tbuckley/cabot-search huggingface dataset:
Prognostic value of plasma hPG<sub>80</sub> (circulating progastrin), alone or in combination with Alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma.
Authors: Alexandre Prieur, Eric Assenat, Marie Dupuy, Sarah Iltache, Berengere Vire, Julien Soulé, Pierre Liaud, Thierry Cousin, Younes Mahi, Dominique Joubert
Journal: Journal of Clinical Oncology (2021)

3033 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis since it is expressed in the advanced stages of the disease. Consequently, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages of the disease. hPG 80 (circulating progastrin), a new drug target for cancer treatment which plays a pivotal role in tumorigenesis, is present in the blood of multiple types of cancers at early stages including HCC. The purpose of this study was to evaluate the prognostic value of plasma hPG 80 in patients with HCC, in combination or not with AFP. Methods: A total of 168 HCC patients (BCLC from 0 to D) managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG 80 was quantified using DxPG 80 Lab kit (ECS-Progastrin) and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG 80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG 80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. Results: The median overall survival (OS) of the full cohort is 20.9 months. HCC patients with high hPG 80 levels (hPG 80 +: &gt;4.5 pM, 105/168) had significantly lower median OS compared to patients with low hPG 80 levels (hPG 80 -: &lt;4.5 pM, 63/168) (12.4 months versus undefined respectively, p &lt; 0.0001). Patients with high AFP (AFP+: &gt;100 ng/mL, 69/165) had significantly lower median OS compared to patients with low AFP (AFP: &lt;100 ng/mL 96/165) (7.2 months versus undefined, p &lt; 0.0001). To improve the stratification, the patients were further categorized into four groups: hPG 80 -/AFP- (n = 42), hPG 80 +/AFP- (n = 54), hPG 80 -/AFP+ (n = 21) and hPG 80 +/AFP+ (n = 48). In the AFP- group, hPG 80 + patients exhibited a significantly worse prognosis than those with hPG 80 - (26.3 months versus undefined, p=0.0087). Similarly, in the AFP+ group, patients with hPG 80 + had a significantly worse survival compared to hPG 80 - patients (5.7 months versus 13.4 months, p = 0.0391). Finally, we evaluated the median OS of AFP+ patients according to BCLC staging. Interestingly, in the group BCLC 0 to B, hPG80+ had a significantly worse prognosis than those with hPG 80 - (15.8 months versus 40.25 months, p=0.0317). Conclusions: Our findings show that hPG 80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and worst prognosis, especially for those patients with negative AFP and early-stage HCC.
Covid-19: Failures of leadership, national and global
Authors: Fiona Godlee
Journal: BMJ (2021)

How well prepared were countries for this pandemic?Back in October 2019 the US and the UK were top of the world rankings as scored by the Global Health Security Index.The Epidemic Preparedness Index also gave them a thumbs up.And yet both countries are among the world's worst performing, whether judged by numbers of deaths from covid-19 or economic outcomes.How could these indexes have got it so wrong?Gurdasani D, Ziauddeen H, Reicher S, McKee M. Covid-19 and the delta variant-we need an urgent focus on mitigations in schools.
Shifting the paradigm: unilateral infiltrates and ARDS?
Authors: Antoni Torres, Enric Barbeta, Tobias Welte
Journal: European Respiratory Journal (2021)

<b>Simple observation of chest radiograph quadrant involvement in ARDS could improve the prediction of mortality. Patients needing mechanical ventilation with unilateral and two quadrants chest radiograph involvement should receive protective ventilation.</b>https://bit.ly/2KqwqVO
Oncology patients’ perspectives on remote patient monitoring for COVID-19.
Authors: Robert Michael Daly, Tara Lauria, Jessie C. Holland, Jericho Garcia, Jibran Majeed, Chasity Walters, Olga Strachna, Kimberly Chow, Caitlin E. Giles, Meghan F Kelly, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2021)

