tbuckley/cabot-search huggingface dataset:
The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and the influence of the NLR in NSCLC patients treated with immunotherapy.
Authors: Francis Proulx-Rocray, Bertrand Routy, Rami Mohamad Nassabein, Omar El Ouarzadi, Wiam Belkaid, Danh Tran-Thanh, Marie Florescu, Mustapha Tehfe, Normand Blais
Journal: Journal of Clinical Oncology (2021)

e21010 Background: ICIs changed the way NSCLC is treated, but not all patients benefit from it. PD-L1 level is used to predict response to therapy, but its performance is sub-optimal. KRAS is important in NSCLC tumorigenesis, but the impact of its mutations in patients treated with ICIs is unclear. Similarly, studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Methods: We conducted a retrospective study including all consenting patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared in co-mutation subgroups using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. Overall response rate (ORR) and safety data was also compared in subgroups and will be detailed at the meeting. Results: We included 100 patients with known KRAS status. From these, 50 were wild-type ( KRAS WT ) and 50 were mutated ( KRAS Mut ). The most frequent mutation was G12C (54%). Co-mutation status for TP53, STK11 and KEAP1 were known for, respectively, 40, 39 and 38 patients. Co-mutations for these genes were present in respectively 19 (47.5%), 8 (20.5%) and 4 (10.5%). Data comparing KRAS Mut and KRAS WT showed non-significant differences in survival (median OS of respectively 21.1 vs. 17.7 months, p = 0.27). The presence of STK11 and/or KEAP1 mutations was associated with a negative impact on survival when compared with wild-type (median OS 7.4 vs 20.4 months, p = 0.001). When the presence of a KRAS mutation was compounded with STK11 and KEAP1, KRAS Mut (vs KRAS WT ) trended to a better prognosis in STK11+KEAP1 WT tumors (median OS of 21.1 for KRAS Mut vs 15.8 for KRAS WT , p = 0.15), but not in STK11+/-KEAP1 Mut tumors (7.4 for KRAS Mut vs 7.0 for KRAS WT ). No influence on survival was seen in relationship to the TP53 co-mutation. Interestingly, the NLR was significantly higher with STK11 mutations (6.66 Mut vs 3.59 WT , p = 00012), slightly lower with TP53 mutations (3.23 Mut vs 4.82 WT , p = 0.047) but not impacted by KEAP1 (3.72 Mut vs 4.20 WT , p = 0.72) or KRAS mutations (4.32 Mut vs 5.21 WT , p = 0.34). Conclusions: The STK11 and KEAP1 mutations are significant adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11 mutations but not by KEAP1 mutations suggesting marked differences in the resistance mechanism for both mutations. In STK11-KEAP1 WT tumors, KRAS mutations seems to be associated with improved survival in NSCLC patient treated with ICIs.
Concerns About Recommendations for Perioperative Cannabis Use
Authors: Karim S. Ladha, Alexander McLaren-Blades, Hance Clarke
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
External cervical resorption—a review of pathogenesis and potential predisposing factors
Authors: Yiming Chen, Ying Huang, Xuliang Deng
Journal: International Journal of Oral Science (2021)

