tbuckley/cabot-search huggingface dataset:
Real-world clinical effectiveness of eribulin in metastatic breast cancer patients with visceral metastases in the United States.
Authors: Sarah Schellhorn Mougalian, Jingchuan Zhang, Jonathan Kish, Marjorie E. Zettler, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2021)

e13058 Background: Eribulin mesylate was approved in the United States (US) in 2010 for the treatment of metastatic breast cancer (mBC) after at least two prior chemotherapeutic regimens, which should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Visceral metastases, including those to the lung and brain, have been identified as poor prognostic features for patients with mBC. The objective of this analysis was to assess the real-world clinical effectiveness of eribulin in mBC patients with visceral metastases when treated in accordance with the US label. Methods: Patients with mBC initiating eribulin consistent with the US label between 2011-2017 were identified through a retrospective, multi-site chart review study conducted in US oncology practices. De-identified, patient-level demographics, clinical characteristics, treatment patterns, and outcomes were entered into an electronic case report form by the patients’ treating physicians. Sites of metastases at initiation of eribulin were indicated by providers. Clinical outcomes assessed included best overall response to eribulin as recorded in the patient’s chart, progression-free survival (PFS), and overall survival (OS). The proportion of patients with either a complete or partial response as their best overall response was calculated. PFS and OS were calculated by the Kaplan-Meier method from the initiation of eribulin for all patients with visceral metastases and subsets reporting lung or brain metastases site, respectively. Results: The analysis included 470 patients with visceral metastases, including 342 with lung metastases and 22 with brain metastases at the time of eribulin initiation. Eribulin was third-line therapy for approximately three quarters of patients in these subgroups, and the remainder received eribulin in fourth line or later. Mean age was 59 years in general (59 and 54 years in those with lung and brain metastases, respectively). Over half of patients (53.6%) had either a complete or partial response to eribulin. Median PFS was estimated at 6.0 months, and median OS was estimated at 10.5 months. Results for the subgroups of patients with lung and brain metastases are shown in the table. Conclusions: The results of this retrospective analysis affirm clinical effectiveness of eribulin in mBC patients with visceral metastases, when used consistent with the US label.[Table: see text]
MRD assessment using NGS in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation: Meta-analysis.
Authors: Osama Mosalem, Mahmoud Abdelsamia, Haitham Abdelhakim
Journal: Journal of Clinical Oncology (2021)

e19002 Background: The presence of measurable residual disease (MRD) preceding hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) is increasingly recognized as a risk factor for leukemic relapse and decreased survival. Over many years, attempts have been looking at developing tools to detect MRD; this includes multiparametric flow cytometry, quantitative polymerase chain reaction, and most recently, next-generation sequencing (NGS). NGS offers higher sensitivity and detection rate of disease-related gene mutations, thereby potentially improving disease outcomes. Our study sought to review the scientific literature that included NGS‐detected molecular MRD in patients with AML who underwent bone marrow transplantation. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, and SCOPUS up until October 2020. Inclusion criteria included articles that reported the association between pre-HSCT MRD detected by NGS and post HSCT outcome in patients with AML. We extracted hazard ratios for the cumulative incidence of relapse (CIR), overall survival (OS) and leukemia free survival (LFS). A random-effect model was utilized to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Results: Six studies met our inclusion criteria. Our meta-analysis showed that the detection of pre-transplant MRD by NGS was associated with increased risk of cumulative incidence of relapse (hazard ratio=2.5, CI= 1.6-3.9, with p-value &lt;0.001) and decreased overall survival (hazard ratio=1.6, CI= 1.6-2.3, p-value 0.005). LFS was significantly higher in those who had negative MRD detection by NGS before transplantation (HR=1.9, CI= 1.3-2.8 with p-value 0.001). These results were independent of the cytogenetic risk of conditioning intensity. There was heterogeneity between our studies (I 2 = 53%, 52%, and 59% for CIR, OS, and LFS, respectively). Conclusions: The application of NGS to detect MRD is a strong predictor of outcome in patients with AML who are undergoing hematopoietic stem cell transplantation. NGS-detected MRD positive status prior to HSCT is indicative of a higher risk of relapse and decreased overall survival in this meta-analysis. Despite the limitations in our study, it demonstrates the value of MRD detection by NGS in HSCT recipients.
Does oxaliplatin pharmacokinetics (PKs) explain associations between body composition and chemotherapy toxicity risk in older adults with gastrointestinal (GI) cancers?
Authors: Grant Richard Williams, Mustafa Al-Obaidi, Joseph Rower, Christian Harmon, Chen Dai, Edward Acosta, Smith Giri, William Zamboni, Andrew T. Lucas, Shlomit Strulov Shachar, Olumide B. Gbolahan, Jeffrey A. Meyerhardt, Bette Jane Caan, Smita Bhatia
Journal: Journal of Clinical Oncology (2021)

