Abnormal Pretreatment Liver Function Tests Are Associated with Discontinuation of Peptide Receptor Radionuclide Therapy in a U.S.-Based Neuroendocrine Tumor Cohort

Abstract

Background Peptide receptor radionuclide therapy (PRRT) is effective for treating midgut neuroendocrine tumors (NETs); however, incorporation of PRRT into routine practice in the U.S. is not well studied. Herein we analyze the first year of PRRT implementation to determine tolerance of PRRT and factors that increase risk of PRRT discontinuation. Materials and Methods Medical records were reviewed and data were abstracted on all patients with NETs scheduled for PRRT during the first year of PRRT implementation at a U.S. NET referral center (August 2018 through July 2019). Logistic regression was used to identify factors associated with PRRT discontinuation. Results Fifty‐five patients (56% male) were scheduled for PRRT over the study period. The most common primary NET location was small bowel (47%), followed by pancreas (26%), and 84% of the NETs were World Health Organization grade 1 or 2. The cohort was heavily pretreated with somatostatin analog (SSA) therapy (98%), non‐SSA systemic therapy (64%), primary tumor resection (73%), and liver‐directed therapy (55%). At the time of analysis, 52 patients completed at least one PRRT treatment. Toxicities including bone marrow suppression and liver function test (LFT) abnormalities were comparable to prior publications. Eleven patients (21%) prematurely discontinued PRRT because of toxicity or an adverse event. Pretreatment LFT abnormality was associated with increased risk of PRRT cancellation (odds ratio: 12; 95% confidence interval: 2.59–55.54; p < .001). Conclusion PRRT can be administered to a diverse NET population at a U.S. NET referral center. Baseline liver function test abnormality increases the likelihood of PRRT discontinuation. Implications for Practice Peptide receptor radionuclide therapy (PRRT) can be successfully implemented at a U.S. neuroendocrine tumor (NET) referral center in a NET population that is diverse in tumor location, grade, and prior treatment history. Toxicity and adverse effects of PRRT are comparable to prior reports; however, 21% of individuals prematurely discontinued PRRT. Patients with baseline liver function test abnormalities were more likely to discontinue PRRT than patients with normal liver function tests, which should be taken into consideration when selecting treatment options for NETs.

Laboratory, Clinical, and Survival Outcomes Associated With Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors

“…Since FDA approval of PRRT, efforts have been targeted at implementation of PRRT within NET clinics across the United States . Results from a 2020 study by our group suggested that PRRT could be successfully administered among a diverse US-based group of patients with NETs, and we found that patients with abnormal liver function tests before PRRT had an increased likelihood of discontinuing PRRT prior to completion of the PRRT treatment course.…”

Evaluation of Hepatotoxicity from Peptide Receptor Radionuclide Therapy in Patients with Gastroenteropancreatic Neuroendocrine Tumors and a Very High Liver Tumor Burden

“…Previously, it has been shown that those with less than 25%, 25%-50%, and more than 50% hepatic involvement did not experience significant hepatotoxicity as a result of PRRT (7). A recent study suggested that pretreatment abnormalities of liver chemistries were associated with increased risk of PRRT cancellation, but that study did not address the liver tumor burden and safety of PRRT in patients with extensive liver metastases (14). Several studies have evaluated the estimated absorbed doses of organs and metastatic lesions of patients treated with 177 Lu-DOTATATE (15)(16)(17) and showed wide variation in the mean absorbed dose to tumor lesions, with sample reported average doses of 4.79 6 4.23 Gy/GBq (15) and 3.85 6 1.74 Gy/GBq (18).…”

Monitoring and Surveillance of Patients with Gastroenteropancreatic Neuroendocrine Tumors Undergoing Radioligand Therapy

“…Patients with hepatic metastasis (mainly those with very high liver burden or impairment [38]) may have an elevated risk of hepatotoxicity after RLT [10], though RLT may continue to be a safe option for these patients [39]. Regardless of tumor burden, baseline hepatic dysfunction may predict premature discontinuation of RLT [40].…”