Plasma Hemoglobin and Red Blood Cell Mass Levels as Dynamic Prognostic Markers for Progression and Survival in Pancreatic Neuroendocrine Tumors

Abstract

There are scarce data on readily available markers enabling immediate risk stratification and personalized management in patients with advanced pancreatic neuroendocrine tumors. This study explores the association of red blood cells-related parameters as prognostic markers in patients harboring pancreatic neuroendocrine tumors. Retrospective analysis of a tertiary medical center database, acquiring data of patients with pancreatic neuroendocrine tumors including demographics, tumor-related parameters and consecutive imaging results, vital status at last follow-up, and red blood cells parameters at baseline, last follow-up, and dynamics (last/baseline ratio). Univariate and multivariable analyses were performed. Sixty-seven patients were identified (mean age at diagnosis of 63±11 years, 56.7% males). Patients with disease progression had lower hemoglobin, red blood cells mass values and hematocrit at the last evaluation (p<0.001 for all comparisons), with red blood cells mass level<3.9 m/μl and a 6% and 9% relative reduction in hemoglobin and hematocrit levels, respectively, associated with an increased risk for disease progression. Similarly, patients deceased during the study period had lower hemoglobin, red blood cells mass values and hematocrit (p<0.03 for all) than those alive, at last follow-up. Eleven percent reduction in hemoglobin level was noted indicating a higher mortality risk (p=0.04). Negative hemoglobin and hematocrit dynamics were independently associated with increased risk for disease progression (p=0.03 and 0.049, respectively). In conclusion, decrease in red blood cells mass, hemoglobin and/or hematocrit levels are all associated with poor prognosis in patients with pancreatic neuroendocrine tumors. We suggest utilizing these parameters as complementary follow-up prognostic markers to radiologic imaging in this patients population.

Key words

prognosis - mortality - hematocrit - neuroendocrine tumor - pancreas - hemoglobin

Publication History

Received: 25 December 2020

Accepted after revision: 13 October 2021

Article published online:
10 December 2021

• References

• 1 Yao JC, Hassan M, Phan A. et al One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26: 3063-3072
• 2 Dasari A, Shen C, Halperin D. et al Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine umors in the United States. JAMA Oncol 2017; 3: 1335-1342
• 3 Darba J, Marsa A. Exploring the current status of neuroendocrine tumours: A populationbased analysis of epidemiology, management and use of resources. BMC Cancer 2019; 19: 1226
• 4 Bu J, Youn S, Kwon W. et al Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification. Ann Hepatobiliary Pancreatic Surg 2018; 22: 66-74
• 5 Gao Y, Gao H, Wang G. et al A meta-analysis of prognostic factor of pancreatic neuroendocrine neoplasms. Sci Rep 2018; 8: 7271
• 6 Lee L, Igarashi H, Fujimori N. et al Long-term outcomes and prognostic factors in 78 Japanese patients with advanced pancreatic neuroendocrine neoplasms: a single-center retrospective study. Jpn J Clin Oncol 2015; 45: 1131-1138
• 7 Benetatos N, Hodson J, Marudanayagam R. Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems. Hepatobiliary Pancreat Dis Int 2018; 17: 169-175
• 8 Gaitanidis A, Patel D, Nilubol N. et al A lymph node ratio-based staging model is superior to the current staging system for pancreatic neuroendocrine tumors. J Clin Endocrinol Metab 2018; 103: 187-195
• 9 Xu SS, Xu HX, Wang WQ. et al Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor. World J Gastroenterol 2019; 25: 6248-6257
• 10 Zhou B, Zhan C, Xiang J. et al Clinical significance of the preoperative main pancreatic duct dilation and neutrophil-to-lymphocyte ratio in pancreatic neuroendocrine tumors (PNETs) of the head after curative resection. BMC Endocr Disord 2019; 19: 123
• 11 Bocchini M, Nicolini F, Severi S. et al Biomarkers for pancreatic neuroendocrine neoplasms (PanNENs) management: An updated review. Front Oncol 2020; 10: 831
• 12 Marotta V, Chiara Zatelli M, Sciammarella C. et al Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame. Endocr Relat Cancer 2018; 25: R11-R29
• 13 Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18: 837-860
• 14 Tirosh A, Papadakis GZ, Millo C. et al Prognostic utility of total 68Ga-Dotatate-avid tumor volume in patients with neuroendocrine tumors. Gastroenterology 2018; 154: 998-1008
• 15 Huang Y, Wei S, Jiang N. et al The prognostic impact of decreased pretreatment haemoglobin level on the survival of patients with lung cancer: a systematic review and meta-analysis. BMC Cancer 2018; 18: 1235
• 16 Hamid UI, Al-Saudi R, Paul I. et al Role of preoperative blood markers as prognostic factors for lung cancer surgery. Asian Cardiovasc Thorac Ann 2019; 27: 288-293
• 17 Franco P, Montagnani F, Arcadipane F. et al The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer. Radiat Oncol 2018; 13: 83
• 18 Nieder C, Dalhaug A, Pawinski A. Contribution of serum biomarkers to prognostic assessment in patients with oligometastatic prostate cancer. In Vivo (Brooklyn) 2019; 33: 465-468
• 19 Chen R, Qiu M, Chen Y. Analysis of the clinicopathological features and prognostic factors of primary hepatic neuroendocrine tumors. Oncol Lett 2018; 15: 8604-8610
• 20 Wang Y, Hong J, Wang J. et al Clinicopathological characteristics and prognostic factors of patients with gastric cancer accompanying neuroendocrine differentiation (NEDGC). Cancer Manag Res 2020; 12: 4217-4225
• 21 Karaman K, Bostanci EB, Aksoy E. et al The predictive value of mean platelet volume in differential diagnosis of non-functional pancreatic neuroendocrine tumors from pancreatic adenocarcinomas. Eur J Intern Med 2011; 22: e95-e98
• 22 Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 2019; 10: 10-27