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We report the impact of 177Lu-DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 d per 4 wk, respectively, compared with 0.99, 1.44, and 2.54 d for high-dose octreotide LAR. The mean differences were 3.11 d (95% CI, 1.35–4.88; P = 0.0007) for abdominal pain, 3.11 d (1.18–5.04; P = 0.0017) for diarrhea, and 1.98 d (0.08–3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated-measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality-of-life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu-DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut neuroendocrine tumors, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu-DOTATATE on health-related quality of life. Title in Web of Science: Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with Lu-177-DOTATATE

Although radiation-induced mesenteritis or peritonitis can potentially exacerbate the risk of bowel obstruction, there are no data in the literature on the incidence of intestinal obstruction related to peptide receptor radionuclide therapy. Methods: The records of all patients treated with 177Lu-DOTATATE at Moffitt Cancer Center between April 2018 and October 2019 were evaluated. The number of patients who developed bowel obstruction within 3 mo of a 177Lu-DOTATATE treatment was divided by the total number of patients with preexisting peritoneal or mesenteric disease. Management strategies and outcomes were evaluated. Results: Of a total of 159 patients treated, 81 had baseline mesenteric or peritoneal disease, among whom 5 (6%) experienced at least 1 episode of bowel obstruction within 3 mo of treatment. Two of the patients underwent surgical exploration during obstruction describing a “frozen abdomen.” All 5 responded at least temporarily to high-dose corticosteroid treatment and regained bowel function, but 2 patients eventually succumbed to progressive peritoneal disease. Conclusion: Peptide receptor radionuclide therapy can lead to bowel obstruction in patients with mesenteric or peritoneal disease, likely by inducing inflammation. Corticosteroids can potentially play a role in treatment and prophylaxis.

With the recent approval of 177Lu-DOTATATE for use in gastroenteropancreatic neuroendocrine tumors, access to peptide receptor radionuclide therapy is increasing. Representatives from the North American Neuroendocrine Tumor Society and the Society of Nuclear Medicine and Molecular Imaging collaborated to develop a practical consensus guideline for the administration of 177Lu-DOTATATE. In this paper, we discuss patient screening, maintenance somatostatin analog therapy requirements, treatment location and room preparation, drug administration, and patient release as well as strategies for radiation safety, toxicity monitoring, management of potential complications, and follow-up. Controversies regarding the role of radiation dosimetry are discussed as well. This document is designed to provide practical guidance on how to safely treat patients with this therapy.

Gastroenteropancreatic neuroendocrine tumors are relatively rare neoplasms, characterized by a propensity to secrete hormones that cause distinct clinical syndromes. During the past decade, the systemic treatment landscape has improved significantly: new options include everolimus, an inhibitor of the mammalian target of rapamycin; sunitinib, an angiogenesis inhibitor; and cytotoxic regimens such as capecitabine and temozolomide. Moreover, the recent approval of the radiolabeled somatostatin analog 177Lu-DOTATATE has had a significant impact on management of neuroendocrine malignancies. In this review, we discuss advances in the medical management of gastroenteropancreatic neuroendocrine tumors within the context of the larger multidisciplinary approach to these diseases.

With the growing use of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT), there are many unanswered questions regarding patient selection. In this document, we review the literature on the use of 177Lu-DOTATATE in neuroendocrine tumors (NETs) of different primary origin, discuss issues of

REPLY: Dr. Wee and colleagues reviewed their database of gastroenteropancreatic neuroendocrine tumor patients treated with 177Lu-DOTATATE and observed patterns of bowel obstruction very similar to those described in our study ( [1][1] ). These corroborating data significantly strengthen the evidence