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Systemic treatment of patients with metachronous peritoneal carcinomatosis of colorectal origin.

ABSTRACT: Combining chemotherapy and targeted therapies has resulted in an enhanced survival in metastatic colorectal cancer (mCRC) patients. However, the result of this palliative treatment in patients with metachronous peritoneal carcinomatosis (PC) remains unknown. The current population-based study aims to investigate the use and effect of palliative systemic treatment in patients with metachronous PC of colorectal origin. Data on metachronous PC were collected between 2010 and 2011 for all patients who were diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Patient demographics and detailed data on chemotherapeutic treatment were collected and compared. Ninety-two patients with metachronous PC received chemotherapy in a palliative setting compared to 94 patients without treatment. In 36 patients, Bevacizumab was added to the treatment (39%). Overall survival was 3.4, 13, and 20.3 months in the no treatment, systemic treatment and systemic treatment + Bevacizumab respectively (P < 0.001). Male gender was a positive predictor and right sided primary tumor location a negative predictor of receiving bevacizumab. Approximately 40% of patients with metachronous PC received bevacizumab in addition to chemotherapy. Treatment with systemic chemotherapy in combination with bevacizumab may increase survival in a patients with metachronous colorectal PC.

SUBMITTER: van Oudheusden TR

PROVIDER: S-EPMC4685443 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

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Project description:In a non-negligible number of patients with metastatic colorectal cancer (mCRC), the peritoneum is the predominant site of dissemination. Cure can be achieved by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but this procedure is associated with long-term morbidity and high relapse rates. Thus, there is a pressing need for improved therapeutic strategies and complementary biomarkers. The present study explored the molecular heterogeneity in mCRC with peritoneal carcinomatosis (PC), and the potential clinical implications thereof. Multi-region immunohistochemical profiling and deep targeted DNA-sequencing was performed on chemotherapy-naïve tumours from seven patients with synchronous colorectal PC who underwent CRS and HIPEC. In total, 88 samples (5-19 per patient) were analysed, representing primary tumour, lymph node metastases, tumour deposits, PC and liver metastases. Expression of special AT-rich sequence-binding protein 2 (SATB2), a marker of colorectal lineage, was lacking in the majority of cases, and a conspicuous intra-patient heterogeneity was denoted for expression of the proposed prognostic and predictive biomarker RNA-binding motif protein 3 (RBM3). Loss of mismatch repair proteins MLH1 and PSM2, observed in one case, was concordant with microsatellite instability and the highest tumour mutational burden. When present in a patient, mutations in key CRC driver genes, i.e., KRAS, APC and TP53, were homogenously distributed across all samples, while less common mutations were more heterogenous. On the same note, copy number variations showed intra-patient as well inter-patient heterogeneity. In two out of seven cases, hierarchical clustering revealed that samples from the PC and lymph node metastases were more similar to each other than to the primary tumour. In summary, these findings should encourage additional studies addressing the potential distinctiveness of mCRC with PC, which might pave the way for improved personalized treatment of these patients.

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Systemic treatment of patients with metachronous peritoneal carcinomatosis of colorectal origin.

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