bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase Ib study of xentuzumab plus abemaciclib and fulvestrant in patients (pts) with advanced hormone receptor-positive (HR+), HER2-negative breast cancer (BC) with visceral or non-visceral disease.
Authors: Yee Douglas , LoRusso Patricia , Sablin Marie Paule , Prat Aleix , Stradella Agostina , Utriainen Meri , Oliveira Mafalda , Yonemori Kan , Naito Yoichi , Hardebeck Molly Catherine , Puig Marta , Hu Joy , Biyukov Tsvetan Nikolov , Iwata Hiroji 
Published: June 2021

1057 Background: Cyclin-dependent kinase (CDK) 4 & 6 inhibitors plus endocrine therapy (ET) are standard of care for advanced HR+ BC. Combining xentuzumab, an insulin-like growth factor (IGF) ligand-neutralizing antibody, with ET and everolimus, suggested progression-free survival (PFS) benefit in pts with advanced HR+ BC and non-visceral disease. Activation of the IGF pathway leads to an increase in cyclin D1, providing a rationale for combining IGF and CDK4 & 6 inhibition. This prospective, open-label study is investigating xentuzumab plus abemaciclib, a CDK4 & 6 inhibitor, with fulvestrant. In dose-finding cohorts, the recommended phase II dose (RP2D) was determined as xentuzumab 1000 mg weekly intravenously plus abemaciclib 150 mg every 12h orally (Q12h). Here, we report preliminary data on disease control rate (DCR) from two expansion cohorts in pts with advanced HR+ BC with visceral (D1) or non-visceral disease (D2). Methods: Postmenopausal women with advanced/metastatic HR+ BC that had progressed on or after ET (including adjuvant ET) were enrolled. Pts could not have received >1 line of ET or any chemotherapy for metastatic disease. No prior CDK4 & 6 inhibitor therapy was permitted. Pts had to have ≥1 documented visceral metastasis in D1 and no visceral metastases in D2. Pts received xentuzumab weekly plus abemaciclib Q12h (at RP2D) plus fulvestrant 500 mg per label. Protocol primary endpoint was PFS rate at 18 months (mos). Secondary endpoints included DCR (complete response [CR], partial response [PR] and non-CR/non-progressive disease [PD] or stable disease [SD] lasting ≥24 weeks [wks]). Results: In D1/D2, 33/31 pts were treated: median age 60/53 years. 19 pts in D2 had bone-only, non-measurable disease. At data cut-off (Jan 2021), median treatment duration was 7.5/9.2 mos in D1/D2; 40 pts remain on treatment. In D1, DCR was 64%: 17 (52%) pts had PR and 4 (12%) had SD lasting ≥24 wks. In D2, DCR was 55%: 5 (16%) pts had PR, 10 (32%) had non-CR/non-PD lasting ≥24 wks and 2 (7%) had SD lasting ≥24 wks. Median duration of disease control was 10.9 mos in each cohort. Some pts had not reached 24 wks; full DCR data will be presented. Most common AEs are shown in the table (≥33% all-grade in either cohort). No hypo/hyperglycemia was reported. Conclusions: Xentuzumab plus abemaciclib and fulvestrant demonstrated encouraging disease control in pts with advanced HR+ BC with visceral and non-visceral disease. The safety profile was manageable, and consistent with the known profiles of the three agents. Clinical trial information: NCT03099174 .[Table: see text]
Prognostic value of pre-infection routine laboratory parameters for COVID-19 mortality in tumor patients: Results of the ADHOK Coronavirus Tumor Registry.
