tbuckley/cabot-search huggingface dataset:
Willingness to travel for CAR-T: A choice-based conjoint analysis.
Authors: Zachary AK Frosch, Esin C. Namoglu, Nandita Mitra, Daniel Jeffrey Landsburg, Sunita Nasta, Judy Shea, Justin E. Bekelman, Carmen E. Guerra, Marilyn M. Schapira
Journal: Journal of Clinical Oncology (2021)

e18503 Background: Chimeric antigen receptor T-cell therapy (CAR-T) is a novel therapy only available at specialized centers. Because patients prefer treatment close to home and provider continuity, preferences may result in unequal access. Sharing follow-up (f/u) with a local provider could increase willingness to travel, but its appeal to patients is unknown. Methods: We conducted a choice-based conjoint analysis to determine the clinical and care delivery factors that patients with diffuse-large B cell lymphoma (DLBCL) value when deciding whether to travel for CAR-T. We recruited from 13 sites within an integrated health system and asked participants to make choices between 12 pairs of treatment options that varied on 5 attributes: travel time, oncologist continuity, whether shared f/u was offered, two-year overall survival (OS), and intensive care unit (ICU) admission rate. Preferences for specific attributes were determined using a generalized estimating equation model with treatment choice as the outcome and the attributes as the variables. Each attribute’s coefficient (importance weight [IW]) represented its value to participants: higher IWs indicated greater value; negative IWs indicated undesirable attributes. Results: We invited 489 patients and 303 (62%) responded. IWs ranged from -0.56 to 1.15 (total cohort) and -2.83 to 2.50 (when modeled by race). Treatments at cancer centers ≥60 minutes away were valued less than those 30 minutes away without collaborative f/u; but were desirable if shared f/u care was offered (Table). Black respondents valued treatments ≥60 minutes away less despite shared f/u care. Participants also valued oncologist continuity (IW 1.15 [0.99, 1.32]), greater OS (IW 0.71 [0.63, 0.79] per 5 percentage point increase), and lower ICU admission rates (IW -0.21 [-0.25, -0.17] per 5 percentage point increase). Oncologist continuity was more highly valued by Black than by White respondents (IW 2.50 [1.74, 3.27] vs 1.09 [0.92, 1.25]). Conclusions: Patients with DLBCL are more likely to select CAR-T therapy at distant cancer centers if f/u care is shared locally. This could represent a strategy to expand access to CAR-T. Travel remains a barrier for Black patients despite shared f/u, suggesting the need to investigate targeted strategies that promote equitable access to CAR-T. [Table: see text]
Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor (NSGCT).
Authors: Jennifer King, Sandra K. Althouse, Clint Cary, Timothy A. Masterson, Richard Foster, Ryan Ashkar, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2021)

5018 Background: The optimal management of patients (pts) with complete response (CR) after first-line chemotherapy remains unsettled with guidelines recommending either surveillance or retroperitoneal LN dissection (RPLND). We present long-term outcomes from a large dataset of pts managed with surveillance after achieving CR to first-line chemotherapy. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT treated between 1990-2017 who achieved a CR after first-line chemotherapy. CR was defined as normalization of tumor markers (AFP+hCG) and no residual mass &gt; 1cm. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Results: 388 pts met eligibility and were included in this analysis. Median age at diagnosis was 28.4 (range, 13-61.5). Primary site was testis in 385 pts (99%). Primary tumor predominant histology was embryonal ca (241), mixed (61), seminoma (31), yolk sac tumor (20), choriocarcinoma (10), and teratoma (14). 126 pts (32.5%) had teratoma in the primary tumor. Metastasis sites were retroperitoneum (295), mediastinal LN (15), pulmonary (149), liver (15), bone (7), and brain (6). IGCCCG risk was good in 325, intermediate in 25, and poor in 32 pts. Pre-chemotherapy retroperitoneal LN size was available in 232 pts: &lt; 3cm in 170 and ≥3cm in 62. Median pre-chemo AFP was 10.7 (1-31,000) and hCG was 16.5 (0-595,930). First-line chemo was BEPx3 in 274, BEPx4 in 30, other regimens in 82 pts. With a median follow-up of 3.9 yrs, 34 pts (8.8%) progressed. At most recent follow-up, 363 (93.6%) pts were alive with no evidence of disease and 10 pts (2.6%) died of their disease. The estimated 2-yr PFS was 90.1% (95% CI: 86.2-93%) and 2-yr OS was 97.8% (95% CI: 95.2-99%). The estimated 2-yr PFS by IGCCCG risk category was 90.4% for good vs 90.4% for intermediate vs 86.5% for poor risk (p = 0.23), and the estimated 2-yr OS was 98.6% for good vs 95.5% for intermediate vs 92.9% for poor risk disease respectively (p = 0.002). For the 34 pts who progressed on surveillance, 16 (4%) progressed in the retroperitoneum only. 3 pts had malignant transformation of teratoma to PNET, adenocarcinoma, or other elements. 11 of progressed pts were treated with surgery, 12 were treated with salvage chemo, and 11 were treated with surgery+chemo. At most recent follow up, 21 of progressed pts had NED, 10 had died of disease, and 3 were lost to follow up. Conclusions: Pts with metastatic NSGCT who achieve CR after first-line chemotherapy can be safely observed with surveillance. Most pts who relapse can be salvaged with surgery and/or chemotherapy.
