tbuckley/cabot-search huggingface dataset:
Impact of ECOG performance status on recurrent/metastatic head and neck squamous cell carcinomas treated with anti-PD1 inhibitors.
Authors: Cameron Chalker, Vicky Wu, Jenna M. Voutsinas, Victoria Hwang, Christina S Baik, Jay Justin Liao, Sylvia Lee, Neal D. Futran, Jeffrey Houlton, Brittany Barber, Upendra Parvathaneni, George E. Laramore, Rafael Santana-Davila, Keith D. Eaton, Renato G. Martins, Cristina P. Rodriguez
Journal: Journal of Clinical Oncology (2021)

e18004 Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard of care for patients with recurrent/metastatic head &amp; neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥ 2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received at least 1 dose of ICI at our institution. Demographic data and clinical outcomes were obtained; the latter included objective response to ICI (ORR), physician-documented CTCAE grade 2+ toxicity (irAE), and any unplanned hospitalization within 100-days of last ICI dose (UH). Associations between demographic data and clinical outcomes were explored using both uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, irAE, and UH were evaluated with logistic regression. This project was approved by our institutional IRB. Results: We identified 152 RMHNSCC patients who were treated with ICI between 1/2013 and 1/2019. ECOG PS was 0 in 42 (27%), 1 in 75 (50%), 2 in 27 (18%), 3 in 2 (1%), and unknown in 6 (4%) patients. The median age was 61 (range: 25 - 90). 124 (82%) were male, 124 (82%) were white, and 69 (45%) were never-smokers. The most common primary sites were the oropharynx (n = 59, 40%), oral cavity (n = 39, 26%), nasopharynx (n = 11, 7%), and larynx (n = 10, 6%). 54 (36%) were p16+ oropharynx cancers. CPS score was available in 10 (6.6%). Single agent ICI was received by 118 (77%) patients. 66 (44%) had a documented irAE and 54 (36%) had an UH. A multivariate model for OS containing PS, smoking status and HPV status showed a strong association between inferior OS and ECOG 2/3 compared to 0/1 (p &lt; 0.001; HR = 3.30, CI = 2.01-5.41), as well as former (vs. never) smoking status (p &lt; 0.001; HR = 2.17, CI = 1.41-3.35). Current smoking (p = 0.25) did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between irAE and any patient characteristic. Conclusions: We observed inferior overall survival among ICI-treated RMHNSCC patients with ECOG 2/3 in our single-institution, retrospective series. Our findings help frame discussion of therapeutic options in this poor-risk population. Further study must be done to determine which interventions are of greatest benefit for RMHNSCC patients with declining performance status.
Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.
Authors: Deepak Kilari, Aniko Szabo, Pooja Ghatalia, Tracy L Rose, Nicole Weise, Matthew D. Tucker, Ariel Ann Nelson, Huaying Dong, Danubia Hester, Luna Acharya, Rohit K. Jain, Benjamin L. Maughan, Ajjai Shivaram Alva, Abhishek Tripathi, Arnab Basu, Vadim S Koshkin, Hamid Emamekhoo, Nancy B. Davis, Arpita Desai, Rana R. McKay
Journal: Journal of Clinical Oncology (2021)

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]
Genomic Surveillance for SARS-CoV-2 Variants Circulating in the United States, December 2020–May 2021
Authors: Prabasaj Paul, Anne Marie France, Yutaka Aoki, Dhwani Batra, Matthew Biggerstaff, Vivien Dugan, Summer Galloway, Aron J. Hall, Michael A. Johansson, Rebecca J. Kondor, Alison Laufer Halpin, Brian Lee, Justin S. Lee, Brandi Limbago, Adam MacNeil, Duncan MacCannell, Clinton R. Paden, Krista Queen, Heather E. Reese, Adam C. Retchless, Rachel B. Slayton, Molly Steele, Suxiang Tong, Maroya S. Walters, David E. Wentworth, Benjamin J. Silk
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1).Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity.In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing.As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC.These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively).Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.*During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern † (VOC) and emergence of the P.1 VOC in the United States.Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally.Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance.Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States.* https://www.hhs.gov/about/agencies/iea/regional-offices/index.html† A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
Accomplishing breakthroughs in behavioural medicine research
Authors: Karina W. Davidson, Simon L. Bacon, Gary G. Bennett, Elizabeth Brondolo, Susan M. Czajkowski, Michael A. Diefenbach, Elissa S. Epel, Karen Matthews, Tracey A. Revenson, John Manuel Ruiz, Suzanne C. Segerstrom, Simon L. Bacon, Gary G. Bennett, Elizabeth Brondolo, Susan M. Czajkowski, Karina W. Davidson, Michael A. Diefenbach, Elissa S. Epel, Karen Matthews, Tracey A. Revenson, John Manuel Ruiz, Suzanne C. Segerstrom
Journal: Nature Human Behaviour (2021)
Predictors of 30-day readmission rate after total gastrectomy in patients with gastric malignancy.
Authors: Miguel Salazar, Estefania Gauto, Shristi Upadhyay Upadhyay Banskota, Pedro Palacios, Trilok Shrivastava, Binav Baral, Pierre Alexander Rodriguez Alarcon, Maha Elsebaie, Nabin Khanal
Journal: Journal of Clinical Oncology (2021)

