tbuckley/cabot-search huggingface dataset:
The landscape of germline mutations and the relationship with tumor mutation burden in Chinese patients with lung cancer.
Authors: Jian Shi, Rongfeng Liu, Guanglei Huang, Lixing Wang, Baoen Shan, Ningning Luo, Qin Zhang, Didi Guo, Yaqing Wu, Yingxue Qi
Journal: Journal of Clinical Oncology (2021)

10522 Background: Lung cancer is one of the most common types of cancer, ranking the first in the incidence and mortality of malignant tumors in the world and China. Although studies have been reported that genetic susceptibility to lung cancer is associated with certain germline mutations, the relationship between lung cancer risk and inherited genetic factors remains relatively elusive. However, the effect of germline mutation on TMB in lung cancer has not been explored. Herein, DNA genomic profiling was performed through NGS with a 539-gene panel to explore the germline mutations and the relationship with TMB in Chinese patients with lung cancer. Methods: We retrospectively analyzed the germline mutations through a comprehensive 539-gene profiling of 3541 Chinese patients with lung cancer. 539-gene panel contained germline mutations in 90 hereditary tumor-associated genes. We screened out the pathogenic and likely pathogenic germline mutations according to the standards and guidelines for the interpretation of sequence variants of The American College of Medical Genetics and Genomics (ACMG), and picked out there is no records in Clinvar database and no literature report. TMB of tissue or blood ctDNA in 3541 patients were further analyzed in with pathogenic mutations (P group), with likely pathogenic mutations (LP group), and no germline mutations group (Non-P group). The difference in TMB was analyzed via the Wilcoxon sign test. Results: In 3541 patients with lung cancer, 177 (4.999%) patients were identified harboring pathogenic or likely pathogenic germline mutations, in which 78 P group and 99 LP group, the rest 3364 were Non-P group. The highest prevalence of germline mutation was found in BRCA2 (0.565%), ATM (0.339%), MUTYH (0.282%), and BRCA1 (0.254%). In 177 patients with pathogenic or likely pathogenic germline mutations, 67 mutations were recorded as UNK (unknow) in Clinvar database and no literature report. The media TMB of tissue in P group, LP group and Non-P group were 5.149, 5.535 and 5.547 respectively. The media TMB of blood ctDNA in P group, LP group and Non-P group were 4.257, 3.945 and 4.483 respectively. There was no statistical difference in TMB between P and Non-P groups (tissue p = 0.98; ctDNA p = 0.5). Conclusions: In our study, we firstly identified 67 novel germline mutations and studied on the relationship between germline mutations and TMB in lung cancer, which expanded the understanding of germline mutations.
The coming-of-age of bedaquiline: a tale with an open ending
Authors: Lorenzo Guglielmetti, Francis Varaine
Journal: European Respiratory Journal (2021)

<b>Future strategic choices in the clinical development of bedaquiline should be guided by the need to generate high-quality evidence and ultimately improve outcomes of tuberculosis treatment, while preventing the emergence of drug resistance</b>https://bit.ly/3iAOCZr
Outcomes of anti-PD-(L1) therapy in combination with chemotherapy versus immunotherapy (IO) alone for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 score 1-49%: FDA pooled analysis.
Authors: Oladimeji Akinboro, Jonathon Joseph Vallejo, Pallavi Shruti Mishra-Kalyani, Erin A. Larkins, Nicole Lauren Drezner, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Journal of Clinical Oncology (2021)

