Incomplete Lutetium-177 DOTATATE Treatment: Predictors of Therapy Completion, Reasons of Discontinuing Therapy, and the Role of Imaging During Therapy

Introduction: ¹⁷⁷Lu DOTATATE radionuclide therapy improves progression free survival for progressive metastatic neuroendocrine tumors of the midgut and pancreas. A typical complete course of treatment is composed of four cycles in doses of 200 mCi every eight weeks, with possible dose reductions for decreases in renal function and hematologic lab values. ¹⁷⁷Lu DOTATATE may be discontinued prior to completion of all four planned cycles for various reasons, usually inability to tolerate radionuclide therapy and/or suboptimal treatment response. This study will investigate the clinical characteristics of patients who did not complete therapy and describe the role cross sectional imaging had on management.

Methods: Patients initiating ¹⁷⁷Lu DOTATATE therapy at a single-center between May 2018 – May 2019 were retrospectively reviewed. Baseline clinical information and number of completed therapy cycles were recorded. Logistic regression of complete versus incomplete therapy outcomes on body mass index (BMI), estimated glomerular filtration rate, lymph node metastasis, bone metastasis, hepatic metastasis, prior external radiation therapy, peritoneal metastasis, and history of liver ablation/embolization procedures was performed, with alpha = 0.05. The categories of metastasis were classified based on presence or absence of at least one lesion in the category. The reason for early discontinuation of ¹⁷⁷Lu DOTATATE and the indication and management impact of cross-sectional imaging obtained between cycles of therapy were also reviewed.

Results: Of the patients who initiated ¹⁷⁷Lu DOTATATE (n=107), 77.6% completed all four planned cycles of ¹⁷⁷Lu DOTATATE. Primary tumor locations were neuroendocrine tumors of the gastrointestinal tract (48.6%) or pancreas (35.5%), with some cases of bronchial carcinoid (4.7%), meningioma (1.9%), unknown primary (5.6%), and single cases of pheochromocytoma, paraganglioma, thymic neuroendocrine tumor, and gastric neuroendocrine tumor.

Patients with bone metastases were less likely to complete therapy (OR 0.21, 95% CI 0.05-0.69). Baseline BMI (OR 1.12, 1.25-1.02) and baseline presence of nodal metastasis (OR 6.90, 1.13-49.8) predicted completion of ¹⁷⁷Lu DOTATATE. A greater portion of patients who did not complete therapy had peritoneal metastasis (70.8% versus 50%; OR 0.28, 0.06-1.02) and previous radiation treatment (29.2% versus 11.3%; OR 0.23, 0.04-1.14); however, these did not reach statistical significance.

Reasons for discontinuing therapy included clinical decline and death (37.5%), tumor progression (29.2%), cytopenia (25%), renal failure (8.4%), insufficient improvement in symptoms or functional status (8.4%), acute dyspnea and lightheadedness following therapy (4.6%), and acute presentation of bowel ischemia (4.6%). Some patients had multiple reasons for discontinuing therapy.

Mid-treatment cross sectional imaging was obtained in 77.5% of complete and 75% of incomplete therapy cases. Imaging contributed to the decision to discontinue ¹⁷⁷Lu DOTATATE in 33.3% of patients not completing therapy, due to radiographic progression, except in one case of acute bowel ischemia.

Conclusions: Bone metastasis strongly predicted incomplete ¹⁷⁷Lu DOTATATE therapy, which may reflect greater bone marrow radiation effects or more advanced disease. Further study may explore the impact of tumor burden in bone. Increased BMI predicted completion, possibly acting as a surrogate screen for cachexia or performance status.

The most common reasons for therapy discontinuation included clinical decline and death, tumor progression, and cytopenia. Imaging contributed to 33.3% of the decisions to discontinue therapy, predominantly by demonstrating tumor progression.

These findings may inform risk stratification discussions with patients. Despite higher relative risks, it still may be safe and effective to treat thin patients who have bone mets with ¹⁷⁷Lu DOTATATE. Future studies of outcomes following incomplete therapy are warranted.