tbuckley/cabot-search huggingface dataset:
Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings.
Authors: Daniel J. George, Neeraj Agarwal, Jennifer R Rider, Benjamin Li, Rohan Shirali, Rickard Sandin, Agnes Hong, Dave Russell, Krishnan Ramaswamy, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2021)

5074 Background: Androgen deprivation therapy (ADT) served as standard of care for mCSPC for decades. Combining ADT with docetaxel (DOC) starting in 2015 or with novel hormonal therapies (NHT) starting in 2017 has demonstrated improved survival compared to ADT alone. This study examined the impact of new evidence on treatment selection for mCSPC patients in real-world oncology practice. Methods: Electronic medical record (EMR) data from a network of U.S.-based oncology practices in the ConcertAI Oncology Dataset were used to retrospectively evaluate treatment patterns in mCSPC patients who initiated first-line (1L) therapy between 2014–2019. We estimated the proportion of mCSPC patients receiving each 1L regimen, duration of therapy until initiation of next regimen, and trends in 1L regimen. Treatment patterns were studied in the overall population and by race/ethnicity. Anti-androgen (AA) use for &lt;90 days was not included. Results: A total of 858 mCSPC patients were included (70% White, 16% Black, 3% Hispanic, and 11% other race/unknown). Median age at mCSPC diagnosis was 69 years, and 63% presented with de novo metastases. The most common mCSPC 1L regimens were ADT + older AA (26.3%, mainly bicalutamide), ADT monotherapy (20.5%), ADT + NHT ± AA (19.2%), and ADT + DOC ± AA (16.4%). The remaining 17.5% received a variety of other therapies, including AA monotherapy (5.9%) or NHT ± AA (5.5%). NHT included abiraterone, apalutamide, and enzalutamide. ADT + NHT ± AA treatment increased each year, while ADT + DOC ± AA treatment peaked in 2017 and then decreased (Table). By contrast, ADT + AA was the most common therapy in 2014 but declined every year. Median duration until initiation of a subsequent regimen was 14.3 months for ADT + NHT ± AA and 10.8 months for ADT + DOC ± AA. Differences in 1L treatment patterns across White and Black patients were not statistically significant in unadjusted analyses. Conclusions: Even in 2019, over half of mCSPC patients treated in real-world settings did not receive 1L therapy now known to significantly improve survival (ADT + NHT or ADT + DOC) over ADT alone. Those who did, received shorter durations of treatment than observed in registrational trials. However, we found no initial evidence of racial disparities in treatment. The disconnect between trial evidence and real-world practice could be due to patient/disease characteristics, cost/access issues, or provider awareness. A better understanding of these contributing factors is worthy of further study.[Table: see text]
Association of electronic-health record (EHR)-derived race with BRCA testing in patients (pts) with breast cancer (BC) with similar genetic ancestry (GA) in a clinicogenomic database (CGDB).
Authors: Yanling Jin, Charlotta Fruchtenicht, Sylvia Hu, Janis Allen, Anne-Marie Meyer, Altovise Ewing, Melanie Huntley
Journal: Journal of Clinical Oncology (2021)

6524 Background: Disparities in health outcomes can be affected by biological factors associated with GA and social determinants of health. These factors can be teased apart using GA data from comprehensive genomic profiling (CGP) in pts with cancer. CGDBs that link EHR data with CGP enable the selection of pts with similar GA. Holding GA constant provides an opportunity to directly study the effects of reported race in health disparities. This study evaluated a published racial disparity (BRCA testing rates in African American [AA] vs White pts with BC) in a population with fixed, similar GA. Methods: The nationwide (US-based) deidentified Flatiron Health and Foundation Medicine (FMI) BC CGDB (Q3 2020) was used. For each pt, GA fractions from 5 geographic ancestry groups (African [AFR]; Admixed American; East Asian; European [EUR]; South Asian) were derived by FMI using an admixture analysis workflow using genes captured in the CGP assay. To focus on BRCA testing in AA vs White pts and find