Purpose: Adjuvant versus neoadjuvant chemotherapy has been extensively discussed in the surgical literature, but much less is known about the optimal timing of peri-ablation chemotherapy. Here, we examine whether the timing of peri-ablation chemotherapy (adjuvant versus neoadjuvant) affects outcomes.
Materials and Methods: From 2013-2019, 651 percutaneous liver ablation procedures were performed in 501 patients. Of these, 96 patients had cytotoxic chemotherapy within 30 days of the patient’s initial thermal ablation of liver metastases. 26 patients had chemotherapy within 30 days after ablation (adjuvant group); 17 patients had chemotherapy within 30 days before ablation (neoadjuvant group); and 53 patients had both adjuvant and neoadjuvant chemotherapy (within 30 days of ablation). In addition, almost all patients (91 of 96; 95%) received chemotherapy more than 30 days before liver ablation. Clinical variables, including histology, size and number of ablated metastases, extrahepatic disease, prior therapies, laboratory values, and KRAS mutations, were also analyzed. Overall survival, and time to local and distant progression, were analyzed using Kaplan Meier, log rank test, and Cox proportional hazards model.
Results: Median overall survival after initial liver ablation was 56 months in the adjuvant group, 43 months in the neoadjuvant group, and 26 months in the adjuvant plus neoadjuvant group (p=0.03). Multivariate analysis, including clinical variables, showed that neoadjuvant chemotherapy was associated with worse overall survival (RR=5.9, p< 0.001), but no difference in time to local or distant progression. Patients who received chemotherapy within 30 days before ablation had slightly lower albumin (4.1±0.3 versus 4.3±0.4), but otherwise, the timing of peri-ablation chemotherapy was not associated with any differences in size or number of ablated metastases, extrahepatic disease, histology, prior therapies, or other characteristics. Number of liver metastases ablated, presence of unablated liver metastases, and low albumin were associated with worse survival. Prior liver resection was associated with better survival.
Conclusion: Among patients who received peri-ablation chemotherapy, cytotoxic chemotherapy within 30 days after thermal ablation of liver metastases was associated with the highest overall survival. The etiology of this association is unknown, and further studies are required.