Matthew Ng

Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery

Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events – it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC. We also detected ctDNA in 11 out of 15 cases at or before clinical or radiological recurrence of CRC, indicating the potential of our assay for early detection of metastasis. We further present data from a patient with multiple primary cancers to demonstrate the specificity of our assays to distinguish between CRC recurrence and a second primary cancer. Our approach can complement current methods for surveillance of CRC by adding an individualised biological component, allowing us not only to point to the presence of residual or recurrent disease, but also attribute it to the original cancer.

Gastric peritoneal carcinomatosis - a retrospective review

AIM To characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care. METHODS We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre. RESULTS We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority (n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001). CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run.

Safety and efficacy of aflibercept in combination with fluorouracil, leucovorin and irinotecan in the treatment of Asian patients with metastatic colorectal cancer

To evaluate the safety and efficacy of the combination therapy of fluorouracil, leucovorin and irinotecan (FOLFIRI) and aflibercept in Asian patients with metastatic colorectal cancer (mCRC), who had progressed after oxaliplatin‐based chemotherapy.

Metastatic gastric cancer: Does the site of metastasis make a difference?

Metastatic gastric cancer has a poor prognosis. We aim to study how clinical features and prognosis differs between different metastatic sites, and to identify prognostic factors for overall survival.

Abstract CT320: Longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track the emergence of metastasis and drug resistance in colorectal cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background. Colorectal cancer (CRC) is the 3rd most common cancer globally. In cancer, the 2 most critical events that adversely affect outcomes are the emergence of metastasis and drug resistance. Blood-based markers permit the non-invasive serial monitoring of patients in order to study and track the emergence and evolution of metastasis and drug resistance. The multiple varied platforms utilize different components of blood (buffy coat, whole blood, plasma). We seek to establish a longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track patient outcomes in colorectal cancer. Methods. In a planned 800 patient study, we prospectively recruit patients with all stages of CRC, focusing on patients with stage 3/4 CRC. At each patients venipuncture performed during his/her routine clinical care, we serially collect additional blood specimens. All major components of the collected blood (buffy coat, red cells, whole blood and plasma) are stored. In patients undergoing primary tumor resection or metastasectomy, frozen tissue specimens are also prospectively collected and banked for subsequent biomarker analysis. A prospective electronic database of clinical information and patient outcomes is simultaneously maintained for the purpose of correlation with molecular assays. Results. To date, we have recruited 450 patients and obtained their serial blood samples. Blood is prospectively collected in an optimized manner to support the pre-analytical requirements of the different platforms. This includes whole blood for immediate assay performance (circulating tumor cells), buffy coat for immediate analysis or storage for pooled analysis (cell based assays, germline polymorphisms, white cell gene expression and assays on peripheral blood mononuclear cells), plasma for storage for pooled analysis (circulating cell free nucleic acids including DNA, miRNA, RNA and methylated DNA, novel proteomic tumor markers, cytokines). Optimization of pre-analytical processing, transport and storage parameters was carried out to enable studies across multiple platforms in this same cohort of patients to be performed in a prospective longitudinal manner. Conclusions. In this ongoing study, we have established a system for the simultaneous evaluation of multiple blood-based biomarkers operating on the various components of blood. Together with paired tissue specimens and a prospectively maintained electronic clinical database, comprehensive comparisons and correlative studies to monitor for metastasis and drug resistance and clinical outcomes in CRC across time can be carried out. Citation Format: Clarinda Chua, Rachel Ten, Thinzar Aung, Maricel Ang, Thein Htut Oo, Su Pin Choo, Matthew Ng, Iain Beehuat Tan. Longitudinal observational study to simultaneously evaluate multiple blood-based biomarkers to track the emergence of metastasis and drug resistance in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT320. doi:10.1158/1538-7445.AM2014-CT320