Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma—Reply

In Reply We thank Gao and colleagues for their interest and comments on our meta-analysis. JUPITER-06 was only published on March 3, 2022. As such, it was not included in the analysis because the systematic search was concluded on October 1, 2021. Notwithstanding, the discordance of our findings and those reported by Wu and colleagues is of interest. The notable findings from the 2-stage meta-analysis conducted by Wu et al appear to be driven by treatment effects from JUPITER-06.

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Luglio 2023

Combination immunochemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and meta-analysis

Objective
To evaluate the efficacy and safety of combination immunochemotherapy regimens for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Design
Meta-analysis and systematic review.

Data sources
PubMed, Embase, Web of Science and Cochrane library and the Clinicaltrials.gov clinical trials registry were searched up to 14 March 2022.

Eligibility criteria for selecting studies
We included randomised controlled trials that compared combination immunochemotherapy with conventional chemotherapy for R/M HNSCC. Primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse effects (AEs).

Data extraction and synthesis
Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.

Results
A total of 1214 relevant papers were obtained after the initial search, and five papers that met the inclusion criteria were included; these studies included a total of 1856 patients with R/M HNSCC. Meta-analysis showed that the OS and PFS of patients with R/M HNSCC in the combination immunochemotherapy group were significantly longer than those in the conventional chemotherapy group (HR=0.84; 95% CI 0.76, 0.94; p=0.002; HR=0.67; 95% CI 0.61, 0.75; p

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Giugno 2023

Distinct single-cell immune ecosystems distinguish true and de novo HBV-related hepatocellular carcinoma recurrences

Objective
Revealing the single-cell immune ecosystems in true versus de novo hepatocellular carcinoma (HCC) recurrences could help the optimal development of immunotherapies.

Design
We performed 5’and VDJ single-cell RNA-sequencing on 34 samples from 20 recurrent HCC patients. Bulk RNA-sequencing, flow cytometry, multiplexed immunofluorescence, and in vitro functional analyses were performed on samples from two validation cohorts.

Results
Analyses of mutational profiles and evolutionary trajectories in paired primary and recurrent HCC samples using whole-exome sequencing identified de novo versus true recurrences, some of which occurred before clinical diagnosis. The tumour immune microenvironment (TIME) of truly recurrent HCCs was characterised by an increased abundance in KLRB1+CD8+ T cells with memory phenotype and low cytotoxicity. In contrast, we found an enrichment in cytotoxic and exhausted CD8+ T cells in the TIME of de novo recurrent HCCs. Transcriptomic and interaction analyses showed elevated GDF15 expression on HCC cells in proximity to dendritic cells, which may have dampened antigen presentation and inhibited antitumour immunity in truly recurrent lesions. In contrast, myeloid cells’ cross talk with T cells-mediated T cell exhaustion and immunosuppression in the TIME of de novo recurrent HCCs. Consistent with these findings, a phase 2 trial of neoadjuvant anti-PD-1 immunotherapy showed more responses in de novo recurrent HCC patients.

Conclusion
True and de novo HCC recurrences occur early, have distinct TIME and may require different immunotherapy strategies. Our study provides a source for genomic diagnosis and immune profiling for guiding immunotherapy based on the type of HCC recurrence and the specific TIME.

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Maggio 2023

SARS-CoV-2 vaccination in patients with GI and hepatobiliary carcinoma: a call for booster vaccination

Bollipo et al1 presented recommendations for SARS-CoV-2 infections in patients with chronic liver diseases (CLDs). Since their publication, at least three SARS-CoV-2 vaccinations are recommended for all persons regardless of comorbidities.2 Cancer and CLD are associated with impaired immune responses to SARS-CoV-2 vaccines.3–6 However, patients with GI cancer, especially with hepatobilary carcinoma (HBC), are under-represented in published studies. In this prospective, longitudinal study, 120 patients with GI cancer, including 32.5% HBC, participated (table 1). Patients under anticancer therapy were analysed compared with patients with GI cancer in follow-up care (≥1 year off anticancer therapy). We present profound data on humoral response rates (SARS-CoV-2 antispike and surrogate neutralisation antibodies (sNAB) using SARS-CoV-2 IgG II Quant chemiluminescent microparticle immunoassay (Abbott Laboratories) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript), respectively). Of note, the ELISA analysing levels of sNAB…

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Maggio 2023

Carcinoma en Cuirasse

This case report describes hyperpigmented, indurated, and sclerotic plaques on the anterior trunk and upper abdomen with overlying scale that were studded with firm, erythematous papules.

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Maggio 2023

Active Surveillance for Low-risk Papillary Thyroid Carcinoma—Reply

In Reply We thank Yang and colleagues for their interest in our nonrandomized controlled trial comparing active surveillance (AS) with immediate surgery (IS) for papillary thyroid carcinoma (PTC). The authors correctly note that guidelines such as those from the American Thyroid Association support AS for PTCs 10 mm or smaller. Our study’s primary purpose was to investigate the safety of AS for tumors falling outside of these standard guidelines in the context of a clinical trial. We elected to study up to 20 mm because this captures all T1 cancers. To our knowledge, there is no biologic distinction between cancers within this stage grouping. Since AS was investigational at the time of study onset, we limited inclusion to 15-mm cancers out of an abundance of caution; we later expanded to all T1 tumors in conjunction with observational data from other groups studying this approach.

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Maggio 2023

Active Surveillance for Low-risk Papillary Thyroid Carcinoma

To the Editor Active surveillance (AS) for low-risk papillary thyroid carcinoma (PTC) has been a focus of research and debate. Recently in JAMA Oncology, Ho and colleagues reported the result of patients with 20-mm or smaller thyroid nodules who chose either AS or immediate surgery. This nonrandomized controlled trial provided new evidence for the management of low-risk PTC. Here, we raise concerns about the study’s design and interpretation of the results.

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Maggio 2023