Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors

Morgan, Rosemary E.; Pommier, Su Ellen J.; Pommier, Rodney F.

doi:10.1016/j.surg.2017.05.030

Cited by 105 publications

(91 citation statements)

References 22 publications

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“…For patients with pancreatic NETs (e.g., gastrinomas, VIPomas, somatostatinomas, and insulinomas), intraoperative tumor localization with Ga-MMC(IR800)-TOC could provide better specificity and stronger NIRF signal than currently used methylene-blue imaging (42,43). Ga-MMC(IR800)-TOC may also enhance the ability of the surgeon to achieve greater debulking of metastatic burden, which can be beneficial both from a symptom management and overall survival standpoint (44). Thus, delineating the tumor with fluorescence might permit more complete cytoreduction and improve outcomes for patients with metastatic NETs.…”

Section: Discussionmentioning

confidence: 99%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS). Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluorescently labeled somatostatin analog, 67/68 Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso-and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs. Results: Direct labeling with 67 Ga/ 68 Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings. Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.

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Section: Discussionmentioning

confidence: 99%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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“…Cytoreductive resection has a purely palliative intent and can be considered in patients with G1/G2 liver metastases too extensive for curative resection, and/or causing excessive hormone-related symptoms. The classically promulgated target of 90% extirpation may not be necessary, with a 70% target possibly beneficial without significant detriment to outcomes [192,197]. Regardless of the resection margin attained, NELM almost invariably recur -median 5-and 10-year disease-free survival after surgery with curative intent is only 29 and 1%, respectively [194].…”

Section: Surgical Management Of Nelmsmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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“…The possible survival benefit of cytoreductive debulking surgery of unresectable NELM (5-year overall survival of 46-81% [17][18][19][20][21] ) would prompt consideration of the place of palliative LT. Here again there are few data on the outcome of palliative LT for NET liver metastases.…”

Section: Outcome Of Palliative Lt For Net Liver Metastasesmentioning

confidence: 99%

Liver Transplantation for Neuroendocrine Tumors: What Have We Learned?

et al. 2018

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Neuroendocrine tumors are slow-growing tumors and associated with prolonged overall survival even in the presence of untreated liver metastases. The presence of liver metastases may be responsible for severe symptoms with impairment of quality of life. Liver resection has been proposed to achieve better symptom control and/or improve overall survival, but this concerns less than 20% of patients with liver metastases. In addition, the chance to be really cured after liver resection is around 40%, which prompts consideration of liver transplantation as the only potential curative treatment. Time has come to move beyond the traditional debate around the best candidates and prognostic factors for liver transplantation. This review gives the opportunity to discuss new insights: (1) outcome of liver transplantation for neuroendocrine liver metastases as compared with hepatocellular carcinoma, (2) outcome of salvage liver transplantation as a secondary procedure after surgical resection of neuroendocrine liver metastases, (3) outcome of palliative liver transplantation for neuroendocrine liver metastases, and (4) the chance to be cured after liver transplantation for neuroendocrine liver metastases.

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Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors

Cited by 105 publications

References 22 publications

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Liver Transplantation for Neuroendocrine Tumors: What Have We Learned?

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