3095 Background: Considerable inter-individual variability in oxaliplatin toxicity exists in older adults with GI cancers. Low lean body mass (LBM), commonly known as sarcopenia, influences toxicity and is not incorporated in standard body surface area-based dosing, which may affect oxaliplatin PK and tolerability, but has not been examined systematically. Methods: We examined oxaliplatin PK in 26 older adults (103 concentrations) with GI cancers (NCT03998202). Using the transverse section at L3, skeletal muscle area (SMA) and total adipose tissue (TAT) were quantified (Slice-O-Matic software) and LBM was calculated (LBM = 0.30 × SMA + 6.06). Noncompartmental methods (WinNonlin 7.0) were used for PK estimates and a one compartment population PK model (PopPK) was developed. Covariates included age, sex, LBM, TAT, weight, BMI, creatinine clearance, BSA, serum albumin, and body composition phenotypes (i.e. low LBM-high TAT, etc.). Results: Median age was 68yrs, 69% male, 88% white, and mostly colorectal (62%) and pancreatic (27%) cancers. There was wide variability in oxaliplatin volume of distribution (Vd: 12.5-259L), peak concentrations (Cmax: 404-3642ng/mL), and clearance (CL: 26.7-270L/hr). Participants with lower LBM had lower Vd (r = 0.51, p&lt; 0.01); those with higher TAT had higher Cmax (r = 0.53, p&lt; 0.01). Higher albumin was associated with lower Cmax (r = -0.49, p= 0.01) and higher CL (r = 0.47, p= 0.01). The phenotype of low LBM + high TAT had the lowest Vd (Relative Risk [RR] 0.32, p= 0.01), lowest CL (RR 0.39, p&lt; 0.01), and highest Cmax (RR 3.3, 95% CI 1.7-6.5, p&lt; 0.01). Eleven patients (44%) had grade 3-5 chemotoxicity. Vd (r = -0.46, p= 0.02) and Cmax (r = 0.44, p= 0.03) were associated with grade 3-5 chemotoxicity. The phenotype of low LBM + high TAT was associated with a 45% higher risk of grade 3-5 chemotoxicity (RR = 1.45, 95% CI 1.1-2.1, p= 0.04), while BSA was not (r = -0.04, p= 0.9). In the popPK model, body composition was associated with PK (TAT with Vd [p = 0.006] and CL [p &lt; 0.001]), as was albumin (Vd p = 0.004; CL p = 0.002), while BSA was not (Vd p = 0.08; CL p = 0.2). Compared to BSA, an additional 11-17% in oxaliplatin PK variability was explained by LBM (11%), TAT (14%), and albumin (17%). Conclusions: Relationships between body composition, oxaliplatin PK, and severe chemotoxicity suggest the need for novel dosing strategies that incorporate body composition to reduce chemotoxicity and improve outcomes. Clinical trial information: NCT03998202.
YAP/TAZ Suppress Drug Penetration Into Hepatocellular Carcinoma Through Stromal Activation
Authors: Kyungjoo Cho, Simon Weonsang Ro, Hye Won Lee, Hyuk Moon, Sojung Han, Hye Rim Kim, Sang Hoon Ahn, Jun Yong Park, Do Young Kim
Journal: Hepatology (2021)