a sufficient population with similar GA but AA or White race, pts with admixture of both EUR and AFR ancestry were selected. The chosen fractions were: Cohort 1=35%-65% AFR and EUR each; Cohort 2=25%-60% AFR and EUR each; Cohort 3=30%-60% AFR. Cohorts overlap but were chosen to increase sample size. In each cohort, documented BRCA testing prevalence, time from diagnosis to BRCA test date, age at BRCA test and overall survival (OS) were compared between races. Other race (OR) and missing race (MR) were also reported. Results: Most pts (4130/6903) in the BC CGDB had ≥75% EUR ancestry; 129 pts had AFR ancestry fractions ≥25% with EUR ancestry &gt;0%. AA pts had the lowest BRCA testing rates (39%, 43%, 44% for Cohorts 1-3, respectively), which were 18%, 10% and 17% lower compared with White pts, respectively (Table). In Cohorts 1-3, AA pts experienced a longer median time between diagnosis and testing (399, 668, 900 days) compared with White pts (93, 667, 106 days). The median age at BRCA test was 16, 9 and 8 years younger in AA pts (49, 47 and 50 years) compared with White pts. Although pts with MR data had the lowest OS compared with the other races within each cohort, the sample size of each arm for all cohorts was too small to make conclusions. Conclusions: This study demonstrated that when holding GA constant, racial disparities persist in BRCA testing patterns and outcome in pts with BC from a CGDB. With increasing availability of linked clinical and genomic data, further exploration of disparities in genetically similar cohorts can provide deeper insight for cancer outcomes and health disparities research.[Table: see text]
Confirmatory germline testing for presumed germline pathogenic variants using tumor-only testing.
Authors: Tomohiro Kondo, Takahiro Yamada, Masahiro Yoshioka, Masakazu Nishigaki, Yoshihiro Yamamoto, Tadayuki Kou, Junichi Matsubara, Masashi Kanai, Shigemi Matsumoto, Manabu Muto, Shinji Kosugi
Journal: Journal of Clinical Oncology (2021)

e22524 Background: Presumed germline pathogenic variants (PGPVs) can be detected in tumor tissues using comprehensive genomic profiling. Clinicians and patients can decide whether to conduct confirmatory germline testing or not. However, the promoting and obstructive factors for confirmatory germline testing are unclear. Methods: This single institutional retrospective study aimed to identify factors related to confirmatory germline testing in patients with PGPVs. Between April 2015 and April 2019, 270 consecutive patients with cancers of unknown primary site, rare tumors, or solid tumors refractory to standard chemotherapy, who underwent tumor-only comprehensive genomic profiling were reviewed. PGPVs were proposed to be disclosed as variants to the patients by our institutional molecular tumor board. Univariate logistic regression analysis was conducted to investigate the relationship between each patient’s characteristics and confirmatory germline testing. Factors showing a statistical relationship (p &lt; 0.10 in univariate analyses) were included in multivariate logistic regression analysis with a backward selection of variables. Statistical significance was set at p &lt; 0.05. Results: Of the 270 patients who underwent tumor-only comprehensive genomic profiling, 77 possessed PGPVs. The most common PGPVs were TP53 (n = 56), APC (n = 9), PTEN (n = 7), RB1 (n = 6), and BRCA2 (n = 6). Among the 77 patients, only 11 (14.3%) chose to undergo confirmatory germline testing. Multivariate logistic regression analysis revealed that the person disclosing the results (experienced oncologists with knowledge of cancer genome medicine vs. others, odds ratio [OR]: 27.7, 95% confidence interval [CI]: 4.60–167) and study period (OR: 0.110, 95% CI: 0.015–0.787) were independently and significantly associated with confirmatory germline testing. Conclusions: These findings indicate that fostering genomic competency in oncologists and collaborating with genetic experts would facilitate cancer patients and their families to receive genetic medical services in the process of cancer genomic profiling.
Retrospective analysis of efficacy of immune checkpoint inhibitors in <i>BRCA</i>-mutant non-small cell lung cancer.
