E189: Adjuvant Hepatic Arterial Infusion Pump Chemotherapy in Patients with Resectable Colorectal Liver Metastases and Extrahepatic Disease

Extrahepatic disease (EHD) has been a contraindication to adjuvant hepatic arterial infusion chemotherapy (HAI) for colorectal liver metastases (CRLM). This study aims to assess outcomes for patients with CRLM and EHD undergoing resection with adjuvant HAI and systemic chemotherapy (HAI-SYS).


Methods:

Patients with resected CRLM followed by adjuvant HAI-SYS between 2000-2020 were identified via retrospective chart review. EHD was deemed “indeterminate”, if lesions were identified on imaging with no biopsy or pathologic confirmation, or “suspicious”, if lesions were pathologically-proven, PET-positive, growing on serial imaging or noted as “suspicious” per reading radiologist. Fisher's Exact test and Wilcoxon Rank Sum test were used to compare characteristics by presence or absence of EHD. Kaplan Meier methods estimated overall survival (OS) from the time of HAI until death.


Results:

Of 744 patients, 341 (45.8%) had evidence of EHD. Among the whole cohort, most patients (75.5%) received neoadjuvant chemotherapy. The most common sites of EHD were lung (26.3%), followed by lymph nodes (19.6%). Suspicious lesions were identified in 17.1% of patients. Patients with EHD were more likely to have multiple CRLM (78.6% vs 70.2%, p=0.012); there were no other significant differences in patient and clinical characteristics between the two cohorts (p >0.05). Patients with EHD had a median OS of 5.8 years, compared to 8.2 years in patients without EHD (p< 0.001, Figure 1). In the subset of patients with suspicious EHD, median OS was 4.2 years in those with EHD versus 8.4 years in patients without EHD (p< 0.001). Median OS for patients with multiple sites of EHD, single site of EHD, and without EHD was 5.1 years (95%CI:3.4-10.2), 5.9 years (95%CI:4.9-7.4), and 8.2 years (95%CI:6.6-12.3), respectively (p=0.003). Median OS was stratified by site of disease: lung only (6.0 years), lymph node only (5.9 years), and peritoneum only (9.5 years), (p=0.06). Patients with EHD were more likely to recur in the liver at 5 years compared to patients without EHD (45.1% vs 34.2%, p< 0.001). The effect of EHD was additive with KRAS status: survival for patients with EHD and KRAS-mutant tumors was worse than for those with EHD and KRAS-wild type tumors (4.2 vs 9.2 years).


Conclusions:

While EHD is associated with worse outcomes for patients undergoing adjuvant HAI-SYS, long-term survival is possible and promising in highly selected patients. Factors associated with worse outcomes include multiple sites of EHD and Ras mutation status.