Authors: Roesch Romina , Suedhoff Thomas , Wendtner Clemens M. , Kullmann Frank , Kubin Thomas , Schaich Markus , Mueller-Naendrup Clemens U. , Augustin Marinela , Hartmann Frank , Illerhaus Gerald , Hebart Holger Frithjof , Seggewiss-Bernhardt Ruth , Graeven Ullrich , Naumann Ralph , Kiani Alexander 
Published: June 2021

10571 Background: Tumor patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection. However, they represent a heterogeneous group of individuals with variable risk. Identification of vulnerable subgroups is important for prioritization of vaccination strategies and possible early therapeutic intervention after infection. Methods: Tumor pts. with PCR-confirmed SARS-CoV-2 infection were included in the multicentric ADHOK registry by 22 institutions. Detailed information about tumor disease and treatment, as well as routine laboratory parameters determined at least 10 days prior to SARS-CoV-2 infection, was collected retrospectively. The primary endpoint was defined as the outcome of the SARS-CoV-2 infection, graded according to the WHO: asymptomatic, mild, moderate, severe, critical, and COVID-19-related death. Results: Until Feb. 5, 2021, 215 pts. (67% with solid tumors, 33% with hematological neoplasms) were included in the registry. 74% of the pts. had an active malignancy. The course of SARS-CoV-2 infection was rather variable: 66% of the pts. remained asymptomatic or showed a mild-to-moderate course, while the rest developed severe or critical disease. The COVID-19-related mortality rate was 24%. Pre-infection routine laboratory values were available for 104 pts., obtained at a median of 21 days before SARS-CoV-2 infection. Compared to COVID-19 survivors, COVID-19 non-survivors showed significantly higher median levels of absolute neutrophil count (ANC: 3.6 vs. 6.4 /nL; p = 0.006, n = 91), neutrophil-to-lymphocyte ratio (NLR: 2.2 vs. 7.2; p = 0.005, n = 75), C-reactive protein (CRP: 9.9 vs. 42.0 mg/L; p = 0.001, n = 104), and lactate dehydrogenase (LDH: 213.0 vs. 267.0 U/L; p = 0.016, n = 78). When categorized by a median split, COVID-19 mortality was significantly higher in pts. with ANC > 4.4 /nL (4% vs. 55%, p < 0.001), NLR > 4.1 (5% vs. 58%, p < 0.001), CRP > 15.4 mg/L (18% vs. 46%, p = 0.003), LDH > 236 U/L (15% vs. 49%, p = 0.003) and lymphocytes < 1.3 /nL (41% vs. 11% p = 0.002). In multivariable analysis, ANC and CRP showed a strong and significant association with COVID-19-related death (OR 23.0 and 7.7, p = 0.007 and 0.029, respectively). To develop an easy-to-apply pre-infection score, we combined ANC and CRP and were able to separate three groups of pts. with significantly different COVID-19 outcomes (p < 0.001) (Table). Conclusions: Our results unveil subgroups of tumor pts. who may be at increased risk of severe COVID-19 and point to pre-infection routine laboratory parameters with potential prognostic power: ANC and CRP may help identify pts. at risk for severe COVID-19 before SARS-CoV-2 infection.[Table: see text]
Incidence and trend of Epstein-Barr virus-related cancer: A surveillance, epidemiology, and end results program based study.
Authors: Shen Jiayi , Luo Meijuan , Liu LiTing , Chen Qiu-Yan , Tang Lin-Quan , Mai Hai-Qiang 
Published: June 2021

10575 Background: Epstein-Barr virus (EBV) infection was highly prevalent, as was found in more than 90% of the adults globally. EBV infection has been found to be related with several types of cancer and classified as group 1 carcinogen by the International Agency for Research on Cancer. The association between EBV infection and malignancy was observed in Burkitt lymphoma (BL), Hodgkin lymphoma (HL), extranodal natural killer (NK)/T-cell lymphoma (NNKTL), gastric cancer (GC) and nasopharyngeal cancer (NPC). In this study, we aimed to analyze the incidence and the trend of incidence of these virus-related cancer and to identify whether the trend was similar between them. Methods: This was a retrospective analysis based on the data from Surveillance, Epidemiology, and End Results (18 registries, 2000-2017), which totally included 71,415 patients. EBV-related cancers were defined as BL, HL, NNKTL, GC and NPC. Age-adjusted incidence rates were displayed as per 100,000 persons. In terms of incidence trend, we calculated the average annual percent change (AAPC). AAPC was considered significantly different from 0 when the P-value was smaller than 0.05. The impact of the epidemiological and clinical characteristics on the incidence trend was estimated, with cancer type, histology, age, sex and race considered. Results: Incidence rates of EBV-related cancers were 6.68 per 100,000 persons in 2000 and 5.80 in 2017, of which the AAPC was -0.8 (95%CI, -1.1 - -0.5, P-value < 0.001). (Table) Similar with EBV-related cancer as a whole, the APCCs of BL, HL and GC were statistically significantly smaller than 0, except that the APCCs of NNKTL and NPC were statistically significantly larger than 0 and not statistically significantly different from 0 respectively. The incidence of EBV-related cancer also decreased in mixed cellularity classical HL, nodular sclerosis classical HL, adenocarcinoma of GC, signet ring cell carcinoma in GC, undifferentiated carcinoma of NPC, squamous cell carcinoma of NPC, patients diagnosed at the age of 20-39 years old and 60-79 years old, male patients and race as white, black or Asian, but increased in classical HL, NOS, nodular lymphocyte predominant HL and non-keratinizing carcinoma of NPC. Conclusions: Incidence of EBV-related cancer decreased during 2000 and 2017, which was consistent in BL, HL and GC.[Table: see text]
The lung cancer obesity paradox: An analysis of 432,924 patients.