1504 Background: Oncology patients are particularly vulnerable to adverse outcomes from COVID-19 and require careful monitoring to identify early deterioration and render higher level care when indicated. Several institutions launched remote patient monitoring programs (RPMPs) to care for patients with COVID-19. We describe patients’ perspectives on a COVID-19 RPMP at a National Comprehensive Cancer Center. Methods: Adult patients who had either tested positive for COVID-19 on an outpatient microbiology test or were discharged after hospitalization for the virus were eligible. Patients enrolled in the RPMP received a daily 10-question electronic patient-reported outcome assessment of COVID-19 symptoms and their responses generated alerts to a centralized monitoring team for new or worsening symptoms. A subset of high-risk patients also received a pulse oximeter which alerted when blood oxygen levels dropped below 93%. RPM was discontinued 14 days after a patient’s positive test result and following 3 days without worsening symptoms or fever. Patients who exited the program and had completed at least one assessment were sent a patient engagement survey. The objective of the survey was to evaluate the patient’s experience with digital monitoring and symptom management for COVID-19. The assessment was structured with objective response questions, including a net promoter score, and free text questions to elicit patient perspectives on RPM value. Free text responses were analyzed using grounded theory to identify primary themes regarding perceived value. Results: The survey was distributed to 452 patients; 241 responded as of June 10, 2020 (53% completion rate). The net promoter score was 91%. The table provides responses to objective questions. Qualitative analysis of free text responses identified the primary themes regarding patient perceived value which included: 1) Security: patients appreciated that the RPMP provided a clinical safety net; 2) Connection: patients appreciated the link to their clinical team during a period of isolation; 3) Empowerment: patients appreciated that the RPMP provided education on the virus and symptom management. Conclusions: RPMPs are perceived to be of value to oncology patients with COVID-19. A key barrier to maintaining these programs is cost. Policymakers should consider how these programs can be reimbursed in the future so that they can continue to provide care to vulnerable patients and keep them at home out of the acute care setting.[Table: see text]
Utilization and outcome of systemic chemotherapy for high-risk early-stage cervical cancer.
Authors: Munetaka Takekuma, Shinya Matsuzaki, Koji Matsuo
Journal: Journal of Clinical Oncology (2021)

e17521 Background: To examine trends and outcomes of systemic chemotherapy for high-risk early-stage cervical cancer. Methods: This retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000-2016. Surgically-treated women with stage T1-2 cervical cancer who had high-risk factors (lymph node metastasis and/or parametrial invasion) and received adjuvant therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for chemotherapy use versus external beam with chemotherapy (CCRT). Results: Among 2, 462 women with high-risk factor, 185 (7.5%) received systemic chemotherapy. Utilization of chemotherapy has significantly increased over time in multivariable analysis (adjusted-odds ratio per 1-year increment, 1.06, 95% confidence interval [CI] 1.02-1.09). In weighted models, adjuvant chemotherapy and CCRT had comparable survival among women aged &lt; 40 (hazard ratio [HR] for all-cause mortality 0.73, 95%CI 0.41-1.33), adenocarcinoma or adenosquamous histologies (HR 0.90, 95%CI 0.62-1.32), and high-risk group based on nodal metastasis alone (HR 1.17, 95%CI 0.84-1.62). In contrast, chemotherapy was associated with increased all-cause mortality compared to CCRT among women aged ≥40 (HR 1.57, 95%CI 1.19-2.06), squamous histology (HR 1.63, 95%CI 1.19-2.22), and high-risk group per parametrial invasion alone (HR 1.87, 95%CI 1.09-3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95%CI 1.06-2.52). Conclusions: Utilization of systemic chemotherapy for high-risk early-stage cervical cancer is increasing in the United States. Survival effects of adjuvant chemotherapy varied per patient and tumor factors, and this indication may be limited to those who are &lt; 40 years with non-squamous histology and absence of parametrial invasion.
Recent updates on three drug combination regimen for relapsed refractory multiple myeloma.
Authors: Tabinda Saleem, Abdul Rafae, Joshua Jonathan Christy, Kiran Kuriakose, Mustafa Nadeem Malik, Emad Kandah, Hafiz Qurashi, Rabia Ali, Faiz Anwer
Journal: Journal of Clinical Oncology (2021)