Background and Aims HCC is the most predominant type of liver cancer affecting 800,000 people globally each year. Various small‐molecule compounds targeting diverse oncogenic signaling pathways have been tested for patients with HCC, and clinical outcomes were not satisfactory. In this study, we investigated molecular signaling that determines the efficiency of drug delivery into HCC. Approach and Results Hydrodynamics‐based transfection (HT) was performed to develop mouse models for HCC induced by various oncogenes. Mice bearing liver cancer were treated with verteporfin at 5 weeks after HT. Multicellular HCC organoid (MCHO) models were established that contained various types of stromal cells, such as hepatic stellate cells, fibroblasts, and endothelial cells together with HCC cells. Tumor organoids were treated with verteporfin, and distributions of the drug in the organoids were assessed using fluorescence microscopy. Murine HCC models developed by HT methods showed that a high Yes‐associated protein/Transcriptional co‐activator with PDZ‐binding motif (YAP/TAZ) activity in HCC cells impaired verteporfin penetration into the cancer. Activation of tumor stroma was observed in HCC with a high YAP/TAZ activity. Consistent with the findings in the in vivo models of HCC, MCHOs with activated YAP/TAZ signaling showed stromal activation and impaired penetration of verteporfin into the tumor organoids. Inhibition of YAP/TAZ transcriptional activity in HCC cells significantly increased drug penetration into the MCHO. Conclusions Drug delivery into liver cancer is impaired by YAP/TAZ signaling in tumor cells and subsequent activation of stroma by the signaling. Disrupting or targeting activated tumor stroma might improve drug delivery into HCC with an elevated YAP/TAZ activity.
First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.
Authors: Martin Reck, Tudor-Eliade Ciuleanu, Manuel Cobo, Michael Schenker, Bogdan Zurawski, Juliana Janoski de Menezes, Eduardo Richardet, Jaafar Bennouna, Enriqueta Felip, Oscar Juan-Vidal, Aurella Alexandru, Hiroshi Sakai, Arnaud Scherpereel, Shun Lu, Luis G. Paz-Ares, David Paul Carbone, Arteid Memaj, Sathiya Marimuthu, Phuong Tran, Tom John
Journal: Journal of Clinical Oncology (2021)

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (&lt; 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]
A multicenter study to develop a non-invasive radiomic model to identify urinary infection stone in vivo using machine-learning
Authors: Junjiong Zheng, Hao Yu, Jesur Batur, Zhenfeng Shi, Aierken Tuerxun, Abudukeyoumu Abulajiang, Sihong Lu, Jianqiu Kong, Lifang Huang, Shaoxu Wu, Zhuo Wu, Ya Qiu, Tianxin Lin, Xiaoguang Zou
Journal: Kidney International (2021)
Sperm Parameters Before and After COVID-19 mRNA Vaccination
Authors: Daniel C. Gonzalez, Daniel E. Nassau, Kajal Khodamoradi, Emad Ibrahim, Ruben Blachman-Braun, Jesse Ory, Ranjith Ramasamy
Journal: JAMA (2021)

Sperm Parameters Before and After COVID-19 mRNA VaccinationTwo mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), received Emergency Use Authorization from the US Food and Drug Administration.Despite high efficacy and few adverse
Clinicopathologic features of Xp11.2 translocation renal cell carcinoma and its response to target therapy.
Authors: Xieqiao Yan, Zhihong Chi, Lu Si, Chuanliang Cui, Yan Kong, Bixia Tang, Lili Mao, Xuan Wang, Bin Lian, Siming Li, Xue Bai, Li Zhou, Jie Dai, Xinan Sheng, Jun Guo
Journal: Journal of Clinical Oncology (2021)

