tbuckley/cabot-search huggingface dataset:
Treatment-related toxicity and improved outcomes with immune checkpoint inhibitors in patients with hepatocellular carcinoma.
Authors: Alessio Cortellini, Thomas Urban Marron, Pallavi Shruti Mishra-Kalyani, Yutao Gong, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Uqba Khan, Ahmed Omar Kaseb, Yi-Hsiang Huang, Celina Ang, Julie A. Schneider, Anjana Pillai, Lorenza Rimassa, Richard Pazdur, Marc Robert Theoret, Steven Lemery, Lorraine Cheryl Pelosof, David James Pinato
Journal: Journal of Clinical Oncology (2021)

4085 Background: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI), however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). This retrospective multi-center study aimed to examine whether trAEs are prognostic in HCC. Methods: We established an international consortium of 10 tertiary-care referral centers located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to test whether the development of clinically significant trAE (i.e. graded &gt;2, trAE2) predicted for improved overall (OS), progression-free survival (PFS), and overall response rates (ORR) following ICI, and subsequently validated this association in a separate cohort of 406 HCC patients receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. Results: In a multi-institutional cohort of 357 patients, 274 (77%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 304, 85%), trAE were reported in 146 patients (41%). Development of trAE2 were associated with longer OS (23.3 versus 12.2 months) and PFS (8.6 months versus 3.7 months). After adjusting for viral aetiology, gender, presence of cirrhosis, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy, trAE2 were confirmed predictors of improved OS (HR 0.55; 95%CI:0.34-0.88) and PFS (HR 0.51; 95%CI: 0.35-0.74). TrAE2 were associated with higher ORR (27% versus 16%) from ICI. The association between trAE2 and patients’ OS (HR 0.49; 95%CI:0.34-0.70) and PFS (HR 0.43; 95%CI:0.32-0.59) was also observed in the FDA dataset. After a 6-weeks landmark selection, trAE2 were confirmed to be associated with improved PFS (HR 0.59; 95%CI:0.39-0.87); the additional analysis adjusted for tumour response and duration of treatment within the FDA cohort further confirmed the association with longer PFS (HR 0.67; 95%CI: 0.47-0.94). Conclusions: Development of trAE2 may correlate with response and survival in patients with HCC receiving ICI, a clinical setting where the lack of biomarkers still represents an unmet need. Prospective studies aimed at understanding the underlying immunologic foundations of such relationship are warranted to identify predictive biomarkers of toxicity and response.
Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC)—NRG-GI004/SWOG-S1610.
Authors: Michael J. Overman, Greg Yothers, Samuel A. Jacobs, Hanna Kelly Sanoff, Deirdre Jill Cohen, Katherine A Guthrie, Norah Lynn Henry, Patricia A. Ganz, Scott Kopetz, Peter C. Lucas, Charles David Blanke, Norman Wolmark, Howard S. Hochster, Thomas J. George, Caio Max Sao Pedro Rocha Lima
Journal: Journal of Clinical Oncology (2021)

TPS3618 Background: The superiority of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H over chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti- epithelial growth factor receptor (EGFr) antibodies in mCRC has been demonstrated in a phase III trial (N Engl J Med 2020; 383:2207). However, more patients had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean progression-free survival (PFS) of 13.7 months. Preclinical models have demonstrated synergistic interactions between FOLFOX, anti-VEGF, and anti-PD-1. We hypothesize that the dMMR/MSI-H mCRC patients may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-L1 therapy (atezo) alone. Methods: Initially a three-arm study, the mFOLFOX6/bev arm was closed to new enrollment on 6-4-20 due to emerging data; the redesigned COMMIT trial was reactivated on 1/29/2021 as a prospective phase III open-label trial that randomizes (1:1) mCRC dMMR/MSI-H pts (N=211) to either atezo monotherapy or mFOLFOX6/bev+atezo combination. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is PFS as assessed by site investigator. Secondary endpoints include overall survival (OS), objective response rate (RECIST v1.1), safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Clinical trial: NCT02997228. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
Impact of multidisciplinary severe immunotherapy complication service on outcomes for cancer patients receiving immune checkpoint inhibition.
Authors: Leyre Zubiri, Gabriel E. Molina, Meghan Mooradian, Sienna Durbin, Michael Dougan, Molly Thomas, Alexander Faje, Michelle Rengarajan, Amanda C Guidon, Steven T. Chen, Mazen Nasrallah, Minna Kohler, Meghan Sise, Tomas G Neilan, Daniel A Zlotoff, Aditya Bardia, Ryan J. Sullivan, Yevgeniy R. Semenov, Alexandra C Villani, Kerry Lynn Reynolds
Journal: Journal of Clinical Oncology (2021)

