To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.
Systematic review and meta-analysis.
PubMed, Embase, Central Register of Controlled Trials, COVID-19 ...Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.
Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.
A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.
82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I
=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I
=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I
=89%; 0.29, 0.11 to 0.58, I
=97%), and solid cancers (0.55, 0.46 to 0.65, I
=78%; 0.44, 0.36 to 0.53, I
=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I
=0%; 0.06, 0.04 to 0.08, I
=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I
=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I
=88%; 0.62, 0.54 to 0.70, I
=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I
=92%; 0.77, 0.66 to 0.85, I
=93%), and solid cancers (0.90, 0.88 to 0.93, I
=51%; 0.89, 0.86 to 0.91, I
=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I
=0%; 0.97, 0.83 to 1.00, I
=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.
Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.
PROSPERO CRD42021272088.
Background
Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ...ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28–8 and Ventana SP-142 assays in GC PD-L1 IHC.
Methods
In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer.
Results
The percentage of PD-L1-positive samples at clinically relevant CPS ≥ 1, ≥ 5 and ≥ 10 cut-offs for the 28–8 assay were approximately two-fold higher than that of the 22C3 (CPS ≥ 1: 70.3 vs 49.4%,
p
< 0.001; CPS ≥ 5: 29.1 vs 13.4%,
p
< 0.001; CPS ≥ 10: 13.7 vs 7.0%,
p
= 0.004). The mean CPS score on 28–8 assay was nearly double that of the 22C3 (6.39 ± 14.5 vs 3.46 ± 8.98,
p
< 0.001). At the clinically important CPS ≥ 5 cut-off, there was only moderate concordance between the 22C3 and 28–8 assays.
Conclusion
Our findings suggest that scoring PD-L1 CPS with the 28–8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.
New insight on the interaction between the immune system and tumor has identified the programmed death-1/programmed death-1 ligand pathway to be a key player in evading host immune response. The ...immune checkpoint modulator, nivolumab (BMS-936558/ONO-4538), is the first PD-1 inhibitor to gain regulatory approval, for the treatment of patients with unresectable melanoma. This review will discuss results from early phase studies of nivolumab in solid tumors including non-small cell lung cancer (NSCLC) as well as studies of nivolumab in combination with chemotherapy, other immune modulators and molecular targeted therapy in patients with NSCLC.
Gastric cancer heterogeneity represents a barrier to disease management. We generated a comprehensive single-cell atlas of gastric cancer (>200,000 cells) comprising 48 samples from 31 patients ...across clinical stages and histologic subtypes. We identified 34 distinct cell-lineage states including novel rare cell populations. Many lineage states exhibited distinct cancer-associated expression profiles, individually contributing to a combined tumor-wide molecular collage. We observed increased plasma cell proportions in diffuse-type tumors associated with epithelial-resident KLF2 and stage-wise accrual of cancer-associated fibroblast subpopulations marked by high INHBA and FAP coexpression. Single-cell comparisons between patient-derived organoids (PDO) and primary tumors highlighted inter- and intralineage similarities and differences, demarcating molecular boundaries of PDOs as experimental models. We complemented these findings by spatial transcriptomics, orthogonal validation in independent bulk RNA-sequencing cohorts, and functional demonstration using in vitro and in vivo models. Our results provide a high-resolution molecular resource of intra- and interpatient lineage states across distinct gastric cancer subtypes.
We profiled gastric malignancies at single-cell resolution and identified increased plasma cell proportions as a novel feature of diffuse-type tumors. We also uncovered distinct cancer-associated fibroblast subtypes with INHBA-FAP-high cell populations as predictors of poor clinical prognosis. Our findings highlight potential origins of deregulated cell states in the gastric tumor ecosystem. This article is highlighted in the In This Issue feature, p. 587.
In an attempt to overcome resistance to immune checkpoint inhibitors (ICI), an ever-increasing number of trials are exploring combination treatment approaches. Outcomes of a novel ICI doublet ...presented by Desai and colleagues are discussed along with emerging novel strategies and a view to future ongoing rational trial design maximising patient benefit.
Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize ...treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine. Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity, and varied mechanisms of drug resistance continue to be challenges to overcome. Large-scale data-sharing and collaborative networks using next-generation sequencing (NGS) platforms promise to take us further into the cancer ‘ome’ than ever before, with the goal of achieving successful precision medicine.
(1) To assess whether Front-of-Pack (FOP) nutrition labels garner attention more readily than more complete, mandated nutrition information (the Nutrition Facts Panel (NFP), required in the US), and ...(2) To determine whether label design characteristics, specifically, color coding and/or coding with facial icons, increase attention to the FOP label.
In two experiments, we tracked the allocation of attention while participants (n=125) viewed novel and commercial packages with varied FOP designs using a change detection methodology.
We found empirical evidence that FOP labels are attended more often, and earlier, than the currently mandated NFP, and that this benefit is due both to its placement on the front of the package and to the design characteristics of the FOP. Specifically, the use of color in FOPs increased attention to the label, but there was no evidence that coding information via facial icons impacted attention.
Our work supports a growing body of evidence supporting the use of FOP labels to attract attention to nutritional information. Findings may be relevant to inform policy decisions on labeling standards.
There are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its ...characteristics in patients receiving taxane- and platinum-based chemotherapy.
Multi-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.
In total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2-53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (r
= 0.15,p < 0.05-r
= 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN.
The historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.
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