External cervical resorption (ECR) refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root. Despite being latent in its initial phase, ECR could cause severe damage to mineralized dental tissue and even involve the pulp if not given timely diagnosis and treatment. Nevertheless, the etiology of ECR is still poorly understood, which adds to the difficulty in early diagnosis. ECR has received growing attention in recent years due to the increasing number of clinical cases. Several potential predisposing factors have been recognized in cross-sectional studies as well as case reports. In the meantime, studies on histopathology and pathogenesis have shed light on possible mechanisms of ECR. This review aims to summarize the latest findings in the pathogenesis and potential predisposing factors of ECR, so as to provide pragmatic reference for clinical practice.
Overexpression of LILRB2 (ILT4) is correlated with immunosuppressive immune infiltration in lung adenocarcinoma.
Authors: Butuo Li, Chao Jiang, Shijiang Wang, Xuanzong Li, Yiyue Xu, Xinyu Fan, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e20519 Background: Immune checkpoint inhibitors have revolutionized the patterns of tumor treatment with significantly improved survival. However, it’s worth noting that the objective response rate of PD-1/PD-L1 inhibitors monotherapy is just 20% in non-small cell lung cancer (NSCLC) patients, and biomarkers for the prognosis of patients receiving PD-1/PD-L1 inhibitors are urgently needed. LILRB2 (ILT4) is known as an immunosuppressive molecule and promotes the development and progression of NSCLC. However, the relationship between LILRB2 expression and immune microenvironment remains unclear in patients with lung adenocarcinoma. Methods: Expression profile and corresponding clinicopathological data of patients with lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database. TIMER 2.0 was used to investigate the relationship between LILRB2 expression and immune infiltrates, including T cell subset, macrophage and so on. Cox proportional hazard model was also performed to evaluate the role LILRB2 expression and immune infiltrations in prognostic prediction of patients with lung adenocarcinoma. Results: 515 patients with lung adenocarcinoma were included in analysis from TCGA dataset. LILRB2 expression was found to have significant negative correlation with CD8+ T cell infiltration (P = 0.0012), and positive correlation with CD4+ T cell infiltration (P &lt; 0.001). There were also significant positive correlations between LILRB2 expression and Treg (P = 0.0083), cancer associated fibroblast (P &lt; 0.001), monocyte (P &lt; 0.001), M2 macrophage (P &lt; 0.001) infiltration, which was regarded as the marker of immunosuppressive microenvironment. Notably, there were also significant association between the expression of LILRB2 and PD-1 (P &lt; 0.001) and PD-L1(P &lt; 0.001). In terms of survival analysis, high level of Treg (HR = 0.86, P = 0.03) and M2 macrophage (HR = 0.84, P = 0.017) infiltration was associated with poor prognosis of patients with lung adenocarcinoma. However, the level of CD8+T cell (HR = 0.93, P = 0.298), CD4+ T cell (HR = 0.933, P = 0.321), and LILRB2 expression (P = 0.56) was not associated with the survival of patient with lung adenocarcinoma. Conclusions: The overexpression of LILRB2 is significantly correlated with immunosuppressive immune infiltration and microenvironment in lung adenocarcinoma and might be the potential predictive biomarkers for the PD-1/PD-L1 inhibitors.
CD4+ T-cell count eligibility by HIV status among participants receiving immunotherapy for cancer diagnoses.
Authors: Thomas A Odeny, Matthew Harry Rosenthal, Kathryn Anne Lurain, Julius Strauss, Thomas S. Uldrick, James L. Gulley, Robert Yarchoan, Ramya Ramaswami
Journal: Journal of Clinical Oncology (2021)

12104 Background: The Food and Drug Administration recommends that patients living with HIV (PLWH) with a CD4+ T cell count (CD4) ≥350 cells/µL should generally be eligible for any cancer clinical trial, but there has been a reluctance to enter patients with lower CD4 counts. Patients with relapsed or refractory cancers may also have low CD4 due to initial cancer therapies, irrespective of HIV status. Immune checkpoint inhibitors (ICI) are safe among PLWH with advanced cancer receiving antiretroviral therapy and CD4 &gt;100 cells/µL. We examined the outcomes of immunotherapy trials by HIV and CD4 status among patients receiving ICI for relapsed/refractory cancers. Methods: We conducted a retrospective cohort study of participants who received ICI for relapsed/refractory cancers in 2 trials (1 specifically in PLWH with CD4 &gt;100 only) from the National Cancer Institute. Primary outcomes were to assess relationship between HIV status and baseline CD4 (&lt;350 vs ≥350 cells/µL) and other characteristics. We stratified 3-year survival by CD4 in PLWH and HIV-negative participants with HPV-related cancers. The Kaplan-Meier method was used to estimate survival rates. Results: Eighty-three participants were included: 26 (31.3%) were HIV-positive and received pembrolizumab and 57 (68.7%) were HIV-negative and received bintrafusp alfa. HIV-negative participants had relapsed HPV related malignancies (cervix, anal, head and neck) whereas participants with HIV had both viral and non-viral associated cancers (Table). While the median screening CD4 was significantly lower among PLWH than HIV-negative participants, there was no difference in the proportion with CD4 &lt;350 (p=0.1). When restricted to HPV related malignancies, 3-year survival rates were 32.2% for CD4 &lt;350 and 21.2% for CD4 ≥350 (p=0.7). Conclusions: In this retrospective study of ICI clinical trials in relapsed and refractory malignancies, there was no significant difference in baseline CD4 (&lt;350 vs ≥350 cells/µL) by HIV status; 50% of HIV-negative participants had CD4&lt;350 cells/µL. Patients with HIV should be included in ICI studies, and CD4 thresholds lower than 350 cells/µL should be considered as to not unfairly exclude PLWH with cancer.[Table: see text]
The efficacy and safety analysis of PD-1 inhibitor combined with interferon-<b>α</b>1b: A real-world study in Chinese metastatic melanoma patients.
Authors: Guannan Zhu, Qiong Shi, Chunying Li, Tianwen Gao
Journal: Journal of Clinical Oncology (2021)