2654 Background: The exponential increase in FDA-approved indications for immune checkpoint inhibitors (ICI) in cancer care has resulted in therapeutic success but also in the occurrence of immune-related adverse effects (irAEs) that can represent a significant clinical challenge. On October 3 2017, the Massachusetts General Hospital (MGH) implemented the Severe Immunotherapy Complications (SIC) Service, a multi-disciplinary care team for patients hospitalized with irAEs. The objectives of this study were to evaluate the impact of SIC Service on 1) healthcare utilization and 2) patients outcomes. Methods: Using pharmacy and hospital admission databases, a list of patients was identified that both received ICI for a malignancy and were hospitalized with severe irAEs in the period prior to initiation of the SIC service and after SIC initiation. The pre-SIC period was defined as an admission between 4/2/2016 through 10/3/2017, and the post-SIC period as an admission from 10/3/2017 through 10/24/2018. The rate of readmission after the index hospitalization was the primary outcome. Secondary outcomes included lengths of stay (LOS) for both initial irAE admissions and readmissions, use of corticosteroids and non-steroidal second-line immunosuppression, ICI discontinuation, and inpatient mortality in the pre- and post-SIC periods. Results: Among 1169 patients treated in the pre-SIC service intervention period; 127 were hospitalized for irAE. Among 1159 patients treated in the post-SIC intervention 122 were hospitalized for irAE. SIC Service implementation was associated with a significant reduction in irAE readmission rates (post-SIC 14.8% vs. pre-SIC 25.9%; odds ratio [OR], 0.46; 95% CI, 0.22-0.95; p=0.036). The length of stay, rates of corticosteroid use, second-line immunosuppression, and ICI discontinuation for irAE, as well as inpatient mortality rates were not significantly different before and after SIC Service implementation. Conclusions: This is the first study to report that establishing a highly subspecialized care team focused on irAEs can be associated with improved clinical outcomes for patients receiving ICI therapy. Such care teams may play an essential part in optimizing irAE care.
Computational features of TIL architecture are differentially prognostic of uterine cancer between African and Caucasian American women.
Authors: Sepideh Azarianpour Esfahani, Pingfu Fu, Haider Mahdi, Anant Madabhushi
Journal: Journal of Clinical Oncology (2021)

