tbuckley/cabot-search huggingface dataset:
Blood-based biomarker analysis in high PD-L1 expressing NSCLC treated with PD-1/PD-L1 based therapy with or without the addition of platinum-based chemotherapy.
Authors: Mary J. Fidler, Victoria Meucci Villaflor, Amol Rao, Balazs Halmos, Erin Marie Bertino, Raymond U. Osarogiagbon, David Paul Carbone
Journal: Journal of Clinical Oncology (2021)

TPS9126 Background: Immunotherapy directed against the programmed death-1 / ligand-1 (PD-1/L1) axis has revolutionized the treatment of advanced non-small cell lung cancer (aNSCLC). Tumor PD-L1 is currently the only biomarker validated for predicting patient response to front line PD-1/L1 directed immunotherapy, yet 20% of patients with ≥50% PD-L1 expression die within six months of starting therapy (Reck et al. 2016). Blood-based agents such as autoantibodies and circulating inflammatory biomarkers have stratified patient outcomes on anti-PD-1/L1 immunotherapy in preliminary studies (Tarhoni, Kollipara et al. 2019; Tarhoni, Fidler et al. 2019). Moreover, a serum-based proteomic test that uses mass spectrometry and machine learning to provide three classifications (Good, Intermediate and Poor) has stratified non-treatment naïve aNSLCC patients treated with nivolumab based on their outcomes (Mueller et al. 2020) and identified a subset of patients who progressed rapidly. This study will evaluate these blood-based biomarkers as predictors of response and early progression in patients with &gt;50% PD-L1 positive aNSCLC treated with immunotherapy regimens. Methods: This is a prospective, observational, multicenter study (NCT04676386) designed to assess biomarkers (serum and plasma) as predictive of early progression in 390 patients with aNSCLC treated with anti-PD 1/PD-L1 immunotherapy with or without platinum-based chemotherapy. Key eligibility criteria are treatment naïve aNSCLC with tumor biopsy PD-L1 tumor proportion score &gt; 50%, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and ability to consent to participate. Prior to enrollment, tumor specimens will be tested for PD-L1 expression according to participating centers’ standard operating procedures. For each treatment cohort of 195 patients, enrollment will proceed in sub-cohorts to ensure a population with 20% patients with ECOG PS2 and a total of 40 patients with squamous cell carcinoma per treatment arm. Patients will be followed for a maximum of 3 years. Blood draw for biomarker assessment will be performed prior to treatment initiation, start of 3rd cycle and investigator assessed progression. Biomarker analysis will be performed retrospectively. As a secondary objective, this study will evaluate proteomic test performance in predicting early overall survival (OS) and rapid progression, and in stratifying patient survival and response. Exploratory analyses will correlate baseline and serial circulating protein analytes and autoantibodies with the proteomic test, response measures (RECIST 1.1) and toxicities. Enrollment opened in February 2021. Clinical trial information: NCT04676386.
A multicenter randomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF trial): Analysis of overall survival.
Authors: Masatoshi Kudo, Kiyoshi Hasegawa, Yoshikuni Kawaguchi, Tadatoshi Takayama, Namiki Izumi, Naoki Yamanaka, Mitsuo Shimada, Masahumi Inomata, Shuichi Kaneko, Hideo Baba, Kazuhiko Koike, Masao Omata, Masatoshi Makuuchi, Yutaka Matsuyama, Norihiro Kokudo
Journal: Journal of Clinical Oncology (2021)

