Article

Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE: Nursing Roles in Managing Patients With Gastroenteropancreatic Neuroendocrine Tumors

Bonita Bennett

Linda Gardner

Pamela Ryan

peptide receptor radionuclide therapy, patient management, GEP-NETs, nuclear medicine
CJON 2024, 28(1), 79-87. DOI: 10.1188/24.CJON.79-87

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a diverse family of cancers that occur within the gastrointestinal tract and pancreas. Peptide receptor radionuclide therapy (PRRT) via 177Lu-DOTATATE is a newer therapeutic option for certain patients with somatostatin receptor–positive GEP-NETs.

Objectives: This review informs on how oncology nurses treating patients with GEP-NETs receiving PRRT using 177Lu-DOTATATE can facilitate care.

Methods: Guidance on the monitoring, management, and care of patients undergoing PRRT for GEP-NETs was developed based on published literature and the nursing experience of the authors. A case study is summarized to highlight key concepts.

Findings: Oncology nurses provide assessment, education, direct care, and emotional support when caring for patients with GEP-NETs receiving PRRT with 177Lu-DOTATATE. As the treatment landscape evolves, so too will these roles and responsibilities.

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    Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are a diverse family of cancers that occur within the gastrointestinal tract and pancreas (Oronsky et al., 2017; Rindi et al., 2022). Although considered rare, GEP-NET incidence has increased, possibly because of improved diagnosis (Dasari et al., 2017; Gatta et al., 2017), making them one of the most common types of digestive system cancer (Cives & Strosberg, 2018; Khan & Pritchard, 2022). The prognosis of patients with GEP-NETs varies widely depending on tumor characteristics, with a median survival of months to decades (Dasari et al., 2017).

    Symptoms of GEP-NETs, such as abdominal pain, diarrhea, nausea, and vomiting, can be nonspecific, delaying diagnosis by more than five years (Basuroy et al., 2018) and resulting in many patients having advanced or metastatic disease at diagnosis (Ter-Minassian et al., 2013). Diagnosis is additionally complicated because GEP-NETs present with diverse clinical syndromes, such as carcinoid syndrome (flushing and diarrhea) or hypoglycemia, depending on the site of origin and the tumor’s ability to produce and secrete hormones. Frontline treatments for advanced metastatic GEP-NETs include surgery (Kohno, 2022; Raymond et al., 2021), locoregional therapy (e.g., radiofrequency ablation, cryoablation, liver-directed therapies) (Raymond et al., 2021; Uri & Grozinsky-Glasberg, 2018), and somatostatin analogs (e.g., octreotide, lanreotide) (Raymond et al., 2021; Strosberg, Halfdanarson, et al., 2017). Multiple treatment options exist for patients with advanced NETs progressing on somatostatin analog therapy, including targeted therapy with everolimus (a mammalian target of rapamycin inhibitor) and sunitinib (a small-molecule kinase inhibitor for pancreatic NETs) (Uri & Grozinsky-Glasberg, 2018); chemotherapy regimens such as capecitabine and temozolomide or 5-fluorouracil (Uri & Grozinsky-Glasberg, 2018); and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE (hereafter referred to as 177Lu-DOTATATE) (Das et al., 2019; Hope et al., 2019; Raymond et al., 2021).

    Nursing Guidance for PRRT

    PRRT is a precision nuclear medicine approach that delivers radioactive compounds to a specific target highly expressed by certain cancer cells (Gomes Marin et al., 2020). As many as 93% of GEP-NETs express somatostatin receptors (SSTRs) (Fjällskog et al., 2003), making them an attractive target for 177Lu-DOTATATE, which binds to SSTR subtype 2 (Novartis, 2023) and emits cytotoxic radiation. Imaging studies with radioactive compounds that target SSTRs are used to visualize SSTR-positive tumors and identify patients likely to benefit from 177Lu-DOTATATE. Clinical studies (e.g., the NETTER-1 international, multicenter, phase 3 trial) have demonstrated the efficacy and safety of 177Lu-DOTATATE in patients with SSTR-positive GEP-NETs (Brabander et al., 2017; Strosberg, El-Haddad, et al., 2017; Strosberg et al., 2021), leading to its approval by the U.S. Food and Drug Administration (2018).

    It is recommended that patients with GEP-NETs undergoing PRRT be treated and managed by an interprofessional team (IPT) of NET specialists, including oncologists, radiologists, endocrinologists, surgeons, gastroenterologists, nuclear medicine physicians, advanced practice providers, and oncology nurses (Burkett et al., 2021). Oncology nurses have many roles in patient care before, during, and after PRRT (see Figure 1), which may vary by institution. This article discusses how oncology nurses can facilitate and coordinate patient assessment, patient education, direct care, symptom management, and supportive care.

