tbuckley/cabot-search huggingface dataset:
Association of social support with overall survival and health care utilization in patients with aggressive hematologic malignancies.
Authors: Netana H. Markovitz, Tamryn Gray, Sunil Mahesh Bhatt, Ryan David Nipp, Nneka Ufere, Julia Rice, Matthew J. Reynolds, Mitchell W. Lavoie, Carlisle E. W. Topping, Madison A. Clay, Charlotta Lindvall, Areej El-Jawahri, Patrick Connor Johnson
Journal: Journal of Clinical Oncology (2021)

e18582 Background: Social support plays a crucial role for patients with aggressive hematologic malignancies as they navigate their illness course. We examined associations of social support with overall survival and health care utilization in this population. Methods: We conducted a cross sectional secondary analysis using data from a prospective longitudinal cohort study of 251 hospitalized patients with aggressive hematologic malignancies at Massachusetts General Hospital from 2014 through 2017. We utilized Natural Language Processing (NLP) to identify extent of patients’ social support (limited versus adequate as defined by NLP-aided chart review of the Electronic Health Record (EHR)). We used multivariable regression models to examine associations of social support with: 1) overall survival; 2) death or readmission within 90 days of discharge from index hospitalization; 3) time to readmission within 90 days; and 4) index hospitalization length of stay. Results: Patients had a median age of 64 (range: 19-93) years, and most were white (89.6%), male (68.9%), and married (65.3%). A plurality of patients had leukemia (42.2%) followed by lymphoma (37.9%) and myelodysplastic syndrome/myeloproliferative neoplasm (19.9%). Using NLP, we identified that 8.8% (22/251) of patients had limited social support. In multivariable analyses, limited social support was associated with worse overall survival (HR = 2.00, p = 0.042) and higher likelihood of death or readmission within 90 days of discharge (OR = 3.11, P = 0.043), but not with time to readmission within 90 days, or index hospital length of stay. Conclusions: In this cohort of hospitalized patients with aggressive hematologic malignancies, we found associations of limited social support with lower overall survival and higher likelihood of death or readmission within 90 days of hospital discharge. These findings underscore the utility of NLP for evaluating extent of social support and the need for larger studies evaluating social support in patients with aggressive hematologic malignancies.
Understanding the role of the gut in undernutrition: what can technology tell us?
Authors: Alex J Thompson, Claire D Bourke, Ruairi C Robertson, Nirupama Shivakumar, Christine A Edwards, Tom Preston, Elaine Holmes, Paul Kelly, Gary Frost, Douglas J Morrison
Journal: Gut (2021)

Gut function remains largely underinvestigated in undernutrition, despite its critical role in essential nutrient digestion, absorption and assimilation. In areas of high enteropathogen burden, alterations in gut barrier function and subsequent inflammatory effects are observable but remain poorly characterised. Environmental enteropathy (EE)—a condition that affects both gut morphology and function and is characterised by blunted villi, inflammation and increased permeability—is thought to play a role in impaired linear growth (stunting) and severe acute malnutrition. However, the lack of tools to quantitatively characterise gut functional capacity has hampered both our understanding of gut pathogenesis in undernutrition and evaluation of gut-targeted therapies to accelerate nutritional recovery. Here we survey the technology landscape for potential solutions to improve assessment of gut function, focussing on devices that could be deployed at point-of-care in low-income and middle-income countries (LMICs). We assess the potential for technological innovation to assess gut morphology, function, barrier integrity and immune response in undernutrition, and highlight the approaches that are currently most suitable for deployment and development. This article focuses on EE and undernutrition in LMICs, but many of these technologies may also become useful in monitoring of other gut pathologies.
A machine learning tool to predict mortality risk among patients with metastatic cancer in outpatient oncology care.
Authors: Brandon Butler, Nadaa Tayiab, Serra Phu, Susan Nga Hoang, Brian Turnwald, Jody S. Garey, Bo He, John Russell Hoverman
Journal: Journal of Clinical Oncology (2021)

