record and 44 (21%) completed germline screening. Of the patients referred to genetics, 17/39 patients (44%) met with a genetic counselor which led to germline screening, 3/39 (8%) patients were referred and saw genetics after receiving germline testing results. Among patients who completed germline screening, 27/44 (61%) had testing initially ordered by their oncologist with referral to genetic counseling based on testing results 3/27 (11%). Conclusions: Despite guideline recommendations, germline testing rates are low among this PDAC population. Genetic counselors are essential members of a multidisciplinary team and guide patient discussions and decision making with regards to germline testing. Typical practice has involved referral to meet with a genetics counselor prior to testing; however many patients elect not to schedule a visit and consequently do not obtain germline screening. Barriers may include costs associated with genetic counseling/testing, time constraints, and patient understanding of the relevance of testing for their cancer care. We observed that offering germline testing to PDAC patients with referral to genetic counseling based on results and patient preference is a viable practice pattern. Upfront clinician driven germline testing may offer an opportunity to improve access to germline screening. Prospective clinical trials are needed to increase rates of germline testing and genetic counseling for PDAC patients.
Risk-stratified FIT for urgent colonoscopy in Lynch syndrome: A clinical service throughout the COVID-19 pandemic.
Authors: Lincoln Anne G , Benton Sally C , Sasieni Peter , Monahan Kevin J 
Published: June 2022

10606 Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. Herein, we report results from a national emergency clinical service implemented during the COVID-19 pandemic which used FIT to prioritize colonoscopy in LS patients while endoscopy services were limited. Methods: Regional genetic and endoscopy services across England were invited to participate. Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 March 2021. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub’s Research Laboratory in Surrey. The Hub sent patients a FIT kit (OC-Sensor™ (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Lab reports with feecal haemoglobin (f-Hb) results were returned electronically for clinical action. LS patients were risk-stratified for colonoscopy based upon the following f-Hb thresholds: (1) f-Hb ≥10µg of Haemoglobin (Hb)/g (µg/g) faeces: triaged for colonoscopy via an urgent two-week wait (2WW) pathway, (2) f-Hb ≤10µg/g: schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits. Results: Fifteen centers across England participated in the clinical service from 9th June 2020 to 31st March 2021. An uptake rate of 64% was observed from this cohort (375/588 invites), though 21 cases were removed from analysis due to repeat FITs, insufficient sample, missing clinical data, or FIT completed after colonoscopy. Of the remaining 354 patients analyzed, 269 patients (76%) had a f-Hb of <6µg/g. 6% (n=23) of patients had a f-Hb that was at or between greater than the limit of detection of the assay (≥6µg/g) yet below 10µg/g.18% (n=62) had FIT results of ≥10µg/g and met criteria for urgent colonoscopy triage via the 2WW pathway. Of the 62 urgently triaged patients, 22 had detectable adenomas, 6 had advanced adenomas (AAs), and 4 were diagnosed with CRC (table). Conclusions: The utility of FIT during the pandemic has demonstrated clinical value for LS patients requiring CRC surveillance. Further longitudinal investigation on the efficacy of FIT in people with LS is warranted and will be examined as part of the multi-center prospective research study “FIT for Lynch Syndrome” (ISRCTN15740250) which is presently recruiting patients in the UK. [Table: see text]