ABSTRACT
BACKGROUND: Short treatment-duration with early restaging is crucial to avoid liver injury after preoperative chemotherapy (preopCTX) for colorectal liver metastases (CRLM). Response evaluation according to response evaluation criteria in solid tumors (RECIST) criteria implies several limitations. Early tumor shrinkage (ETS; ≥20% size reduction <6-12 weeks) or morphological criteria (MC) may better predict oncological outcome. METHODS: In patients undergoing resection after preopCTX between 2003-2017 pathological and radiological response was reassessed according to Blazer classification, ETS, MC, and RECIST within 90 days and correlated with survival. RESULTS: Seventy-two patients were included, with a median of two (1-10) liver lesions, 53% bilobar involvement, and 7% extrahepatic disease. PreopCTX was applied for 3 months in median (1-6). During restaging after a median of 62 days, presence of ETS was associated with improved median overall survival (OS; 57.1 vs 33.7 months; P = .010) and disease-free survival (16 vs 7.2 months; P = .025). MC significantly correlated with major pathological response (P = .021). When combining ETS with optimal MC, presence of one or both factors was associated with pathological response (61.5% and 92.3%; P = .044) and OS in log-rank (P = .011), and multivariable analysis (hazard ratio [HR] 0.41; 95% confidence interval [CI], 0.19-0.90 and HR 0.32; 95%CI, 0.11-0.97). CONCLUSION: Response-grading by combined ETS/MC criteria less than 90 days after preopCTX initiation predicts pathological response and postoperative survival in CRLM.
ABSTRACT
BACKGROUND: Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM. METHODS: Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed. RESULTS: 259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006). CONCLUSIONS: Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.