9001 Background: IO + chemotherapy ± anti-angiogenics comprise FDA-approved 1L regimens for metastatic NSCLC, with IO-only therapy approved only for PD-L1-positive NSCLC. Patients with PD-L1 scores 1-49% have many therapeutic options, and little is known about how subgroups of patients experience benefit across treatment regimens. Methods: Data was pooled from 8 randomized controlled trials investigating anti-PD-(L)1 therapy as IO-only or in chemo-IO regimens for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay, and analysis was conducted for patients whose tumors had PD-L1 score 1-49%. Tumor-infiltrating immune cell staining was not considered. OS and PFS were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial and adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 2108 patients with NSCLC and PD-L1 score 1-49% were identified for this analysis. Baseline characteristics were: 37% aged 65-74 years and 12% aged ≥75; 67% male; 79% white; 65% ECOG ≥ 1; and 85% smokers. Median follow-up was 12.1 months. This pooled analysis showed that patients receiving chemo-IO (N=639) had longer PFS and OS compared to patients treated with IO alone (N=529), with median PFS 7.7 vs 4.2 months (HR 0.60; 95% CI 0.48, 0.76) and median OS 21.4 vs 14.5 months (HR 0.68; 95% CI 0.52, 0.90). All results presented are considered exploratory and hypothesis generating. Conclusions: This exploratory pooled analysis suggests that chemo-IO may improve efficacy outcomes over IO alone in most subgroups of patients with advanced NSCLC with PD-L1 score 1-49%. Patients 75 and over experienced similar outcomes across therapeutic options.[Table: see text]
Analysis of Risk Factors Regarding Short- and Long-Term Mortality of Critically Ill Patients with Hematologic Malignancies or Following Stem Cell Transplantation Requiring Treatment on the Intensive Care Unit
Authors: Timo Funk, Martin Schiller, Gerlinde Egerer, Carsten Müller-Tidow, Anthony D. Ho, Uta Merle, Nicola Lehners
Journal: Blood (2017)
The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort
Authors: Rachel C. Newsome, Josee Gauthier, Maria C. Hernandez, George E. Abraham, Tanya O. Robinson, Haley B. Williams, Meredith Sloan, Anna Owings, Hannah Laird, Taylor Christian, Yilianys Pride, Kenneth J. Wilson, Mohammad Hasan, Adam Parker, Michal Senitko, Sarah C. Glover, Raad Z. Gharaibeh, Christian Jobin
Journal: Gut Microbes (2021)

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.
Evaluation of emergency department (ED) visits by oncology patients: A running comparison to admissions and ED visits under the CMS OP-35 ruling.
Authors: Nada Alsuhebany, Jamie Brown, Jacquelyne Echave, Emad Elquza, Hani M. Babiker, Ivo Abraham, Ali McBride
Journal: Journal of Clinical Oncology (2021)

e18683 Background: The incidence of emergency department (ED) visits by oncology patients has grown in recent years. Some visits are medically unnecessary or could be prevented with improved prophylactic measures. Centers for Medicare &amp; Medicaid Services (CMS) implemented the Hospital Outpatient Quality Reporting (OQR) Program, to which hospitals must report data on quality measures of care furnished in the outpatient setting. One of the proposed measures, OP-35, evaluates admissions and ED visits by patients receiving outpatient chemotherapy, assessing for ten potentially preventable visits. These ten visit reasons included are: anemia, nausea, vomiting, dehydration, neutropenia, diarrhea, pain, pneumonia, fever, and sepsis. This study evaluated the incidence and reasons for ED visits by patients receiving outpatient chemotherapy, as well as outcomes following these visits in order to assess appropriate prophylactic treatment related to outpatient chemotherapy at our institution. Methods: This single-center, retrospective chart review was conducted at The University of Arizona Cancer Center. We collected data using an electronic medical record and included oncology patients with active cancer who had ED visits from January 1, 2018, to December 31, 2018. Data points included baseline demographics; malignancy; ED visit reason; clinic visit history; past ED visits; treatment and supportive care data; and outcome of the ED visit. Results: Study authors included 205 of the 1,659 screened encounters. Approximately 70% of the encounters involved patients with solid tumors and 30% with hematologic malignancies. Nearly 50% of hematologic malignancy patients presented to the ED for potentially preventable reasons, while 32.8% of solid tumor patients had potentially preventable visits. The most common preventable ED visit reasons in both groups were pain, fever, nausea, vomiting, and dehydration. In our analysis, over 90% of patients presenting for neutropenia and fever had received appropriate growth factor prophylaxis when indicated based on their chemotherapy regimen. Of the patients presenting for nausea or vomiting, it was determined 95.3% had received appropriate antiemetic prophylaxis. Conclusions: This study showed that the incidence of potentially preventable visits was numerically higher in the hematologic cancer group compared with the solid tumor group. In addition, this study showed that a number of patients who were admitted to the ED with nausea/vomiting or neutropenia/fever received appropriate guideline-recommended prophylactic or supportive care therapy, regardless of the OP-35 proposed CMS core measure determination that these visit reasons should be considered preventable. These findings highlight the need for CMS to further review OP-35 to include information addressing the use of appropriate supportive care in the future.
Combination therapy with vincristine, immunoglobulin and glucocorticosteroid (VIG regimen) is very effective for the management of grade 3/4 or steroid-refractory immune-related adverse events (irAE) secondary to PD-1 blockade.
Authors: Zhan-Hong Chen, Li Wei, Tian-tian Wang, Qu Lin, Xiangyuan Wu
Journal: Journal of Clinical Oncology (2021)