5585 Background: Although the vast majority of endometrial cancer (EC) is early-stage and thus, curable by surgery, chemotherapy, and radiotherapy (with at least 85% 5-year OS), a fraction of them are aggressive neoplasms such as high-grade or deeply invasive lesions and thus exhibit poor prognosis. African American (AA) women are disproportionately affected by high-grade EC and have 80% higher mortality rate compared with Caucasian American (CA) women. In this work, we evaluated the prognostic ability of computational measurements of architecture of tumor-infiltrating lymphocytes (ArcTIL) from H&amp;E slide images for EC. We also investigated the presence of morphologic differences in terms of ArcTIL features between AA and CA women and whether ArcTIL based population-specific models were more prognostic of OS in AA women compared to a population-agnostic model. Methods: The study included digitized H&amp;E tissue slides from 445 post-surgery EC patients from TCGA, with further chemotherapy, or radiotherapy, including only the AA and CA patients, patients without reported race or from other populations were excluded. The dataset was divided into discovery (D1, n = 300), and a validation set (D2, n = 145), while ensuring population balance between two splits (D1(AA) = 65, D1(CA) = 235, D2(AA) = 37, D2(CA) = 108). A machine learning approach was employed to identify tumor regions, and tumor-associated stroma on the diagnostic slides and then used to automatically identify TILs within these compartments. Graph network theory based computational algorithms were used to capture 85 quantitative descriptors of the architectural patterns of intratumoral and stromal TILs. A multivariable Cox regression model (MCRM) was used to create population specific-prognostic models (M AA , M CA ) and a population-agnostic model (M AA+CA )) to predict OS. All 3 models were evaluated on D2(AA), D2(CA), and D2. Results: M AA identified 4 prognostic features relating to interaction of TIL clusters with cancer nuclei in stromal compartment and was prognostic of OS on D2(AA) (see Table) but not prognostic in D2(CA) nor D2(AA+CA). M CA and M AA+CA identified respectively 7 and 6 prognostic features relating to interaction of TIL clusters with cancer nuclei (both in the epithelial and stromal regions) and were prognostic of OS on D2(CA) and D2, but not prognostic in D2(AA). Conclusions: Our findings suggest an important role of stromal TIL architecture in prognosticating OS in AA women with EC, while epithelial TIL features were more prognostic in CA women. These findings need to be validated in larger, multi-site validation sets.[Table: see text]
Laparoscopic bowel resection combined with hand-assisted endoscopic balloon dilation for Crohn’s disease with multiple bowel strictures
Authors: Jia Ke, Jiancong Hu, Min Zhang, Wei Wang, Ping Lan, Xiaojian Wu, Min Zhi
Journal: Endoscopy (2021)

Stricturoplasty is a common surgical technique for patients with multiple bowel obstruction caused by Crohn's disease [1] [2] [3], Here, we present an innovative case of hand-assisted laparoscopic bowel resection combined with hand-assisted endoscopic balloon dilation (EBD).
The effects of tislelizumab treatment on the health-related quality of life of non-small cell lung cancer patients who progressed on a prior platinum-containing regimen.
Authors: Cai Zhou, Dingzhi Huang, Yiyuan Ma, Zhenyu Pan, Gisoo Barnes, Boxiong Tang
Journal: Journal of Clinical Oncology (2021)

9069 Background: Anti-PD-1/L1 therapies have improved overall survival (OS) by 2-4 months vs docetaxel in patients with advanced non−small cell lung cancer (NSCLC) who progressed after receiving a platinum regimen. Tislelizumab, an anti-PD-1 antibody, has been tested as monotherapy in the RATONALE (NCT 03358875) trial, which found that tislelizumab prolonged OS (median OS difference 5.3 months in ITT population) as compared to docetaxel, improved progression-free survival (median 4.1 vs 2.6 months), as well as overall response rate (ORR difference = 14.9%).Here we report health-related quality of life (HRQoL) of patients receiving tislelizumab vs docetaxel in this clinical trial. Methods: NSCLC patients in this open-label, multicenter Phase 3 study were randomized to either the tislelizumab or docetaxel. HRQoL was measured using the QLQ-C30 global health status/quality of life score (GHS/QoL) from EORTC QLQ-C30 as well as the lung cancer specific subscales of the EORTC QLQ-LC13. Descriptive analysis for the GHS/QoL score was performed for baseline through cycle 10; changes from baseline to cycle 12 were examined for the symptom subscales. Results: 805 patients were randomized to tislelizumab (n = 535) or docetaxel (n = 270). Patients were 77% male with an average age of 60 years (range 28-88 years). The compliance rates were mostly &gt; 98% and were similar across arms. The GHS/QoL score in the tislelizumab arm improved relative to baseline from cycles 5 through 10 while declining in cycles 6 through 10 in the docetaxel arm. The tislelizumab arm showed a reduction from baseline at cycle 12 in the symptom scores of coughing, chest pain, and dyspnea while patients in the docetaxel arm experienced an increase in symptoms. Conclusions: The study results show that tislelizumab monotherapy improved HRQoL in patients who previously failed treatment with a platinum containing chemotherapy; this is especially important as the NSCLC patients treated with tislelizumab not only experienced improvements in OS, but also reductions in their symptomology. Clinical trial information: NCT 03358875.
Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost Opportunities
Authors: Jesse D. Schold, Anne M. Huml, Emilio D. Poggio, John R. Sedor, Syed A. Husain, Kristin L. King, Sumit Mohan
Journal: Journal of the American Society of Nephrology (2021)

