Professional Statements and Societal Positions Guidelines
The National Comprehensive Cancer Network (NCCN) guidelines (v.2.2022 ) for neuroendocrine and adrenal tumors have published key eligibility criteria for patients treated with lutetium 177 dotatate for neuroendocrine tumors. Eligibility criteria include low or intermediate grade neuroendocrine tumor (proliferation index Ki-67
<
20%), detection of somatostatin receptor expression using somatostatin-based receptor imaging, and adequate bone marrow, renal and hepatic function. Table 15 summarizes the NCCN guidelines for neuroendocrine and adrenal tumors.
44,
Table 15. Recommendations for Use of Lutetium 177 Dotatate for Neuroendocrine Tumors
Treatment Category | Recommendation Category |
Mid-gut recurrent, locoregional advanced or distant metastases gastrointestinal neuroendocrine tumors after disease progression on somatostatin analogues | 1 |
Bronchopulmonary/thymic distant metastases neuroendocrine tumors if there is clinically significant tumor burden and low grade (typical) tumor or evidence of progression or intermediate grade (atypical) tumor or symptomatic disease | 2A |
Locoregional or recurrent advanced or distant metastases gastrointestinal neuroendocrine tumors after disease progression on somatostatin analogues | 2A |
Locoregional or recurrent advanced or distant metastases pancreatic neuroendocrine tumors after disease progression on somatostatin analogues | 2A |
Locally unresectable or distant metastases paraganglioma/pheochromocytoma (consider use if somatostatin receptor-positive) | 2A |
The NCCN guidelines also provide a category 2A recommendation to consider the use of lutetium 177 dotatate for treatment of patients with locally unresectable bronchopulmonary or thymus neuroendocrine tumors and locally unresectable or distant metastatic pheochromocytoma or paraganglioma. For pheochromocytoma and paraganglioma, the guidelines additionally note that data are limited for use in this setting. Due to lack of randomized data, the NCCN encourages participation in clinical trials of lutetium 177 dotatate for rare groups of neuroendocrine tumors including pancreatic neuroendocrine tumors, pheochromocytomas, paragangliomas, and bronchopulmonary/thymic neuroendocrine tumors.
The NCCN guidelines (v.2.2022 ) for neuroendocrine and adrenal tumors gives iobenguane I 131 category 2A recommendation for treatment of patients with locally unresectable or distant metastatic pheochromocytoma or paraganglioma with positive MIBG (iobenguane) scan.
Somatostatin Receptor-Based Imaging
Preferred somatostatin receptor (SSTR)-based imaging options to assess receptor status include SSTR-positron emission tomography (PET)/computed tomography (CT) or SSTR-PET/magnetic resonance imaging (MRI). Octreotide single-photon emission computed tomography (SPECT)/CT may be used only if SSTR-PET is not available, as it is much less sensitive for defining SSTR-positive disease. Appropriate SSTR-PET radiotracers include Gallium 68 (Ga 68) dotatate, Ga 68 dotatoc, or Copper 64 (Cu 64) dotatate. SSTR-positive status is confirmed when uptake in measurable lesions is greater than the liver.
Lutetium 177
The recommended dose of lutetium 177 (Lu 177) dotatate is 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses.
There are theoretical concerns regarding the competition between somatostatin analogues and Lu 177 dotatate for somatostatin receptor binding. Therefore, the following is recommended
- Do not administer long-acting somatostatin analogues for 4 to 6 weeks prior to each Lu 177 dotatate treatment.
- Stop short-acting somatostatin analogues 24 hours before each Lu 177 dotatate treatment.
- Both long-acting and short-acting somatostatin analogues can be resumed 4 to 24 hours after each Lu 177 dotatate treatment.
Lu 177 dotatate is a radiopharmaceutical and should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
Lu 177 dotatate should be discontinued permanently if the patient develops hepatotoxicity defined as bilirubinemia greater than 3 times the upper limit of normal (grade 3 or 4), or hypoalbuminemia less than 30 g/L with a decreased prothrombin ratio less than 70%.
Lu 177 dotatate should be discontinued permanently if patient develops renal toxicity defined as a creatinine clearance of less than 40 mL/min calculated using Cockcroft-Gault equation with actual body weight, or 40% increase in baseline serum creatinine, or 40% decrease in baseline creatinine clearance calculated using Cockcroft-Gault equation with actual body weight.
Table PG1 describes the grading of severity used in the Common Toxicity Criteria for Adverse Events (version 4.03).
Table PG1. Common Toxicity Criteria for Adverse Events, Version 4.03
Grade | Description |
1 | Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. |
2 | Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living and refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. |
3 | Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. |
4 | Life-threatening consequences; urgent intervention indicated. |
5 | Death related to adverse event. |
Iobenguane I 131
- Iobenguane I 131 is administered intravenously as a dosimetric dose followed by 2 therapeutic doses administered 90 days apart.
- The recommended dosimetric dose is 185 to 222 MBq (5 to 6 mCi) in individuals greater than 50 kg and 3.7 MBq/kg (0.1 mCi/kg) in patients 50 kg or less.
- The recommended therapeutic dose is 18,500 MBq (500 mCi) in individuals greater than 62.5 kg and 296 MBq/kg (8 mCi/kg) in individuals 62.5 kg or less.
- Thyroid-blocking medications should be given prior to administration and after each dose.
- Iobenguane I 131 is a radiopharmaceutical and should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
- Iobenguane I 131 should be discontinued if:
- Platelet count is less than 80,000 mcL or absolute neutrophil count (ANC) is less than 1,200/mcL.
- Individual has liver dysfunction defined as aspartate aminotransferase or alanine aminotransferase ≥ 2.5 times the upper limit of normal or total bilirubin > 1.5 times the upper limit of normal or develops liver disease (including hepatitis and chronic alcohol abuse).
- Individual develops renal toxicity defined as a creatinine clearance of < 30 mL/min.