1560 Background: End-of-life management is a well-known challenging aspect of cancer care. In particular, timely hospice enrollment is a leading quality metric in the Oncology Care Model that has substantial room for improvement. An automated algorithmic tool that can incorporate the wealth of available EHR data and rapidly identify patients with a high risk of imminent mortality could be a valuable asset to supplement important clinical decisions and improve timely hospice care. Methods: A retrospective study cohort was formed using patients with metastatic cancer from US Oncology Network (USON) practices participating in the Oncology Care Model (OCM) between January 1, 2017 and June 30, 2019. Patients were required to have at least one record for lab values and vital signs in the EHR database. Patients were excluded from the study cohort if they were not enrolled in the OCM program or did not have a diagnosis for metastatic cancer. The patients satisfying the selection criterion were used to train and optimize the model. The training dataset was also used for internal validation and hyperparameter tuning until the final model was produced. As external validation, the final model was independently tested on 3 separate holdout datasets including OCM patients between July 1, 2019 and March 31, 2020. To avoid bias, all holdout datasets used for validation were excluded from the model. Results: A multivariable model to predict 90-day mortality was developed using a retrospective dataset derived from EHR data and Medicare claims data. A logistic regression algorithm using L1 (lasso) regularization yielded the best performance compared to other model candidates. The performance on the training cohort was given by a cross-validated AUC score of 0.85 (95% CI, 0.84 to 0.86). Further, external validation conducted using 3 independent holdout datasets demonstrated impressive generalizability marked by stable performance scores across multiple time periods (AUC between 0.84 and 0.85). Conclusions: This study builds upon previous work and further establishes the utility of machine learning to predict risk of imminent mortality for advanced cancer patients using available EHR data. A data-driven tool that estimates the probability of 90-day mortality could be leveraged as a powerful supplementary aid to clinicians managing end-of-life care at oncology practices.
Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients
Authors: Arne Sattler, Eva Schrezenmeier, Ulrike A. Weber, Alexander Potekhin, Friederike Bachmann, Henriette Straub-Hohenbleicher, Klemens Budde, Elena Storz, Vanessa Proß, Yasmin Bergmann, Linda M.L. Thole, Caroline Tizian, Oliver Hölsken, Andreas Diefenbach, Hubert Schrezenmeier, Bernd Jahrsdörfer, Tomasz Zemojtel, Katharina Jechow, Christian Conrad, Sören Lukassen, Diana Stauch, Nils Lachmann, Mira Choi, Fabian Halleck, Katja Kotsch
Journal: Journal of Clinical Investigation (2021)

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.
Real-world experience of pancreatic cancer molecular profiling in a tertiary center.
Authors: Kai Sun, Charisma Mylavarapu, Aubrey Crenshaw, Yuqi Zhang, Enshuo Hsu, Jiaqiong Xu, Marilyn Niravath, Juan Carlos Nicolas, Stephen Jones, Maen Abdelrahim
Journal: Journal of Clinical Oncology (2021)

e22526 Background: NCCN has recommended universal genetic testing of pancreatic cancer. Liquid biopsies have been approved by the FDA to facilitate detection of targetable mutations in various solid tumors. Methods: To investigate how oncologists follow NCCN guidelines and utilize liquid biopsies in pancreatic cancer, we retrospectively queried patient records from 7/2016 to 6/2020 in our institutional system. Those retrieved but with pancreatic cancer care from other 2 local institutions are also included. Demographics, cancer stage on diagnosis, year of diagnosis, molecular profiling (MP) and treatment setting (community vs academic) are recorded and analyzed. Results: A total of 500 pancreatic cancer patient records were identified. Of these, 234 patients were excluded due to incomplete records. Among the remaining 266 patients, 113 (42.5%) had MP performed. Younger patients and those treated at an academic setting were more likely to have MP (P= 0.0051 and 0.0010 respectively). The trend of increased utilization of MP over the years is also statistically significant (p&lt; 0.0001). Gender, ethnicity or stage on diagnosis are not statistically significant between groups. (Table). Conclusions: MP is being increasingly utilized. However, more awareness is needed among oncologists, especially those who practice in the community setting.[Table: see text]
Interventions to alleviate financial toxicity among patients with cancer: A systematic review.
Authors: Asad Arastu, Andrew Hamilton, Emerson Yu-sheng Chen
Journal: Journal of Clinical Oncology (2021)