    “FIGURE1”

    Patient Assessment

    Patients referred for PRRT must be carefully selected based on disease progression, imaging studies, and other clinical parameters. Nurses coordinate with staff, patients, and the IPT in many ways, and their roles can differ by institution (Hendifar et al., 2022). Sometimes they are involved with scheduling appropriate screening tests that must be performed prior to treatment (Hendifar et al., 2022). They help ensure that patients attend appointments by stressing the importance of each consultation; discussing transportation and family support with patients; confirming insurance authorization; addressing other financial considerations; and following up with patients, the IPT, and laboratory technicians to avoid delays or miscommunications (Myers & Chitwood, 2020), particularly considering that the timing of required laboratory tests and imaging studies may vary by institution.

    PRRT involves the infusion of a radioactive substance, and nurses can help ensure that strict radiation safety protocols are observed to keep radiation exposure as low as reasonably achievable (Baldwin et al., 2015; Burkett et al., 2021; Hope et al., 2019; Kendi et al., 2019). Nurses can also help identify signs of specific adverse events (AEs) associated with radiation exposure, such as hematologic toxicities, that may occur after therapy and help appropriately address them (Burkett et al., 2021; Kendi et al., 2019; Mittra, 2018; Novartis, 2023). Nurses are a resource not only for assessing patient needs (e.g., medical, social, emotional) but also for reviewing care plans with providers, which may include discussion of comorbidities and possible complications (Hendifar et al., 2022).

    Patient Education

    Requirements for patient education programs have been incorporated into U.S. Nuclear Regulatory Commission (2017) regulations governing nuclear medicine departments (Steves & Dowd, 1999). Nurses are well positioned to educate patients about PRRT because they are a point of contact between patients and PRRT treatment centers and can help answer questions that arise from discussions with the IPT (Burkett et al., 2021; Hendifar et al., 2022; Hope et al., 2019; Kendi et al., 2019; Myers & Chitwood, 2020). Prior to initiation of PRRT, the nurse can help educate patients about the reasons why PRRT is an appropriate therapy for them, what pretreatment screening procedures will be necessary, what the patient can expect to experience on treatment day and afterward, radiation safety, and accurate sources of information about PRRT.

    Rationale for treatment: Patients may be more likely to undergo necessary procedures, adhere to radiation safety instructions, and follow up with care providers if they understand why PRRT is an appropriate therapy for them (Gold & McClung, 2006). Thus, the rationale for PRRT is a necessary topic in pretreatment conversations among patients, the IPT, and nurses. These conversations educate patients about why PRRT has been selected as a potentially effective treatment by explaining the role of PRRT as a targeted therapy for SSTR-positive tumors. Nurses can also help patients and caregivers understand that although PRRT may not be curative, it can slow tumor growth and improve quality of life by controlling GEP-NET–related symptoms (Strosberg, El-Haddad, et al., 2017; Strosberg et al., 2018, 2021).

    Pretreatment screening procedures: Pretreatment education includes explanations of the required monitoring procedures for AEs and their timing. This education helps patients recall and understand the need to complete laboratory and imaging studies before their therapy begins. Nurses can facilitate discussion of the need and timing for any imaging studies prior to beginning PRRT, including computed tomography, magnetic resonance imaging, and SSTR positron-emission tomography scans (Burkett et al., 2021; Hendifar et al., 2022; Myers & Chitwood, 2020; Novartis, 2023).

    Nuclear medicine consultation: Consultation of the IPT with a nuclear medicine physician regarding the importance of and pretreatment requirements for PRRT can be discussed with the patient by a nurse (Abbott et al., 2018; Hope et al., 2019; Kendi et al., 2019; Mittra, 2018) to clarify whether PRRT is the best treatment option (Burkett et al., 2021). Nurses can help explain that treatment and management discussions among different specialties are necessary in the event of comorbidities like functional impairments (e.g., renal, hepatic, cardiac) that may make PRRT delivery more challenging (Burkett et al., 2021; Mittra, 2018).

    Managing patient expectations: Nurses can supplement the work of the IPT by educating and managing patient and caregiver expectations before, during, and after administration of PRRT (Hendifar et al., 2022). This helps patients and caregivers prepare mentally and physically and minimizes the risk of misunderstanding. Education about PRRT administration occurs prior to the first day of treatment, during which patients are made aware that PRRT is an IV treatment necessitating placement of a peripheral IV line by a nurse on treatment day (Kendi et al., 2019; Mittra, 2018). Nurses can also reiterate the approximate length of the procedure, as well as when and how long the patient will be at the treatment center, to facilitate advance preparations. Total treatment time is based on individual patients’ needs and institutional processes. Other information to discuss with patients and caregivers includes rules about visitation and oral intake before and during infusion.

