The prognostic ad predictive value of primary tumor sidedness in the mCRC pts
Authors: E. Sezer, K. Eser, A. Onder, B. Ozturk, V. Ercolak, Z. Oruc
Journal: Annals of Oncology (2018)

Introduction: The prognostic and predictive value of primary tumor sidedness in the pts with metastatic colorectal cancer (mCRC) is well known today. Right-sided primary was associated with high mutational burden, microsatellite instability, worse prognosis, more BRAF mutation rates and poor anti-EGFR response. We aimed to investigate the effects of tumor sidedness on survival, RAS-RAF mutation rates and responses to biologic agents in the pts with mCRC. Methods: A retrospective study with mCRC pts performed in two different centers. Tumor sides were categorized as left (from rectum to splenic flexura) and right (from caecum to hepatic flexura) sided. The effects of tumor sidedness on treatment responses and survival rates and RAS-RAF status of mCRC pts were investigated using the log rank test. The Kaplan- Meier survival estimates were calculated. Results: A total of 317 (F/M=127/190) pts were included to study. Median age was 61±12 (range: 23-89) years. Primary tumor was categorized as right-sided in 72 (23.2%) pts, and left-sided in 231 (74.5%). Initial tumor stages were 66 (%22) pts were stage I-II, 115 (36%) were stage III and 135 (42%) were stage 4. 38 (18.1%) pts have two or above metastatic site. Approximately a half of pts was at stage 4. Liver, peritoneum and loco-regional relapses were most common sites. Metastasectomy rate was 23%. Kras, nras and braf mutation rates were 31.7, 5 and 6.3%, respectively. Median follow-up was 22 (range: 1.3-274) months. Kras mutation rates were similar between right and left sided tumors, braf mutation rates were significantly increased in right-sided tumors (40.6 vs 7.7%, p < 0.0001). Median PFS (12.9 vs. 12.2 months) and OS (27.5 vs. 22.5 months) were similar between left and right-sided tumors. First line biologic agent and chemotherapy regimens were similar between two groups. Bevacizumab and anti-EGFR usage were 75 and 23%, respectively. Median PFS with first-line bevacizumab was 13.4 and 12.3 months, with Anti-EGFR was 12.5 and 16.9 months in the pts with right and left-sided tumors, respectively. Median OS with first line bevacizumab was 16.9 and 28.8 months, with anti-EGFR 23.9 and 39.3 months in right and left-sided tumors, respectively. Median PFS and OS differences were not reached statistically significance. Median OS was similar between braf wild and mutant tumors (27.2 vs 19.2 months). There was no significant surival difference between kras wild (29.1 months) and mutated (24.7 months) groups. Conclusion: In concordance with literature, right sided primary was associated with higher BRAF mutation rates and poor survival. RAS and RAF mutation rates were similar to literature. However, most of old cases, we can obtain ras mutation status after first line therapy, so in the ras wild type tumors, first line anti-EGFR usage was lower than the current practice. Despite of low-percentage of anti-EGFR usage at first line, our results showed that the pts with left-sided primary, with first line anti-EGFR treatment, median OS was 39.3 months. In the pts with right sided primary, the OS difference between first line anti-EGFR and anti-VEGF treatments were not significant.