Authors: Miles Brittany , Mackey James David 
Published: June 2021

10578 Background: The lung cancer obesity paradox is the unexpected inverse relationship between body mass index (BMI) and lung cancer mortality. While there is a growing body of evidence to support the existence of the obesity paradox in lung cancer, little is known about its magnitude and relationship to cancer incidence and its impact on outcomes from surgery, chemotherapy, immunotherapy, and radiation treatment. Methods: To evaluate the impact of obesity on lung cancer incidence, we used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 69 Million patients in 49 large Healthcare Organizations. We evaluated 2 patient cohorts of 216,462 adult smokers aged 18 to 75 that were matched for age, race, gender, and ethnicity. One cohort of patients carried a diagnosis of overweight and obesity (ICD-10 code E66), while the other cohort required exclusion of those diagnoses. Results: We found a statistically significant decrease in lung cancer incidence for patients with obesity (1.407% vs 2.039%, p < 0.0001), in addition to superior overall survival (95.344% vs 92.039%, p < 0.0001). A subset analysis of patients who contracted lung cancer showed a statistically significant benefit in median survival in favor of patients with overweight and obesity (851 vs 602 days, p value 0.0009). Conclusions: These findings support the existence of the obesity paradox in lung cancer, and its positive impact on both lung cancer incidence and outcome.
Evaluation of proband adherence and satisfaction with a prospective cascade testing protocol.
Authors: Smith Maria , Hwang Kristina , Smith Julia Anne , Pothuri Bhavana 
Published: June 2021

10593 Background: We sought to evaluate the feasibility of a Cascade Testing (CT) protocol for family members of probands with actionable germline mutations associated with endometrial or ovarian cancer. Here, we characterize proband compliance with contacting family members for CT and proband satisfaction/regret. Methods: In this prospective study, consenting patients with pathogenic germline mutations associated ovarian or endometrial cancer completed a demographic survey and were asked to contact first- and second-degree relatives with genetic testing results. After a 1–3-month period, probands completed a survey indicating how many relatives had been contacted. At 3 months following consent, probands were asked to complete the validated Impact of Event Scale (IES) and Decision Regret Scales (DRS). Characteristics of probands who contacted relatives and those who did not were compared. Results: The study has accrued 57 probands since opening in March 2019. Germline mutations identified in the 57 probands include 27 BRCA1 (47.4%); 21 BRCA2 (36.8%); 3 BRIP1 (5.3%); 2 MLH1 (3.5%); 2 MSH2 (3.5%); 3 MSH6 (5.3%); 3 PMS2 (5.3%); 1 EPCAM (1.8%); 1 RAD50 (1.8%). Twenty-four (42.1%) probands had a history of cancer (breast 12; ovarian 8; uterine 2; other 5). Of the probands, 32 (56.1%) completed follow-up questionnaires and 29 (50.9%) had contacted relatives about participating in CT. In total, 67 relatives were contacted. Probands contacted an average of 1 relative, ranging from 1-20. Of the 29 probands who contacted relatives, 13 (44.8%) completed IES and DRS questionnaires. The median IES score was 0 out of 75 (IQR 0.0-4.5) and the median DRS score was 0 out of 100 (IQR 0.0-11.3). When comparing characteristics of probands who contacted relatives with those who did not, those with annual household incomes <$75,000 were more likely to contact relatives vs those with incomes ≥$75,000 (77.8% vs 39.5%; p=0.01). There was no association between contacting relatives and personal cancer history, race/ethnicity, education status, or age (Table). Conclusions: Half of probands enrolled in this study contacted relatives about CT, and those with household incomes <$75,000 were more likely to contact relatives than those with higher incomes. Overall, probands reported little/no regret or distress after contacting relatives about genetic testing results.[Table: see text]
Assessing somatic and germline variants in cancer patients.