e14577 Background: The management of grade 3/4 or steroid-refractory immune related adverse events (irAE) is based on a paucity of retrospective data analysis. Our initial experience with the combination therapy with Vincristine (VCR), immunoglobulin (IVIG) and glucocorticosteroid (VIG regimen) showed clinical improvement in a wide variety of irAEs. As a result, we recommend the use of VIG regimen for the management of grade 3/4 or steroid-refractory irAEs. Methods: The character and clinical course of irAEs were abstracted from the medical record and analyzed. The components of VIG regimens are as follows: Methylprednisolone (MP) 2-10mg/kg for 3days, VCR 1.4mg/m2 (≤2mg) continuous infusion for 4-8 hours on day 3 once a week with Immunoglobulin (IVIG) 0.4g/kg for 3-5 days. The dose of MP and IVIG will be reduced quickly after irAE improves. VCR 1.4mg/m2 once a week will be used for 1 to 3 times according to the improvement. Clinical improvement was defined as either: documentation of resolution of symptoms and normalisation of biochemical tests or hospital discharge within 14 days. Results: A total of 25 patients had grade3/4 or steroid-refractory irAEs after receiving immune checkpoint inhibitors and then received VIG regimen. Among them, 22 patients have been significantly improved, with an improvement rate of 88%. Twenty-three patents were treated in the inpatient setting (92%). The index grade 3/4 irAE was pneumonitis in 28%, immune mediated hepatotoxicity(IMH) in 28%, rash/SJS/TEN in 24%, cerebritis in 8 % and one case each of ITP, Near blindness and severe oral mucositis. In 7 patients with severe IMH, the range of total bilirubin was 80-481umol/L and ALT 35-5000u/L. Six patients with IMH recover well but one patient did not recover to normal due to IMH complicated with pneumonitis and TEN . Clinical improvement was noted in 22/25 patients (88%), 11 patients (44%) required a single dose, while 12 patients (48%) required two doses, 2 patients(8%) required three doses of VCR 1.4mg/m2 continuous infusion for 4-8 hours. What is impressive is that the two patients with encephalitis were significantly relieved within 2 weeks after using the VIG regimen. One patient with TEN (SCORETEN 3)was significantly improved and discharged from our hospital 11 days after using the VIG regimen. A patient with near-blind eyesight recovered to normal 3 days after using the VIG regimen. Conclusions: VIG regimen may be an effective therapeutic option for the management of grade3/4 or steroid-refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the efficacy and safety of VIG regimen.
Health disparities in New Zealand Māori with pancreatic cancer at Lakes District health board.
Authors: Laura Camburn, Prashanth Hari Dass
Journal: Journal of Clinical Oncology (2021)

