Identification of pharmacogenetic biomarkers for efficacy of cytoreductive surgery plus hyperthermic intraperitoneal mitomycin C in patients with colorectal peritoneal metastases.

INTRODUCTION: Mitomycin C (MMC) is commonly used in patients with colorectal peritoneal metastases (CPM) treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). MMC requires metabolic activation prior to exert its cytotoxic effect of which the main activating enzymes are NQO1 and POR. However, not all patients are able to activate MMC for example due to polymorphisms in the genes encoding these enzymes. The aim of this study was to investigate the association of NQO1∗2, NQO1∗3, and POR∗28 with the efficacy of CRS + HIPEC with MMC in patients with CPM. METHOD: A retrospective follow-up design was used to study genetic association in patients with histologically proven CPM treated with CRS + HIPEC with MMC with respect to peritoneal recurrence rate after 3 months (primary endpoint), after 6 months, disease-free survival and overall survival. Genetic polymorphisms NQO1∗2, NQO1∗3, and POR∗28 were tested for association. RESULTS: A total of 253 patients were included. In NQO1∗3 carriers the peritoneal recurrence rate 3 and 6 months after HIPEC was significantly higher than in wild type patients, respectively 30.0% vs 3.8% (p = 0.009) and 40.0% vs 12.1% (p = 0.031). In line with these results, NQO1∗3 was associated with a shorter disease-free survival (HR 2.04, 95% CI [1.03-4.03]). There was no significant association with overall survival (HR 1.42, 95% CI [0.66-3.07]). CONCLUSION: Carriership of the NQO1∗3 allele is associated with worse peritoneal recurrence rate and disease-free survival. These results suggest that individualization of patients treated with CRS + HIPEC based upon pharmacogenetics may be beneficial.

Radioguided Intraoperative Margins Evaluation (RIME): preliminary results of a new technique to aid breast cancer resection.

AIMS: Women undergoing breast-conserving surgery for cancer can present residual disease. We have developed a technique called Radioguided Intraoperative Margins Evaluation (RIME) that uses a radiopharmaceutical to distinguish normal and cancer tissues. The aim of this study was to assess whether RIME is a feasible technique, and if it could help in breast cancer resection with free margins, minimizing residual disease. METHODS: Twenty-three breast cancer patients programmed for mastectomy were selected. Before surgery, the patients were submitted to scintimammography with 99mTc-sestamibi to estimate the optimal time to begin radioguided surgery. Twenty patients were submitted to magnetic resonance imaging (MRI), to evaluate skin, deep fascia and to detect other tumor foci. At the beginning of the surgery, the same dose of 99mTc-sestamibi was intravenously injected into patients. Tumor resection was performed under guidance of a gamma-probe, characterizing the RIME technique. Finally, modified radical mastectomy was performed. Tumor and residual breast were histopathologically examined. RESULTS: The RIME technique was successfully performed in all patients. The principal tumor was removed by this technique and provided 82.6% of histologically free margins (mean margins, 4.8 mm). Additionally, 47.8% of patients were without residual disease. The mean size of residual carcinoma was 3.67 mm and generally located near the tumor bed (<1.5 cm). There was no significant association between presence of residual disease and tumor size or margin status. CONCLUSION: RIME is a feasible technique that could help tumor resection with free margins; however, it seems to be limited for small carcinoma foci.