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A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

ABSTRACT: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity and mortality. We aim to generate and validate a biomarker set predicting sensitivity to Mitomycin-C to refine selection of patients with colorectal peritoneal metastasis (CPM) for this treatment. A signature predicting Mitomycin-C sensitivity was generated using data from Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas. Validation was performed on CPM patients who underwent CRS-HIPEC (n?=?62) using immunohistochemistry (IHC). We determined predictive significance of our set using overall survival as a surrogate endpoint via a logistic regression model. Three potential biomarkers were identified and optimized for IHC. Patients exhibiting lower expression of PAXIP1 and SSBP2 had poorer survival than those with higher expression (p?=?0.045 and 0.140, respectively). No difference was observed in patients with differing DTYMK expression (p?=?0.715). Combining PAXIP1 and SSBP2 in a set, patients with two dysregulated protein markers had significantly poorer survival than one or no dysregulated marker (p?=?0.016). This set independently predicted survival in a Cox regression model (HR 5.097; 95% CI 1.731-15.007; p?=?0.003). We generated and validated an IHC prognostic set which could potentially identify patients who are likely to benefit from HIPEC using Mitomycin-C.

SUBMITTER: Shannon NB

PROVIDER: S-EPMC6646658 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

Shannon Nicholas Brian NB Tan Joey Wee-Shan JW Tan Hwee Leong HL Wang Weining W Chen Yudong Y Lim Hui Jun HJ Tan Qiu Xuan QX Hendrikson Josephine J Ng Wai Har WH Loo Li Yang LY Skanthakumar Thakshayeni T Wasudevan Seettha D SD Kon Oi Lian OL Lim Tony Kiat Hon TKH Tan Grace Hwei Ching GHC Chia Claramae Shulyn CS Soo Khee Chee KC Ong Chin-Ann Johnny CJ Teo Melissa Ching Ching MCC

Scientific reports 20190722 1

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity and mortality. We aim to generate and validate a biomarker set predicting sensitivity to Mitomycin-C to refine selection of patients with colorectal peritoneal metastasis (CPM) for this treatment. A signature predicting Mitomycin-C sensitivity was generated using data from Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas. Validation was perfor ...[more]

PMID: 31332257

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Project description:BACKGROUND:There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. METHODS:Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75?mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150?mg/m2) on day 1, and S-1 was administered orally(80?mg/m2/day)on days 1-14 of a 3-week?cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). RESULTS:A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1?months, 95% confidence interval [CI] 16.7-25.6?months) in comparison with the palliative chemotherapy group(10.8?months, 95%CI 7.3-14.2?months, p?=?0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI?<?6) was significantly better than that of patients with high PCI (PCI???6)(20.1 vs.11.3?months, p?=?0.006). CONCLUSION:Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. TRIAL REGISTRATION:This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.

Dataset Information

A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

Publications

A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

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