Hong Zhou

Background: The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta‐analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment.Methods: A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome.Results: A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post‐neoadjuvant treatment and post‐surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly.Conclusion: Our comprehensive meta‐analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

Article: A novel hypoxia-related genes signature for prognosis and immunotherapeutic sensitivity in uterine carcinosarcoma patients - Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2022 September;181(9):670-9 - Minerva Medica - Journals

Background: Nowadays, immune checkpoint inhibitors (ICIs) have become one of the essential immunotherapies for cancer patients. However, the impact of antibiotic (ATB) use on cancer patients treated with ICIs remains controversial.Methods: Our research included retrospective studies and a randomized clinical trial (RCT) with cancer patients treated with ICIs and ATB, from the public database of PubMed, Web of Science, Embase, Cochrane, clinical trials, and JAMA. The survival outcomes included progression-free survival (PFS) and overall survival (OS). Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were performed to determine the concrete association between ATB use and the prognosis of cancer patients treated in ICIs.Results: Our results revealed that ATB use was associated with poor survival outcomes, including OS (HR: 1.94, 95% CI: 1.68–2.25, p <0.001) and PFS (HR: 1.83, 95% CI: 1.53–2.19, p <0.001). The subgroup analysis learned about the association between ATB use and the prognosis of cancer patients with ICI treatment, including 5 cancer types, 3 kinds of ICI, 5 different ATP windows, broad-spectrum ATB class, and ECOG score. ATB treatment was associated with poor OS of non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), esophageal cancer (EC), and melanoma (MEL) in patients treated in ICIs, while non-small-cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were associated with poor PFS. Meanwhile, it was strongly related to the ICI type and ATB window. Furthermore, it is firstly mentioned that the use of broad-spectrum ATB class was strongly associated with poor PFS.Conclusion: In conclusion, our meta-analysis indicated that ATB use was significantly associated with poor OS and PFS of cancer patients treated with ICI immunotherapy, especially for patients with ATB use in the period of (−60 days; +30 days) near the initiation of ICI treatment. Also, different cancer types and the ICI type can also impact the survival outcome. This first reveals the strong relationship between the broad-spectrum ATB class and poor PFS. Still, more studies are needed for further study.

Background. To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method. Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95 Confidence Interval (CI). Result. This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.101.54]), and poor PFS (HR: 1.25 [1.091.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR=1.48 [1.26, 1.74], Worldwide: HR=1.54 [1.24, 1.91]), and poor PFS (Europe: HR=1.36 [1.18, 1.57], Worldwide: HR=1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR=1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR=1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR=1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR=1.33 [1.19, 1.49]), and poor OS (30: HR=1.89 [1.29, 2.78], ±30: HR=1.44 [1.27, 1.64]) and poor PFS (30: HR=1.51 [1.11, 2.05], ±30: HR=1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion. Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.

The DNA damage repair (DDR) genes are increasingly gaining attention as potential therapeutic targets in cancers. In this study, we identified the DDR genes associated with the tumor mutation burden (TMB) and prognosis of cervical squamous cell carcinoma (CESC) based on The Cancer Genome Atlas (TCGA) database. Through LASSO Cox regression, the prognostic signature involving five DDR genes (ACTR2, TEX12, UBE2V1, HSF1, and FBXO6) was established, and the risk score was identified as an independent risk factor for CESC. The nomogram consisting of the five genes accurately predicted the overall survival (OS) and the immunotherapeutic response of CESC patients. Finally, the loss of the copies of the transcription factor (TF) SP140 in CESC patients may decrease the expression of FBXO6, improve DNA repair function, and reduce the diversity of neoantigens, thereby lowering the response to immunotherapies. Therefore, the DDR gene signature is a novel prognostic model and a biomarker for immunotherapies in CESC patients.