e16109 Background: Total gastrectomy with lymph node dissection is curative for early gastric malignancy which accounts for 1.5% of cancer cases in the U.S. Readmissions are common postoperatively, and are associated with increased morbidity, mortality, hospital costs and decreased quality of life. We hence aim to identify incidence, impact and independent predictors for readmission in patients who underwent total gastrectomy in gastric malignancy. Methods: We conducted a retrospective cohort study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for total gastrectomy with a concomitant diagnosis of gastric malignancy. T-test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. ICD 10 codes were used to identify diagnoses and procedures. Results: A total of 1,779 patients with gastric malignancy underwent total gastrectomy. The 30-day readmission rate was 18.5%. Main causes for readmission were sepsis, ventricular fibrillation, recurrent STEMI. Readmitted patients were more likely to be on chemotherapy. (40.1% vs 27.2%; P&lt;0.01) and more likely to be discharged to a skilled facility (13.5% vs 17.9%; P&lt;0.01). The total health care in-hospital economic burden of readmission was $6.5 million in total charges and $25 million in total costs. Independent predictors of readmission were major bleeding, respiratory failure requiring mechanical ventilation, peripheral parenteral nutrition, history of non-alcoholic hepato-steatosis, and prolonged length of stay. Conclusions: Readmissions after gastrectomy in patients with gastric malignancies are associated with lower in-hospital mortality yet pose a substantial economic burden on healthcare. The lower mortality might be explained by the relatively stable course and lower comorbidities of patients who become eligible for discharge after surgery. Further studies are suggested. Modifiable risk factors like malnutrition and sepsis warrant special attention to decrease readmissions and improve overall outcomes.[Table: see text]
GUNC: detection of chimerism and contamination in prokaryotic genomes
Authors: Askarbek Orakov, Anthony Fullam, Luis Pedro Coelho, Supriya Khedkar, Damian Szklarczyk, Daniel R. Mende, Thomas S. B. Schmidt, Peer Bork
Journal: Genome biology (2021)

Abstract Genomes are critical units in microbiology, yet ascertaining quality in prokaryotic genome assemblies remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects and quantifies genome chimerism based on the lineage homogeneity of individual contigs using a genome’s full complement of genes. GUNC complements existing approaches by targeting previously underdetected types of contamination: we conservatively estimate that 5.7% of genomes in GenBank, 5.2% in RefSeq, and 15–30% of pre-filtered “high-quality” metagenome-assembled genomes in recent studies are undetected chimeras. GUNC provides a fast and robust tool to substantially improve prokaryotic genome quality.
Predictive Performance of CAGE-B and SAGE-B Models in Asian Treatment-Naive Patients Who Started Entecavir for Chronic Hepatitis B
Authors: Hye Yeon Chon, Jae Seung Lee, Hye Won Lee, Ho Soo Chun, Beom Kyung Kim, Won Young Tak, Jun Yong Park, Young-Oh Kweon, Do Young Kim, Sang Hoon Ahn, Se Young Jang, Soo Young Park, Seung Up Kim
Journal: Clinical Gastroenterology and Hepatology (2021)
Real-world analysis of disease progression after CDK 4/6 inhibitor (CDKi) therapy in patients with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC).
Authors: Malinda West, Andy Kaempf, Shaun Goodyear, Thomas Kartika, Jessica Ribkoff, Zahi Ibrahim Mitri
Journal: Journal of Clinical Oncology (2021)