Kidney transplantation is associated with the best outcomes for most patients with ESKD. The national Kidney Allocation System prioritizes patients with Estimated Post-Transplant Survival (EPTS) scores in the top 20% for expedited access to optimal deceased donor kidneys.We studied adults aged ≥18 years in the United States Renal Data System with top 20% EPTS scores who had been preemptively waitlisted or initiated dialysis in 2015-2017. We evaluated time to waitlist placement, transplantation, and mortality with unadjusted and multivariable survival models.Of 42,445 patients with top 20% EPTS scores (mean age, 38.0 years; 57% male; 59% White patients, and 31% Black patients), 7922 were preemptively waitlisted. Among 34,523 patients initiating dialysis, the 3-year cumulative waitlist placement incidence was 37%. Numerous factors independently associated with waitlisting included race, income, and having noncommercial insurance. For example, waitlisting was less likely for Black versus White patients, and for patients in the lowest-income neighborhoods versus those in the highest-income neighborhoods. Among patients initiating dialysis, 61% lost their top 20% EPTS status within 30 months versus 18% of patients who were preemptively listed. The 3-year incidence of deceased and living donor transplantation was 5% and 6%, respectively, for patients who initiated dialysis and 26% and 44%, respectively, for patients who were preemptively listed.Many patients with ESKDqualifying with top 20% EPTS status are not placed on the transplant waiting list in a timely manner, with significant variation on the basis of demographic and social factors. Patients who are preemptively listed are more likely to receive benefits of top 20% EPTS status. Efforts to expedite care for qualifying candidates are needed, and automated transplant referral for patients with the best prognoses should be considered.This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_07_30_JASN2020081146.mp3.
The effectiveness and safety of eribulin therapy in HR-positive HER2-negative metastatic breast cancer post-CDK4/6 inhibitor therapy in Russian clinical practice.
Authors: Irina Vladimirovna Kolyadina, Larisa Bolotina, Lyudmila Zhukova, Liubov Yu Vladimirova, Alexander Sultanbaev, Elena Karabina, Inna Ganshina, Elena Ovchinnikova, Irina Vladimirovna Kolyadina, Galina Antonova, Mikhail Volkonsky, James Kolokolov, Elena Zueva, I Akopyan, Natalia Fadeeva, Irina Evstigneeva, Svetlana Orlova, Anna Vasilevskaya, Oxana Shalaeva, Oxana Shirokova
Journal: Journal of Clinical Oncology (2021)

