Response to COVID-19 vaccination in patients on cancer therapy:Analysis in a SARS-CoV-2-naïve population

Background: Cancer patients have increased morbidity and mortality from COVID-19, but may respond poorly to vaccination. The Evaluation of COVID-19 Vaccination Efficacy and Rare Events in Solid Tumors (EVEREST) study, comparing seropositivity between cancer patients and healthy controls in a low SARS-CoV-2 community-transmission setting, allows determination of vaccine response with minimal interference from infection. Methods: Solid tumor patients from The Canberra Hospital, Canberra, Australia, and healthy controls who received COVID-19 vaccination between March 2021 and January 2022 were included. Blood samples were collected at baseline, pre-second vaccine dose and at 1, 3 (primary endpoint), and 6 months post-second dose. SARS-CoV-2 anti-spike-RBD (S-RBD) and anti-nucleocapsid IgG antibodies were measured. Results: Ninety-six solid tumor patients and 20 healthy controls were enrolled, with median age 62 years, and 60% were female. Participants received either AZD1222 (65%) or BNT162b2 (35%) COVID-19 vaccines. Seropositivity 3 months post vaccination was 87% (76/87) in patients and 100% (20/20) in controls (p =.12). Seropositivity was observed in 84% of patients on chemotherapy, 80% on immunotherapy, and 96% on targeted therapy (differences not satistically significant). Seropositivity in cancer patients increased from 40% (6/15) after first dose, to 95% (35/37) 1 month after second dose, then dropped to 87% (76/87) 3 months after second dose. Conclusion: Most patients and all controls became seropositive after two vaccine doses. Antibody concentrations and seropositivity showed a decrease between 1 and 3 months post vaccination, highlighting need for booster vaccinations. SARS-CoV-2 infection amplifies S-RBD antibody responses; however, cannot be adequately identified using nucleocapsid serology. This underlines the value of our COVID-naïve population in studying vaccine immunogenicity.</p

From the International Association for the Study of Lung Cancer Early Detection and Screening Committee: Terminology Issues in Screening and Early Detection of Lung Cancer-International Association for the Study of Lung Cancer Early Detection and Screening Committee Expert Group Recommendations.

IntroductionTo facilitate global implementation of lung cancer (LC) screening and early detection in a quality assured and consistent manner, common terminology is needed. Researchers and clinicians within different specialties may use the same terms but with different meanings or different terms for the same intended meanings.MethodsThe Diagnostics Working Group of the International Association for the Study of Lung Cancer Early Detection and Screening Committee has analyzed and discussed relevant terms used on a regular basis and suggests recommendations for consensus definitions of terminology applicable in this setting. We explored how to reach consensus to define relevant and unambiguous terminology for use by health care providers, researchers, patients, screening participants, and family.ResultsTerms and definitions for epidemiologic and health-economical purposes included the following: standardized incidence and mortality rates, LC-specific survival, long-term survival and cure rates, overdiagnosis, overtreatment, and undertreatment. Terms and definitions for defining screening findings included the following: positive, false-positive, negative, false-negative, and indeterminate findings and additional and incidental findings. Terms and definitions for describing parameters in screening programs included the following: opportunistic versus programmatic screening, screening rounds, interval or interim diagnoses, and invasive and minimally invasive procedures. Terms and definitions for shared decision-making included the following: LC screening-possible harms and risks and LC risk and modifiers prior and posterior to a measure.ConclusionsA common set of terminology with standard definitions is recommended for describing clinical LC screening programs, the discussion about effectiveness and outcomes, or the clinical setting. The use of the terms should be clearly defined and explained

A double‐blind, placebo‐controlled study of vortioxetine in the treatment of binge‐eating disorder

Background: Binge-eating disorder (BED) is associated with impaired quality of life and has a number of untoward public health associations. There are few established pharmacological treatments for BED, and available options are not suitable for all individuals. Vortioxetine is a recently developed pharmacological agent with effects on the serotonergic but also other neurochemical systems, which has yet to be evaluated in this context. Method: Eighty adults with BED were recruited for a double-blind, placebo-controlled study. Participants received 12-week treatment with vortioxetine (10 mg/day for 1 week, then increasing to 20 mg/day) or placebo in a parallel design. The primary efficacy outcome measures were binge-eating frequency and weight. Safety data were collected. Effects of active versus placebo treatment were characterized using linear repeated measures models. Results: Both vortioxetine and placebo treatment were associated with significant reductions in binge-eating frequency. Vortioxetine did not differentiate significantly from placebo on any efficacy measure. Frequency of adverse events did not differ between groups. Discussion: Vortioxetine was not more effective than placebo in the treatment of BED. The ability to detect pharmacological treatment benefit may have been hindered by the relatively high placebo response and drop out. Future work should seek to better understand and predict placebo response in BED, with a view to more targeted treatment interventions and, potentially, sample enrichment.</p

Early T Cell Infiltration Correlates with Anti-CTLA4 Treatment Response in Murine Cancer Models

Immune checkpoint inhibitor (ICI) Abs are a revolutionary class of cancer treatment, but only ~30% of patients receive a lasting benefit from therapy. Preclinical studies using animals from the same genetic backgrounds, challenged with the same cancer models, also show nonuniform responses. Most mouse studies that have evaluated tumor-infiltrating leukocytes after ICI therapy cannot directly correlate their findings with treatment outcomes, because terminal methods were used to acquire immune infiltrate data. In the present study, we used fine-needle aspiration (a nonterminal sampling method) to collect multiple aspirates over several days from s.c. implanted P815, CT26, and 4T1 mouse cancer models treated with ICI Abs. These aspirates were then analyzed with flow cytometry to directly correlate tumor-infiltrating leukocyte populations with treatment success. We found that the P815 and CT26 models respond well to anti-CTLA4 therapies. Among P815-challenged animals, mice that regressed following anti-CTLA4 treatment showed significant increases in CD8+ T cells on days 3, 5, and 7 and in CD4+ T cells on days 5 and 7 and a decrease in macrophages and monocytes on days 3, 5, and 7 after treatment. Similar results were obtained in the CT26 model on day 11 posttreatment. Our study is the first, to our knowledge, to directly correlate early tumor infiltration of T cells with anti-CTLA4 treatment success, thus providing a mechanistic clue toward understanding why alloidentical mice challenged with identical tumors do not respond uniformly to ICI therapies.</p