Safety and effectiveness of lu-177 dotatate prrt after regional hepatic radio or chemo embolization in patients with somatostatin expressing neuroendocrine tumors

Objectives There are several therapeutic modalities for management of somatostatin receptor expressing neuroendocrine neoplasms. Peptide Receptor Radionuclide Therapy (PRRT) with Lu-DOTA-(Tyr3)-Octreotate (177Lu-DOTATATE) and chemo or radionuclide hepatic embolization (CRHE) are among the common therapies provided to the patients. This study evaluates the safety and effectiveness of PRRT in patients with prior history of CRHE.

Methods We retrospectively reviewed 143 patients with somatostatin expressing neuroendocrine tumors who underwent LU-177 PRRT for their previous history of hepatic embolization. Statistical analysis was performed regarding safety and efficacy of Lu-177 PRRT in patients with and without prior CRHE using resampling procedures and Correlation Coefficient (r).

Results Out of 143 patients, 92 patients (64.3%) did not have Hepatic Embolization (Group 1) and 51 patients (35.6%) had prior history of Hepatic Embolization (Group 2). Among HE positive patients, 30 (58.8%) patients had prior chemo embolization (CHE) ranging from 1 to 6 cycles, mean 1.74 cycles; 10 (19.6%) patients had prior Radionuclide hepatic embolization (RHE) ranging from 1 to 6 cycles, mean 0.68 cycles and 11 Patients (21.5%) had both CHE and RHE ranging from 1 to 2 CHE and 1 to 3 RHE, mean 1.4 cycle. Proportion of toxicity in patients with and without prior history of hepatic embolization was comparable (PV= 0.246), and null hypothesis could not be rejected (>0.05). This means that both positive and negative history of hepatic embolization share the same toxicity risk. There were no statistically significant correlation (r) between prior hepatic embolization (either chemo or radionuclide) and any type of toxicity [renal toxicity (chemo: 0.17, radio:-0.03), hepatotoxicity (chemo:-0.38, radio: 0.13) or hematotoxicity (chemo:-0.04, radio:-0.09)]. Similarly we did not find any correlation in time interval between “hepatic embolization (chemo and/or radionuclide) and first cycle of LU-177 PRRT” and any type of toxicity [renal toxicity (chemo:-0.10, radio:-0.15), hepatotoxicity (chemo: 0.17, radio:-0.59) or hematotoxicity (chemo:-0.17, radio:-0.04)]. Among 51 patients with any prior history of CRHE, 54% experienced stable disease (SD), 15.6% experienced partial response / complete response (PR/CR), and 21.6% experienced progressive disease (PD) following Lu-177 PRRT(8.8% were not evaluable). Among 92 patients without any prior history of CRHE 40.2% experienced SD, 16.3% experienced PR/CR, and 35.8% experienced PD following Lu-177 PRRT (7.7% were not evaluable). Total of 70 % of patients who had CRHE, experienced benefit (PR/CR+ SD) from LU-177 PRRT, and 21.6% experienced progression. Total of 56.5 % of patients who did not have CRHE experienced benefit (PR/CR+ SD) from LU-177 PRRT, and 35.8% experienced progression. Patients with pervious history of CRHE showed more SD following PRRT when compared to the patients who did not have any prior HE (PV=0.048). Patients with pervious history of CRHE showed less PD following PRRT in comparison with patients who did not have any prior history of HE (PV=0.046). Both CRHE and NHE status share the same probability for developing PR/CR following LU-177 PRRT (PV=0.506).

Conclusions Our review on 143 patients treated with LU-177 DOTATATE from 2010 to 2015 did not show any clinically or statistically significant toxicity by using LU-177 PRRT in patients who had prior history of chemo hepatic embolization and/or radionuclide hepatic embolization regardless of frequency of embolization (1 to 6 cycles) or time interval between any type of embolization and first cycle of LU-177 PRRT (4.2 - 134.8 months). Prior history of CRHE is not a contraindication for subsequent PRRT. Our study also suggests a statistically significant higher response rate in patients with previous history of CRHE.