Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors

Titan, Ashley L.; Norton, Jeffrey A.; Fisher, Andrea T.; Foster, Deshka S.; Harris, E. John; Worhunsky, David J.; Worth, Patrick J.; Dua, Monica M.; Visser, Brendan C.; Poultsides, George A.; Longaker, Michael T.; Jensen, Robert T.

doi:10.1001/jamanetworkopen.2020.24318

Cited by 23 publications

(19 citation statements)

References 41 publications

(85 reference statements)

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“…Despite its associated risk of morbidity and mortality [4,[29][30][31][32], pancreatic surgery with curative intent has a favourable effect on survival in panNEN patients [2,3,33,34] and is therefore recommended in the guidelines [6,7,35]. Unfortunately, recurrence rates after surgery reach up to 69%, depending on the tumour grade, stage, size, and the duration of the studies' follow-up [9,12,21,30,[36][37][38][39][40], limiting the prognosis of these patients. In contrary to locally advanced pancreatic adenocarcinoma [41], no systemic induction treatment strategy is advocated by the guidelines for locally advanced or oligometastatic panNENs before surgery since the high-quality evidence supporting induction or neo-adjuvant treatment with PRRT or other agents is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Surgery is the first treatment option for panNENs larger than 2 cm as this is the only curative treatment option [6,7]. Local vascular involvement, adjacent organ invasion, and presence of liver metastases can prevent a curative resection due to the complexity or impossibility of a surgical resection [8,9] and the increased recurrence risk [10][11][12][13][14]. Given the high percentage of patients presenting with advanced disease stages, there is an unmet need for therapeutic induction and neo-adjuvant strategies that can effectively downstage the disease to allow for less extensive curative surgical intervention and improve the long-term outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

Minczeles

Eijck

Gils

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE induces objective response in up to 57% of pancreatic neuroendocrine neoplasms (panNENs). Therefore, PRRT may comprise a downstaging option for panNEN patients who are not eligible for upfront curative surgery or are at high risk for recurrence. The aim of this study was to assess the potency of induction PRRT for locally advanced panNENs and to evaluate the effect of surgery after PRRT on overall survival (OS). Methods Retrospective cohort study of panNEN patients treated with induction 177Lu-DOTATATE. Results After PRRT, 26 out of 49 patients underwent pancreatic surgery with curative intent (PRRT + surgery). Partial objective response was obtained in 62% of the PRRT + surgery group versus 26% of the patients not undergoing panNEN surgery (PRRT-only group, p = 0.02). Downstaging in tumour-vessel interface was observed in 38% of all patients with at least one involved vessel. Median OS was 14.7 years (95% CI 5.9–23.6) for the PRRT + surgery group compared to 5.5 years (95% CI 4.5–6.5) for the PRRT-only group (p = 0.003). In the Cox proportional hazards analysis, surgery was not significantly associated with OS after propensity score adjustment with cumulative activity, performance status, tumour size after PRRT, and tumour grade. Median progression-free survival was 5.3 years (95% CI 2.4–8.1) for the PRRT + surgery group and 3.0 years (95% CI 1.6–4.4) for the PRRT-only group (p = 0.02). Conclusion Early administration of PRRT followed by surgery is associated with favourable long-term outcomes in patients with locally advanced or oligometastatic panNEN and can be considered for selected patients with vascular involvement and/or increased risk of recurrence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

Minczeles

Eijck

Gils

et al. 2022

Eur J Nucl Med Mol Imaging

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“…In the advanced pNEN group, the median survival time for 16 patients who underwent resections of adjacent organs was 90 mo, and the 5-year OS (84%) was not significantly different from that in the isolated pNEN group ( P = 0.175), which indicated that nonmetastatic locally advanced pNENs showed a favorable prognosis after surgery. A case series study reviewed 99 locally advanced pNEN patients who underwent surgical resection between 2003 and 2018, including 84 G1/G2, 1 G3, and 14 ‘tumor grade not available’ patients[ 31 ]. The 5-year disease-free survival (DFS) was 61%, and the 5-year OS was 91%.…”

Section: Surgery For Locally Advanced Gep-nenmentioning

confidence: 99%

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Que¹,

Zhang²,

Bao³

et al. 2022

WJGS

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Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.

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“…However, in accordance with the previous studies, the authors did not find any difference of overall 5 years survival after extended pancreatectomy. In a recent study including 99 patients with non-metastatic T3/T4 panNENs who underwent vascular and/or near organ resection, Titan et al reported a 91% five-year survival and a 35% recurrence rate, the latter being favorized by surrounding organ resection (excluding blood vessel) in multivariate analysis (HR 6.15 [95% CI, 1.61–23.55], p = 0.008) [ 143 ].…”

Section: Surgery For Locally Advanced Diseases (Stage Iii)mentioning

confidence: 99%

What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review

Frey

Mirallié

Bras

et al. 2021

Cancers

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Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a “wait and see” strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.

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Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors

Cited by 23 publications

References 41 publications

Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

Induction therapy with 177Lu-DOTATATE procures long-term survival in locally advanced or oligometastatic pancreatic neuroendocrine neoplasm patients

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review

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