Thiru Prasanna1, Christos S Karapetis2,3, David Roder4,5, Jeanne Tie6,7,8, Robert Padbury3,9, Timothy Price10, Rachel Wong7,11,12, Jeremy Shapiro13, Louise Nott14,15, Margaret Lee7,11, Yu Jo Chua1,16, Paul Craft1,16, Cynthia Piantadosi17, Michael Sorich18, Peter Gibbs6,7, Desmond Yip1,16. 1. a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia. 2. b Department of Medical Oncology , Flinders Medical Centre , Bedford Park , Australia. 3. c Flinders Clinical and Molecular Medicine, Surgery, Flinders University , Bedford Park , Australia. 4. d South Australian Health & Medical Research Institute (SAHMRI) , Adelaide, Australia. 5. e School of Health Sciences, University of South Australia , Adelaide , Australia. 6. f Department of Medical Oncology , Western Hospital , Melbourne , Australia. 7. g Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia. 8. h Department of Medical Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia. 9. i Department of Surgery , Flinders Medical Centre , Adelaide, Australia. 10. j The Queen Elizabeth Hospital and University of Adelaide , Adelaide , Australia. 11. k Department of Medical Oncology , Eastern Health , Melbourne , Australia. 12. l Faculty of Medicine, Nursing and Health Sciences , Monash University , Melbourne , Australia. 13. m Cabrini Haematology and Oncology Centre , Melbourne , Australia. 14. n Department of Medical Oncology , Royal Hobart Hospital , Tasmania , Australia. 15. o Menzies Research Institute , Hobart , Australia. 16. p ANU Medical School, Australian National University , Canberra , Australia. 17. q Flinders Centre for Innovation in Cancer , Bedford Park , Australia. 18. r College of Medicine and Public Health , Flinders University , Adelaide , Australia.
Abstract
BACKGROUND: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
BACKGROUND: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS:Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
Authors: Craig A Bollig; Christopher I Newberry; Tabitha L I Galloway; Robert P Zitsch; Elyse K Hanly; Vivian L Zhu; Nitin Pagedar; Rohit Nallani; Andres M Bur; William C Spanos; Jeffrey B Jorgensen Journal: Laryngoscope Date: 2020-10-24 Impact factor: 3.325