e13030 Background: CDKi with endocrine therapy (ET) is approved treatment of metastatic HR+/HER2- breast cancer based on PFS benefit vs ET alone. Outcomes data following CDKi discontinuation (dc) is limited, with trials ongoing in this setting. The reported phenomenon of rapid progression within 4 months of CDKi dc raises concern over CDKi impact on HR+/HER2- MBC biology. This study aims to define outcomes after CDKi dc and identify predictors of progression. Methods: This is a retrospective review of women ≥18 years with HR+/HER2- MBC who received CDKi between 4/1/14 and 12/1/19. Patient and tumor characteristics, pre and post CDKi tx, and reason for CDKi dc were collected. Time to event outcomes from date of CDKi dc (primary = PFS, secondary = Overall Survival, OS) were analyzed with Kaplan Meier estimators and Cox regression. Results: Analysis included 140 patients (median age 65 years), with most MBC (84%) arising from earlier stage disease. 51% of MBCs had visceral disease, and 66% received tx prior to CDKi. The most common CDKi was palbociclib (93%); and most common ET were letrozole (52%) and fulvestrant (40%). Median CDKi tx duration was 9 months (3.5 – 17.4) with 80% dc due to progression. Post CDKi txs included chemotherapy (44%), ET (24%), targeted tx (21%), no further tx (7%) and CDKi tx (4%). Median follow up was 12 months. mPFS post CDKi dc were 6.5 months (95% CI: 5.0 – 7.9) and 11.3 months (95% CI: 4.6 – 23.7) in patients who dc CDKi due to progression or other reasons, respectively (HR 1.77, 95%CI: 1.10-2.85). Among 112 patients who progressed on CDKi, estimated 4-month incidence of post CDKi progression or death was 31% (Table ). mOS post CDKi dc was 15.4 months (95%CI: 13.3-19.0) and mOS post CDKi initiation was 26.5 months (95% CI: 23.3 – 34.3). Visceral disease (HR 1.45, 95%CI: 1.01-2.08) and progression as reason for CDKi dc (HR 1.77, 95%CI: 1.1-2.85) were predictors of PFS (p &lt; 0.05). Receiving fulvestrant with CDKi (HR 1.42, 95%CI: 0.96-1.0), prior chemotherapy in the metastatic setting (HR = 1.39, 95% CI: 0.90 – 2.14), and shorter CDKi duration were associated with non-significant increased risk of PFS. Conclusions: Rapid progression or death at 4 months occurred in 31% of MBCs following CDKi dc due to progression. Ongoing studies to define clinical and molecular characteristics of rapidly progressing tumors are underway to develop targeted tx approaches and improve outcomes.[Table: see text]
Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf).
Authors: Evangelos Terpos, Ashraf Badros, Rakesh Popat, Paula Rodríguez-Otero, Asim Farooq, Bennie Jeng, Simona Degli Esposti, Eric Lewis, Ira Gupta, Joanna Opalinska, Antonio Palumbo, Suzanne Trudel
Journal: Journal of Clinical Oncology (2021)

8033 Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]
An analysis of characteristics and content of highly used books for the general population in the cancer space on Amazon.com.
Authors: Ryan M O'Keefe, Caitlin E. Keaveny, Alicia M. Vesey, Mackenzie R. Jordan, Grace A. Hamilton, Nicole B. Letendre, Simonai E. Santiago, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2021)

