ABSTRACT
BACKGROUND: Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated. METHODS: In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC. RESULTS: In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis. CONCLUSIONS: PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.
Subject(s)
Colorectal Neoplasms/therapy , Lymphatic Metastasis/therapy , Microsatellite Instability , Mitomycin/therapeutic use , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Colorectal Neoplasms/genetics , Cytoreduction Surgical Procedures , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy , Lymphatic Metastasis/genetics , Male , Middle Aged , Mutation , Palliative Care , Peritoneal Neoplasms/genetics , Prognosis , Prospective Studies , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.