Elevated Alkaline Phosphatase Prior to Transarterial Chemoembolization for Neuroendocrine Tumors Predicts Worse Outcomes

Onesti, Jill K.; Shirley, Lawrence A.; Saunders, Neil; Davidson, Gail W.; Dillhoff, Mary; Khabiri, Hooman; G, Guy; Dowell, Joshua D.; Schmidt, Carl; Shah, Manisha H.; Bloomston, Mark

doi:10.1007/s11605-015-2998-6

Cited by 12 publications

(17 citation statements)

References 24 publications

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“…As far as biological markers are concerned, CgA is known to be a surrogate marker of tumor burden (Baudin et al 1998) and was associated with a worse OS in univariate analysis, but which was not significant in multivariate analysis. We did not find an association between ALP and OS, as suggested in other studies (Hauck et al 2016, Onesti et al 2016. A solution may come from the inclusion of molecular prognostic factors (Cwikla et al 2015, Schmitt et al 2016, Viudez et al 2016) and/or the development of prognostic scores (Modlin et al 2010, Viudez et al 2016.…”

Section: :2supporting

confidence: 40%

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

Foulfoin¹,

Graillot²,

Adham³

et al. 2017

Endocrine-Related Cancer

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The choice of first-line treatment for metastatic pancreatic neuroendocrine tumors (mP-NET) is mainly based on prognostic factors. ENETS-2016 guidelines stratified treatment according to 3 groups: Group 1, patients in whom all lesions could be removed; Group 2, patients with Ki67 <10%, low tumor burden, no symptoms and stable disease, for whom a watch-and-wait strategy or somatostatin analogs are proposed; Group 3, symptomatic patients or with Ki67 >10% or significant tumor burden or progressive disease, for whom a systemic chemotherapy is proposed. This retrospective study aimed to determine patient distribution, characteristics and outcome among these 3 groups. Patients with mP-NET diagnosis from 2004 to 2016 were categorized into the three groups. Prognosis was calculated using the Kaplan-Meier method. All treatments were recorded, and consistency with ENETS guidelines was explored. 104 patients were analyzed: 64% synchronous mP-NET, 80% grade 2 tumors and median overall survival (OS) of 104 (95% CI: 65-143) months. There were 15 patients in ENETS Group 1, 16 in Group 2 and 73 in Group 3. Median OS was not reached in Groups 1 and 2 and was 64 months (35-93) in Group 3. High liver tumor volume, high-grade tumor and progressive disease were associated with worse OS in multivariate analysis. The first-line treatment was in accordance with guidelines in 82%. 77% percent of deceased patients received less than 4 lines of treatment. Most patients are in Group 3 and do not receive all available treatments. Thus, trials are warranted to improve first-line chemotherapy. Alternative treatments may be considered for less aggressive disease.

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Section: :2supporting

confidence: 40%

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

Foulfoin¹,

Graillot²,

Adham³

et al. 2017

Endocrine-Related Cancer

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“…In a series of 137 metastatic NETs[ 11 ], including 115 with liver metastases, the AP level was normal in 60% of the cases. In another series of patients planning to receive transarterial chemoembolization for metastatic NETs, only 22 of 109 (including 7 with bone metastases) had an elevated AP level[ 12 ]. These data are in accordance with our findings showing that 67% of patients with liver metastases had normal AP values.…”

Section: Discussionmentioning

confidence: 99%

“…Clancy et al[ 11 ] reported that the AP value was associated with OS. In a series of 109 patients, Onesti et al[ 12 ] performed univariate analysis of the prognostic factors for OS and found that the AP level, grade and tumor burden were associated with the prognosis. In multivariate analysis, only the AP level had prognostic value.…”

Section: Discussionmentioning

confidence: 99%

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

et al. 2017

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BackgroundIn our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET).Patients and methodsWe retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients.ResultsSerum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017).ConclusionsSerum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

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“…The clinical predictive factors for poor response with liver-directed therapy’s efficacy include higher age [ 347 , 348 ] and poorer performance status (≥1) [ 349 , 350 , 351 ]. In terms of biomarkers, elevated pre-treatment levels of serum CgA [ 347 ], pancreastatin [ 342 , 352 ], bilirubin [ 353 ], alkaline phosphatase [ 354 , 355 ], and Child-Pugh score [ 351 , 355 ] are associated with worse OS post liver-directed therapies ( Table 5 ). In another study, a worse PFS/OS was reported in patients with increased CgA levels after TACE [ 356 ].…”

Section: Predictive Factors For Response To Liver-directed Therapies ...mentioning

confidence: 99%

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

Lee

Ramos-Álvarez

Jensen

2022

Cancers

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Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.

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Elevated Alkaline Phosphatase Prior to Transarterial Chemoembolization for Neuroendocrine Tumors Predicts Worse Outcomes

Abstract: Elevated AP prior to TACE for metastatic NET portends a worse survival outcome, even more so than tumor grade or extent of hepatic disease.

Cited by 12 publications

References 24 publications

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

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