Implications for Advanced Practice Providers in Management of Neuroendocrine Carcinoma and FDA-Approved Lutetium Lu 177-DOTA- Octreotate Peptide Receptor Radionuclide Therapy

摘要

Background: Neuroendocrine carcinomas (NETs) are biologically diverse tumors arising from neo-plastic neuroendocrine cells. Symptoms occur by stimulation of hormone hypersecretion and vary dependent on the endocrine organ involved and the spread of the disease. Treatment options have traditionally been limited and solely focused on tumor stabilization and symptom management. Symptom reduction and slowed tumor growth is achieved by blocking excessive serotonin production with SSAs. SSAs have been the primary treatment for carcinoid syndrome associated with neuroendocrine tumors 7, 8. The recent FDA approval of Lutetium Lu-177 DOTA- octreotate Peptide Receptor Radionuclide Therapy (PRRT) can potentially offer neuroendocrine patients prolonged disease stabilization and symptom management in SSA refractory patients. PRRT involves an intravenous infusion of a somatostatin analogue that is bound to a radionuclide, typically Yttrium-90 or Lutetium-177. This delivers a cytotoxic dose of radiation to cells with somatostatin positive receptors, which are excessive in NETs. PRRT therapy proposes future implications for the Advanced Practice Provider (APP) including patient education of approved use, safety profile, screening and evaluation of appropriate patients, coordination of care, and symptom management. Approaches: The International Atomic Energy Agency, Oncology and Dosimetry Committees and the Society of Nuclear Medicine and Molecular Imaging collaborated in 2013 to develop clinical guidelines and provide guidance for patient selection, implementation, and evaluating outcomes. Patients are screened for clinical parameters including renal, hepatic, and bone marrow function. Once accepted, the patient is admitted for 23 hours observation. Patients are administered standard anti-emetics followed by an amino acid solution for renal protection prior to administration of the radionuclide compound. The amino acid administration is followed by the radionuclide compound infused over approximately 30 minutes followed by additional amino acids to prevent dose limiting renal toxicities of the radiolabeled compounds 9. Patients typically receive PRRT infusions every 2 months for 4-6 total doses. PRRT gained FDA approval in the United States on January 26, 2018. A large academic research facility located in the mid-east initiated a patient registry once PRRT was FDA approved and accrued 38 initial patients. The patients were prioritized by symptom severity and remaining viable treatment options. The facility initiated PRRT in February 2018 and to date, 36 patients have received at least one dose of PRRT. Outcomes: Two patients died from disease while waiting for treatment. Six patients died after receiving at least one dose of PRRT therapy due to co-morbidities, respiratory failure, fall complications, and/or treatment complications. Two patients developed myelosuppression precluding further dosing. Summary: PRRT can offer neuroendocrine patients symptom reduction and deceleration in tumor growth. APPs have been involved in every stage of development and delivery of PRRT therapy to patients as well as post therapy monitoring and management of symptoms. Implications for APPs: A dedicated Neuroendocrine APP clinic could potentially reduce the facilitys current 6-month wait list by identifying and evaluating appropriate patients, streamlining intake procedures, interacting with payer sources, and addressing patient needs.