核医学与放射治疗

Intra-arterial ¹⁷⁷Lu-DOTATATE Therapy in Patients with Metastatic Neuroendocrine Tumours in Liver Dominant Disease “A Novel Theranostic Approach to Augment Therapeutic Potential”: Feasibility and Safety Profile

Abstract

Sundaraiya S, Rajan A, Palaniswamy M, Uthappa MC, Ramprabhu and Venugopal K

Purpose: The aim of the study was to assess the feasibility, safety, tolerability and efficacy of intra-arterial infusion of ¹⁷⁷Lu-DOTATATE in patients with well differentiated liver dominant metastatic NET.

Method: Four patients with well differentiated grade II liver dominant neuroendocrine metastasis (Ki67 index ≤ 20%) were included in this study with ⁶⁸Ga-DOTANOC avid liver metastasis with or without extra hepatic disease. Each patient underwent intra-arterial (IA) administration of 7.4 GBq ¹⁷⁷Lu-DOTATATE through selective hepatic arterial catheterization, along with amino acid infusions over 4-6 hours at intervals of 8-12 weeks, with a total of 12 cycles (two patients received 4 cycles of IA infusion, third received only two cycles of IA infusion and the last one received 2 cycles IV followed by 2 IA cycles). All patients received 30 mg long acting octreotide (LAR) on day 5 of ¹⁷⁷Lu-DOTATATE therapy. Follow up imaging with ⁶⁸Ga-DOTANOC PET/CT whole body scan was done after 8 weeks of completion of the second and fourth cycles of ¹⁷⁷Lu-DOTATATE respectively and compared with baseline imaging to determine response to treatment. Complete blood counts including platelet counts were monitored on a weekly basis until they reached nadir levels. The clinical response, safety and toxicity profiles as well as tumor markers were assessed pre and post treatment, with a time frame of up to 3 months after last treatment.

Results: All patients tolerated the IA infusion of ¹⁷⁷Lu-DOTATATE therapy well, with none experiencing any significant procedure related acute side effects. None of the patients developed acute radiation induced liver disease or renal toxicity. Only one patient developed grade 1 to 2 hematological toxicity. Remaining others was stable with none developing severe grade 3 or 4 hematological toxicity. Only one patient developed transient increase of hepatic enzymes, which normalized subsequently with no decrease in the total bilirubin levels. None of them showed compromise in their quality of life, with a definite improvement in one of them. Two patients showed partial response to therapy according to RECIST criteria and patients showed stable disease. None of them had disease progression. All 4 patients reported significant improvement in symptoms and sense of well-being after treatment initiation. Concordant decrease in serum chromogranin A levels were seen in two patients. Although there was rise in the serum chromogranin A in one patient, he showed good partial radiological response, was asymptomatic, clinically well with no deterioration in his performance status.

Conclusion: Our initial experience of IA administration of ¹⁷⁷Lu-DOTATATE therapy in patients with liver dominant metastases is promising, feasible, safe and tolerable. The preliminary therapeutic potential of this therapy is encouraging. However, further prospective studies are needed to show its impact in improving clinical outcomes, median survival and progression free survival.