BRAF mutations and survival with surgery for colorectal liver metastases: A systematic review and meta-analysis.

INTRODUCTION: Mutations in the BRAF gene (BRAFmut) are associated with an unfavorable prognosis in patients with metastatic colorectal cancer (CRC). The aim of this meta-analysis was to evaluate the prognosis of colorectal cancer (CRC) patients with liver metastases and the potential benefits of liver resection in patients with BRAFmut CRC. MATERIAL AND METHODS: A systematic search of PubMed, Cochrane Central Controlled Trials, and Embase databases was conducted on May 31, 2023. The inclusion criteria were as follows:1) reporting of outcomes in patients with BRAFmut CRC who underwent surgery for liver metastases and/or comparison of outcomes between those who underwent and those who did not undergo resection; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. RESULTS: 34 studies were included. Median follow up was 48 months for prognostic BRAF status meta-analysis. BRAFmut status showed a significantly increased risk of mortality (hazard ratio [HR] = 2.56, 95% confidence interval [CI] 2.04-3.22; P < 0.01) and relapse (HR = 1.97, 95% CI 1.44-2.71; P < 0.01). Resection of liver metastases was associated with a survival benefit (median follow up 46 months). The HR for survival was 0.44 (95% confidence interval [CI] 0.33-0.59; P < 0.01) in favor of surgery. CONCLUSIONS: and Relevance: Our analysis indeed confirms that BRAF mutation is associated with poor survival outcomes after liver resection of CRC metastases. However, upon quantitatively assessing the survival benefit of surgical intervention in patients with BRAF-mutated CRC liver metastases, we identified a significant 56% reduction in the risk of death.

Immune checkpoint inhibitor doublets: Are they beneficial for older patients? A systematic review and meta-analysis.

INTRODUCTION: The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts. MATERIALS AND METHODS: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches. RESULTS: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01). DISCUSSION: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.

10 years or less of extended adjuvant endocrine therapy for postmenopausal breast cancer patients: A systematic review and network meta-analysis.

INTRODUCTION: Adjuvant hormonal therapy, with or without prior chemotherapy, has been widely recognised as the preferred treatment strategy for resected breast cancer (BC) for a minimum duration of 5 years. If the effectiveness of therapy beyond a 5-year period has been established, there is still ongoing debate regarding the optimal duration for this prolonged period. A network meta-analysis (NMA) was conducted to ascertain the optimal duration of extended therapy for resected BC in postmenopausal women. MATERIAL AND METHODS: A comprehensive search was conducted on online databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, to identify all randomised trials on extended duration of endocrine therapy. The search was limited to trials that had been published before 30th April 2023. The study focused on evaluating disease-free survival (DFS) as the primary outcome, with overall survival (OS) as the secondary endpoint. Under the Bayesian framework, NMA was performed using the GeMTC package. The relative rankings of the treatments were determined by utilising surface under the cumulative ranking curve (SUCRA) p scores. A network meta-regression analysis was employed to ascertain the impact of the baseline characteristics of the disease and the initial treatments administered. RESULTS: In the overall population, increasing the duration by 5 years did not result in a significantly better DFS compared to durations of 2-3 and 3-4 more years (hazard ratio [HR] = 0.97, 95% confidence interval [CI] [0.88-1.08] and HR = 0.87, 95% CI [0.72-1.06]). This effect was independent of adjuvant chemotherapy and nodal status. However, the effect of 5 more years of AI was significantly better in node-positive BC and in those who received some years of tamoxifen instead of aromatase inhibitors (AIs) as initial adjuvant therapy. OS was not affected by the administration of extended endocrine therapy. CONCLUSIONS: We conclude that an extended course of AI lasting 2-3 years, following an initial 5-year treatment, may be considered an appropriate regimen for achieving DFS benefits. In node-positive BC cases, it has been observed that a duration of 10 years provides a greater advantage compared to shorter durations, especially when tamoxifen is administered initially. Therefore, it is suggested that a longer duration is a potential standard of care in these cases.