Genetic and clinical characterization of multigene hereditary breast and ovarian cancer (HBOC) panels in Málaga (Spain).
Authors: Bella Pajares, Marcos Iglesias Campos, Tamara Díaz, Rafael Jesus Peralta, Emilio Alba, Antonia Marquez
Journal: Journal of Clinical Oncology (2021)

e22530 Background: Next Generation Sequencing (NGS) technologies have transformed hereditary breast and ovarian cancer (HBOC) testing process. Several multigene panels (MP) include from 10 to 100 candidate cancer susceptibility genes, but there is a debate about what genes should and should not be tested because of lack of actionability. Few studies have been reported about MP in Europe or Spanish cancer families and no studies in Andalusian population (southern Spain). Methods: We investigated a panel of 17 known genes of high/moderate-risk for HBOC in 938 clinically suspicious HBOC Andalusian families (SEOM 2015 criteria), tested from 2017 to 2019. Multigene panel including BRCA,1 BRCA2, CHEK2, PALB2, BRIP1, ATM, MLH1, MSH2, MSH6, PMS2, CDH1, NF1, PTEN, p53, STK11, RAD51C and RAD51D was performed. Results: We identified 130 patients who carried a high- or moderate-risk pathogenic variants: 61 in BRCA2 (47%), 30 in BRCA 1 (23%), 10 in CHEK2 (8%), 7 in ATM (5%), 7 in PALB2 (5%), 4 in RAD51 (3%), 4 in BRIP1 (3%), 4 in MSH6 (3%), 2 in MLH1 (1,5%) and 1 in MSH2. We detected 220 patients carry variants of uncertain significance (VUS), with a total of 248 VUS (some patients carried more than one VUS): 46 (19%) in ATM, 38 (15%) in BRCA 2, 28 (11%) in MSH6, 19 (8%) in PMS2, 17 (7%) in BRIP1, 16 (6%) in NF1, 14 (6%) in MSH2 and 12 (5%) in CDH1 and PALB2. The most frequent criteria in the entire cohort was “High-grade epithelial non-mucinous ovarian cancer”, reported in 243 cases (26%)”, whereas “Breast cancer (BC) diagnostic under 35” was the most frequent criteria between positives (48 cases (40%)). One case carried two pathogenic variants: BRCA2 and MUTYH. Conclusions: This is the first study reporting the mutational profile of MP gene testing in Andalusia. 70% of mutations were due to BRCA1 and 2 followed by far by CHEK2, ATM and PALB2. We also identified a large amount of VUS in BRCA2, ATM and MSH6. MP improve the diagnostic in andalusian HBOC patients.
Single agent activity of ONC201 in non-midline H3 K27M-mutant diffuse gliomas.
Authors: Yazmin Odia, Ashley Love Sumrall, Timothy Francis Cloughesy, Phioanh Leia Leia Nghiemphu, Matthew David Hall, Doured Daghistani, Minesh P. Mehta, Andrew B. Lassman, Isabel Arrillaga-Romany, Sharon L. Gardner, Rohinton Tarapore, Guangrong Lu, Joshua E. Allen, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2021)

e14037 Background: H3 K27M-mutant diffuse midline glioma is an invariably lethal form of brain cancer that disproportionately affects children and young adults and has no effective treatment following front-line radiation. The initial disease definition in the 2016 WHO Classification of Tumors of the Central Nervous System regarded the H3 K27M mutation as pathognomonic, though the definition was updated in 2018 restricting the diagnosis to histologically diffuse gliomas that involve midline CNS structures (cIMPACT-NOW update 2). ONC201 is an investigational anti-cancer small molecule, DRD2 antagonist and ClpP agonist that has induced durable tumor regressions by RANO-HGG criteria in a registration cohort of recurrent diffuse midline glioma, H3 K27M-mutant patients treated with single agent ONC201. Methods: We present 7 patients with H3 K27M-mutant diffuse gliomas were enrolled in ONC201 clinical studies, though excluded from the registration cohort due to involvement of non-midline CNS structures, all within the cerebral hemispheres (3 frontal, 1 temporal, 1 frontotemporal, 1 parietal, and 1 corona radiata). Results: Two of the 7 patients underwent objective responses by RANO-HGG criteria as assessed by investigator, which was associated with clinical benefit that included increased mobility and level of alertness. Conclusions: These results demonstrate that H3 K27M-mutant diffuse gliomas occur outside of midline CNS structures, and suggest that ONC201 has single agent activity in H3 K27M-mutant gliomas irrespective of CNS location.
