Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma

Abstract

Background & Aims: Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinomas (PDACs) are detected could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC. Methods: We collected data from 219 patients with a diagnosis of PDAC (patients) and 657 healthy individuals (controls) from the Rochester Epidemiology Project, from 2000 through 2015.

Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

“…Pancreatic-protocol CT can accurately detect early-stage pancreatic cancers and performs similarly to MRI in detecting evidence of cancer/high-grade dysplasia associated with intraductal papillary mucinous neoplasms (IPMN) 61. In addition, CT can, in principle, also be used to quantify changes in abdominal fat and lumbar muscle mass with the emergence of pancreatic cancer 62 63. Observation of this early wasting could help to detect early pancreatic cancers, although this approach has not been tested in prospective studies.…”

“…Population guidelines recommend fasting glucose or HbA1c testing for individuals with risk factors for diabetes such as overweight or obesity,72 although there are concerns about the potential to overtreat individuals with pre-diabetes. Epidemiological studies show that 0.4% to 0.8% of patients with new-onset diabetes aged ≥50 will be diagnosed with pancreatic cancer within 3 years 62 73–75. A model incorporating weight loss, age and trend in glucose level can help to identify patients with new-onset diabetes more likely to have pancreatic cancer76; other models incorporating additional parameters are being evaluated 77.…”

Metabolic Alterations as a Signpost to Early Pancreatic Cancer

“…10 As this cross-talk is occurring within the tumor mass, further interactions occur between the growing tumor and the larger system of which it is a part; namely, the host organism. It is this organismal interaction that Sah et al 5 have interrogated in their current manuscript. Evaluating pancreatic cancer patients and age-and sex-matched noncancer controls from the Rochester Epidemiology Project, they investigated metabolic changes in the 5 years preceding a pancreatic cancer diagnosis.…”

“…In contrast, patients who present with earlier stage disease can be treated aggressively with multimodality therapy and achieve long-term survival. 3,4 In this issue of Gastroenterology, Sah et al 5 characterize the metabolic alterations that occur before a diagnosis of pancreatic cancer, with important implications for earlier cancer detection.…”

“…3 Second-line treatment options have emerged over the past few years. These include antiangiogenic TKIs such as regorafenib 4 and cabozantinib, 5 the anti-VEGFR2-blocking antibody ramucirumab for patients with elevated alpha-fetoprotein, 6 and the anti-PD1 immune checkpoint inhibitors nivolumab 7 and pembrolizumab. 8 In addition to inhibiting VEGFR1-3, cabozantinib is an inhibitor of MET, a target that is up-regulated in preclinical models after treatment with sorafenib.…”