Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors.

Published on May 1, 2021in Oncologist5.55
· DOI :10.1002/ONCO.13686
Alex John Liu2
Estimated H-index: 2
(Mayo Clinic),
Benjamin Edward Ueberroth1
Estimated H-index: 1
(Mayo Clinic)
+ 6 AuthorsMohamad Bassam Sonbol17
Estimated H-index: 17
(Mayo Clinic)
INTRODUCTION Recent classification of neuroendocrine neoplasms has defined well-differentiated high-grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma (NEC). The optimal treatment for NET G3 has not been well-described. This study aims to evaluate metastatic NET G3 response to different treatment regimens. MATERIALS AND METHODS This is a retrospective study of NET G3 patients within the Mayo Clinic database. Patients' demographics along with treatment characteristics, responses, and survival were assessed. Primary end points were progression-free survival (PFS) and overall survival (OS). Secondary end points were objective response rate (ORR) and disease control rate (DCR). RESULTS Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki-67 index was ≥55% in 26.7% of cases. Treatments included: capecitabine + temozolomide (CAPTEM) (n=20), lutetium 177 DOTATATE (PRRT) (n=10), carboplatin/cisplatin + etoposide (EP) (n=8), FOLFOX (n=7), and everolimus (n=2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% CI 2.96-16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however median PFS durations were quite distinct at 2.94 and 13.04 months respectively. PRRT had ORR 20%, DCR 70%, and median PFS 9.13 months. CONCLUSIONS Among NET G3 patients, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3 but responses appear to be short-lived. Prospective studies evaluating different treatments effects in NET G3 patients are needed to determine an optimal treatment strategy. IMPLICATIONS FOR PRACTICE High-grade well differentiated neuroendocrine tumors (NET G3) are considered different entity from low-grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide (CAPTEM) is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well-differentiated NET, PRRT seems to have some efficacy in these tumors.
#1Leonidas Apostolidis (University Hospital Heidelberg)H-Index: 7
#2Arianna Dal Buono (Charité)H-Index: 2
Last. Marianne Pavel (FAU: University of Erlangen-Nuremberg)H-Index: 54
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4607Background: Well differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications...
4614Background: The capecitabine/temozolomide regimen has significant activity in advanced NETs. Concerns exist regarding risk of opportunistic infections and long-term myelotoxicity. Analysis of l...
#4Francis J. Giles (NU: Northwestern University)H-Index: 34
Purpose: Immune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (non-pancreatic) neuroendocrine neoplasm cohort of SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART). Experimental Design: We performed a prospective, open-label, multicenter phase 2 clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (non-pancreatic) neuroendocrine c...
#1Halfdan Sorbye (University of Bergen)H-Index: 42
#2Grace Kong (University of Melbourne)H-Index: 20
Last. Simona Grozinsky-Glasberg (HUJI: Hebrew University of Jerusalem)H-Index: 31
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Peptide receptor radionuclide therapy (PRRT) is an established treatment for grade 1 and 2 gastroenteropancreatic neuroendocrine tumors with an increased uptake on somatostatin receptor imaging (SRI). Patients with metastatic high-grade (WHO G3) gastroenteropancreatic neuroendocrine neoplasms (NET G3 and NEC) represent a heterogeneous subgroup with poor prognosis and standard platinum-etoposide chemotherapy have limited therapeutic benefit. However, there is promising emerging evidence supportin...
#1Patrick Walsh McGarrah (Mayo Clinic)H-Index: 5
#2Timothy J. Hobday (Mayo Clinic)H-Index: 33
Last. Thorvardur R. Halfdanarson (Mayo Clinic)H-Index: 28
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617Background: Currently, there is no published data on the efficacy of SSAs for well-differentiated G3 NETs. Randomized trials have demonstrated a progression-free survival (PFS) benefit and limit...
#1Iris D. Nagtegaal (IARC: International Agency for Research on Cancer)H-Index: 85
#2Robert D Odze (IARC: International Agency for Research on Cancer)H-Index: 1
Last. Ian A. Cree (IARC: International Agency for Research on Cancer)H-Index: 60
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The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table ​(Table1).1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification...
