The State of Peptide Receptor Radionuclide Therapy and Its Sequencing among Current Therapeutic Options for Gastroenteropancreatic Neuroendocrine Tumors

Raymond, Lauren M.; Korzun, Tetiana; Kardosh, Adel; Kolbeck, Kenneth J.; Pommier, Rodney F.; Mittra, Erik

doi:10.1159/000516015

Cited by 7 publications

(5 citation statements)

References 68 publications

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“…Therefore, the pooled data from our systematic review show that tumor debulking plays a key role in controlling paraneoplastic hypercalcemia in patients with well-differentiated NEN, so surgical treatment should be indicated whenever feasible. PRRT was administered in a limited number of cases; however, given its capability to control functioning tumors [ 105 ] and its potential role as a neoadjuvant therapy [ 106 , 107 , 108 ], PRRT could be prescribed either before surgery or in patients with progressive metastatic inoperable disease to reduce tumor secretion and tumor burden.…”

Section: Discussionmentioning

confidence: 99%

What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature

Giannetta

Sesti

Modica

et al. 2022

JPM

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Background: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature. Methods: We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN. Results: The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome. Discussion: The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth.

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Section: Discussionmentioning

confidence: 99%

What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature

Giannetta

Sesti

Modica

et al. 2022

JPM

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“…There is no current consensus on the sequencing of approved therapies, particularly with respect to PRRT. Available evidence is mostly derived from retrospective and, therefore, potentially biased series [ 8 , 74 , 185 ]. A recent retrospective multicenter Italian study showed that [ 177 Lu]Lu-DOTA-TATE, as well as non-conventional-dose somatostatin analogues [ 186 ], are better tolerated than chemotherapy or everolimus, with no significant difference in PFS [ 187 ].…”

Section: Somatostatin Analogues For Targeted Therapymentioning

confidence: 99%

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Ambrosini

Zanoni

Filice

et al. 2022

Cancers

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Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with [68Ga] for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.

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“…There are no robust categorized levels of evidence on optimal treatment strategies (i.e., order of administration, number of cycles, efficacy of combinations, and switching criteria) for scenarios often encountered in clinical practice. Currently available clinical data on treatment sequencing are restricted to a small number of retrospective studies [ 45 ].…”

Section: Translating Clinical Research Into Therapeutic Strategymentioning

confidence: 99%

Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review

Chauhan

Rivero

Ramirez

et al. 2022

Cancers

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Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.

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The State of Peptide Receptor Radionuclide Therapy and Its Sequencing among Current Therapeutic Options for Gastroenteropancreatic Neuroendocrine Tumors

Cited by 7 publications

References 68 publications

What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature

What Lies behind Paraneoplastic Hypercalcemia Secondary to Well-Differentiated Neuroendocrine Neoplasms? A Systematic Review of the Literature

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Treatment Sequencing Strategies in Advanced Neuroendocrine Tumors: A Review

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