e21507 Background: Clinical data on PD-1 inhibitor combined with interferon in metastatic melanoma treatment were still limited. The objective of this study was to assess the efficacy and safety of PD-1 inhibitor/interferon-α1b combination therapy for Chinese metastatic melanoma patients in the real world. Methods: We reviewed patients diagnosed as metastatic melanoma and had received PD-1 inhibitor (pembrolizumab, 2 mg/kg, every 3 weeks, intravenously or toripalimab 240mg every 2 weeks, intravenously) combined with interferon-α1b(10μg/kg, every other day, subcutaneously) in Xijing Hospital from Dec 2018 to Nov 2020. Efficacy and safety profiles were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 and Common Terminology Criteria for Adverse Events version 5.0, respectively. Results: In total 65 patients were reviewed in this study, including 13 cases with ECOG performance status ≥2. Acral and mucosal cases accounted for 47.7% and 23.1% respectively. In 27(41.5%) patients, the combination therapy was used as the first line treatment, whereas in the rest 38 patients as second or subsequent lines. The median follow-up period was 8 months (1.5-21 months). Median OS was 15 months (95CI%: 10.62-19.38 months). Median PFS was 6 months (95CI%: 2.54-9.46 months). 6-month and 1-year PFS rate were 48.1% and 35.3%. 6-month and 1-year OS rate were 80.9% and 59.8%. Objective response was seen in 18.46% cases, with 12.31% of patients exhibiting ongoing response. The best confirmed disease control rate was 73.85%. Multivariate analysis demonstrated that overall survival was significantly associated with ECOG performance status ≥2 (OR=3.32，95%CI=1.14-9.66 ), regardless of age(≥65), elevated LDH, PD-1 inhibitor type and the line of the combination therapy. Select treatment related AEs (TRAEs) of any grade were observed in 57(87.69%) patients. The leading 3 TRAEs were lymphopenia, fatigue and fever. Grade 3 to 4 TRAEs were recorded in 2 cases. Grade 4 hyponeutrophilia occurred in a patient with ECOG status 3 using interferon-α1b plus toripalimab and resulted in discontinuation of both PD-1 inhibitor and IFN-α1b. Grade 3 headache was reported by one patient using interferon-α1b plus pembrolizumab and was solved with celecoxib 200mg daily. No drug-related deaths were reported. Conclusions: PD-1 inhibitor combining interferon-α1b therapy shows promising efficacy and acceptable toxicity in this real-world cohort of Chinese metastatic melanoma patients.[Table: see text]
Supporting the mental well-being of healthcare professionals during a pandemic.
Authors: Ana Maria Lopez, Lisa Capparella, Miriam Pomerantz, Kristine Naputo, Amy Leader, C. Virginia Virginia O'Hayer
Journal: Journal of Clinical Oncology (2021)

11037 Background: Burnout amongst healthcare professionals has been well-documented as a phenomenon that compromises the quality and viability of patient-centered care, particularly in oncology. Due to the extraordinary demands of the pandemic, burnout has emerged as a public health crisis that warrants immediate attention to preserve the wellbeing of healthcare staff. At the onset of the pandemic, The Sidney Kimmel Cancer Center (SKCC) at Jefferson, an urban NCI-designated cancer center, translated its support offerings to virtual events. Initially, healthcare providers (HP) sought support by attending patient programs. In response, SKCC initiated virtual programming to support the well-being and needs of the HP team. Methods: Within weeks of the state shutdown due to the pandemic, programs were initiated to address HP self-reported distress: Coping Effectively and Mindfulness Moments Each 30-minute session was facilitated by a licensed psychologist and social worker. Coping Effectively offers strategies from evidence based treatment including Dialectical Behavior Therapy, Acceptance and Commitment Therapy, and Cognitive Behavioral Therapy, to cope with distress and burnout. Mindful Moments draws from Mindfulness Based Stress Reduction practices including observing breath and guided meditations. These programs have been offered consistently throughout the pandemic. Schwartz Rounds, geared towards supporting the human side of healthcare, provided “hot” topic moderated discussions, four of which focused on the pandemic These discussions allow for HP to come together to discuss difficult topics and emotions impacting a variety of professionals. All programming was evaluated with a single question to measure the impact of the session on reducing distress. Each program began and ended with a poll asking, “How distressed do you currently feel?” Attendees respond on a Likert scale from 0 to 10, in which10 indicated the highest level of distress. Results: Since March 31 st , 340 staff have attended Mindful Moments and 236 staff have attended Coping Effectively. From March 2020-February 2021, 382 attendees measured their distress before and after attending a staff program. Schwartz Rounds hosted 471 HP from a variety of disciplines. Participants were asked to complete an evaluation following rounds. 31% of program participants’ completed an evaluation form and 89% rated the program exceptional/very good. Conclusions: Despite the challenges of COVID-19, the pivot to virtually create programs to support staff during the pandemic was swift and thoughtful. The increased attendance and the feedback from evaluations are promising indicators of decreasing burnout amongst HP. How Distressed do you Currently Feel? (Average Score scale 1-10)[Table: see text]
Time to regain lost ground: Tuberculosis in the COVID-19 era
Authors: Dominik Zenner
Journal: Eurosurveillance (2021)