Authors: Ricker Charité , Amundson Erika , Algaze Sandra , Ciccone Marcia , Dong Stephen , D'souza Anishka , Felicetti Kimberly , Hernandez Daisy , Jayachandran Priya , Kang Irene , Narayanan Kavitha , Thomas Jacob Stephen , Tulpule Varsha , Umayam Rebecca , Xia Bing , In Gino Kim 
Published: June 2021

10601 Background: The increasing integration of somatic and germline testing into oncology practice allows physicians to target oncologic therapy and identify those with cancer predisposition. We explored the impact of a somatic assay (liquid biopsy, LB) on the identification of patients appropriate for germline genetic testing. Methods: We identified a cohort of diverse cancer patients with LB to assess for targetable somatic gene variants at LAC+USC Medical Center between 2016 and 2020 (n= 467). To enrich the cohort for variants that may reflect germline findings, we focused on the 46 patients (9.9%) who had at least one variant identified with a cell-free DNA (cfDNA) fraction of 25.00% or greater. Retrospective chart review extracted demographics and medical history with variables related to cancer history and treatment. LB variants were classified based on whether germline confirmation was indicated and the results of germline tests, when done, were reviewed. Results: Table summarizes the characteristics of the 46 patients identified to have at least one variant on LB in ≤ 25% of the cfDNA. The most frequently mutated genes on LB were TP53 (n=18, 39%), KRAS (n=11, 24%), APC (n=8, 17%), BRCA2 (n=7, 15%), PIK3CA (n=6, 13.0%), and BRCA1 (n=4, 9%). Seventeen patients (40%) were referred for genetic counseling and 13 (30%) underwent germline testing of whom 10 (77%) carried pathogenic variants (PV). All germline PV were concordant with LB variants identified. Four patients with PV BRCA2 on LB and confirmed to be germline, had lung or biliary tract diagnoses, which are not part of the typical BRCA-tumor spectrum. Thirty-three patients were not referred for genetic counseling, though 24 (72%) had LB-identified variants in cancer predisposition genes and 18 (54%) merited a genetics referral. Among patients with germline mutations, three (23%) had targeted therapy and two (15%) had preventive surgery to address second primary cancer risk. Among the 467 patients with LB results, there were an additional 13 patients (not included in the enriched group) known to have a cancer predisposition gene PV. Only two (15%) had findings on LB reports that suggested germline testing would be indicated. Conclusions: While the purpose of somatic testing is to identify targeted therapy, it can provide germline insight, especially for patients not typically referred for genetic assessment. Further education and guidance is needed to assure that this aspect of somatic testing is appreciated by oncology providers and acted upon.[Table: see text]
Prospective genomic testing of unselected cancer patients yields insights about cancer susceptibility and noncancer disease with therapeutic implications.
Authors: Gray Stacy W. , McDonnell, MD, PhD Kevin , Idos Gregory , Hong Christine , Solomon Ilana , Sturgeon Duveen , Bonner Joseph D. , Smith Sidney A. , Morales Pichardo Jennifer , Woodhouse Melissa , Sobotka Elise , Zukin Elyssa , Courdy Samir , King Elisabeth , Xia Xiaoyu , Szelinger Szabolcs , LoBello Janine , Hamilton Stanley R. , Trent Jeffrey M. , Gruber Stephen B. 