e18841 Background: Financial toxicity (FT) has become a recognized side effect associated with cancer diagnosis and treatment; however, there is little data on what interventions have proven to be effective at mitigating the financial burden patients might face. Methods: A systematic review following the Preferred Reporting Items for Systematic Reviews and Met-Analysis (PRISMA) guidelines was conducted in MEDLINE, Embase, and PsycInfo. Broad terminology to capture FT and all possible interventions was used to identify articles published through June 25, 2020 in MEDLINE and July 31, 2020 in Embase and PsycInfo. We excluded systematic reviews, studies not conducted in the United States, with non-adult participants, or those that did not examine an intervention to directly alleviate FT. Two independent reviewers (AA and EYC) reviewed all abstracts to identify which articles met inclusion criteria. An inductive approach was used to thematically categorize unique intervention strategies. Results: A total of 1126 abstracts were identified from the initial search strategy, and 9 met final inclusion criteria. Across these studies, 12 distinct strategies were reported in 27 unique occurrences. They were mapped into four broad domains: 1) patient assistance programs (PAPs) through pharmaceutical company and/or charity sponsored programs, 2) financial navigators who provide counseling and community resources, 3) direct coverage through free medications or payments, and 4) indirect coverage for related services (e.g. transportation). Direct coverage was most commonly proposed, 15/27 (56%) of interventions, followed by PAPs 5/27 (18%), financial navigators 4/27 (15%), and indirect costs 3/27 (11%). These interventions led to outcomes including: cost savings to patients in 5/9 studies (56%), alleviated fears surrounding cost of treatment in 2/9 (22%), earlier medication fills in 1/9 (11%), and decreased anxiety on a self-reported Likert scale in 1/9 (11%). Conclusions: While potential solutions to FT from cancer care remain unclear, this systematic review demonstrates that particular implemented strategies have lessened patient expenses, improved therapy adherence, or helped patients live better. Additional resources could help equip providers and institutions on how to use existing infrastructure (PAPs) or how to deploy additional workforce to diminish FT.
Novel application of Kaplan-Meier methods to model tolerance for nonadherence to imatinib in patients with chronic myeloid leukemia (CML) in the ADAGIO study.
Authors: Mavis Obeng-Kusi, Karen MacDonald, Marie-Anne van Lierde, Ivo Abraham
Journal: Journal of Clinical Oncology (2021)

7038 Background: Although adherence to imatinib treatment has been shown to be critical for attaining treatment response among patients with CML, some studies have suggested a 7.3-9.9% nonadherence tolerance margin before loss of treatment effects. We aimed to model probabilistically the margin of tolerance required to ensure treatment response among patients prescribed imatinib and the margin, if any, before treatment response is at risk. Methods: We performed a post hoc analysis of the ADAGIO study conducted in Belgium on 169 evaluable patients ( Blood 2009). Using the pill count ratio as, what in conventional survival analysis would be, the time variable, we modeled the cumulative likelihood of treatment response as a function of increasing pill count adherence. We applied Kaplan-Meier methods to model the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) (as defined by the European Leukemia Net) response as a function of 90-day pill count adherence. Kaplan-Meier methods thus estimated the tolerance for nonadherence to imatinib by calculating the 1 minus Kaplan-Meier estimate for treatment response. Results: Analyses (see Table) showed that ̃100% adherence of prescribed dose is associated with probabilities (rounded) of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90% adherence. (of 0.7698 (MMR). Increasing the intake of imatinib from 90% to 100% of the prescribed dose increased the likelihood of the various treatment responses by 1.95 to 2.35-fold. Conclusions: Our findings challenge any previously estimated tolerance for nonadherence. There is virtually no margin for nonadherence if the objective is to optimize the likelihood of treatment response, and only a minimal margin to avoid impaired treatment response. Under such adherence, response rates similar to those in the pivotal IRIS trial can be obtained. Clinicians must assess and promote patient adherence, and patients must be perfectly adherent.[Table: see text]
Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.
Authors: Anahat Kaur, Shuai Wang, Tarek N. Elrafei, Lewis Steinberg, Abhishek Kumar
Journal: Journal of Clinical Oncology (2021)

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]
High-Dose Melphalan-Based Sequential Conditioning Chemotherapy Followed By Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)
Authors: Christoph Groth, Nina Kristin Steckel, Jan-Henrik Mikesch, Rudolf Trenschel, Hellmut Dietmar Ottinger, Carsten Müller-Tidow, Christoph Schliemann, Christian Reicherts, Eva Schmidt, Wolfgang E. Berdel, Georg Lenz, Markus Ditschkowski, Dietrich W Beelen, Matthias Stelljes
Journal: Blood (2017)
Improving access to timely pain management in an underserved oncology clinic: A palliative care-oncology partnership.
Authors: Aaron Chan, Radu Firtat, Christopher Metchnikoff, Phillis Wu, Katherine Yu
Journal: Journal of Clinical Oncology (2021)

