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Resistant functioning and/or progressive symptomatic metastatic gastroenteropancreatic neuroendocrine tumors

efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy in this setting

Kalshetty, Ashwinia,c; Ramaswamy, Anantb,c; Ostwal, Vikasb,c; Basu, Sandipa,c

doi: 10.1097/MNM.0000000000000926

Background and aims Functioning and symptomatic disease resistant to conventional therapies constitutes a subset amongst neuroendocrine tumors (NETs) that are commonly considered for peptide receptor radionuclide therapy (PRRT). The aim of this study was to evaluate the efficacy of 177Lu-DOTATATE PRRT in this group with objective assessment criteria.

Materials and methods A total of 46 patients with refractory or progressive symptomatic GEP-NETs (previously treated at various stages with long-acting octreotide, chemotherapy, multikinase inhibitors, etc.) who had undergone treatment with PRRT were retrospectively analyzed. These patients were evaluated for response on three scales: clinical, biochemical parameters (tumor marker levels), and imaging (functional molecular and contrast enhanced anatomic). They were classified as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) on each scale. Furthermore, the patients were classified as (a) those who gained benefit from PRRT and (b) those who were nonresponders using predefined criteria.

Results Ninety-one percent of the patient population had liver metastases, with a mean serum chromograninA level of 3307 U/ml, consistent with high volume tumor burden and refractory symptoms. Clinical symptomatic response on an analogue scale showed 54% CR, 35% PR, and 6% SD, whereas 4% showed worsening of symptoms. Biochemically, 17% CR, 28% PR, and 28% SD were observed, whereas 12% showed PD. On evaluation by imaging (PERCIST and RECIST 1.1 criteria), we observed 4% CR, 39% PR, and 36% SD, whereas 19% showed PD. The clinical scale showed the highest overall benefit of 95.6% in the population studied.

Conclusion The data support the evidence that PRRT could be potentially beneficial in resistant, refractory, and progressive symptomatic groups of GEP-NETs with functional disease burden. The use of a multidimensional response evaluation should be adopted (rather than only anatomical–functional imaging) and needs to be considered while managing this subset of patients.

aRadiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe

bDepartment of Medical Oncology, Tata Memorial Hospital

cHomi Bhabha National Institute, Mumbai, India

Correspondence to Sandip Basu, MBBS(Hons), DRM, DNB, MNAMS, Radiation Medicine Centre (BARC), Tata Memorial Hospital Annexe, Jerbai Wadia Road, Parel, Mumbai 400012, India Tel: +91 222 414 9428; fax: +91 222 415 7098; e-mail:

Received July 6, 2018

Received in revised form September 25, 2018

Accepted September 27, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.