Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Apostolidis, Leonidas; Buono, Arianna Dal; Merola, Elettra; Jann, Henning; Jäger, Dirk; Wiedenmann, Bertram; Winkler, Eva C.; Pavel, Marianne

doi:10.3390/cancers13081936

Cited by 27 publications

(36 citation statements)

References 33 publications

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“…However, current international guidelines provide different indications; the ENETS guidelines state that PRRT may be considered for G3 NETs (although further data are needed) and even NECs with SSTR-expressing disease [ 8 ], while the NANET guidelines emphasize the limited data on PRRT in these subgroups [ 142 ]. It is also worth mentioning that current evidence suggests that PRRT may potentially be a superior first-line therapeutic option for G3 NET patients with Ki-67 ≤ 55%, as compared to platinum-based chemotherapy (providing high SSTR expression with no discordant FDG-avid lesions) [ 144 ].…”

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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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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“…SAEs were rare, with a low discontinuation rate. Regarding the use of temozolomide-based therapy for NENs G3, data from the literature describes CAPTEM as the most commonly used treatment for NETs G3, with a DCR of 65% (35% objective response) and a median PFS of 9.4-12 mo[ 135 ]. Instead, the few data available regarding the use of this temozolomide-based regimen in GEP-NECs report poorer disease control in this subset of patients compared to all NETs (HR: 2.70)[ 136 ], with a median PFS of 1.8 mo and a median OS of 7.8 mo observed in unresectable extra-pulmonary NECs after platinum-based chemotherapy failure[ 137 ].…”

Section: Advanced or Metastatic Diseasementioning

confidence: 99%

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Merola¹,

Michielan²,

Rozzanigo³

et al. 2022

WJGS

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Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

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“…NET des Gastrointestinaltrakts sindim Gegensatz zu pNETwenig chemosensitiv und die klassische Chemotherapie ist in der Therapie von NET des Intestinaltrakts nicht etabliert [3-5, 11, 12]. Als individualisierte Therapieansätze könnennach Ausschöpfung der etablierten leitliniengerechten Therapieoptionenjedoch auch Capecitabin-basierte Therapieprotokolle bei NET des Dünndarms [11,36] oder Oxaliplatin-basierte Chemotherapie mit FOLFOX bei höherproliferativen NET des Dünndarms [3,11,37,38] jeweils erwogen werden.…”

Section: Chemotherapie Bei Netunclassified

“…Bei Kontraindikation gegenüber Cisplatin sollte eine Therapie mit Carboplatin/Etoposid erfolgen [3-5, 11, 12]. Die Prognose von NEC im Stadium IV ist ungünstig [53][54][55]. Unter der palliativen Chemotherapie mit Platin/ Etoposid zeigte das NORDIC Study Register eine ORR von 44 % bei hochproliferativen NEC mit Ki-67 > 55 % versus eine geringere ORR von 25 % bei geringer proliferativen NEC Ki-67 < 55 % und NET G3.…”

Section: Systemtherapie Von Neuroendokrinen Karzinomen (Nec) Des Gep-systemsunclassified

“…Das mediane PFS lag in allen Subgruppen bei 5 Monaten, das mediane Gesamtüberleben (OS) lag bei den NEC bei 11 Monaten und bei den NET G3 bei 33 Monaten [53,54]. Bei NEN mit Ki-67 < 55 %/vornehmlich NET G3 führen Capecitabin/Temozolomid oder FOLFOX zu höheren ORR im Vergleich zu Platin/Etoposid [55][56][57]. NET G3 sollen deshalb mit Chemotherapieprotokollen in Analogie zu NET G2 behandelt werden [3-5, 11, 12].…”

Section: Systemtherapie Von Neuroendokrinen Karzinomen (Nec) Des Gep-systemsunclassified

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Medikamentöse Systemtherapie bei Neuroendokrinen Neoplasien des GastroEnteropankreatischen Systems

Auernhammer

Bock

Westphalen

et al. 2021

Der Nuklearmediziner

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ZusammenfassungNeuroendokrine Neoplasien (NEN) des GastroEnteroPankreatischens Systems (GEP-Systems) im inoperablen fortgeschrittenen Stadium erfordern eine differenzierte Systemtherapie abhängig von Klassifikation und Grading, Primärtumorlokalisation, Somatostatinrezeptorexpression, Tumordynamik, Tumorlast und Funktionalität. Somatostatinanaloga, Peptid Rezeptor Radionuklid Therapie (PRRT), Streptozotocin- oder Temozolomid-basierte Chemotherapieprotokolle und molekular zielgerichtete Therapien mit Everolimus oder Sunitinib sind jeweils etablierte Therapieoptionen bei verschiedenen neuroendokrinen Tumoren (NET). Neue vielversprechende Therapieansätze sind Multityrosinkinaseinhibitoren (TKIs) wie Surufatinib, Cabozantinib, Lenvatinib oder Pazopanib. Cisplatin/Etoposid ist die Standard 1st-line Chemotherapie bei neuroendokrinen Karzinomen (NEC). Bisher zeigten die meisten klinischen Studien zur Immuntherapie bei NET G1/G2 enttäuschende Studienergebnisse, aber die mögliche Effektivität der kombinierten Checkpoint-Inhibition sollte bei höherproliferativen NEN G3 weiter untersucht werden. Molekularpathologie mit Next Generation Sequencing (NGS) und personalisierte Therapie spielen auch bei den NEN eine zunehmende Rolle.

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Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Cited by 27 publications

References 33 publications

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Medikamentöse Systemtherapie bei Neuroendokrinen Neoplasien des GastroEnteropankreatischen Systems

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