Preview this article: Time to regain lost ground: Tuberculosis in the COVID-19 era, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/26/24/eurosurv-26-24-1-1.gif
Serious infections and cardiovascular complications among patients with chronic lymphocytic lymphoma treated with first-line ibrutinib or bendamustine/rituximab.
Authors: Debra E. Irwin, Stephen Thompson, Rinat Ribalov, Azhar Choudhry
Journal: Journal of Clinical Oncology (2021)

e19503 Background: Clinical trials have shown positive outcomes associated with ibrutinib monotherapy (IM) and bendamustine / rituximab combination (BR) therapy in patients with chronic lymphocytic lymphoma (CLL) compared to other standard treatments, but limited real-world data exist. This study evaluated serious infections and cardiovascular complications in CLL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients were diagnosed with CLL, treatment naïve, and continuously enrolled for ≥12 months prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions between the treatment groups were tested. Multivariate logistic regression models for lower respiratory tract infection (LRTI) and atrial fibrillation (AF) were also conducted to determine the adjusted odds of hospitalization. Results: Of 2,138 CLL patients, 810 had IM and 512 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older and more likely to have had an LRTI during baseline compared to BR patients, otherwise both groups had similar baseline characteristics. Hospitalization for serious infections was more common during follow-up among IM patients than BR patients (17.7% vs. 13.1%; p = 0.027). Specifically, 10.2% of IM patients had a bacterial infection hospitalization compared to 5.7% of BR patients (p = 0.004) and 10.7% of IM patients had a LRTI hospitalization compared to 6.6% of BR patients (p = 0.012). After adjusting for baseline characteristics, IM patients did not have significantly higher odds of a LRTI hospitalization (OR = 1.51; p = 0.069). Hospitalization for cardiovascular complications was more common during follow-up among IM patients than BR patients (18.3% vs. 11.9%; p = 0.002). Specifically, 8.4% of IM patients had an AF-related hospitalization versus 2.7% of BR patients (p &lt; 0.001). After adjusting for baseline characteristics, IM patients were more likely to have a hospitalization for AF versus BR patients (OR = 3.89; p &lt; 0.001). Conclusions: In a real-world setting, serious infections and cardiovascular complications were more common among CLL patients treated with first-line IM compared to BR during 12 months of follow-up. IM patients were more likely than BR patients to have an inpatient admission due to AF after adjusting for other patient characteristics.
Correlation between driver mutation and immune microenvironment in colorectal cancer patients.
Authors: Xiaochen Cai, Yuezong Bai, Xiaochen Zhao, Longgang Cui, Hui Chen
Journal: Journal of Clinical Oncology (2021)

e15513 Background: Immune checkpoint inhibitor (ICI) therapy has made great achievements, but ICI monotherapies show less effectiveness in colorectal cancer patients. Biomarker exploration have carried out from PD-L1 expression, neo-antigen, gene mutation, etc., but no satisfactory results have been obtained. Methods: Patients, Colorectal cancer patients. Methods, Multi-color immunohistochemistry (multi-IHC) was used to evaluate CD8+ T cells, macrophages and natural killer cell (NK cell) in tumors and tumor stroma. The Shapiro-Wilk method was used to test the normality of the data, and the t-test or Mann-Whitney U test was used according to the test results. A two-sided P &lt; 0.05 was considered a significant difference. Results: The study included 72 colorectal cancer patients, including 26 female (36.7%) and 46 male (63.8%), with a median age of 59.5 (50-67.3). There were 6 patients (8.3%) with BRAF mutation, 43 patients (59.7%) with KRAS mutation, and 56 patients (77.8%) with TP53 mutation. The results of immunohistochemistry showed that, BRAF mutation Vs BRAF wild-type or KRAS mutation Vs KRAS wild-type, the number or proportion of CD8+ T cells, macrophages or NK cells in tumor and tumor stroma were not statistically different. For TP53 mutation Vs TP53 wild-type, the number and proportion of CD8+ T cells or macrophages in tumor and tumor stroma were not statistically different. There was no statistical difference in the number and proportion of NK cells in tumor. But, the median number of NK cells in tumor stroma was 345 Vs 129, p = 0.06, and the proportion of NK cells was 5.2% Vs 1.39%, p = 0.02. Conclusions: There is no significant change in the immune microenvironment of colorectal cancer patients with BRAF mutation and KRAS mutation. There are more NK cells in tumor stroma of colorectal cancer patients with TP3 mutation.