Peptide receptor radionuclide therapy for patients with advanced pancreatic neuroendocrine tumors

Ramage, John; Naraev, Boris G.; Halfdanarson, Thorvardur R.

doi:10.1053/j.seminoncol.2018.08.004

Cited by 59 publications

(60 citation statements)

References 68 publications

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“…Peptide receptor radiotherapy (PRRT) targets the SSR using an SSA attached to a radioactive isotope such as Lu 177 or Y 90 and is effective in those tumours overexpressing the SSR on radionuclide imaging. The NETTER-1 study (Strosberg et al 2017) demonstrated the efficacy of Lu-177dotatate in midgut NETs and results of this and other retrospective studies in PanNETs (Ramage et al 2018) have led to its FDA approval in advanced GEP-NETs. However, to date, it has not been possible to drug all of the pathways identified as PanNET drivers.…”

Section: Clinical Implications Molecular Targeted Therapiesmentioning

confidence: 86%

The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours

Pipinikas

Berner

Sposito

et al. 2019

Endocrine-Related Cancer

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Neuroendocrine neoplasms (NENs) are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1–3% of all neoplasms developing in the pancreas. Despite having a low background mutation rate, driver mutations in MEN1, DAXX/ATRX and mTOR pathway genes (PTEN, TSC1/2) are implicated in disease development and progression. Their increased incidence coupled with advances in sequencing technologies has reignited the interest in PanNEN research and has accelerated the acquisition of molecular data. Studies utilising such technological advances have further enriched our knowledge of PanNENs’ biology through novel findings, including higher-than-expected presence of germline mutations in 17% of sporadic tumours of no familial background, identification of novel mutational signatures and complex chromosomal rearrangements and a dysregulated epigenetic machinery. Integrated genomic studies have progressed the field by identifying the synergistic action between different molecular mechanisms, while holding the promise for deciphering disease heterogeneity. Although our understanding is far from being complete, these novel findings have provided the optimism of shaping the future of PanNEN research, ultimately leading to an era of precision medicine for NETs. Here, we recapitulate the existing knowledge on pancreatic neuroendocrine tumours (PanNETs) and discuss how recent, novel findings have furthered our understanding of these complex tumours.

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Section: Clinical Implications Molecular Targeted Therapiesmentioning

confidence: 86%

The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours

Pipinikas

Berner

Sposito

et al. 2019

Endocrine-Related Cancer

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“…G3 welldifferentiated tumors have a similar SSTR expression to that of G1 and G2 pNETs tumors. There are only two studies which included all grades of NENs with analyses by grade; and three studies limited to patients with G3 GEP NEN (19). The median PFS and OS with 177Lu-DOTATATE PRRT for patients with G3 NEN were between 7-14 and 23-31 months, respectively (20).…”

Section: Discussionmentioning

confidence: 99%

Large Cell Metastatic Pancreatic Neuroendocrine Carcinoma Treated with Somatostatin Analogues - Case Report and Literature Review

et al. 2019

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We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

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“…3 5 Furthermore, many other radiation free therapies for pancreatic NEN are available and have been approved. 5 That being said, pancreatic NEN have shown significantly higher response rates to PRRT when compared with other NEN. 6 Some metastatic or inoperable pancreatic NEN patients are still alive more than 12 years after the beginning of PRRT.…”

Section: Descriptionmentioning

confidence: 99%

“…1 2 4 PRRT has become a new and useful option in the management of many NEN. [1][2][3][4][5][6][7][8][9] Namely, outcome superiority over placebo or SSAs for midgut NEN has been established with high level evidence. Such is not the case, however, for pancreatic NEN, hindering its incorporation into international guidelines.…”

Section: Descriptionmentioning

confidence: 99%