Radiological heterogeneity in response to chemotherapy is associated with poor survival in patients with colorectal liver metastases

Background: In patients with colorectal liver metastases (CLM) there is limited knowledge about the occurrence of radiological heterogeneity in response to chemotherapy. Methods: A retrospective analysis was performed in the CAIRO and CAIRO II studies on the incidence of intermetastatic heterogeneity in patients with CLM and its association with survival. Mixed response (MR) was defined as >30% difference in individual lesion response, with all lesions showing a similar behaviour; true mixed response (TMR) as two lesions showing progression versus response; homogeneous response (HR) as similar behaviour of all lesions. Patients were classified according to the Response Evaluation Criteria in Solid Tumours (RECIST) categories (partial response (PR), stable disease (SD), progressive disease (PD), complete response (CR)) and then subdivided into MR and TMR in order to compare survival. Results: In the CAIRO and CAIRO II studies, 140 and 150 patients with liver-only disease were identified. 73/290 (25.2%) patients showed MR, and 25/290 (8.6%) patients TMR, and 192/290 (66.2%) patients HR. Overall survival (OS) at 1-4 years was significantly higher for the homogeneous partial responders category compared to other response categories. Median OS was 22.0 months for the entire population. In the partial response category, patients with MR showed significant poorer survival compared to patients with HR (median OS 23.7 versus 36.0 months, respectively, p = 0.019). Multivariate analysis identified four independent predictors for OS: serum lactate dehydrogenase (LDH) level (p = 0.002), number of first-line chemotherapy cycles (p = 0.001), resection of primary tumour (p = 0.001) and response category (p = 0.012). Conclusion: Radiological heterogeneity is present in approximately 35% of patients with CLM. Partial responders according to the RECIST criteria, show a significant poorer survival if classified as heterogeneous partial responder compared to homogeneous partial responders. (c) 2013 Published by Elsevier Ltd.