Dataset Information

MTOR inhibitors and risk of ovarian cysts: a systematic review and meta-analysis.

ABSTRACT:

Objective

To summarise the available evidence on frequency of ovarian cyst development during mammalian target of rapamycin inhibitors (mTORi) treatment.

Methods

PubMed/Medline and EMBASE databases were searched, from 1990 up to March 2020, using the following keywords: 'tacrolimus', 'sirolimus', 'temsirolimus', 'everolimus', 'deforolimus', 'mTOR' and 'ovarian cysts' (Limit: Human, English, full article). Studies were selected for the review if they met the following criteria: clinical studies, studies reporting original data, studies reporting the number of patients using mTORi, studies reporting the number of patients with ovarian cysts.We selected 7 of 20 retrieved studies. Study design, population, sample size, criteria for diagnosis of ovarian cysts, drug doses and follow-up length were extracted. Pooled estimate of incidence was calculated for ovarian cysts as a percentage, with 95% CI.

Results

Four hundred-six women were included in the selected studies. The pooled incidence was 37.0% (95% CI 16.0% to 58.1%) for all ovarian cysts, and 17.3% (95% CI 5.6% to 29.1%) for clinically significant ovarian cysts. Based on two articles, comparing mTORi and non-mTORi for immunosuppression, pooled OR for ovarian cyst incidence was 4.62 (95% CI 2.58 to 8.28).

Conclusion

Ovarian cyst development is a common adverse event during immunosuppression treatment with mTORi. These cysts are benign conditions, but they require pelvic ultrasound follow-up and in some cases hospital admission and surgery.

SUBMITTER: Parazzini F

PROVIDER: S-EPMC8475133 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known as checkpoint inhibitors, have been approved. This review aims to establish whether these three drugs - ipilimumab, nivolumab, and pembrolizumab - offer greater efficacy and tolerability compared to control interventions (placebo, immunotherapy, or chemotherapy) in patients with stage III or IV unresectable cutaneous melanoma.A search on four major medical and scientific databases yielded 7,553 records, of which seven met the inclusion criteria, with a total study population of 3,628. Only prospective Phase II or III randomized controlled trials on checkpoint inhibitors for patients with unresectable cutaneous melanoma that reported data on survival (overall or progression-free), tumor response, or adverse events were included. Three meta-analyses were carried out.The hazard ratio for progression or death was 0.54 (95% confidence interval [CI]: 0.44-0.67), and the odds ratio for best overall response rate was 4.48 (95% CI: 2.77-7.24), both in favor of checkpoint inhibitors. However, control treatments were associated with an insignificantly lower rate of discontinuation of treatment due to adverse effects or treatment-related adverse events (odds ratio =1.63 [95% CI: 0.55-4.88]).This study finds that checkpoint inhibitors are more effective than control interventions, both in terms of survival and tumor response, and yet no less tolerable. PD1 therapies (nivolumab and pembrolizumab) appear to offer greater efficacy than CTLA4 therapy (ipilimumab). The combination of nivolumab and ipilimumab was, however, the most effective, but significantly less tolerable than monotherapy. The lack of published clinical data does, however, limit this study. Further research is needed in two areas in particular: 1) to determine the optimal use of checkpoint inhibitors, specifically in terms of combination therapy, and 2) to identify reliable biomarkers to predictive responders and guide treatment assignment.

Project description:Published data on the relationship between matrix metalloproteinases (MMPs) polymorphisms and ovarian cancer risk have implicated inconclusive results. To evaluate the role of MMPs polymorphisms in ovarian cancer risk, a meta-analysis and systematic review were performed.MMPs polymorphisms which could be quantitatively synthesized were involved in meta-analysis. Five comparison models (homozygote model, heterozygote model, dominant model, recessive model, additive model) were carried out, a subgroup analysis was performed to clarify heterogeneity source. The remaining polymorphisms which could not be quantitatively synthesized were involved in systematic review.10 articles with 20 studies were included in this paper. Among those studies, 8 studies involving MMP1 rs1799750 and MMP3 rs34093618 could be meta-analyzed and 12 studies involving 12 polymorphisms could not. Meta-analysis showed that no associations were found between MMP1 rs1799750 (homozygote model: OR = 0.93, 95%CI = 0.70-1.23, POR = 0.60; heterozygote model: OR = 1.09, 95%CI = 0.78-1.54, POR = 0.61; dominant model: OR = 1.02, 95%CI = 0.83-1.25, POR = 0.84; recessive model: OR = 0.95, 95%CI = 0.75-1.21, POR = 0.67; additive model: OR = 1.00, 95%CI = 0.85-1.17, POR = 0.99), MMP3 rs34093618 (homozygote model: OR = 1.25, 95%CI = 0.70-2.24, POR = 0.46; heterozygote model: OR = 1.08, 95%CI = 0.51-2.31, POR = 0.84; dominant model: OR = 0.97, 95%CI = 0.68-1.38, POR = 0.85; recessive model: OR = 1.12, 95%CI = 0.69-1.80, POR = 0.65; additive model: OR = 1.01, 95%CI = 0.79-1.31, POR = 0.91) and ovarian cancer. Furthermore, similar results were detected in subgroup analysis. The systematic review on 12 polymorphisms suggested that MMP2 C-735T, MMP7 A-181G, MMP8 rs11225395, MMP9 rs6094237, MMP12 rs2276109, MMP20 rs2292730, MMP20 rs12278250, MMP20 rs9787933 might have a potential effect on ovarian cancer risk.In summary, polymorphisms of MMPs might not be associated with ovarian cancer risk. However, it is necessary to conduct more larger-scale, multicenter, and high-quality studies in the future.