Abstract GMM-056: IGF-AXIS SIGNALING DURING OVULATION IS RESPONSIBLE FOR THE STEMNESS CELL EXPANSION AND TRANSFORMATION OF FALLOPIAN TUBE FIMBRIAL EPITHELIUM
Authors: Tang-Yuan Chu, Che-Fang Hsu, Hsuan-Shun Huang
Journal: Clinical Cancer Research (2019)

Abstract Recent studies have unveiled the fallopian tube fimbria as the major tissue-of-origin and incessant ovulation as the main etiological risk factor of ovarian high-grade serous carcinoma (HGSC) but the mechanism of cancer initiation remains elusive. In a series of study we have found a subset of preovulatory follicular fluids (FF) contain high level of ROS that induce DNA double strand breaks as well as apoptosis to the fimbrial epithelial cells in vitro and in vivo. We also found hemoglobin in pelvis, most likely contributed by retrograde menstruation of previous cycles, reduces the ovulatory ROS level extracellularly and results in a shifting from the apoptotic to the survival fate of ROS-stressed fimbrial epithelial cells. These initiating factors in FF, although may contributes to the TP53 mutation and other early genetic hits in the genesis of HGSC, cannot fully transform the immortalized fimbrial epithelial cells, with loss of p53 and Rb. In this study, we demonstrated that IGF axis proteins, including IGFBP2- and IGFBP6-bound IGF2 as well as the IGFBP-lytic enzyme PAPP-A are abundantly present in ovulatory FF, and disclosed their effect on the fallopian tube fimbrial epithelium. Upon engaging with glycosaminoglycans (GAG) on the membrane of fimbrial epithelial cells, PAPP-A cleaves IGFBPs and releases bioactive IGF2 in close proximity to its receptor IGF-1R. This leads to stemness activation and clonal expansion of primary and immortalized fimbrial epithelial cells, and to malignant transformation of p53/Rb- and p53/CCNE1-disrupted fimbrial secretory cells. By antibody depletion, we proved each component of this IGF axis is essential and confers the majority of the transformation/regeneration activities in FF. Two signaling pathways, IGF-1R/ AKT/mTOR and IGF-1R/AKT/NANOG, are responsible for the phenotypes. Among them, IGF-1R and NANOG were critical since blocking their expression or function lead to a complete loss of the transformation. Given that ovulation is an acute inflammatory process inevitably damaging the ovarian surface and the fimbriae, IGF axis in FF takes a role of tissue repair and, in situations when the ROS-induced TP53/Rb mutations accumulated in stem cells, may lead to carcinogenesis of the fallopian tube fimbria. Citation Format: Tang-Yuan Chu, Che-Fang Hsu, Hsuan-Shun Huang. IGF-AXIS SIGNALING DURING OVULATION IS RESPONSIBLE FOR THE STEMNESS CELL EXPANSION AND TRANSFORMATION OF FALLOPIAN TUBE FIMBRIAL EPITHELIUM [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-056.
Correlation of patient characteristics with clinical outcomes of camrelizumab combined with apatinib for unresectable hepatocellular carcinma (uHCC): An observational retrospective analysis.
