Outcomes and Prognostic Factors of Patients with Metastatic Colorectal Cancer Who Underwent Pulmonary Metastasectomy with Curative Intent: A Brazilian Experience.

BACKGROUND: We aimed to identify clinicopathological and molecular features associated with progression-free survival (PFS) and overall survival (OS) after pulmonary metastasectomy for metastatic colorectal cancer in a retrospective cohort in Brazil. MATERIALS AND METHODS: We did a retrospective review of thoracic surgeries performed in a single large academic hospital in Brazil from January 1985 to September 2019. Demographics, previously described prognostic factors, and clinicopathological and molecular characteristics were abstracted. Univariate Cox regression was performed for each variable, and, when significant, data were dichotomized to provide clinically meaningful thresholds. RESULTS: Records from 698 patients were reviewed. Fifty-eight patients underwent pulmonary metastasectomy with curative intent. Of those, 53.4% had a single metastatic lesion. The median size of the largest lesion was 1.5 cm. Results of RAS, RAF, and mismatch repair testing and of cytokeratin 20 (CK20) and CDX2 testing were available for 13.8% and 58.6% of the sample, respectively. Median PFS was 14 months, median OS was 58 months, and 5-year survival was 49.8%. Unfavorable prognostic factors for OS included disease-free interval (DFI) <24 months, synchronous presentation, size of the largest lesion ≥2 cm, and loss of CK20 expression. Presenting with more than one lesion was prognostic for PFS but not for OS. CONCLUSION: In this Brazilian cohort, our findings corroborate existing data supporting DFI, synchronous presentation, and number and size of lesions as prognostic factors. Furthermore, we found that loss of CK20 expression may be associated with more aggressive disease and shorter OS. Additional molecular prognostic factors after pulmonary metastasectomy for colorectal cancer should be further explored. IMPLICATIONS FOR PRACTICE: This study consolidates disease-free interval, synchronous presentation, and number and size of lesions as clinically relevant data that may help guide therapy for patients with colorectal cancer and lung metastases who are candidates for curative-intent metastasectomy. Additionally, in this sample, lack of cytokeratin 20 expression in metastases was associated with shorter progression-free survival and overall survival, suggesting that biomarkers also may have a role in guiding therapy in this setting and that additional biomarkers should be further explored.

Li-Fraumeni and Li-Fraumeni-like syndrome among children diagnosed with pediatric cancer in Southern Brazil.

BACKGROUND: Pediatric cancers are a feature in patients with Li-Fraumeni syndrome and its variant Li-Fraumeni-like syndrome (LFS/LFL). To the best of the authors' knowledge, TP53 germline mutations are currently the only molecular defect known to be associated with this disease. Recently, a specific germline mutation in this gene, p.R337H, has been reported at a high prevalence in Brazil. METHODS: The prevalence of LFS/LFL was investigated in children with cancer who were diagnosed with tumors on the LFS/LFL spectrum and in a small consecutive series of controls without cancer. The prevalence of the germline p.R337H mutation and of other germline TP53 mutations was investigated in a general group of children with cancer and exclusively in children fulfilling the clinical criteria for LFS/LFL, respectively. RESULTS: Among the 65 children without cancer, 1.5% had a family history of LFL whereas of the 292 children with cancer, 25.3% had a family history of LFL (P < .001). Screening for the p.R337H mutation identified 11 carriers (3.7%), 9 of whom were diagnosed with adrenocortical carcinomas (ACC) and 2 of whom were diagnosed with choroid plexus carcinomas. One of the ACC probands was homozygous mutant. The Brazilian founder haplotype and loss of heterozygosity at the p.R337H locus were present in all carriers. In addition, direct sequencing of the entire TP53 coding region and gene rearrangement analysis of probands fulfilling the criteria for LFL (Eeles 2 criteria, Birch and/or Chompret criteria) and who were negative for the p.R337H mutation revealed a DNA-binding domain pathogenic mutation, p.G245S, in 1 child. CONCLUSIONS: TP53 p.R337H testing should be offered to Brazilian children diagnosed with ACC and choroid plexus carcinoma. A significant percentage of children with cancer in southern Brazil fulfill the criteria for LFL and should be referred for genetic risk assessment.