4093 Background: The initial report of the multicenter SURF trial (surgery vs. radiofrequency ablation [RFA] for small hepatocellular carcinoma [HCC]) showed that recurrence-free survival (RFS) did not differ significantly between patients undergoing surgery and RFA. The focus of the present report was to assess the effect on overall survival (OS). Methods: The SURF trial was a multicenter, open-label, randomized, controlled, phase 3 trial conducted in 49 institutions in Japan. Patients (aged between 29 and 79 years) with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. Before enrollment, both liver surgeons and hepatologists who perform RFA confirm that all the patients can be treated using both surgery and RFA. Patients were then randomly assigned in a 1:1 ratio to undergo surgery or RFA, stratified by age, hepatitis-C virus infection, numbers of HCC, largest HCC diameter, and institution. The co-primary endpoints were RFS and OS. As per the protocol, RFS was reported previously at 3 years after the last accrual of patients. OS was planned at 5 years after the last accrual. This trial is registered in UMIN000001795. Results: During 2009–2015, 308 patients were enrolled. After excluding ineligible patients, the surgery and RFA groups included 150 and 152 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range, 1.5–2.2 cm) in the surgery group and 1.8 cm (interquartile range, 1.5–2.3 cm) in the RFA group. The median (range) follow-up period was 6.4 (0.4–10.8) years in the surgery group and 6.6 (0–10.7) years in the RFA group. OS did not differ significantly between the surgery and RFA groups as the 5-year OS (95% confidence interval [CI]) was 74.6% (66.5%–81.0%) in the surgery group and 70.4% (62.2%–77.3%) in the RFA group (hazard ratio (HR), 0.96; 95% CI, 0.64–1.43; P= 0.828). The analysis after long-term follow-up in the current report showed that RFS was not significantly different between the surgery and RFA groups: the 5-year RFS (95% CI), 54.7% (46.0%–62.5%) vs. 50.5% (42.1%–58.3%); HR 0.90; 95% CI 0.67–1.22; P= 0.498. Conclusions: SURF trial revealed that OS and RFS were not significantly different between patients undergoing surgery and RFA for small HCC (≤ 3 cm and 3 nodules). Clinical trial information: 000001795.
Association of the presence of estrogen and progesterone receptors in uterine carcinosarcoma with improved survival and increased immunogenicity.
Authors: Nathaniel L. Jones, Sharon Wu, Joanne Xiu, Rodney Paul Rocconi, Britt Kristina Erickson, Premal H. Thaker, Jubilee Brown, Thomas J. Herzog, Robert W. Holloway, Wolfgang Michael Korn, Matthew A. Powell, Annelise M. Wilhite
Journal: Journal of Clinical Oncology (2021)

5588 Background: Recent data has shed light on molecular profiles of uterine carcinosarcoma (UCS), but few have correlated molecular profiles with prognosis. In a preliminary data analysis, we found that hormone receptors (HR)—estrogen receptor (ER) and progesterone receptor (PR)—expression was associated with improved OS. Here, we investigate the molecular profile differences between ER+/- and PR +/- tumors. Methods: Tumor samples were analyzed using Next-Generation sequencing of DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing) and RNA (NovaSeq, whole transcriptome sequencing) and immunohistochemistry (IHC) at the Caris Life Sciences Laboratory (Phoenix, AZ).ER and PR tested by IHC on whole tumor (cut-off: +1, 10%). PD-L1 IHC used SP-142 (cut-off &gt;1%). MSI was tested by FA, IHC an NGS. TMB was measured by totaling somatic mutations per tumor (high &gt; 10 mutations per MB). Immune cell fraction was calculated by QuantiSeq. Overall survival (OS) information was obtained from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Statistical significance was determined by chi-square and Wilcoxon rank sum test and p-values adjusted for multiple comparisons (q) to be &lt;0.05. Results: 1,144 UCS tumors were included. (ER+, n=261; PR+, n=197; HR+ (ER+ and PR+), n=168). Median OS for patients with hormone receptor (HR)+ tumors was significantly longer than for patients with HR- tumors (months: 34.8 vs 17.4; HR(95% CI): 0.67 (0.53-0.84), p&lt;0.01). This remained significant for ER (29.4 vs 17.3) and PR (25.3 vs 18.7) individually. ER+ tumors had fewer alterations in the TP53 pathway (71.4% vs 82.1%) in the WNT (19.5% vs 5.8%) pathway than ER- tumors (q&lt;0.05). PR+ tumors had similar findings in the TP53 and WNT pathways, and also more alterations in the DNA damage sensor pathway. Both ER+ and PR+ UCS tumors had significantly increased MSI-H (ER: 10.9% vs 5.5%, PR: 12.9% vs 5.5%) and TMB-H (ER: 16.8% vs 6.0%; PR: 19.5% vs 6.1%) (all q&lt;0.05) compared to ER- and PR- tumors. They also had increased T-reg cells in their immune micro-environment and increased expression of the immune checkpoint gene IDO1 (q&lt;0.05; Table). Conclusions: HR+ tumors have distinct molecular profiles from HR- tumors. ER+ and PR+ UCS tumors appear more immunogenic with more frequent MSI-H status, TMB-H, increased infiltrating regulatory T-cells and IDO1 expression, suggesting possible benefit with immune-oncology (IO) therapy. This may contribute to the observed improved OS, but more data are needed to determine if HR status is a marker of response to IO therapy.[Table: see text]
Website of the Week: Help the medicine go down
Authors: Giselle Jones
Journal: BMJ (2003)

Taking medicine, the theme of this week's BMJ, is an experience shared by all of us at some point in our lives. For the lucky, medicine taking is confined to the odd painkiller. For others it involves accommodating complex and inflexible medication regimes into their daily lives (p 837). Assuming the right drug is prescribed in the first place, the success of medication relies on remembering when and how to take it (tablets and suppositories are all too easily confused—see p 863).