e16559 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 translocation RCC was found in 41 cases. The median PFS and Median OS was 6.3 months (4.4 - 8.8) and 17.3 months (12.4 - 21.8) for the whole cohort, respectively. First-line treatment mainly included sunitinib (n = 12), sorafenib (n = 13), axitinib (n = 6), and pazopanib (n = 4), and the median PFS of these regimens was 5.4 months, 5.1 months, 9.4 months, 8.3 months, respectively. Twenty-three patients received subsequent therapies, the median PFS and the median OS was 4.3 months and 12 months for the second-line therapy(n = 21), 4.3 months and 14.1 months for the third-line therapy(n = 11), 2.4 months and 9.6 months for the fourth-line therapy(n = 6). Conclusions: Metastatic Xp11.2 translocation RCC is an aggressive disease. Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) agents appeared to demonstrate some efficacy, the combination of VEGFR-TKI and immune checkpoint inhibitor (ICI) might be a useful tool for the treatment of metastatic Xp11.2 translocation RCC.
EPEN-10. UNRAVELLING THE TUMOR IMMUNE MICROENVIRONMENT OF POSTERIOR FOSSA A EPENDYMOMAS ON RNA AND PROTEIN EXPRESSION LEVELS
Authors: Fenna F. Feenstra, Friso Calkoen, Johan M Kros, Lennart Kester, Mariëtte Kranendonk, Jasper van der Lugt, Dana A M Mustafa
Journal: Neuro-Oncology (2021)

Abstract Background Ependymomas account for 8–10% of pediatric brain tumors, and the standard therapy of surgery and radiation has not changed for the past two decades. Characterization of the tumor immune microenvironment (TIME) is of great importance in order to find better therapies. However, the TIME of ependymomas is still not defined. In this retrospective observational study we aimed to unravel the TIME of ependymomas at mRNA and protein expression levels. Methods Ependymoma samples from two locations were selected: Posterior Fossa (PF-A, n=8), and supratentorial (ST, n=5). Targeted gene expression profile using the PanCancer immune profile panel of NanoString technology was performed. Data were analyzed using the nSolver software. In addition, 8 samples were subjected to RNA bulk sequencing, and the sequenced data were connected to the expression data of the same samples. To validate some of the findings, immunohistochemistry was performed. Results Unsupervised hierarchical clustering showed that PF-A ependymomas can be divided into two groups based on the expression of their immune-related genes. PF-A that showed high immune-expression clustered closely to the ST ependymomas. Significant expressions of genes related to “antigen-processing” and “adhesion” pathways were found in the immune-active groups. On the contrary, the PF-A that had low expressions of immune-related genes showed a high expression of BMI1 that has a prognostic and therapeutic value. Connecting gene expression to bulk sequence data validated the findings. In addition, immunohistochemical analysis confirmed that protein expression for some of the findings. Conclusion The TIME varies in ependymomas based on the location of the tumor. Moreover, the immune-related expression profiles indicated that PF-A ependymomas can be divided into two groups: immune-active and immune-not active PF-A. The prognostic and therapeutic values of the immune activity of PF-A should be further studied.
Patterns of telehealth utilization during the COVID-19 pandemic and preferences for post-pandemic telehealth use: A national survey of oncology clinicians.
Authors: Christopher Manz, Nancy N. Baxter, Nefertiti C. duPont, Merry Jennifer Markham, Caitlin Drumheller, Lela Durakovic, Angela Kennedy
Journal: Journal of Clinical Oncology (2021)