    Because nurses are part of the monitoring and management team, they are also positioned to prepare patients for how they may feel on and after treatment day, and they can reassure patients that the IPT and the PRRT team will be prepared to treat any AEs that may arise (Hope et al., 2019; Kendi et al., 2019; Mittra, 2018). Hypersensitivity reactions to PRRT are uncommon, but AEs may occur. Patients may also feel healthy immediately following treatment but eventually develop fatigue and loss of appetite afterward. Nurses can work with the IPT, which may include a dietitian, to provide nutritional information to help counteract any weight loss.

    Finally, nurses can provide patients and caregivers with information about the total duration of the PRRT journey. In most cases, PRRT is performed in four sessions over the course of about six months, and in rare instances, a short hospital stay may be required (Novartis, 2023).

    Ensuring patients receive accurate information about PRRT: Many patients search the internet to find information about treatments they have been prescribed and learn about PRRT experiences from other patients. They may expect that their own treatment journey will be the same as another patient’s journey. Nurses may need to answer questions about PRRT based on information that patients have obtained on their own and, if needed, direct patients to reliable, verified sources of information (Hendifar et al., 2022). Each institution can obtain packets of educational materials about PRRT from pharmaceutical or equipment manufacturers and patient advocacy organizations that nurses can provide to patients and caregivers. In addition, it is important to stress that every patient’s experience with PRRT is different, and patients may not experience the same AEs as others.

    Radiation safety considerations: After receiving PRRT, patients become a source of radiation exposure (Kendi et al., 2019). During patient orientation and on release from the treatment center, nurses can review radiation safety practices with patients that must be observed in the clinic and following discharge to protect their families and close contacts (see Figure 2). Although the details of radiation safety precautions are generally discussed with the patient by a physician or technologist, nurses can reinforce patient understanding and serve as trustworthy sources of validated information (Burkett et al., 2021; Hendifar et al., 2022; Hope et al., 2019; Kendi et al., 2019). This is particularly important given that patients can access a wide range of information about radiation online. Face-to-face or virtual discussion with nurses can help corroborate information to prevent misunderstanding.

    Direct Patient Care

    Patient orientation: On arrival at the treatment center, nurses who will be monitoring the patient during 177Lu-DOTATATE infusion can orient the patient to the treatment room and patient restroom. As part of this orientation, all radiation safety protocols in use in the clinic can be explained to the patient (Hope et al., 2019). Some institutions choose to provide the patient with scrubs or a hospital gown or ask the patient to bring a spare set of clothing to change into to prevent contamination of personal belongings. The importance of hydration and frequent urination following PRRT treatment is also highlighted during orientation.

    Patient preparation and administration of concomitant medications: After orientation, the patient is prepared for treatment. When the patient is comfortable in the treatment chair, an IV line (some institutions use two lines) is placed by the nurse (Kendi et al., 2019; Mittra, 2018). An infusion of amino acid solution must be started 30 minutes before 177Lu-DOTATATE is administered, and this should continue throughout the PRRT treatment and for at least three hours afterward. The amino acid solution protects the kidneys from radiation damage and is a critical aspect of treatment (Abbott et al., 2018; Burkett et al., 2021; Novartis, 2023). Therapy with 177Lu-DOTATATE requires administration of other concomitant medications, which the nurse can coordinate with the infusion team, nuclear medicine department, and/or other IPT members (Hope et al., 2019; Kendi et al., 2019; Mittra, 2018; Novartis, 2023). For example, nausea is a common AE resulting from amino acid administration, and antiemetics are usually given 30–60 minutes before amino acid administration begins (Abbott & Jacene, 2018). Other concomitant medications that may be administered by oncology nurses include hypersensitivity prophylaxis.

    AE monitoring and management during infusion of PRRT: During administration of 177Lu-DOTATATE, nurses can ensure that the patient remains hydrated and monitor the patient for any AEs (Burkett et al., 2021; Kendi et al., 2020; Myers & Chitwood, 2020). Refer to Table 1 for an evidence-based comprehensive checklist of AEs and their associated management and education strategies developed to aid nurses as they manage patients during and after PRRT. Most infusions last four to six hours. The most common AEs occurring during and immediately after infusion are nausea and fatigue (Novartis, 2023). Nurses can monitor the patient’s IV site for signs of extravasation, swelling, or pain and rapidly intervene by applying warm/cold packs, compression, and elevation, while the radiation safety team monitors and determines appropriate skin dosing to account for these issues (Hope et al., 2019). In patients with preexisting heart failure, nurses can monitor for fluid overload resulting from administration of amino acids and administer diuretics as prescribed, if needed (Burkett et al., 2021).