MedicAlarm (www.medicalarm.co.uk) offers products designed so that you “never forget your medicine again!” They range from a beeping electronic pill box with a handy self contained slug of water, to a vibrating sports wrist watch “for everybody who does not want the world around him or her to know they are on medication.” That is, until your arm starts vibrating.

For those with a greater sense of adventure, try the “Motivator Bedshaker” (www.globalassistive.com/motiv.html): connect it to an alarm clock and place it under your mattress where it will literally shake you awake. Quite miraculously it claims to wake even the heaviest sleeper without disturbing others, which must be a relief not only to your sleeping partner but also to the rest of the household.

The next step from remembering your medication is actually taking it properly, which is especially challenging in children. Long gone are the days of Mary Poppins when “a spoonful of sugar” was all that was required to help the medicine go down (www.niehs.nih.gov/kids/lyrics/spoonful.htm). Children are more likely to take responsibility for taking medicine if they understand why they are taking it and how it works. Those with asthma can go to www.asthma.org.uk/kidszone to learn about asthma medicines and how they work, and find an easy guide to using inhalers properly. Parents of younger children who refuse to open their mouth for the choo-choo may find the tips on how to get kids to take medicines helpful at www.kidsmeds.com
PCSK9 inhibitor evolocumab to increase anticancer activities and reduce cardiotoxicity during doxorubicin and trastuzumab, as sequential treatment, through MyD88/NF-kB/mTORC1 pathways.
Authors: Vincenzo Quagliariello, Simona Buccolo, Martina Iovine, Andrea Paccone, Annamaria Bonelli, Ernesta Cavalcanti, Domenica Rea, Michelino De Laurentiis, Gerardo Botti, Nicola Maurea
Journal: Journal of Clinical Oncology (2021)

e15039 Background: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapy to treat hypercholesterolaemia and related cardiovascular diseases. Evolocumab, a PCSK9 inhibitor, reduced the risk of cardiovascular events in patients with atherosclerotic cardiovascular diseases when added to maximally tolerated statin therapy (± ezetimibe), and recent data from the ODYSSEY OUTCOMES trial indicate that alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduces the risk of cardiovascular events in patients with a recent acute coronary syndrome. Methods: Human fetal cardiomyocytes (HFC cell line), human HER2+ breast cancer cells were exposed to subclinical concentration of doxorubicin, trastuzumab, sequential treatment of both (all 100 nM), alone or in combination with evolocumab (50 nM) for 24 and 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Evolocumab co-incubated with doxorubicin alone or in sequence with trastuzumab exerts cardioprotective effects, enhancing cell viability of 35-43% compared to untreated cells (p &lt; 0,05 for all); in cardiomyocytes Evolocumab reduced significantly the cardiotoxicity through MyD88/NF-KB/cytokines axis and mTORC1 Fox01/3α mediated mechanisms. In human HER2+ breast cancer cells, co-exposure of Evolocumab with doxorubicin and trastuzumab increased significantly cell apoptosis and necrosis through the involvement of key cytokines involved in chemoresistence. Conclusions: We demonstrated, for the first time, that the PCSK9 inhibitor evolocumab exerts direct effects in cardiomyocytes and human HER2+ breast cancer cells during doxorubicin and trastuzumab exposure turning on a new light on its possible use in the management of breast cancer therapies.
Implementation of virtual mentoring to optimize collection of patient-reported data in the COVID-19 era: A prospective cohort study with adaptive design.
Authors: Karineh Kazazian, Jessica Bogach, Wendy Johnston, Carol Jane Swallow
Journal: Journal of Clinical Oncology (2021)