1580 Background: Rarely used in routine practice pre-pandemic, telehealth utilization for cancer care rose significantly during the COVID-19 pandemic. Increased familiarity with telehealth has led to calls to continue its use after the pandemic ends. Yet national patterns of oncology telehealth utilization by visit type, preferences for telehealth use post-pandemic and barriers to telehealth for patients with cancer have not been described. Methods: 9,336 survey invitations were emailed to US-based ASCO members who have agreed to receive communications. Survey distribution was equally divided over five US regions, and practice type (e.g., academic, community) was reflective of ASCO membership proportions. The survey was open and data collected from January 4-28, 2021. Non-respondents received two reminder emails at week intervals. Analysis is descriptive. Results: 200 respondents completed the survey (2%). Respondents were 72% medical oncologists, 66% urban, 64% academic-affiliated, and from 42 states. 99% currently offered telehealth. 63% used telehealth for &lt;=30% of all patient visits in the last 30 days; 18% used telehealth for more than half of visits. Telehealth utilization varied by visit type (table). 64% reported that the care delivered in telehealth visits was similar quality to in-person visits (29% worse). Assuming no regulatory or financial barriers to telehealth use after the pandemic, 92% would like to use telehealth for at least some visit types; only 8% prefer not to use telehealth. 20% would like to use telehealth for all visits types, and 64%, 54%, 33% and 17% would like to use telehealth for survivorship, symptom management, evaluation of patients receiving treatment and new patient visits, respectively (multiple selections allowed). Major barriers to telehealth were lack of patient access to technology (reported by 81%), limited patient technological proficiency (80%), language barriers (45%), uncertainty about future reimbursement (41%) and lack of administrative resources to support clinicians (33%). 68% agreed that the barriers increase cancer care disparities. Conclusions: Telehealth utilization was widespread during the COVID pandemic and varied by visit type. Most respondents plan to use telehealth in the future, but report barriers to continued use that worsen disparities.[Table: see text]
PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus <i>nab</i>-Paclitaxel–Treated Advanced Triple-Negative Breast Cancer
Authors: Hope S Rugo, Sherene Loi, Sylvia Adams, Peter Schmid, Andreas Schneeweiss, Carlos H Barrios, Hiroji Iwata, Véronique Diéras, Eric P Winer, Mark M Kockx, Dieter Peeters, Stephen Y Chui, Jennifer C Lin, Anh Nguyen-Duc, Giuseppe Viale, Luciana Molinero, Leisha A Emens
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background In the phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced or metastatic triple-negative breast cancer patients who were programmed death-ligand 1 (PD-L1)+ (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry assay. Here we evaluate 2 other PD-L1 assays for analytical concordance with SP142 and patient-associated clinical outcomes. Methods Samples from 614 patients (68.1% of intention-to-treat population) were centrally evaluated by immunohistochemistry for PD-L1 status on IC (VENTANA SP142, SP263, Dako 22C3) or as a combined positive score (CPS; 22C3). Results Using SP142, SP263, and 22C3 assays, PD-L1 IC ≥1% prevalence was 46.4% (95% confidence interval [CI] = 42.5% to 50.4%), 74.9% (95% CI = 71.5% to 78.3%), and 73.1% (95% CI = 69.6% to 76.6%), respectively; 80.9% were 22C3 CPS ≥1. At IC ≥1% (+), the analytical concordance between SP142 and SP263 and 22C3 was 69.2% and 68.7%, respectively. Almost all SP142+ cases were captured by other assays (double positive), but several SP263+ (29.6%) or 22C3+ (29.0%) cases were SP142– (single positive). A+nP clinical activity vs placebo+nP in SP263+ and 22C3+ patients (progression-free survival [PFS] hazard ratios [HRs] = 0.64 to 0.68; overall survival [OS] HRs = 0.75 to 0.79) was driven by double-positive cases (PFS HRs = 0.60 to 0.61; OS HRs = 0.71 to 0.75) rather than single-positive cases (PFS HRs = 0.68 to 0.81; OS HRs = 0.87 to 0.95). Concordance for harmonized cutoffs for SP263 (IC ≥4%) and 22C3 (CPS ≥10) to SP142 (IC ≥1%) was subpar (approximately 75%). Conclusions 22C3 and SP263 assays identified more patients as PD-L1+ (IC ≥1%) than SP142. No inter-assay analytical equivalency was observed. Consistent improved A+nP efficacy was captured by the SP142 PD-L1 IC ≥1% subgroup nested within 22C3 and SP263 PD-L1+ (IC ≥1%) populations.