Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: A retrospective multicentric cohort study.

OBJECTIVES: Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLC patients receiving these treatments. METHODS: A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of VTEs after ICIs was estimated using competing risk analysis, and the association of these events with survival and response to treatment was determined. Finally, univariate and multivariate tests were performed to identify VTE risk factors. RESULTS: The cumulative incidence of VTEs in the cohort was 14.8% (95% CI = 7.4-22.2%) for an incidence rate of 76.5 (95% CI = 59.9-97.8) thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. VTEs were not correlated with overall survival, progression-free survival, or objective response to ICIs. Age ˂ 65 years old (HR = 2.00; 95% CI = 1.11-3.59) and tumors with PD-L1 1-49% (HR = 3.36; 95% CI = 1.19-9.50) or PD-L1 ≥ 50% (HR = 3.22; 95% CI = 1.21-8.57) were associated with more VTEs after 12 months of ICI initiation. Also, a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 2.06; 95% CI = 1.09-3.89) and active smoking (HR = 2.00; 95% CI = 1.12-3.58) are probable risk factors of VTEs. CONCLUSION: This study suggests that the incidence of VTEs in NSCLC patients treated with ICIs is comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, VTEs were not associated with a decreased survival or response to therapy. Patient age < 65 and tumors with PD-L1 ≥ 1% were associated with a higher risk of VTEs under ICIs.

Prevalence of Celiac Disease in Patients with Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) frequently coexists with other autoimmune diseases, including celiac disease (CeD). Although the prevalence of CeD is high among cohorts with PBC, few studies have directly compared this prevalence to those among individuals with other liver diseases (OLD). AIM: To compare the prevalence of CeD between a cohort with PBC and a cohort with OLD. METHODS: Retrospective study from January 2013 to December 2016. All consecutive patients with an anti-transglutaminase (tTG) assay requested by a hepatologist and a diagnosis of chronic liver disease were included. CeD diagnosis was confirmed by duodenal biopsies. RESULTS: We included 399 consecutive patients (53.1 years SD 14.0, 54.1% women), notably 51 individuals with PBC and 348 individuals with OLD. PBC group included significantly more women (90.2% versus 48.9% P < 0.0001). The prevalence of CeD was higher in the group with PBC compared to the group with OLD (11.8 versus 2.9%, P < 0.003). In the OLD group, the prevalence of CeD was comparable regardless of the etiologic subgroup (nonalcoholic steatohepatitis 2.7% versus alcoholic liver disease 4.3%, versus viral 1.5% versus other autoimmune liver diseases 3.3%, NS). The presence of gastrointestinal symptoms at the time of the tTG assay was comparable between PBC and OLD groups (31.4 versus 29.6%, NS). CONCLUSION: There is a higher prevalence of CeD in the PBC group compared to other liver diseases.

Durvalumab therapy following chemoradiation compared with a historical cohort treated with chemoradiation alone in patients with stage III non-small cell lung cancer: A real-world multicentre study.

BACKGROUND: The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups. METHODS: In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use. RESULTS: Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression <1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006). CONCLUSIONS: This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Physiologic colonic uptake of 18F-FDG on PET/CT is associated with clinical response and gut microbiome composition in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. METHODS: Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. RESULTS: The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3 months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6 months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. CONCLUSIONS: Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.

High mortality among hospital-acquired COVID-19 infection in patients with cancer: A multicentre observational cohort study.

INTRODUCTION: Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centres have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer. METHODS: Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020 in the provinces of Quebec and British Columbia in Canada. Patient's baseline characteristics including age, sex, comorbidities, cancer type and type of anticancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalisation, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation. RESULTS: A total of 252 patients (N = 249 adult and N = 3 paediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N = 233). One hundred and six patients (42.1%) received active anticancer treatment in the last 3 months before COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection than that in a contemporary community-acquired population (27 days versus unreached, hazard ratio (HR) = 2.3, 95% CI: 1.2-4.4, p = 0.0006. Multivariate analysis demonstrated that hospital-acquired COVID-19, age, Eastern Cooperative Oncology Group status and advanced stage of cancer were independently associated with death. INTERPRETATION: Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer.

Discordance Between Serology and Histology for Celiac Disease in a Cohort with Coexisting Liver Disorders.

BACKGROUND: The liver and celiac disease (CeD) share a complex relationship. While in some patients, isolated hypertransaminasemia is the only manifestation of CeD, liver diseases (LD) may also be associated with the presence of isolated tissue transglutaminase antibodies IgA (tTG IgA) without histologic evidence of CeD. AIMS: To examine the yield of tTG IgA testing (a) in the workup for chronic liver disease (CLD) or cytolysis and (b) to identify biopsy-confirmed CeD (BxCeD) among patients with concomitant LD. METHODS: Retrospective study including two cohorts. Cohort 1 represented 444 consecutive individuals without known CeD for which liver specialists requested tTG IgA. Incidence of positive tTG and BxCeD was evaluated. Cohort 2 included 212 consecutive individuals with positive tTG IgA and subsequent duodenal biopsies. The frequency and clinical characteristics of individuals without BxCeD were examined, with and without concurrent LD. RESULTS: The rate of first time positive tTG IgA among the tests requested by a liver specialist (cohort 1) was 2.0% (n = 9). However, 33.0% (n = 3) of these patients did not have BxCeD. Cohort 2 included 33 individuals with coexisting LD, of which 42.4% did not have BxCeD, compared with 16.2% of the patients without LD (P < 0.001). The majority of the patients without BxCeD (65.1%) showed an increase < 3 times upper limit of normal of tTG IgA. CONCLUSIONS: Although there is clinical value in testing for CeD in the context of LD, there could be a high rate of positive CeD serology unaccompanied by histologic signs in patients with coexisting LD.

Efficacy of immune checkpoint inhibitors in older patients with non-small cell lung cancer: Real-world data from multicentric cohorts in Canada and France.

BACKGROUND: Age-related immune remodelling is thought to be associated with resistance to immune checkpoint inhibitors (ICIs) in cancer. Patients older than 70 years, representing >50% of the population with non-small cell lung cancer (NSCLC) according to SEER database, are underrepresented in clinical trials exploring ICIs. The objective of this study was to determine if patients with NSCLC older than ≥70 years had inferior clinical outcomes with ICIs. METHODS: We conducted a retrospective analysis of 381 patients treated with anti-PD-(L)1 ICI for advanced NSCLC at the Dijon Cancer Center (n = 177), University of Montreal Hospital (n = 106) and Quebec Heart and Lung Institute (n = 98). Age was considered as a categorical variable. Patients' baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features. RESULTS: Among 381 patients included, 335 (88%) received ICI after platinum chemotherapy. The median age was 66 (range 37-89) and 33% were older than 70 years of age. Considering age as a categorical variable, differences in age were not associated with PFS or OS. Subgroup analysis and multivariate cox regression did not reveal significant interaction of age with outcomes. ECOG performance status was the only significant factor in the three cohorts. CONCLUSIONS: Unlike previously described in the era of chemotherapy, age was not associated with outcomes in NSCLC patients treated with ICI.