Efficacy of pembrolizumab in advanced cancer of the vulva: a systematic review and single-arm meta-analysis.

Introduction: Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer. Materials and methods: Following a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I2 and the Cochrane Q χ2 statistics. Results: Out of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses. Discussion and conclusion: This study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023391888.

Health risks of titanium dioxide (TiO2) dust exposure in occupational settings - A scoping review.

Titanium dioxide (TiO2) is an inorganic compound with many applications, for example in paint, sunscreen or as food coloring. There have been concerns regarding its safety and according to IARC, the existing evidence is not substantial enough to rule them out, leading to the substance being classified as possibly carcinogenic to humans (2B). This work aims to provide a comprehensible overview about epidemiological studies on occupational health risks and methodological aspects. A literature search was conducted in two databases (MEDLINE and Web of Science). The search focused on occupational exposure since this setting provides the highest amounts of TiO2 exposure. Of 443 unique search results, ten were included in this study, with publication dates ranging from 1988 to 2022. Seven of them are retrospective cohort studies and three have a case-control study design. Main outcomes of most studies were all-cause mortality and lung cancer mortality. For all-cause mortality, most cohort studies reported no association with TiO2 exposure. For lung cancer mortality, a significantly increased risk was found in a study population from Europe. The analysis results of working cohorts from the US comparing exposed workers' mortality rates with those of the general population were unobtrusive. However, one US cohort found an elevated mortality risk for all causes and lung cancer based on a reference population of company workers unexposed to TiO2. Case-control studies did not indicate an increased risk for cancer related to TiO2. Recent publications partly questioned the validity of those earlier findings, claiming insufficient confounder analysis, most notably for smoking, as well as the presence of the healthy worker effect, masking a potential health risk. In conclusion, the associations between occupational TiO2 exposure and mortality are unclear, but concerns regarding possible health risks recently re-emerged based on new analytical approaches, highlighting methodological difficulties that could have limited the inferential value of previously conducted studies.

Are Routine Chest X-rays Necessary following Thoracic Surgery? A Systematic Literature Review and Meta-Analysis.

(1) Background: The number of chest X-rays that are performed in the perioperative window of thoracic surgery varies. Many clinics X-ray patients daily, while others only perform X-rays if there are clinical concerns. The purpose of this study was to assess the evidence of perioperative X-rays following thoracic surgery and estimate the clinical value with regard to changes in patient care. (2) Methods: A systematic literature research was conducted up until November 2021. Studies reporting X-ray outcomes in adult patients undergoing general thoracic surgery were included. (3) Results: In total, 11 studies (3841 patients/4784 X-rays) were included. The X-ray resulted in changes in patient care in 488 cases (10.74%). In patients undergoing mediastinoscopic lymphadenectomy or thoracoscopic sympathectomy, postoperative X-ray never led to changes in patient care. (4) Conclusions: There are no data to recommend an X-ray before surgery or to recommend daily X-rays. X-rays immediately after surgery seem to rarely have any consequences. It is probably reasonable to keep requesting X-rays after drain removal since they serve multiple purposes and alter patient care in 7.30% of the cases.