e24034 Background: Cancer patients and supporters frequently turn to written resources for assistance and empowerment in decision-making. Previous work has analyzed misinformation available on search and social media platforms; however, little attention has been paid to amazon.com (AMZ) despite 37% of cancer patients seeking information from books. Previous work also suggests there is a preponderance of vaccine-hesitant books on AMZ. Here, we report the first analysis of the characteristics and content of books, excluding medical textbooks, in the cancer space. Methods: On 11/25/20, the top 100 books were pulled from the “Best Sellers in Cancer” (BS) page on AMZ. Queries were also performed using keywords “cancer treatment” (CT), and “natural cancer treatment” (NCT), filtering for books. Non-sponsored results from the first 5 pages per search were pulled. 2 coders were trained to manually collect variables on genre, advice, terminology (TN) in the description, author, and publisher; disagreement was settled by a third coder. Books were excluded if they were not in English, duplicates within the same query, did not focus on human cancer, or were medical textbooks. Chi square testing was used to compare results of CT v. NCT. Analysis was performed using R software. Results: 56, 60, and 70 books were included for BS, CT, and NCT, respectively. For BS, 15 (26.8%) were memoirs, 12 (21.4%) dietary guides, 11 (19.6%) treatment guides, 6 (10.7%) self-help, and 4 (7.1%) cookbooks. 16 (28.6%) focused on one tumor subtype; breast was the most common (9, 56.3%). Many appeared to offer non data-driven advice (Table). Many BS books employed “war” TN (ex: fight, battle), “hype” TN (ex: game-changing), spiritual TN (ex: faith, God, prayer), and CAM TN (ex: supplement, herb) (Table). Many also insinuated offering a cure, or a novel therapy (Table). Compared with CT books, NCT books were more likely to offer non-data driven advice and be published independently, and less likely to have an MD/DO author (Table). Conclusions: Nonscientific advice is present in many non-medical text cancer books available on AMZ, including BS books. Patients seeking information on AMZ about NCT are likely to find books offering non-data driven advice or that insinuate a cure or new/novel information. Future work should investigate opportunities to regulate such content or to direct patients towards high-quality resources on platforms like AMZ.[Table: see text]
Safe use of livers from deceased donors older than 70 years in recipients with HCV cirrhosis treated with direct-action antivirals. Retrospective cohort study
Authors: Carlos Jiménez-Romero, Iago Justo, Alberto Marcacuzco, Virginia García, Alejandro Manrique, Álvaro García-Sesma, Jorge Calvo, Inmaculada Fernández, Cristina Martín-Arriscado, Óscar Caso
Journal: International Journal of Surgery (2021)
Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas.
Authors: Robert Hsu, Yasmine Baca, Joanne Xiu, Rongfu Wang, Joseph Nicholas Bodor, Chul Kim, Hina Khan, Hirva Mamdani, Misako Nagasaka, Sonam Puri, Stephen V. Liu, Wolfgang Michael Korn, Jorge J. Nieva
Journal: Journal of Clinical Oncology (2021)

e21000 Background: Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in some types of gastric and breast cancer and reports of expression in one-third of lung cancer tumors. Here, we characterize the molecular subtype of lung cancers expressing KK-LC-1 to plan rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. Methods: A total of 9790 non-small cell lung cancer (NSCLC) tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. PD-L1 expression was tested by IHC using 22c3 (Dako) and TPS scores were reported. Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Statistical significance was determined using chi-square/Fisher-Exact and adjusted for multiple comparisons (adjusted p &lt; 0.05). Results: Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median 3.25 vs. 1.17 transcripts per million (TPM), p &lt; 0.0001). There is statistically higher expression of KK-LC-1 in pan wild type (3.95 TPM) compared to tumors with EGFR mutation (1.95 TPM), ALK fusion (0.6 TPM), MET exon-14-skip mutation (1.22 TPM), RET fusion (1.42 TPM), and ROS1 fusion (1.78 TPM). Tumors within the highest quartile of KK-LC-1 expression (Q4) had a greater proportion of TMB &gt; 10 mutations per megabase (mt/MB) (44% vs. 28%) compared to Q1. No difference was seen in PD-L1 expression. In adenocarcinoma, Q4 had a higher TMB compared to Q1 (9 mt/MB vs. 5 mt/MB). There was a higher KRAS mutation prevalence in Q3/Q4 (34.8%/35.0%) than Q1/Q2 (22%/29%) but a lower ALK fusion prevalence in Q3/Q4 (1.0%/0.5%) compared to Q1/Q2 (3.3%/2.6%). Increased KK-LC-1 expression is associated with increased M1 Macrophage abundance. Conclusions: In our population, KK-LC-1 expression was higher in adenocarcinoma. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with higher TMB while lower levels of expression were seen in driver positive cancers including EGFR, ALK, MET, RET and ROS1. TCR-T therapy directed against KK-LC-1 should be explored in patients whose clinical features reflect these characteristics.