BRAF Mutations in Colorectal Liver Metastases: Prognostic Implications and Potential Therapeutic Strategies

Xin

2023

Clin Colon Rectal Surg

Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM remains high. The progress of genome sequencing technologies has greatly improved the molecular understanding of colorectal cancer. In the era of genomics and targeted therapy, genetic mutation analysis is of great significance to guide systemic treatment and identify patients who can benefit from resection of CRLM. RAS and BRAF mutations and microsatellite instability/deficient deoxyribonucleic acid (DNA) mismatch repair status have been incorporated into current clinical practice. Other promising molecular biomarkers such as coexisting gene mutations and circulating tumor DNA are under active investigation. This study aimed to review the prognostic significance of molecular biomarkers in patients with CRLM undergoing metastasectomy based on the current evidence.

Section: Brafmentioning

confidence: 91%

Section: Brafmentioning

confidence: 99%

Section: Brafmentioning

confidence: 99%

Section: Brafmentioning

confidence: 99%

Section: Brafmentioning

confidence: 99%

See 3 more Smart Citations

Impact of Molecular Status on Metastasectomy of Colorectal Cancer Liver Metastases

Xin

2023

Clin Colon Rectal Surg

Real‐world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer

et al. 2023

Cancer Medicine

Background BRAF mutation occurs in 5%–10% of metastatic colorectal cancers (mCRCs). Patients with BRAF mutant mCRC exhibit a specific metastatic pattern and poor prognosis. Survival outcomes are heterogeneous in cases of mCRC with a BRAF mutation. The optimal first‐line therapy is still controversial. Methods We retrospectively reviewed the medical records of patients with mCRC between June 2010 and December 2021. Clinicopathologic characteristics, treatment and BRAF mutation testing results were collected. Patients with a BRAF mutation were included. Kaplan–Meier methods and log‐rank tests were used to analyze and compare survival. Cox proportional hazards regression was used to establish the predictive nomogram model. Results Of the 4475 mCRC, 261 have a BRAF mutation, including 240 V600E and 21 non‐V600E mutants. The median overall survival (OS) was 18.2 months in the BRAF V600E mutant group versus 38.0 months in the non‐V600E mutant group (p = 0.022). ECOG score, tumor differentiation, liver metastasis, bone metastasis and primary tumor resection were independent prognostic factors for the OS of BRAF V600E mutant mCRC. A nomogram model was established using these factors. The median OS was 39.3 m, 18.2 m and 10.7 m for the low‐risk, intermediate‐risk and high‐risk groups defined by this model, respectively (p < 0.0001). Patients who received first‐line triplet chemotherapy ± bevacizumab had comparable progression free survival (PFS) and OS compared with those treated with doublets ± bevacizumab. Conclusion BRAF V600E mutant mCRCs exhibit unfavorable and heterogeneous prognosis. The first‐line intensive chemotherapy did not confer a marked impact on the PFS and OS.

AI-Enhanced RAIN Protocol: A Systematic Approach to Optimize Drug Combinations for Rectal Neoplasm Treatment

Dashti,

Kiaei,

Boush

et al. 2024

Preprint

BackgroundRectal cancers, or rectal neoplasms, are tumors that develop from the lining of the rectum, the concluding part of the large intestine ending at the anus. These tumors often start as benign polyps and may evolve into malignancies over several years. The causes of rectal cancer are diverse, with genetic mutations being a key factor. These mutations lead to uncontrolled cell growth, resulting in tumors that can spread and damage healthy tissue. Age, genetic predisposition, diet, and hereditary conditions are among the risk factors. Treating rectal cancer is critical to prevent severe health issues and death. Untreated, it can cause intestinal blockage, metastasis, and deteriorate the patient’s quality of life. Effective treatment hinges on finding the right drug combinations to improve therapeutic outcomes. Given the intricacies of cancer biology, treatments often combine surgery, chemotherapy, and radiation, with drugs chosen to target different tumor growth mechanisms, aiming to reduce the tumor and limit side effects. The continuous advancement in cancer treatments highlights the need for ongoing research to discover new drug combinations, offering patients improved recovery prospects and a better quality of life. This background encapsulates a detailed yet succinct understanding of rectal neoplasms, their origins, the urgency of treatment, and the quest for effective drug therapies, paving the way for discussions on treatment advancements and patient care impacts.MethodThis study employed the RAIN protocol, comprising three steps: firstly, utilizing the GraphSAGE model to propose drug combinations for rectal neoplasm treatment Each node in the graph model is a drug or a human gene/protein that acts as potential target for the disease, and the edges are P-values between them; secondly, conducting a systematic review across various databases including Web of Science, Google Scholar, Scopus, Science Direct, PubMed, and Embase, with NLP investigation; and thirdly, employing a meta-analysis network to assess the efficacy of drugs and genes in relation to each other. All implementations was conducted using Python software.ResultThe study evaluated the efficacy of Oxaliplatin, Leucovorin, and Capecitabine in treating Rectal Neoplasms, confirming their effectiveness through a review of 30 studies. The p-values for individual drugs were 0.019, 0.019, and 0.016 respectively, while the combined use of all three yielded a p-value of 0.016.ConclusionGiven the significance of rectal neoplasms, policymakers are urged to prioritize the healthcare needs of affected individuals. Utilizing artificial intelligence within the RAIN protocol can offer valuable insights for tailoring effective drug combinations to better address the treatment and management of rectal neoplasms patients.Abstract FigureHighlightsRectal cancers, evolving from benign polyps to malignancies, underscore the critical need for timely and effective treatment to prevent severe health complications.Genetic mutations, a pivotal factor in rectal cancer, trigger uncontrolled cell growth and necessitate targeted drug therapies to combat tumor spread.The RAIN protocol, leveraging the GraphSAGE model and systematic reviews, offers a novel approach to identify potent drug combinations for rectal neoplasm treatment.The study’s findings advocate for policy intervention to ensure that healthcare systems adequately support individuals battling rectal neoplasms, with AI-driven protocols enhancing patient care.