e20039 Background: Two drug regimens comprising proteasome inhibitors, immunomodulatory agents, or a monoclonal antibody are the standard of care for multiple myeloma. However, due to the increased relapse incidence, multiple different combination therapies are under study to treat relapsed and refractory multiple myeloma (RRMM). Methods: A comprehensive data search was done across various data sets, including PubMed, Cochrane, and Embase, using MeSH terms and keywords to include all phase III clinical trials involving three-drug regimens in the last five years. Results: We report eleven clinical trials evaluating three-drug combination regimens vs. two-drug regimens for RRMM. In 2015 Stewart et al. reported ORR of 87.1% vs. 66.7% in 396 patients treated with Carflizomib (K), Lenalidomide (R), and dexamethasone (d) compared to 396 patients treated with Rd alone. Lonial et al. reported ORR of 79% vs 66% for Eltozumab + Rd (n321) vs Rd (n=325). In 2016 San-Miguel et al. treated 387 patients with bortezomib, panobinostat + d, and 381 patients with bortezomib + d, with ORR of 40.3% vs. 35.8%. Shah J et al. compared Pembrolizumab, pomalidomide + d (n=125) to pomalidomide + d (n=124) with ORR of 34% vs 40% respectively. In 2018, Elotuzumab, pomalidomide (P) + d (n=60) vs. Pd (n=57) combination studied by Dimopoulos et al. resulted in an ORR of 53% vs. 26%. In 2019 Schjesvold et al. compared isatuximab, Pd (n=154), with Pd (n=153) with an ORR of 60% and 35%, respectively. Most recently, in 2020, Kumar et al. reported ORR of 82% with venetoclax, bortezomib (V) +d (n=194) compared to ORR of 68% with Vd (n=97). Mateos et al. reported ORR of 85% with VDd (n=251), vs 63% with Vd (n=247). Bahlis et al. reported ORR of 92.9% in 268, and Suzuki et al. reported ORR of 90.2% in 52 patients treated with DRd vs. ORR of 76.4% in 283 and ORR of 72.1% in 44 patients treated with Rd alone. In another trial, Dimopoulos et al. resulted in an ORR of 53% with KDd (n=312) compared to 75% with Kd (n=154). A summary of adverse effects is listed in table. Conclusions: Three drug regimen showed better results compared to two-drug regimens with a similar safety profile. A longer follow-up of these trials is needed to confirm this.[Table: see text]
Tripartite motif 16 ameliorates nonalcoholic steatohepatitis by promoting the degradation of phospho-TAK1
Authors: Lin Wang, Xin Zhang, Zhi-Bin Lin, Pei-Jun Yang, Hao Xu, Juan-Li Duan, Bai Ruan, Ping Song, Jing-Jing Liu, Zhen-Sheng Yue, Zhi-Qiang Fang, Heng Hu, Zhen Liu, Xiao-Li Huang, Ling Yang, Song Tian, Kai-Shan Tao, Hua Han, Ke-Feng Dou
Journal: Cell Metabolism (2021)
Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic hepatitis C virus in low- and middle-income settings
Authors: Josephine Walker, Nyashadzaishe Mafirakureva, Lara Marquez, Jack Stone, Aaron G. Lim, Linda Campbell, Gul Ghuttai Khalid, Momoko Iwamoto, Khawar Aslam, Yves Wailly, Hassaan Zahid, Dmytro Donchuk, Camille Fortas, Gregoire Falq, Kyi Piar Soe, Antoine Chaillon, Vincent Lo Re Iii, Adriane Wynn, Craig McIntosh, Derek Johnson, Jean-Marc Zosso, Aude Nguyen, Susan Kiene, Stephanie Brodine, Richard Garfein, Reuben Hastings, San Kimchamroeun, Mickael Le Paih, Jean-Philippe Dousset, Suna Balkan, Tonia Marquardt, Esther Mucara, C. Ines Gonzalez, Walter Kizito, Yvonne Nzomukunda, Peter Cherutich, Charles Cleland, John Lizcano, Nok Chhun, Ann Kurth, Helgar Musyoki, Parinita Bhattacharjee, Wanjiru Waruiru, Ben Mundia, David Maman, Niklas Luhmann, Joanna Coast, Anne Loarec, Natasha Martin, Peter Vickerman
Journal: Journal of Hepatology (2020)
Novel biomarkers for head and neck squamous cell carcinoma: A retrospective study.
Authors: Shengjin Dou, Lin Zhang, Rongrong Li, Debin Sun, Lijia Wu, Guopei Zhu
Journal: Journal of Clinical Oncology (2021)