Authors: Gang Liu, Liansheng Gong, Wenxuan Zhou, Xiaoli Li, Fei Wang, Tingting He, Juan Zhao
Journal: Journal of Clinical Oncology (2021)

e16120 Background: There is limited data on clinical parameters to evaluate the therapeutic effects on immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agent for uHCC. Here, we assessed efficacy and safety of camrelizumab combined with apatinib for uHCC from real-world data, and performed the retrospective subgroup analysis to investigate the potential factors related to therapy response and patients survival as well. Methods: We evaluated clinical data and outcome of 26 uHCC patients who received camrelizumab 200 mg intravenously every 2 weeks combined with apatinib 250 mg qd between May 2019 and Jul 2020. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were evaluated using independent central review mRECIST and RECIST 1.1. Treatment related adverse events (TRAEs) and immune-related adverse events (irAEs) were evaluated. Results: The patients’ characteristics of our cohort are summarized in Table. Overall, our study shows that ORR was 57.7% (mRECIST), DCR was 84.62% (mRECIST), median PFS (mPFS) and OS (mOS) were 11 months and 18.2 months, respectively. For subgroup analysis, patients with first-line therapy (n=22) had dramatically better mPFS than non-first-line (15.0 vs. 4 months; p=0.01). Patients with baseline serum alpha-foetoprotein (AFP) &gt; 400 ng/ml shows better therapeutic efficacy ( p&lt;0.001). The patients with decreased AFP level after treatment had significantly longer mPFS (15.0 vs. 4 months; p&lt;0.001) and mOS (NR vs. 5.7 months; p&lt;0.001) than others. Overall, 14 (53.85%) patients had grade≥3 TRAEs, only 3 (11.54%) patients had grade≥2 irAEs. Conclusions: The first up-to-date real-world evidence indicates that both the baseline and post-treatment AFP level might be independent prognostic factors to evaluate the therapeutic efficacy and clinical outcome on the combination therapy of camrelizumab and apatinib. While larger sample sizes and longer follow-up study are needed to verify reliability of statistical results.[Table: see text]
Efficacy of gefitinib combined with bevacizumab versus gefitinib in advanced <i>EGFR</i> L858R NSCLC.
Authors: Xinmin Zhao, Xianghua Wu, Huijie Wang, Hui Yu, Si Sun, Yu Feng, Jialei Wang
Journal: Journal of Clinical Oncology (2021)

e21185 Background: 60-80% of EGFR+ NSCLC could benefit from the treatment of EGFR TKIs. However, as a result of acquired resistance, median progression-free survival (PFS) associated with EGFR-TKIs monotherapy was rarely longer than 11 months. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) play an important role in the angiogenesis and progression of NSCLC. The combination of EGFR-TKIs and anti-vascular drugs that inhibit the EGFR and VEGF/VEGFR pathways may be a potential therapeutic option for EGFR-mutant NSCLC. The purpose of our study was to evaluate whether gefitinib combined with bevacizumab is associated with an increased PFS benefit compared with gefitinib alone. Methods: This study is a randomized, open-controlled, single-center study. A total of 43 advanced non-squamous NSCLC patients with EGFR L858R mutations were enrolled, including 24 in the experimental group and 19 in the control group. The experimental group received gefitinib combined with bevacizumab (gefitinib 250 mg, QD+bevacizumab 7.5 mg/kg, Q3W), and the control group received gefitinib monotherapy (250 mg, QD). Response to treatment was evaluated after one month of the treatment, followed by once every two months, and adverse events were graded. The primary endpoint was PFS, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety and tolerability evaluation. Samples at baseline (tissue or liquid biopsy), 43 days after treatment (liquid biopsy), and disease progression were subjected to genomic (139-gene NGS panel) profiling. Results: As of December 31, 2020, 22 patients were evaluable (12 for experimental group, 10 for control group). The ORR of the experimental group and the control group were 42% vs 60%, respectively, with no significant difference (experimental group: CR = 0, PR = 5, SD = 7, PD = 0; control group: CR = 0, PR = 6, SD = 4, PD = 0). Main adverse reactions included skin rash (n = 16), diarrhea (n = 24), hypertension (n = 2), proteinuria (n = 1). Other special cases developed fever, nausea and vomiting, elevated platelets, conjunctivitis, back pain, which were manageable. 36 patients with baseline liquid biopsy samples can be evaluated (33 plasma and 3 pleural fluid samples). Of these, EGFR L858R were detectable in 86% (n = 31) of patients. The most common co-mutated gene was TP53 (57%), followed by DNMT3A (49%) and TET2 (17%). Mutation profiles were comparable between the two groups. Conclusions: Compared to gefitinib monotherapy, gefitinib combined with bevacizumab in the treatment of non-squamous NSCLC with EGFR L858R showed similar efficacy and safety profiles.