Authors: Shaomu Chen, Si Li, Dongsheng Chen, Mingzhe Xiao
Journal: Journal of Clinical Oncology (2021)

e21067 Background: Efficacy of BRCA1/2 inhibitor in non-small cell lung cancer (NSCLC) is under investigation in serval clinical trials. Meanwhile immune checkpoint inhibitor (ICI) has become one of the standard therapies for advanced NSCLC, while its efficacy in BRCA mutant NSCLC is not clear. This study assessed the efficacy of anti-PD-(L)1/CTLA-4 in advanced BRCA-mutant NSCLC. Methods: Data of cohort OAK, POPLAR and Rizvi et al.,2018 was downloaded. Efficacy including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were reviewed for BRCA1/2 mutant and wild-type group. The impact of mutant gene ( BRCA1, BRCA2), histological types (adenocarcinoma, squamous) and tumor mutation burden ranges (TMB, &gt; 10 SNVs/Mb, &lt; 10 SNVs/Mb) was analyzed if information was available. Results: A total of 809 ICI-treated advanced NSCLC patients, including 53 (6.6%) with BRCA1/2 mutation, were identified. In OAK/POPLAR cohort (atezolizumab monotherapy, 2nd line or more), TMB in BRCA1/2 mutant group was significant higher (19.2 vs. 10.24, P=0.008) than group of wild-type. The ORR of mutant group was 21.9% (Table), median PFS was 2.5 months, median OS was 9.5 months. The ORR and PFS were comparable between mutant and wild-type groups, while OS of the mutant group was significantly shorter than that in wild-type group (mOS, 9.5 months vs. 14.1 months, P= 0.02). Within mutant group, no significant difference of ORR, PFS and OS were found between mutant gene ( BRCA1 vs. BRCA2), histological type (adenocarcinoma vs. squamous) and TMB range (&gt;10 vs. &lt;10). In Rizvi’s cohort (anti-PD-(L)1 /CTLA-4 mono- or combination therapy, 1 st line or more), TMB in mutant group was also significant higher (22.2 vs. 9.1, P=0.04) than wild-type group. ORR, PFS for mutant and wild-type groups were 25.0% vs. 20.1%, 3.2 months vs. 3.4 months, without significant difference. Within mutant group, superior PFS was found in adenocarcinoma subgroup (mPFS, 5.5 months vs. 1.2 months (squamous subgroup), P = 0.008) and BRCA2-mutant subgroup tend to have superior PFS (mPFS 5.5 months vs. 1.8 months, P=0.08) than BRCA1-mutant subgroup. Conclusions: This retrospective multicohort analysis showed a trend of worse survival in BRAC-mutant NSCLC patients after ICI treatment compared to those in wild-type group, in spite of higher TMB level. Analysis with more samples are needed to provide more precise treatment reference. [Table: see text]
A better classification of wet markets is key to safeguarding human health and biodiversity
Authors: Bing Lin, Madeleine L Dietrich, Rebecca A Senior, David S Wilcove
Journal: The Lancet Planetary Health (2021)

SummaryWet markets have been implicated in multiple zoonotic outbreaks, including COVID-19. They are also a conduit for legal and illegal trade in wildlife, which threatens thousands of species. Yet wet markets supply food to millions of people around the world, and differ drastically in their physical composition, the goods they sell, and the subsequent risks they pose. As such, policy makers need to know how to target their actions to efficiently safeguard human health and biodiversity without depriving people of ready access to food. Here, we propose a taxonomy of wet markets, oriented around the presence of live or dead animals, and whether those animals are domesticated or wild (either captive-reared or wild-caught). We assess the dimensions and levels of risk that different types of wet markets pose to people and to biodiversity. We identify six key risk factors of wet markets that can affect human health: (1) presence of high disease-risk animal taxa, (2) presence of live animals, (3) hygiene conditions, (4) market size, (5) animal density and interspecies mixing, and (6) the length and breadth of animal supply chains. We also identify key factors informing risk to biodiversity. Finally, we recommend targeted, risk-adjusted policies to more efficiently and humanely address the dangers posed by wet markets.
非アルコール性脂肪肝炎の初期段階を診断するための血清中アディポネクチン濃度、HOMA-IR、および血清中タイプ・コラーゲン7S濃度を組み合わせた評価の有用性
Authors: Shimada M, Ozaki K, Fukura M, Kawahara H, Yano H, Tsuchishima M, Takase S, Tsutsumi M
Journal: Hepatology (2005)
Clinical outcomes in patients with malignant brain tumors admitted to the ICU.
