Stereotactic Ablative Radiotherapy for the Management of Liver Metastases from Neuroendocrine Neoplasms

Abstract

Liver metastases are common in patients with metastatic well-differentiated neuroendocrine neoplasms (WD-NEN). Given the rather indolent clinical course of WD-NEN, patients may expect to have prolonged survival even in the setting of metastatic disease. Treatment modalities must therefore maximize tumor control, maintain quality of life and minimize treatment side effects. Although commonly used to treat liver metastases for other cancer histologies, the role of stereotactic ablative radiotherapy (SABR) is not well understood in this unique patient population. The purpose of this study is to evaluate the safety and efficacy of SABR in treating well-differentiated neuroendocrine liver metastases (WD-NELM). An institutional REB approved retrospective review of patients with WD-NELM treated with SABR was performed spanning January 2015 to July 2019. Demographic, treatment details and clinical/radiographic follow-up data were abstracted from the patients’ clinical and radiation planning records. RECIST 1.0 criteria were applied to each individual target to evaluate the overall response rate to treatment. One-year survival was calculated for local control and systemic progression. All stats were calculated using R Studio version 1.1.463. Toxicity was reported as per CTCAE v 5.0 criteria. Twenty-five patients were identified that matched the search criteria with a total of 53 individual liver metastases treated with SABR. The median number of liver metastases treated per patient was 2 (range: 1-4) with a median size of 2.5 cm (range 0.7-9.7 cm). The median radiation dose delivered was 50Gy/5 fractions (range 25Gy/5 - 60 Gy/3) with a median biologically effective dose (BED10) of 100 (range 39-180). The median follow-up was 14 months (range 2-54 months). Twenty-four of the 25 patients were still alive at time of data analysis. Most patients (68%) had midgut tumors (small bowel, pancreas), were Grade II (80%) and had high volume intrahepatic and/or extrahepatic disease (76%). Almost all patients (96%) remained on systemic somatostatin analogues despite having radiographic disease progression. The best overall response was: CR = 2, PR = 13, SD = 30 and PD = 2. The best treatment response based on changes in axial diameter was -100% (median: -16%, range: -100% to 47%). The objective response rate was 32%, with initial disease improvement or stability in 96% of all lesions treated. The median time to best response was 9 months (range: 3-16 mos). The 1-year local control and PFS were 92% (CI 85-99.9%) and 44% (CI 28-70.1%) respectively. No Grade III/IV acute or late toxicity was identified. Liver SABR is a safe and effective means of providing local control for NELM. This treatment modality should be considered a care option in select patients in concert with strategies to manage systemic disease.