Published: June 2021

10603 Background: Clinicians have used strict criteria to determine eligibility for cancer susceptibility (CS) testing and have limited genetic assessment to cancer-related genes. However, half of all CS mutation carriers are missed by criteria-based testing and there may be an unrecognized opportunity to modify care for patients who have rare but actionable genetic disorders as defined by the American College of Medical Genetics (ACMG). With the aim of improving patient outcomes through precision genomics, we initiated an enterprise-wide program to offer somatic and germline sequencing to all patients. Methods: We offer consented patients clinical grade paired somatic & germline WES/ RNA seq and panel germline testing for cancer (156 genes) and ACMG disorders (59 genes). Results are reviewed by a Precision Oncology Tumor Board. Somatic results are returned by the treating team. Germline results are returned by phone (genetic counselor, GC) followed by a clinic visit (GC+MD) for those with pathogenic/likely pathogenic (P/LP) mutations and selected variants of uncertain significant. We evaluated the proportions of patients with somatic findings suggestive of germline conditions and those carrying P/LP mutations in CS and ACMG genes. Results: 1,804 patients enrolled and received somatic sequencing: 52% female; 51% non-Hispanic White/ 20% Hispanic White/ 18% Asian/ 4% Black/ 7% other; median age 64. Review of somatic data suggest that 14% have findings suggestive of germline conditions based on factors such as TMB, MSI, and young age. Of the patients offered germline testing, >95% opted to receive CS/ACMG results. To date, we have sequenced 684 patients for CS and 647 for ACMG. 18% of patients had P/LP mutations in CS genes and 4% had P/LP mutations in ACMG non-cancer genes (Table). Conclusions: Prospective somatic/germline sequencing of unselected cancer patients reveals tumor findings suggestive of germline disorders and identifies patients with CS and non-cancer genetic conditions. These findings highlight the promise of a comprehensive sequencing approach to help guide cancer treatment, management of unrecognized cancer risk and the need for concomitant management of rare disorders such as arrhythmogenic cardiomyopathy and susceptibility to adverse reactions with anesthesia.[Table: see text]
Mutant PPM1D and TP53 populate the hematopoietic compartment after peptide receptor radionuclide therapy (PRRT) exposure.
Authors: Singh Abhay , Mencia-Trinchant Nuria , Griffiths Elizabeth A. , Gupta Medhavi , Gravina Matthew , Tajammal Rutaba , Faber Mark G , Yan LunBiao , Sinha Eti , Hassane Duane C. , Guzman Monica L. , Iyer Renuka V. , Wang Eunice S. , Thota Swapna 
Published: June 2021

10605 Background: Mutations in TP53 and PPM1D are putative drivers associated with therapy related-myeloid neoplasm (T-MN) and have been identified in pre-treatment blood samples obtained at the time of primary malignancy, predating clinically evident T-MN. Genomic analysis of patients(pts) who undergo leukemogenic therapies will help understand T-MN biology and devise risk mitigation strategies. PRRT (Lu 177) for neuroendocrine tumors is associated with enhanced risk of T-MNs. The mechanism for T-MN induced by PRRT is largely elusive due to the novelty of this drug. Methods: We analyzed initial (n=13) and serial blood samples (n=4) prior to and following PRRT for clonal mutations in order to elucidate the role of PRRT in exerting selective pressures on HSCs. Genomic DNA was analyzed using a targeted myeloid 100-gene panel and a variant allele frequency (VAF) cutoff 1% was used to call clonal hematopoiesis (CH). Results: Fifty-four percent pts had CH, despite relatively young age of cohort (median age 58 years, range 41-75) and minimal chemo-radiotherapy exposure; baseline characteristics and molecular profile of cohort is published [Singh et al. Blood 2020; 136 (Supplement 1): 35–36]. Serial sample analysis in 4 pts (Table 1) demonstrates that PRRT exposure is associated with clonal evolution and accompanying cytopenias in 75% (3/4) pts. Pt-1 (age 67) with normal baseline hemogram developed persistent cytopenias after PRRT, accompanied by emergence and expansion of mutant- PPM1D (m PPM1D; VAF 20%). These data suggest that cytopenias result from repopulation of the HSC compartment by m PPM1D cells. In Pts 2 and 3 (age 74 and 75), we note expansion of m TP53 and m PPM1D clones respectively, also associated with the development of cytopenias. Pt-4 was younger (age 59) and developed no cytopenias. Exposure to PRRT was associated with loss of m TET2 and m DDX41, possibly due to lack of clonal fitness of m TET2/DDX41 clones and the relatively young HSC microenvironment. Conclusions: We conclude that mutations in PPM1D and TP53 are clinically relevant, contribute to clonal cytopenias and may increase risk of future T-MN. The temporal association of m TP53 and m PPM1D expansion with PRRT exposure in our analysis suggests selection of these clones in response to PRRT-induced stress, outcompeting wild type and less therapy-resistant HSCs. Our study along with others will inform future efforts to strategize methods of surveillance and early detection for clonality assessment and chemoprevention, to reduce adverse effects of leukemogenic therapies.[Table: see text]