COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

Discrepancies between tumor genomic profiling and germline genetic testing.

BACKGROUND: Tumor genomic profiling (TGP) often incidentally identifies germline pathogenic variants (PVs) associated with cancer predisposition syndromes. Methods used by somatic testing laboratories, including germline analysis, differ from designated germline laboratories that have optimized the identification of germline PVs. This study evaluated discrepancies between somatic and germline testing results, and their impact on patients. PATIENTS AND METHODS: Chart reviews were carried out at a single institution for patients who had both somatic and designated germline genetic testing. Cases with discrepant results in which germline PVs were not detected by the somatic laboratory or in which variant classification differed are summarized. RESULTS: TGP was carried out on 2811 cancer patients, 600 of whom also underwent designated germline genetic testing. Germline PVs were identified for 109 individuals. Discrepancies between germline genetic testing and tumor profiling reports were identified in 20 cases, including 14 PVs identified by designated germline genetic testing laboratories that were not reported by somatic testing laboratories and six variants with discrepant classifications between the designated germline and somatic testing laboratories. Three PVs identified by designated germline laboratories are targets for poly adenosine diphosphate-ribose polymerase (PARP) inhibitors and resulted in different treatment options. Of the PVs identified by designated germline laboratories, 60% (n = 12) were in genes with established associations to the patients' cancer, and 40% of the PVs were incidental. The majority (90%) of all discrepant findings, both contributory and incidental, changed management recommendations for these patients, highlighting the importance of comprehensive germline assessment. CONCLUSIONS: Methods used by somatic laboratories, regardless of the inclusion of germline analysis, differ from those of designated germline laboratories for identifying germline PVs. Unrecognized germline PVs may harm patients by missing hereditary syndromes and targeted therapy opportunities (e.g. anti-programmed cell death protein 1 immunotherapy, PARP inhibitors). Clinicians should refer patients who meet the criteria for genetic evaluation regardless of somatic testing outcomes.

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Comparison of updated Vitek Yeast Biochemical Card and API 20C yeast identification systems.

The updated Vitek Yeast Biochemical Card (YBC) was compared with the API 20C by using 409 germ tube-negative yeasts and Geotrichum spp. that were either clinical or proficiency sample isolates. The API 20C was the reference standard. The 409 isolates represented nine genera and 21 species. Morphology agars were inoculated and interpreted for each isolate. The API 20C identified 406 isolates (99.3%), while the Vitek YBC identified 367 (89.7%). Both systems identified the majority of yeasts after 24 h of incubation--73.4% were identified by the API 20C and 77.4% were identified by the Vitek YBC. The Vitek 24-h reading had some incorrect identifications. These included 14 isolates of Candida tropicalis that were identified as Candida parapsilosis (91 to 97% reliability) and 3 isolates of Candida krusei that were called Blastoschizomyces capitatus (Geotrichum capitatum), Candida rugosa, and Candida zeylanoides. In total, the Vitek YBC misidentified 30 isolates, while the API 20C misidentified 3 isolates. In addition, results for 14 isolates with the Vitek YBC were listed under the category "no identification." Morphology agars were required for identification with 89 isolates (21.9%) when the API 20C was used and with 50 isolates (12.6%) when the Vitek YBC was used. Apart from the price of the Vitek instrument, the API 20C costs $1.28 more per test than the Vitek YBC. Overall, the updated Vitek YBC compares favorably with the API 20C in the identification of common yeasts such as Torulopsis glabrata, C. parapsilosis, and Cryptococcus neoformans. However, problems were encountered with the Vitek system in the identification of C. tropicalis, C. krusei, Trichosporon spp., and some Cryptococcus spp. The routine use of morphology agars with either method is recommended.

Hypothermia produced by peripheral and central injections of chlorpromazine in aged rabbits.

Hypothermia produced by IV administration of chlorpromazine (CPZ, 0.5-2.0 mg/kg) in a thermoneutral environment was greater in rabbits 2-4.5 years old than in animals under 24 months of age. One microgram CPZ given intracerebroventricularly (ICV) produced greater hypothermia in the older animals in tests performed in a thermoneutral environment while 0.25 and 0.5 microgram doses did not. The hypothermogenic effect of all three ICV doses of CPZ was enhanced in older rabbits exposed to cold. The brain of the older rabbit appears to be more sensitive to the hypothermogenic effects of CPZ. The findings suggest that this widely used tranquilizer can contribute to accidental hypothermia of the aged.