A Clinical Guide to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients

Becx, Morticia N.; Minczeles, Noémie S; Brabander, Tessa; Herder, Wouter W. de; Nonnekens, Julie; Hofland, Johannes

doi:10.3390/cancers14235792

Cited by 24 publications

(14 citation statements)

References 121 publications

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“…It remains unclear if, and how long SSA should be continued after PRRT as a maintenance therapy. Opinions favoring the early consideration of PRRT are accumulating (31,32).…”

Section: Discussionmentioning

confidence: 99%

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies

Sira

Zsíros²,

Bidiga³

et al. 2023

Front. Endocrinol.

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BackgroundSplanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition.Case reportHere we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.

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“…It remains unclear if, and how long SSA should be continued after PRRT as a maintenance therapy. Opinions favoring the early consideration of PRRT are accumulating (31,32).…”

Section: Discussionmentioning

confidence: 99%

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies

Sira

Zsíros²,

Bidiga³

et al. 2023

Front. Endocrinol.

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“…40 Patients who are at risk for severe hematological toxicity include those with "decreased renal function, pre-existent cytopenias, extensive tumor mass, age over 70, extensive bone metastases (due to the risk of persistent cytopenia), and pre-treatment with myelotoxic chemotherapy." 41 Treatment with PRRT should not necessarily be withheld for patients with these characteristics, but they are factors to be considered as part of the MDT discussion. Everolimus is recommended as a second- or later-line option for patients who are SSTR-negative or may not be candidates for PRRT.…”

Section: Recommendationsmentioning

confidence: 99%

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline

Del Rivero,

Perez,

Kennedy

et al. 2023

JCO

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PURPOSE To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)–positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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“…F or more than 2 decades, radiolabeled somatostatin receptor treatment (peptide receptor radionuclide therapy [PRRT]) has been used as a well-established treatment option for patients with low-grade neuroendocrine tumors (NETs). 1 Over time, the radionuclide was changed iteratively, with 177 Lu currently being the preferential radionuclide for PRRT in patients with NET. [1][2][3][4][5][6] The prospective phase 3 NETTER1 trial had crucial impact on the therapy stratification for patients with metastasized G1 (Ki67 <3%) and G2 (Ki67 3% to 20%) midgut NETs.…”

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confidence: 99%

“…1 Over time, the radionuclide was changed iteratively, with 177 Lu currently being the preferential radionuclide for PRRT in patients with NET. [1][2][3][4][5][6] The prospective phase 3 NETTER1 trial had crucial impact on the therapy stratification for patients with metastasized G1 (Ki67 <3%) and G2 (Ki67 3% to 20%) midgut NETs. In this study, patients receiving 177 Lu-DOTATATE showed significantly better progression-free survival (PFS) and overall survival (OS) rates compared with patients in the octreotide-treated control group.…”

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confidence: 99%

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confidence: 99%

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Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies

Trautwein,

Hinterleitner,

Kiefer

et al. 2024

Clin Nucl Med

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Aim/Introduction Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor–positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET–based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor–positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.

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A Clinical Guide to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients

Cited by 24 publications

References 121 publications

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline

Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies

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