e18554 Background: Global health disparities between ethnicities have been well documented in pancreatic cancer treatment &amp; outcomes. However, pancreatic cancer treatment &amp; survival outcomes between ethnicities, particularly NZ Māori have been poorly documented in our region. Aim to review whether health disparities existed between Māori and New Zealand European patients (NZE) treated with pancreatic cancer. Methods: Patients diagnosed with pancreatic cancer at LDHB between 01 Jul 2014 to 31 Mar 2020 were identified using the faster cancer treatment data. This was cross checked against surgical and Oncology referrals. Electronic notes were reviewed to collect data on ethnicity, patient demographics, presentation, treatment and survival. Results: A total of 69 patients; 25 identified as Māori and 44 NZE. Performance status at presentation was similar between Māori and NZE patients; 64% and 61% respectively, having ECOG 0-1. Majority of patients presented with unresectable locally advanced or metastatic disease (Māori 92% vs NZE 82%). 9% presented with resectable disease, 4% were borderline resectable, only 4 (6%) patients underwent surgical resection. Median overall survival was 34 days for Māori versus 94 days for NZE patients. 72% of Māori patients had an OS &lt; 60 days compared to 39% of NZE, however OS at 6 months was similar in both groups (28% Māori v 27% NZE). For locally advanced disease, similar rates of receipt of chemotherapy (71% vs 62%) were documented between Māori and NZE respectively. Of the 16 Māori patients with metastatic disease at presentation none received palliative chemotherapy compared to 6 / 23 (26%) NZE. Conclusions: Regardless of ethnicity relatively small numbers of our patients have curative surgery which is of concern. Despite adequate performance status at presentation and comparable outcomes in the locally advanced setting, NZ Māori were less likely to receive palliative chemotherapy in the metastatic setting. Further research is warranted to explain and reduce this disparity.
A single dose of the SARS-CoV-2 vaccine BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses
Authors: Alexandra Tauzin, Manon Nayrac, Mehdi Benlarbi, Shang Yu Gong, Romain Gasser, Guillaume Beaudoin-Bussières, Nathalie Brassard, Annemarie Laumaea, Dani Vézina, Jérémie Prévost, Sai Priya Anand, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Guillaume Goyette, Julia Niessl, Olivier Tastet, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Leonidas Stamatatos, Andrew T. McGuire, Catherine Larochelle, Pradeep Uchil, Maolin Lu, Walther Mothes, Gaston De Serres, Sandrine Moreira, Michel Roger, Jonathan Richard, Valérie Martel-Laferrière, Ralf Duerr, Cécile Tremblay, Daniel E. Kaufmann, Andrés Finzi
Journal: Cell Host & Microbe (2021)
HPV-mediated anal squamous cell carcinoma and precancerous lesions in HIV positive patients.
Authors: Omar Bushara, Brian Finkelman, Sam Weinberg, Katrina Krogh, Aparna Kalyan, Guang-Yu Yang
Journal: Journal of Clinical Oncology (2021)