e24091 Background: Prior to the COVID-19 pandemic, all patients attending ambulatory clinic at cancer centers in Ontario, Canada completed the Edmonton Symptom Assessment Scale (ESAS), as per governmental cancer agency mandate. At our center, completion was via touch pad, with assistance by clinic volunteers. As of mid-March 2020, clinic appointments were conducted virtually whenever possible, and touch pads removed from clinic. Our purpose here was to explore how these changes impacted the collection of patient-reported outcomes, in particular the recognition of severe symptoms. Methods: We performed a prospective cross-sectional cohort study to test the feasibility of remote completion of the ESAS by patients scheduled for appointments at a weekly surgical oncology clinic at a major cancer center. Patients were identified serially based on date of clinic appointment. Patients in the initial study cohort were asked to complete and return the ESAS virtually (V). Given low completion rates, the ensuing study cohort was asked to complete a hard-copy (HC) ESAS. For the final cohort, we used an adaptive approach, providing remote, personal mentoring by a member of the health care team to support virtual ESAS completion (virtual-mentored, VM). Results: Between May-July 2020, a total of 174 patients were included in the study: 53% were female, and median age was 62 (19-90) yrs. Age, gender and tumor site did not differ between the three cohorts. For the V cohort, 20/43 patients successfully completed and returned the ESAS electronically (completion rate 44%). For the HC cohort, 49/50 completed the form (98%). For the VM cohort (n=78), the completion rate was 74%. Questionnaire completion was not predicted by age, gender or tumor site, although patients who completed the ESAS were more likely to be under active investigation/treatment vs. surveillance (p=.04). Of the 127 ESAS forms completed in all patient cohorts, 117 reported at least 1 symptom score ≥1. There were no significant differences in individual symptom scores (e.g. tiredness, wellbeing-see Table) reported between cohorts. Of all completed forms, 42% had a depression score ≥2 and 27% an anxiety score ≥4, indicating significant psychosocial distress. Conclusions: We have identified significant barriers to the virtual completion of ESAS forms, with lack of predictive variables. The severe degree of psychological distress reported by ̃50% of respondents demonstrates the need for ongoing regular collection and review of these data.[Table: see text]
Animated patient’s guide to lung cancer enables shared decisions and improves health outcomes.
Authors: Manish Patel, Shanda H. Blackmon, Arkadiusz Z. Dudek, Naomi Fujioka, Shirley Kern, Nancy Torrison, Pasi A. Janne
Journal: Journal of Clinical Oncology (2021)

e18634 Background: Informed patients have better health outcomes. In a study of 1,057 patient encounters with 3,552 clinical decisions, only 9% resulted in informed medical decisions.The complexity of treatments and patients' limitations in health literacy (especially common in underserved communities) make it difficult for patients to engage in SDM. In 2017, A Breath of Hope Lung Foundation introduced An Animated Patient’s Guide to Lung Cancer (APG), an online resource aimed at improving patient knowledge. Methods: APG consists of animations, expert FAQ videos, slide shows, infographics, patient-experience videos, knowledge-assessment tools, and learner feedback. Video views, duration of use, and learner responses to multiple-choice questions on the APG website were collected for 33 months – through August 2020. Total APG views, most frequently viewed animations and expert videos were monitored on the website and on YouTube, to measure learner responses to outcome-based questions, and learner intent-to-implement changes. Results: 212,336 total views: 142,998 unique visitors: 59% from U.S. and 41% from 50 other countries. Unique U.S. visitors: 43,872 patients, 16,030 caregivers, and 7,593 health providers. 94% reported they will ‘use new information to better self-manage their lung cancer’ (n = 277); 98% ‘will discuss information learned with their doctor’ (n = 455), and 93% ‘plan to discuss treatment options with their doctor’ (n = 272). Conclusions: Multimedia ‘animated’ formats of learning tailored to the needs and learning styles of lung cancer patients provides effective learning, informed patients, increased management skills, and improved engagement in shared decision making.
Oncotype Dx score associated to pathological features to better prognosticate the risk of recurrence for breast cancer patients.
Authors: Fernando Namuche, Rossana Ruiz, Zaida Morante, Claudio J. Flores, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2021)

e12562 Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, it puts aside important clinical features. Our objective is to develop a model that uses routine clinical parameters associated with Oncotype Dx score to estimate the recurrence rate in our population. Methods: We retrospectively reviewed ODX and pathology reports from 371 early BC patients diagnosticated between 2014 and 2016 in a specialized cancer center, with a 5 year follow up. Variables were selected first with a univariate cox regression, then the statistically significant variables underwent a multivariate cox regression. The β coefficients from selected variables were used to create the prediction formula. Results: Among the tested variables, ki67, estrogen receptor (ER) and ODx score were significantly associated with Recurrence. The linear predictor is: (0.1331 x Ki67) + (0.4232 x ER)+(0.2112xODx score). The threshold score for this equation was set on 33 (median value) to discriminate low and high estimated risks for recurrence. The correct classification rate (CCR) for the training and validation sets was 76% and 68%, respectively. Conclusions: It is possible to optimize the Oncotype Dx to better determine a recurrence score with selected pathological features.
American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 2
Authors: Jeffrey R. Curtis, Sindhu R. Johnson, Donald D. Anthony, Reuben J. Arasaratnam, Lindsey R. Baden, Anne R. Bass, Cassandra Calabrese, Ellen M. Gravallese, Rafael Harpaz, Andrew Kroger, Rebecca E. Sadun, Amy S. Turner, Eleanor Anderson Williams, Ted R. Mikuls
Journal: Arthritis & Rheumatology (2021)

Objective To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID‐19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). Methods A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID‐19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9‐point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. Results Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID‐19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. Conclusion These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID‐19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.