Authors: Sarah Maus, Glenn Jay Lesser, Richa Bundy, Fang-Chi Hsu, Peter John Miller
Journal: Journal of Clinical Oncology (2021)

e14034 Background: Primary brain malignancy is distinct from other oncologic diagnoses in its presentation and course. Recent treatment advances have modestly improved survival; yet, prognoses for afflicted patients remain grim, which often leads to non-oncology providers questioning the pertinence of aggressive critical care in this population. By relating patient and disease factors with mortality rates in malignant brain tumor (MBT) patients admitted for critical care, we seek to identify valuable prognostic factors and clarify the expected outcomes following intensive care unit (ICU) admission among these patients. Methods: A single-institution retrospective review was performed of 80 primary MBT patients admitted to neuro- or medical ICUs over a five-year period. The Electronic Health Record (EHR) was queried to identify MBT patients who had been admitted to the ICU. Patients undergoing planned surgical resection or with post-operative complications were excluded, as were patients with brain metastases. A matched control group of 80 solid tumor (ST) patients (excluding brain tumors) was included for comparison. Similar aged matched controls were randomly identified via EHR over the same time period to include non-brain, ST patients admitted to the ICU. Demographic, oncologic, and admission data were related to outcomes, which included complication rates (ICU mortality, six-month mortality) and change in Karnofsky Performance Status (KPS) score. Results: The average age was 55.9 (20-83) and 62.8 (27-89) years in the MBT and ST group, respectively (p = 0.10). ICU mortality was 15% and 21% (p = 0.411) and six-month mortality was 46% and 65% (p = 0.10) in the MBT and control groups, respectively. The most common reasons for ICU admission were seizures (36%) and septic shock (21%) among MBT patients, compared to hypoxic respiratory failure (43%) and septic shock (30%) among ST patients. The MBT group’s KPS score decreased by 23.6 ± 26.82 during their ICU admission, while the control group KPS decreased by 27.0 ± 28.3 (p = 0.87). Average length of ICU stay was 3.82 ± 4.4 days in the MBT group, compared to 2.95 ± 1.83 days in the control ST group (p = 0.29). Average length of hospital stay was 9.07 ± 9.0 days in the MBT group and 8.67 ± 7.76 days in the ST group (p = 0.92). Conclusions: No significant difference was observed in ICU or 6-month mortality when comparing primary MBT and ST patients. Change in KPS score across ICU admissions was similar among the two groups. Our data indicate that despite their guarded prognosis, MBT patients fare no worse than those with other solid tumor types at our institution in the critical care setting. These similarities in mortality and functional scores justify medical ICU admission in patients with primary brain malignancy, and should inform intensivist and oncologist admission patterns.
Efficacy finding cohort of a cancer peptide vaccine, TAS0313, in treating recurrent glioblastoma.
Authors: Yoshiki Arakawa, Yoshiko Okita, Yoshitaka Narita
Journal: Journal of Clinical Oncology (2021)

2038 Background: TAS0313 is a cancer vaccine cocktail comprising three long peptides with a total of 12 cytotoxic T lymphocyte (CTL) epitope peptides. These peptides were derived from eight cancer-associated antigens (EGFR, KUA, LCK, MRP3, PTHRP, SART2, SART3, and WHSC2) that are overexpressed in various cancer types including glioblastoma (GBM). We performed a single-arm, multicenter efficacy confirmatory cohort study as part of the TAS0313 Phase I/II study in patients with recurrent GBM. Methods: The enrolled patients with histologically or cytologically confirmed grade IV GBM (including gliosarcoma, giant cell glioblastoma, and epithelioid glioblastoma) had at least one of the following HLA types: HLA-A*02:01, -A*02:06, -A*02:07, -A*11:01, -A*24:02, -A*31:01, or -A*33:03. Eligible patients were those who received standard radiotherapy and temozolomide, had a confirmed first or second recurrence, or progression with measurable disease outcomes with good performance status (Karnofsky Performance Status score &gt; 70). TAS0313 (27mg) was subcutaneously administered on days 1, 8, and 15 of cycles 1 and 2 and day 1 of cycle 3 or later in 21-day cycles until disease progression or unacceptable toxicity occurred. Tumor response was evaluated using The Response Assessment in Neuro-Oncology criteria. The antigen-specific CTL and immunoglobulin G (IgG) were analyzed by ELISPOT assay and Luminex assay, respectively, before and after treatment. The primary objective was to evaluate the efficacy of TAS0313. Secondary and exploratory methods were used to evaluate the safety and immune response of TAS0313. Results: As of 10th September 2020, 10 patients have been treated with TAS0313 (eight with GBM and two with gliosarcoma). The median age of participants was 56.5 [range, 33–69 years], and methylation status of the MGMT promoter was methylated in four patients, unmethylated in four, and unknown in two. The best overall response was partial response 1/10 (10.0%) and stable disease 4/10 (40.0%). One case showed 69.1% tumor shrinkage. The treatment of two patients was ongoing for over 7 months. The 6-month progression-free survival (PFS) rate was 25.0%, and the median PFS was 2.3 months. The most common adverse drug reactions (ADRs) were grade 1–2 injection site reactions and pyrexia. There were no grade 4 or 5 ADRs. In some patients, TAS0313 treatment was confirmed to increase CTL and IgG levels compared with pre-treatment samples. Conclusions: TAS0313 showed promising efficacy with expected immune responses and favorable safety and tolerability in patients with recurrent GBM. Further investigation of TAS0313 is warranted to validate our findings. Clinical trial information: JapicCTI-183824.