In 2017, the World Health Organization (WHO) classification for pancreatic NET was updated to include a new category of well-differentiated high-grade (Ki 67 > 20%) pancreatic tumors (NET G3), distinct from high-grade poorly differentiated neuroendocrine carcinoma (NEC). NET G3 are considered a molecularly, radiologically, and prognostically distinct entity compared to NEC and NET G1/G2. The optimal first-line management in NET G3 and sequencing therapies remains a challenge awaiting future tria...
#1Arvind Sahu (University of Melbourne)H-Index: 9
#2Michael Jefford (Peter MacCallum Cancer Centre)H-Index: 41
Last. Michael Michael (Peter MacCallum Cancer Centre)H-Index: 57
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Introduction. Capecitabine-temozolomide (CAPTEM) has significant activity in patients (pts) with metastatic low grade pancreatic neuroendocrine tumors (NETs). However, there is limited data regarding its activity in pts with metastatic well-differentiated intermediate and high grade pancreatic and nonpancreatic NETs. The objective of this study was to assess the functional imaging response, survival, and tolerability of CAPTEM in this population. Methods. A retrospective audit of pts with metast...
#2Nicola Fazio (IEO: European Institute of Oncology)H-Index: 45
Last. Halfdan SorbyeH-Index: 42
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Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were respon...
#1David ChanH-Index: 14
#2Emily K. Bergsland (UCSF: University of California, San Francisco)H-Index: 47
Last. Linda Wu (Cornell University)H-Index: 1
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321Background: G3 NENs are aggressive, and optimal systemic treatment is unclear. Temozolomide (TEM)-based regimens have been used to treat grade 1-2 NETs, but their efficacy in G3 NENs (Ki-67 > 20%) remains undetermined. Aims: To assess the clinical efficacy of TEM-containing regimens in advanced grade III gastroenteropancreatic NENs (GEPNENs). Methods: A multicentre retrospective review (2008-2017) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen. The p...
Cited By5
#1Jin Cheon KimH-Index: 52
#2Jihun Kim (UOU: University of Ulsan)H-Index: 28
Last. In Ja Park (UOU: University of Ulsan)H-Index: 25
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Purpose null To evaluate the validity of robot-assisted curative operation for rare anorectal tumors, characterized by biological heterogeneity and anatomical complexity. null Methods null The present study evaluated 16 consecutive patients including three with anorectal squamous cell carcinoma (ARSCC), four with anorectal mucosal melanoma (ARMM), seven with anorectal neuroendocrine tumor (ARNET), and two with other types of anorectal tumors. null Results null Of the three patients with ARSCC af...
#1He-Li GaoH-Index: 4
#2Jia DongH-Index: 1
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Abstract null null Objective null The role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic Pancreatic Neuroendocrine Tumors (PanNET) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced G1/G2 PanNET. null null null Methods null In total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib ...
Background null Grade 3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs) are often aggressive, and the optimal treatment is unclear for this subgroup of neuroendocrine neoplasms (NENs). Temozolomide (TEM)-based regimens have been increasingly used to treat grade 1-2 NENs, but their efficacy in G3 NENs remains undetermined. We aimed to assess the clinical efficacy of TEM-containing regimens in advanced grade 3 GEPNENs. null Materials and methods null A multicenter retrospective review...
#1Melissa Frizziero (University of Manchester)
#2Alice DurandH-Index: 2
Last. Sara CingarliniH-Index: 24
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Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (...
#3Jorge Hernando (Hebron University)H-Index: 5
#7Annemiek M. E. Walenkamp (UG: University of Groningen)H-Index: 32
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There is no standardized treatment for grade 3 neuroendocrine tumors (G3 NETs). We aimed to describe the treatments received in patients with advanced G3 NETs and compare their efficacy. Patients with advanced digestive G3 NETs treated between 2010 and 2018 in seven expert centers were retrospectively studied. Pathological samples were centrally reviewed, and radiological data were locally reviewed. We analyzed RECIST-defined objective response (OR), tumor growth rate (TGR) and progression-free ...
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