    “TABLE1”

    AE management between cycles and after completion: Because the manifestation of certain AEs may be delayed, close monitoring of the patient is necessary by nurses and the IPT following PRRT (Brabander et al., 2017; Strosberg et al., 2021). PRRT is usually given in four cycles separated by eight weeks or longer, so rapid identification of any AEs is necessary to determine whether the next cycle of PRRT can be given as planned or must be postponed or canceled altogether (Burkett et al., 2021; Novartis, 2023). Common AEs that can occur between cycles of PRRT and after PRRT completion include fatigue and myelosuppression (Novartis, 2023). Nurses can help gather information about the patient’s current health status between cycles and flag items for review by the IPT (Myers & Chitwood, 2020). Figure 3 presents a case study that illustrates the importance of appropriate monitoring for AEs.

    Patient discharge: Discharge summaries are usually provided by the nurse. Instructions contain information on what to do about urgent symptoms and a 24-hour emergency call number, as well as reinforcement of radiation safety practices outside the clinic. Patients and caregivers can be encouraged to communicate electronically with the clinic or nurses through online patient portal applications, if available, or by telephone for nonemergency AEs or other questions, because these communications will become part of their medical record. Follow-up telephone calls by nursing staff also help monitor patients after therapy (Myers & Chitwood, 2020). Knowing that a qualified professional is available to answer questions and address issues and symptoms when other members of the IPT are out of immediate contact gives the patient peace of mind and improves their overall PRRT experience.

    Implications for Nursing

    Nurses can serve as navigators in the coordination of care for patients with GEP-NETs undergoing PRRT. Although institutional practices may vary, oncology nurses can be involved in scheduling treatment and imaging, following up with patients, educating and advising about radiation safety and risk, and directly monitoring and managing patients, and they can be a consistent point of contact for patients, caregivers, and IPT physicians. Overall, nurses may facilitate the coordination and organization of all aspects of the PRRT process. The roles and responsibilities of nurses will evolve in tandem with developments in the PRRT treatment landscape, including PRRT-based combination therapy and PRRT retreatment (Yordanova & Ahmadzadehfar, 2021). Combination strategies will require coordination of PRRT cycles with those of other therapies, and nurses will be an asset in that process. For example, nurses can also closely monitor patients for AEs that may be more common with combination therapy compared to monotherapy. Should PRRT retreatment become a standard of care, the roles of the nurse summarized in this review will need to continue for additional cycles of PRRT. Finally, patients may want to consider enrolling in PRRT clinical trials, and nurses can provide information on such trials being conducted.

    “IMPLICATIONS”

    Conclusion

    The 177Lu-DOTATATE PRRT patient journey necessitates collaboration and communication among IPT members, patients, and caregivers; extensive patient monitoring before, during, and after therapy; and adequate patient education. Oncology nurses who care for patients undergoing PRRT are encouraged to lead coordination efforts within the IPT to proactively navigate these intricacies while addressing the needs of the patient. Maintaining medication lists and health histories, facilitating communication and education, and critically assessing the onset of AEs at any time during and following PRRT treatment are just a few key ways that nurses can support patients, families, and care teams throughout their PRRT journey.

    About the Authors

    Bonita Bennett, BSN, RN, is a nurse coordinator in the neuroendocrine tumor program in the Department of Medicine at the University of Pennsylvania in Philadelphia; Linda Gardner, MSN, RN, VA-BC, is the nuclear medicine theranostics nurse manager in the Department of Nuclear Medicine at University of California, Los Angeles, Health; and Pamela Ryan, BSN, RN, ONN-CG, was, at the time of writing, a nurse navigator in the neuroendocrine tumor center at Ochsner Medical Center—Kenner in Louisiana. The authors take full responsibility for this content. Writing and editorial support was provided by Jennifer Olson, PhD, at Ashfield MedComms, an Inizio company, through support from Novartis. The article has been reviewed by independent peer reviewers to ensure that it is objective and free from bias. Gardner can be reached at lgardner@mednet.ucla.edu, with copy to CJONEditor@ons.org. (Submitted February 2023. Accepted September 21, 2023.)

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