RESUMEN
BACKGROUND: Colorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear. CASE PRESENTATION: We present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8-11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease. CONCLUSIONS: To the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.
RESUMEN
BACKGROUND: Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled. OBJECTIVE: We aimed to retrospectively assess the activity of imatinib 400 mg in both the adjuvant and the advanced settings. PATIENTS AND METHODS: We performed a multicenter study of patients with KIT exon 9-mutated GIST starting imatinib at 400 mg daily. We examined the relapse-free survival (RFS) among high-risk patients either receiving or not receiving adjuvant imatinib. In patients with advanced disease, progression-free survival (PFS, progression under imatinib 400 mg), time to imatinib failure (TIF, progression under imatinib 400, then 800 mg upon first progression), and overall survival (OS) were analyzed. RESULTS: In the post-operative setting (n = 37), 20 patients received adjuvant imatinib. Median RFS in high-risk patients receiving adjuvant imatinib (n = 14) was not reached (95% CI 17.5-46.6) versus 13.6 months (95% CI 4.7-13.6) for those who did not (p = 0.37), after a median follow-up of 58 months. RFS at 36 months was 63% (30.3-96.6) versus 40% (95% CI 0-82.9), p = 0.2. In advanced disease (n = 28), median PFS, TIF and OS were 12.7 months (95% CI 6.1-18.2), 21.0 months (95% CI 17.4-28.1) and 47.0 months (95% CI 33.5-69.2), respectively. CONCLUSIONS: Despite the limitations of a retrospective analysis and the small number of patients, the benefit of adjuvant imatinib 400 mg daily in high-risk patients appeared relevant. Patients with advanced disease receiving imatinib 400 mg with subsequent dose escalation had a TIF similar to that observed with an initial dose of 800 mg. Intra-patient dose escalation in this setting might be an option.