3520 Background: Anal cancer affects over 8,000 patients per year in the United States and the incidence is increasing. A significant risk factor for anal cancer and precancerous lesions is human papilloma virus (HPV), with up to 90% of cases being associated with HPV infection. Another emerging risk factor is HIV co-infection. In the present study, we further address if CD4 count is a significant factor for driving higher-grade HPV-mediated anal squamous lesions in HIV/HPV co-infection patients with a single institution large cohort. Methods: A retrospective cohort of HPV-positive patients with anal biopsies was obtained from 2002-2020. Information on the grade of their anal lesion, HIV status, and CD4 count (cells/mm 3 ) were collected. In patients with HIV, the most recent CD4 count up to one year prior to or one month after their biopsy was utilized in our analysis. Lesions were grouped into low grade squamous intraepithelial lesions (LSIL) and higher grade squamous intraepithelial lesions (HSIL), carcinoma in situ (CIS), or squamous cell carcinoma (SCC). The Center for Disease Control CD4 count levels to define HIV status were utilized in our sub-analyses. The distribution of lesion grades was compared between HIV-negative and -positive patients, and between HIV-negative and three subgroups of HIV-positive patients using the Fisher’s exact test. Results: Our cohort comprised of 3,354 total HPV-positive patients. 2,036 of these patients were HIV-negative and 1318 were HIV-positive. The proportion of higher grade lesions was significantly higher in HIV/HPV co-infected patients regardless of CD4 count (Table). The full cohort of HIV-positive patients had lower rates of LSIL (60.8% vs. 74.0%) and higher rates of higher-grade lesions (39.2% vs. 26.0%) (p&lt;0.001) compared to HIV-negative patients. The distribution of lesion grades was also significantly different between HIV-negative patients and all HIV-positive patient subgroups, with all subgroups having higher rates of higher-grade lesions than HIV-negative patients (all p&lt;0.001). Conclusions: Our data show that HIV-HPV co-infection is a risk factor for higher grade anal lesions, regardless of CD4 status. This suggests that CD4 count is not the only factor responsible for the increased risk of higher-grade anal lesions, as the groups of HIV-positive patients with CD4 counts between 200-499 and above 499 still had a higher rate of higher-grade lesions than HIV-negative patients. Further research into other HIV-related immunologic changes that increase risk for higher-grade HPV-driven anal lesions is warranted.[Table: see text]
The efficacy and clinical survival outcome of different first-line treatments in EGFR-mutant non-small cell lung cancer with brain metastases.
Authors: Huijuan Wang, Ruyue Xing, Mina Zhang, Xiaojuan Zhang, Jinpo Yang, Mengmeng Li, Zhiyong Ma
Journal: Journal of Clinical Oncology (2021)

2028 Background: Brain metastasis is one of the most important factors for poor prognosis of lung cancer, and the incidence of brain metastasis in EGFR-mutant(m+) advanced NSCLC is more common. The first-generation EGFR TKI is a standard first-line treatment. The purpose of this study is to explore the best method for EGFRm+ NSCLC with brain lesions, and to find out correlative factors influencing survival outcome. Methods: The clinical data of NSCLC with brain metastases was retrospectively analyzed. All patients had received 1st generation EGFR TKI, and patients were divided into 4 group, group A : EGFR TKI monotherapy, group B: EGFR TKI plus chemotheapy(CT),Group C:EGFR TKI plus bevacizumab, group D :EGFR TKI plus CT plus bevacizumab.The efficacy of intracranial and extracranial lesions and survival outcome were analyzed. Results: A total of 584 EGFRm+ advanced NSCLC patients from December 2017 to May 2020 were screened,and 228(39%) had brain metastasis at baseline in the treatment-naive. Among them, 194pts had complete medical record and follow-up data. At the follow-up date (January 1, 2021), 147pts had disease progressed and 78pts had died. Intracranial PFS of group A,B,C,D were 11.1m(n = 97), 11.3m(n = 59)，21.2m(n = 19), and 18.9m(n = 19), respectively. No difference was found between A and B group (P = 0.745), so as C and D group (P = 0.684).But, the intracranial PFS of group C+D(with bevacizumab) was significantly longer than group A+B(11.3m (95%CI 12.2-14.8) vs 21.0m (95%CI 15.2-22.7), P = 0.007).The extracranial PFS of groups A, B, C, and D were 11.0m, 14.3m, 21.7m, and 18.9m, respectively,and the P value were 0.006, 0.002, and 0.011, respectively when compared with group A. The mOS of groups A,B were 27.8m and 24.2m,respectively, but group C and D had not yet reached. The intracranial ORR of group A, B, C, and D were 17.9% (14/78), 37.3% (19/51), 60.0% (9/15), and 66.7% (10/15), respectively. The extracranial ORR were 48.5% (47/97), 81.1% (43/53), 73.7% (14/19), and 73.7% (14/19),respectively. Conclusions: For EGFR-mutant NSCLC with brain metastases, the first-generation EGFR-TKI plus bevacizumab can significantly improve the efficacy of intracranial lesions, delay the progression of intracranial lesions, and prolong suvival time, Although the first-generation EGFR-TKI plus CT could improve extracranial ORR when compared with ERGF-TKI monotherapy, it has limited efficacy on intracranial lesions and could not increase survival time.