e18010 Background: PDL-1 and tumor mutation burden are only useful to select a small portion of patients with head and neck squamous cell carcinoma for immunotherapy, more biomarkers are in an urgent need for the majority. Methods: Ninety-nine recurrent/metastatic patients were analyzed. PD-1 cohort including 78 patients; Non-PD-1(NPD-1) cohort including 28 patients received anti-EGFR antibody and harbored at least one of EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations (including 7 patients received with both treatment). Patients were evaluated as no clinical benefit (NCB) if experiencing progressive disease or stable disease lasting &lt; 6 months and were discontinued from immunotherapy within 3 months; otherwise, patients were evaluated as clinical benefit (CB). Tumor genomic DNA was isolated from formalin-fixed paraffin-embedded tissue for the targeted sequencing by a 769-gene panel. R package was used for fisher test to evaluate the variants. p &lt; 0.05 was set as significant. Results: With median age of 57 years old, this study included 75 (75.8%) oral squamous cell carcinoma patients,17 (17.2%) oropharyngeal carcinoma patients and 7 others. Sixty-nine (69.7%) patients have PD-L1 CPS≥1, 27 (27.3%) patients have CPS＜1 and 3 (3.0%) have an unknown CPS. The estimated 10-month progression-free survival of the NPD-1 cohort and PD-1cohort were 60.0%and 47.6% (p = 0.06) respectively. In NPD-1 cohort, 23 patients were evaluated as CB (78.3%), and in PD-1 cohort, 41 were evaluated as CB (52.6%) (p = 0.00682), indicating EGFR amplification/mutation, CCND1 amplification, FGF3/4/19 amplification, or CDKN2A/B mutations may be negatively correlated with immunotherapies. There were 14 patients who harbored either EGFR amplification or SNV mutation. Of the 8 patients who received NPD-1 treatment, 7 were CB (87.5%); Of the 8 patients who received PD-1 treatment, 2 were CB (25%) Statistically, the difference between NPD-1 treatment group and PD-1 treatment group was significant with a p value of 0.04056. There were 16 patients who harbored CCND1 amplification, or FGF3/4/19 amplification. Of the 12 patients who received NPD-1 treatment, 10 were evaluated as CB (83.3%); Of the 7 patients who received PD-1 treatment, 1 was evaluated as CB (14.3%). The difference was significant with a p value of 0.00627. There were 44 patients who obtained CDKN2A/B mutations. Of the 12 patients who received NPD-1 treatment, 11 acquired CB (81.7%); Of the 33 patients who received PD-1 treatment, 18 acquired CB (54.5%). The difference was significant with a p value of 0.03325. Conclusions: We for the first time showed that genetic-altered EGFR, FGF3/4/19, CCND1 and CDKN2A/B were negatively correlated with anti-PD-1 therapy in clinical cohorts retrospectively and these genetic aberrations may serve as novel immune-negative biomarkers for immunotherapies.
Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease
Authors: Gérard Socié, Leslie S. Kean, Robert Zeiser, Bruce R. Blazar
Journal: Journal of Clinical Investigation (2021)

As a result of impressive increases in our knowledge of rodent and human immunology, the understanding of the pathophysiologic mechanisms underlying graft-versus-host disease (GVHD) has dramatically improved in the past 15 years. Despite improved knowledge, translation to clinical care has not proceeded rapidly, and results from experimental models have been inconsistent in their ability to predict the clinical utility of new therapeutic agents. In parallel, new tools in immunology have allowed in-depth analyses of the human system and have recently been applied in the field of clinical GVHD. Notwithstanding these advances, there is a relative paucity of mechanistic insights into human translational research, and this remains an area of high unmet need. Here we review selected recent advances in both preclinical experimental transplantation and translational human studies, including new insights into human immunology, the microbiome, and regenerative medicine. We focus on the fact that both approaches can interactively improve our understanding of both acute and chronic GVHD biology and open the door to improved therapeutics and successes.
The efficacy and safety profile of anlotinib plus docetaxel as second-line treatment in advanced non-small cell lung cancer.
Authors: Zhiqiao Xu, Yan Zhang
Journal: Journal of Clinical Oncology (2021)

