Radioembolization Is Effective in Neuroendocrine Tumors With Liver Metastases

Radioembolization is an effective treatment option for patients with neuroendocrine neoplasms (NENs) and liver metastases, demonstrating a disease control rate (DCR) of >90% in an international, retrospective study.¹

“In a broad spectrum of NENs and at different moments of the disease, radioembolization is safe, effective, and can relieve symptoms, even in heavily pretreated, progressive patients with high intrahepatic tumor load,” the study authors, led by Arthur J. A. T. Braat, MD, wrote in their report. “In one-fourth of patients, objective response might improve after the commonly used 3-month evaluation scan.”

Previously, radioembolization was seen as promising for patients with NENs and liver metastases, especially as few toxicities are seen from treatment. Yet, data to date on radioembolization in this patient population have been limited.

The study aimed to fill the gaps of currently available literature by looking at a larger group of patients who had received radioembolization and addressing baseline characteristics and their effects on response rates and survival.

A retrospective analysis was conducted of 244 patients with NENs and liver metastases who underwent treatment with radioembolization with Y-90 resin microspheres between July 2004 and May 2016 and had at least a 3-month follow-up scan. Although approximately 10% of the patients received multiple radioembolization treatments, the study focused on first treatment only, as repeated radioembolizations could cause increased toxicity.

The primary endpoint of the study was radiologic response at 3 and 6 months after treatment by both RECIST 1.1 and modified RECIST (mRECIST) criteria. Follow-up imaging at 6 months, however, was only available for 51.6% of patients.

A majority of the patients had an ECOG score of 0 (47.2%) or 1 (43.0%), and 91% had progressive disease before radioembolization. Most patients had World Health Organization/European Neuroendocrine Tumor Society grade 1 (39.3%) or grade 2 (35.7%) disease, 10.2% had grade 3 disease, and the grade was unknown in 14.8%.

The primary tumor, which was most commonly in the small bowel (34.9%) or pancreas (31.2%), was surgically resected in 45.5% of patients. Extrahepatic metastases were also noted in 66% of patients, notably in the lymph nodes (47.1%).

Most patients had diffuse liver metastases, and type III liver involvement was noted in 95.1%; 40.2% had more than 50 intrahepatic lesions and 14.5% had an intrahepatic tumor load of ≥75%. The majority (95.1%) had received multiple prior treatments.

The objective response rate (ORR) was 15.7% at the first assessment, which was approximately 3 months after treatment, and 28.5% at the second, which was about 6 months after treatment, by RECIST 1.1 criteria, and they were 42.8% and 62.9%, respectively, by mRECIST criteria. The DCRs by RECIST 1.1 criteria were 91.3% and 91.4% at first and second follow-up, respectively, and 91.3% and 91.4%, respectively, by mRECIST criteria (TABLE).

“This is the first time a prolonged response for at least 6 months has been objectively demonstrated in patients with available imaging after 6 months, and in approximately one-quarter of those patients, the optimal time to evaluate treatment might be later than 3 months,” Braat et al wrote.

Responses did not appear to correlate with NEN grade or primary tumor origin by both mRECIST and RECIST 1.1 criteria.

Median overall survival (OS) after radioembolization was 2.6 years overall (95% CI, 2.2-3.0). This was significantly longer in patients with grade 1 and 2 neuroendocrine tumors (NETs; 3.1 and 2.4 years, respectively) compared with those with grade 3 NETs/neuroendocrine carcinomas (0.9 years; P <.001).

Three months after radioembolization, 32% of patients had no toxicities versus 55% at 6 months. Known radioembolization-related adverse events (AEs), including fatigue, abdominal pain, and nausea, were observed in 56% of patients within the first 3 months, and persisted in 6% at 6 months. Missing data on toxicity were noted in 12% and 39% of patients at 3 and 6 months, respectively.

According to multivariate analysis, DCR by RECIST 1.1 at 3 months was predictive of a better median OS (HR, 0.4; P <.01) and grade 3 disease, whereas unknown NET grade, intrahepatic tumor load &ge;75%, and presence of extrahepatic disease were all predictive of a worse median OS. The results of the study were consistent with a prior meta-analysis looking at radioembolization in NENs.²

&ldquo;Prospective randomized controlled studies on radioembolization in NENs are desperately needed, although it should also be recognized that clinical experience, captured in high-quality retrospective study cohorts, is indispensable in this difficult-to-study heterogeneous patient population. Currently, treatment algorithms typically place radioembolization after failure of systemic treatments. However, in [patients with NEN] with disease limited or &lsquo;dominant&rsquo; to the liver, radioembolization might be a more appropriate choice prior to, or in combination with, first-line systemic treatment,&rdquo; the study authors concluded.

References:

1. Braat AJAT, Kappadath SC, Ahmadzadehfar H, et al. Radioembolization with 90Y resin microspheres of neuroendocrine liver metastases: international multicenter study on efficacy and toxicity. Cardiovasc Intervent Radiol. 2019;42(3):413-425. doi: 10.1007/s00270-018-2148-0.
2. Devcic Z, Rosenberg J, Braat AJA, et al. The efficacy of hepatic 90Y Resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis. J Nucl Med. 2014;55(9):1404-1410. doi: 10.2967/jnumed.113.135855.