e13035 Background: EMPOWER trial demonstrated the benefit of eribulin administrated post CD4/6i in patients (pts) with HR+ HER2-negative (HR+HER2-) metastatic breast cancer (MBC). There are several important limitations to this trial: &gt; 60% of pts were stage IV at the time of treatment initiation, eribulin used in late lines (2L only in 30% pts) and follow-up data were immature. Current study aimed to provide additional data on the real-world effectiveness and safety of eribulin monotherapy in this setting. Methods: Observation study of eribulin monotherapy in standard regimen enrolled 54 pts (median age 56; range 29-79 years) with HR+ HER2- MBC received at least one dose of eribulin post CDK 4/6i in metastatic settings; 24% pts had de novo metastatic BC, 76% - recurrent BC; 77% received palbociclib, 21% ribociclib, 2% both drugs; 49% pts received CDK4/6i with fulvestrant and 51% with AI. CDK4/6i was used: 49% pts in 1L, 36% in 2L, 16% in 3L. Median DOR of CDK4/6i treatment was 9.07 months (range 2-38). 94% pts received anthracyclines and taxanes, eribulin was used in 2L in 60%, 30% in 3L, 8% in 4L, 2% in 5L. The most common sites of metastases (Mts) were bones (78%), liver (73%), lung (56%) and brain (8%); visceral Mts were seen in 90% pts. Median follow-up – 11,5 months (range 3-36). Results: Median cycles of eribulin therapy was 10,5 (range 1-44); objective response rate was seen in 24%, stabilization - 67%, progression - in 9%. Median PFS was 10.0 months, there were no significant differences in the different subgroups (visceral/no visceral; recurrent/de novo BC; age; CDK4/6i as 1L vs 2L, fulvestrant vs AI), p &gt; 0,05. Median PFS was higher in pts with lung Mts vs non-lung (24 vs 9,1 months, p = 0.056). Most common AEs all grades were neutropenia (26%), anemia (9%), asthenia (9%), polyneuropathy (11.1%). AE did not affect the effectiveness of eribulin (p = 0.648). Dose reduction was in 19% pts and did not affect the effectiveness of eribulin (p = 0.612). At median follow-up of 11.5 months, 92.5% of patients still alive. Conclusions: As post-CDK4/6i therapy, eribulin in HR+HER2- MBC pts was effective and well tolerated, regardless of age, line of CDK4/6, CDK 4/6i combination partner. Patients with metastasis to the lung have better mPFS. Results in this real-world population of pts with HR+HER2- MBC were consistent with the EMPOWER study, and support administration of eribulin in 2-3 lines as an effective option for post-CD4/6i pts.
Randomized phase 2 study of nivolumab (nivo) plus either standard or reduced dose bevacizumab (bev) in recurrent glioblastoma (rGBM).
Authors: Manmeet Singh Ahluwalia, Yasmeen Rauf, Hong Li, Patrick Y. Wen, David M. Peereboom, David A. Reardon
Journal: Journal of Clinical Oncology (2021)

2015 Background: Trials with anti-PD1 in rGBM have shown limited efficacy. VEGF is highly up regulated proangiogenic growth factor in GBM contributing to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. Methods: 90 patients with first-recurrent GBM were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Single cell RNA sequencing with CITE-seq was used to analyze blood samples from pre- and 8 weeks post-treatment among 8 responders and 8 non-responders. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. Results: 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 of 88 patients were MGMT methylated (2 indeterminate). Overall OS was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p = 0.14), while OS was better for arm A in age &gt; 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P = 0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P = 0.90). Single cell RNA sequencing with CITE-seq was used to analyze blood samples from 16 patients, baseline and 8 weeks post treatment. Standard dose bevacizumab treated patients had decreased myeloid derived suppressor cells and an inflammatory response gene signature at 8 weeks. Most frequent toxicities ( &gt; 20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. Conclusions: Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab may benefit older but not younger patients. Ongoing response evaluation and immunocorrelative data will be presented. Clinical trial information: NCT03452579.
Abstract 15736: Correlates of Self-Care in Patients With Heart Failure Vary by Self-Care Activities: Medication Adherence, Dietary Sodium Adherence, and Symptom Management
Authors: Seongkum Heo, Debra K Moser, Terry A Lennie, Mary Fischer, Songthip Ounpraseuth, Mary N Walsh, JinShil Kim
Journal: Circulation (2018)

Introduction: Poor self-care is very common in patients with heart failure (HF) and adversely affects HF symptoms, hospitalization, and mortality. Different factors may be associated with each type...