e21068 Background: Docetaxel is a standard second line treatment in advanced NSCLC, but the treatment effect is limited. Previous studies, such as REVEL, demonstrated that anti angiogenic therapy combined with docetaxel had significantly therapeutic efficacy. Anlotinib is an oral multi target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c Kit. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC, and this study aims to investigate the efficacy and safety of Anlotinib combined with docetaxel in second-line treatment in advanced non-small cell lung cancer (NSCLC). Methods: This is a single-center, single-arm clinical trial. A group of 30 patients of histologically or cytologically confirmed, locally advanced stage IIIB-IV NSCLC and with ECOG PS 0-1 were admitted to the Kaifeng Central Hospital Cancer Center. Patients who progressed after first-line treatment were treated with anlotinib (12 mg p.o., QD d1 to 14, q3w) combined with docetaxel (75mg/m 2 , iv, QD, d1 to 14, q3w) as the second-line therapy. The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 30 patients were enrolled from October 2018 to April 2020. At data cutoff (Sept. 30, 2020), 30 patients were available for efficacy analysis. The median progression-free survival (mPFS) was 7.5 months (2.0-18.5). Among these patients, there was 1 CR, 9 PR, 15 SD, 5 PD, resulting in the ORR = 33.33% and the DCR = 83.33%. The Cox multivariate analysis showed that stage is an independent risk factor affecting prognosis ( p= 0.003). The most common grade 3 AEs were leukopenia (23,3%), neutropenia (13.3%), hypertension (13.3%), which can be controlled, and no grade 4 or grade 5 AEs occurred. Conclusions: Second line anlotinib plus docetaxel showed clinical benefit in advanced NSCLC patients in terms of PFS, ORR and DCR, and the incidence of adverse reactions are tolerable. This combination might be a promising option for patients advanced NSCLC.
Long-term trend of quality-adjusted time without symptoms or toxicities (Q-TWiST) of nivolumab+ipilimumab (N+I) versus sunitinib (SUN) for the first-line treatment of advanced renal cell carcinoma (aRCC).
Authors: Robert J. Motzer, Toni K. Choueiri, Jessica May, Youngmin Kwon, Nifasha Rusibamayila, Marc Botteman, Melissa Hamilton, Flavia Ejzykowicz, David Cella
Journal: Journal of Clinical Oncology (2021)

6568 Background: After a minimum follow-up of 48 months (mos), the CheckMate 214 trial (phase 3, NCT02231749) continued to demonstrate a significant overall (OS) and progression-free (PFS) survival benefit for N+I vs. SUN in aRCC patients (pts) with intermediate (I) or poor (P) International Metastatic RCC Database Consortium (IMDC) risk factors (median OS: 48.1 vs. 26.6 mos, HR: 0.65, 95% confidence interval [95% CI]: 0.54, 0.78; 48-mos PFS: 32.7% vs. 12.3%, HR: 0.74, 95% CI: 0.62, 0.88) (Albiges et al. ESMO Open 2020). To further understand the clinical benefits and risks of N+I vs. SUN, we evaluated the Q-TWiST over time using up to 57 mos of follow-up in CheckMate 214. Methods: OS was partitioned into 3 states: time with any grade 3 or 4 adverse events (TOX), time without symptoms of disease or toxicity (TWiST), and time after progression (REL). The Q-TWiST is a metric that combines the quantity and quality (i.e., “utility”) of time spent in each of the 3 states TWiST, TOX, and REL. Prior research (Revicki et al, Qual Life Res, 2006) has established that relative gains in Q-TWiST (i.e., Q-TWiST gain divided by OS in SUN) of ≥ 10% and ≥ 15% can be considered as “clinically important” and “clearly clinically important”, respectively. Non-parametric bootstrapping was used to generate 95% CIs. To observe changes in quality-adjusted survival gains over time, absolute and relative Q-TWiST were calculated up to 57 mos at intervals of 12-mos. Results: With 57-mos follow-up, compared to SUN pts, N+I pts (N = 847) had significantly longer time in TWiST state (+7.1 mos [95% CI: 4.2, 10.4]). The between-group differences in TOX state (0.3 mos [95% CI: -0.2, 0.8]) and REL state (-1.2 mos [95% CI: -4.1, 1.5]) were not statistically significant. The Q-TWiST gain in the N+I vs. SUN arms was 6.6 mos (95% CI: 4.1, 9.4), resulting in a 21.2% relative gain. Q-TWiST gains progressively increased over the follow-up period and exceeded the “clinically important” threshold around 27 mos (Table). These gains were driven by steady increases in TWiST gains from 0.4 mos (after 12 mos) to 7.1 mos (after 57 mos). Conclusions: In CheckMate 214, N+I resulted in a statistically significant and “clearly clinically important (≥ 15%)” longer quality-adjusted survival vs. SUN, which increased over the longer follow-up time. Q-TWiST gains were primarily driven by time in “good” health (i.e., TWiST), which largely resulted from the long-term PFS benefits seen for N+I vs. SUN. Clinical trial information: NCT02231749. [Table: see text]