North American Adult T Cell Leukemia Lymphoma (ATLL) Is Characterized By Distinct, Therapeutically Targetable Mutations in Epigenetic Modifiers
Authors: Urvi A Shah, Yanhua Wang, Orsolya Giricz, Shanisha Gordon, Tushar Damodar Bhagat, Yun Mai, Yongqiang Wei, Nadege Gitego, Gaurav Choudhary, Kith Pradhan, Matthias Bartenstein, Ronald Rice, Swati Goel, Ioannis Mantzaris, Aditi Shastri, Olga Derman, Adam F. Binder, Kira Gritsman, Noah Kornblum, Ira Braunschweig, Amit Verma, B. Hilda Ye, Murali Janakiram
Journal: Blood (2017)
Association of Social and Behavioral Risk Factors With Mortality Among US Veterans With COVID-19
Authors: J. Daniel Kelly, Dawn M. Bravata, Stephen Bent, Charlie M. Wray, Samuel J. Leonard, W. John Boscardin, Laura J. Myers, Salomeh Keyhani
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The US Department of Veterans Affairs (VA) offers programs that reduce barriers to care for veterans and those with housing instability, poverty, and substance use disorder. In this setting, however, the role that social and behavioral risk factors play in COVID-19 outcomes is unclear. <h3>Objective</h3> To examine whether social and behavioral risk factors were associated with mortality among US veterans with COVID-19 and whether this association might be modified by race/ethnicity. <h3>Design, Setting, and Participants</h3> This cohort study obtained data from the VA Corporate Data Warehouse to form a cohort of veterans who received a positive COVID-19 test result between March 2 and September 30, 2020, in a VA health care facility. All veterans who met the inclusion criteria were eligible to participate in the study, and participants were followed up for 30 days after the first SARS-CoV-2 or COVID-19 diagnosis. The final follow-up date was October 31, 2020. <h3>Exposures</h3> Social risk factors included housing problems and financial hardship. Behavioral risk factors included current tobacco use, alcohol use, and substance use. <h3>Main Outcomes and Measures</h3> The primary outcome was all-cause mortality in the 30-day period after the SARS-CoV-2 or COVID-19 diagnosis date. Multivariable logistic regression was used to estimate odds ratios, clustering for health care facilities and adjusting for age, sex, race, ethnicity, marital status, clinical factors, and month of COVID-19 diagnosis. <h3>Results</h3> Among 27 640 veterans with COVID-19 who were included in the analysis, 24 496 were men (88.6%) and the mean (SD) age was 57.2 (16.6) years. A total of 3090 veterans (11.2%) had housing problems, 4450 (16.1%) had financial hardship, 5358 (19.4%) used alcohol, and 3569 (12.9%) reported substance use. Hospitalization occurred in 7663 veterans (27.7%), and 1230 veterans (4.5%) died. Housing problems (adjusted odds ratio [AOR], 0.96; 95% CI, 0.77-1.19;<i>P</i> = .70), financial hardship (AOR, 1.13; 95% CI, 0.97-1.31;<i>P</i> = .11), alcohol use (AOR, 0.82; 95% CI, 0.68-1.01;<i>P</i> = .06), current tobacco use (AOR, 0.85; 95% CI, 0.68-1.06;<i>P</i> = .14), and substance use (AOR, 0.90; 95% CI, 0.71-1.15;<i>P</i> = .41) were not associated with higher mortality. Interaction analyses by race/ethnicity did not find associations between mortality and social and behavioral risk factors. <h3>Conclusions and Relevance</h3> Results of this study showed that, in an integrated health system such as the VA, social and behavioral risk factors were not associated with mortality from COVID-19. Further research is needed to substantiate the potential of an integrated health system to be a model of support services for households with COVID-19 and populations who are at risk for the disease.
Prolonged overall survival observed in patients with locally advanced gastric cancer receiving prophylactic simplified heated intraperitoneal chemotherapy after D2 surgery.
Authors: Junchi Cheng, Yunshan Yang, Haijun Zhong
Journal: Journal of Clinical Oncology (2021)

e16110 Background: Despite advances in surgery and adjuvant chemotherapy, intraperitoneal recurrence is highly frequent in gastric cancer (GC) with a dismal prognosis. In this retrospective study, we aimed to evaluate the effectiveness of adding simplified prophylactic heated intraperitoneal chemotherapy (sp-HIPEC) between surgery and systemic chemotherapy. Methods: Clinical data of 170 patients diagnosed as having locally advanced GC and receiving D2 surgery were retrospectively reviewed. Of the patients, 99 received sp-HIPEC, followed by systemic postoperative chemotherapy, and 71 received only systemic postoperative chemotherapy. Overall survival and recurrence rates between the groups were compared. Results: The median survival was 30.3 and 17.2 months for the sp-HIPEC and systemic groups, respectively (hazard ratio, 0.56; 95% CI, 0.10-0.97). The 3- and 5-year survival rates were 48.2% vs 41.4% and 22.9% vs 14.4%, respectively. Moreover, adding sp-HIPEC significantly reduced peritoneal relapse rate.Both regimens were well tolerated. Conclusions: Adding sp-HIPEC between surgery and systemic chemotherapy may benefit the overall survival without causing additional treatment toxicity.