A multicenter observational study of lenvatinib for unresectable hepatocellular carcinoma in Japan.
Authors: Namiki Izumi, Masatoshi Kudo, Kenta Motomura, Yoshitaka Inaba, Yoshio Katamura, Yasuteru Kondo, Kazuhisa Yabushita, Katsuaki Motoyoshi, Junji Furuse
Journal: Journal of Clinical Oncology (2021)

e16118 Background: Lenvatinib is an oral tyrosine kinase inhibitor that has been available for treatment of unresectable hepatocellular carcinoma (uHCC) in Japan since March 2018. We conducted a multicenter prospective observational study to evaluate the safety and efficacy of lenvatinib in clinical practice. Methods: This study conducted as a prospective study, and enrolled patients with uHCC initially receiving lenvatinib as systemic therapy who gave informed consent from July 2018 through January 2019. The observation period per patient was 12 months and e-CRF was used. Results: 713 patients were registered at 133 clinical sites. The safety analysis set and efficacy analysis set were 703 patients. Patient baseline characteristics included median age:73.0 years (25 to 94), male/ female: 564/139, bodyweight: &lt; 60kg/≥60kg: 323/380, HBV/HCV/alcohol/NAFLD or NASH: 137/287/167/88, Child-Pugh classification A/B or higher: 624/75, BCLC stage A/B/C/D: 57/291/332/11, Vp 0/1/2/3/4: 520/31/52/60/22, with/without extrahepatic metastasis: 236/461. Previous treatment (local and systemic therapy) for hepatocellular carcinoma is with/without TACE: 513/190, median number of TACE treatment: 3.0 times (1 to 26), with/without HAIC: 74/629, with/without TKI pretreatment: 131/572. The initial dose was 8 mg (80.5%) and 12 mg (68.2%) in patients with &lt; 60 kg and ≥60 kg, respectively. Median relative dose intensity was 64.2% and the treatment continuation rate at 3 and 12 months after administration of lenvatinib were 67.3% and 24.8%. Regarding safety, the incidence of treatment-related adverse events (TRAEs) was 84.9% (grade 3 or higher: 42.5%). Common TRAEs (incidence rate ≥10%) were decreased appetite (23.9%), malaise (21.8%), hypertension (21.3%), proteinuria (18.3%), palmar-plantar erythrodysesthesia syndrome (16.5%), hypothyroidism (15.8%), and diarrhea (13.9%). TRAEs of grade 3 or higher （incidence rate ≥2.5%） were proteinuria (6.7%), hypertension (6.4%), malaise (3.8%), decreased appetite (3.6%), platelet count decreased (3.3%), palmar-plantar erythrodysesthesia syndrome (2.7%), diarrhea (2.7%) and hepatic encephalopathy (2.6%). The incidence of TRAEs leading to discontinuation of lenvatinib was 32.9％, and main TRAEs leading to discontinuation of lenvatinib were (incidence rate ≥2%) decreased appetite (6.3%), malaise (4.7%), proteinuria (3.3%) and hepatic encephalopathy (2.4%). Regarding efficacy, the ORR and DCR was 39.5% (95% CI: 35.1, 43.9) and 78.9% (75.1, 82.5) in 494 patients who were evaluated for the best response by mRECIST. The median OS was 498.0 days (95% CI: 439.0, -) in 703 patients. Conclusions: The incidence of TRAEs leading to discontinuation of lenvatinib tended to be higher than in phase 3 REFLECT trials (19.7%), but the safety profile and effectiveness findings for lenvatinib in this study were consistent with previous reports.