e18672 Background: In the 4 years since inception, the palliative care (PC) clinic at Olive-View UCLA Medical Center (OVMC) cared for less than 6% of pain-positive cancer patients based on guidelines put forth by ASCO. As with other under-resourced safety-net settings, the demand for PC services at OVMC far exceeds the manpower available for optimal pain management in oncology patients. This year long project aims to improve pain management in a busy oncology clinic via enhanced identification and prompt treatment of cancer pain by Oncologists. Methods: At the project start, Oncologists were surveyed to identify key elements to be incorporated into formal didactics on pain management principles, case-based discussions and real-time mentoring. At the weekly oncology clinic, patients were screened for pain using the multi-modal PEG scale: Average Pain intensity (P), interference with Enjoyment of life (E), and interference with General activity (G) over the preceding week. The Oncologist was notified of the PEG score if a patient had an average score ≥4 (0-10 scale) for review and intervention. Patients were screened using the same method at subsequent visits. EHR of patients with PEG scores ≥4 were reviewed to determine whether therapeutic interventions were made by the Oncologist. A comparison of PEG scores to the standard nursing intake pain scores was also conducted. Results: Over a 4-month period, 513 PEG forms were administered, 37% of which resulted in a pain score ≥4. Of the 172 patients who screened positive, 54 patients were screened at follow up visit(s). Comparing the pain-positive cohort, we observed an average decrease in pain by 25.5% (7.1 to 5.3) in patients who received intervention as opposed to 7.4% (5.0 to 4.7) in patients who did not receive intervention by their Oncologist. Further, there was a remarkable divergence between the average PEG score (6.7) and nurse intake pain score (1.4) in this patient cohort. Conclusions: Our findings suggest that improved Oncologist real-time pain assessment and intervention incorporating a validated pain screening tool leads to timely pain management in cancer patients. Implementation of a Palliative Care-Oncology partnership promotes provider awareness and confidence in treating patients with complex pain. A functional pain assessment, using PEG, can more accurately reflect pain compared to the current standard nursing intake process. Particularly in resource challenged settings where access to PC is limited, facilitating timely pain management through training and mentoring of oncologists or other primary providers can be a sustainable model to improve patient access to primary palliative care. Given the early indicators of success we hope to expand this workflow in training other healthcare providers within our County safety net system. Research Sponsor: California Health Care Foundation.
Dual Covalent Inhibition of PKM and IMPDH Targets Metabolism in Cutaneous Metastatic Melanoma
Authors: Marwa Zerhouni, Anthony R. Martin, Nathan Furstoss, Vincent S. Gutierrez, Emilie Jaune, Nedra Tekaya, Guillaume E. Beranger, Patricia Abbe, Claire Regazzetti, Hella Amdouni, Mohsine Driowya, Patrice Dubreuil, Frédéric Luciano, Arnaud Jacquel, Meri K. Tulic, Thomas Cluzeau, Brendan P. O'Hara, Issam Ben-Sahra, Thierry Passeron, Rachid Benhida, Guillaume Robert, Patrick Auberger, Stéphane Rocchi
Journal: Cancer Research (2021)

Overcoming acquired drug resistance is a primary challenge in cancer treatment. Notably, more than 50% of patients with BRAFV600E cutaneous metastatic melanoma (CMM) eventually develop resistance to BRAF inhibitors. Resistant cells undergo metabolic reprogramming that profoundly influences therapeutic response and promotes tumor progression. Uncovering metabolic vulnerabilities could help suppress CMM tumor growth and overcome drug resistance. Here we identified a drug, HA344, that concomitantly targets two distinct metabolic hubs in cancer cells. HA344 inhibited the final and rate-limiting step of glycolysis through its covalent binding to the pyruvate kinase M2 (PKM2) enzyme, and it concurrently blocked the activity of inosine monophosphate dehydrogenase, the rate-limiting enzyme of de novo guanylate synthesis. As a consequence, HA344 efficiently targeted vemurafenib-sensitive and vemurafenib-resistant CMM cells and impaired CMM xenograft tumor growth in mice. In addition, HA344 acted synergistically with BRAF inhibitors on CMM cell lines in vitro. Thus, the mechanism of action of HA344 provides potential therapeutic avenues for patients with CMM and a broad range of different cancers. SIGNIFICANCE: Glycolytic and purine synthesis pathways are often deregulated in therapy-resistant tumors and can be targeted by the covalent inhibitor described in this study, suggesting its broad application for overcoming resistance in cancer.