Body fat, metabolic changes before pancreatic cancer diagnosis may aid in early detection
Click Here to Manage Email Alerts
Key takeaways:
- In the last 6 months prior to PDAC diagnosis, visceral and subcutaneous adipose tissue decreased by 12.9% and 14.7%, respectively.
- LDL, total cholesterol and triglycerides also decreased before diagnosis.
In the 36 months prior to diagnosis of pancreatic ductal adenocarcinoma, researchers observed “predominant changes” in patients’ body composition and biochemical markers, which may serve as potential biomarkers for early cancer detection.
“Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is currently the third leading cause of cancer-related mortality in the United States,” Derk C.F. Klatte, MD, a research fellow in the department of gastroenterology and hepatology at the Mayo Clinic in Jacksonville, and colleagues wrote in Clinical Gastroenterology and Hepatology. “Early detection is critical for improving survival rates but is difficult because of the lack of specific symptoms in the early stages of the disease.”
They continued: “Various metabolic and body composition parameters have been described in patients before diagnosis of PDAC, some occurring several years before diagnosis, providing a promising avenue for identifying markers for early detection.”
In a retrospective cohort study, researchers used the Mayo Clinic’s cancer registry to identify 9,221 adult patients with a PDAC diagnosis (median age, 68 years; 54.6% men), of whom 21% (n = 1,990) had at least one abdominal CT scan within 36 months prior to diagnosis. Eighteen percent of patients (n = 1,690) were eligible for body composition biomarker analysis, of whom 30.5% had two or more pre-diagnostic CT scans, while 36% of patients (n = 3,306) were included in a blood-based biomarker analysis. Overall, 1,482 patients were included in both analyses.
According to researchers, the “most pronounced and sustained changes” were observed in visceral (–1.94 cm2/m2; 95% CI, –2.39 to –1.48) and subcutaneous (–2.59 cm2/m2; 95% CI, –3.17 to –2.02) adipose tissue area indices every 6 months closer to diagnosis. The most notable changes occurred in the last 6 months prior to diagnosis, during which visceral and subcutaneous adipose tissue decreased by 12.9% and 14.7%, respectively, and skeletal muscle area decreased by 6.3%.
In addition, researchers reported vertebral bone area decreased by 10.1% during this time, while vertebral bone density increased by 5.6%.
Over the 3-year study period, researchers observed a “sustained decreasing trend” in LDL (–2.83 mg/dL; 95% CI, –3.31 to –2.34), total cholesterol (–2.69 mg/dL; 95% CI, –3.18 to –2.2) and triglycerides (–1.86 mg/dL; 95% CI, –2.61 to –1.11), as well as an increase in fasting blood glucose before diagnosis. Other markers, including albumin, C-reactive protein, hemoglobin and white blood cells, showed “no distinct changes” prior to a PDAC diagnosis.
Further analysis showed an 8.2% reduction in LDL was observed up to 3 years before diagnosis, with “similar deviations” observed in total cholesterol and triglycerides, which decreased by 8.3% and 11.7%, respectively, in the last 6 months before diagnosis.
“Over a 36-month period, the earliest and most predominant changes were observed in adipose tissue and related serum lipid markers,” Klatte and colleagues wrote. “In addition, the onset of sarcopenia and osteopenia in the months before diagnosis highlights the broad systemic impact of PDAC on body composition. By unravelling the temporal sequence of these changes, we have taken a step toward identifying biomarkers that may aid in the detection of PDAC at its earliest stages.”
They continued: “Further research is warranted to validate and extend these findings to PDAC risk-prediction models, ultimately paving the way for improved risk assessment and selective screening of individuals at high risk for this devastating malignancy.”
Perspective
Back to Top
Syed A. Mohiuddin, MD
The overall 5-year survival rate from pancreatic cancer is dismal at 13%, largely because 85% of pancreatic cancer is diagnosed at an advanced stage or after invasion into nearby tissues or distant organs.
However, if detected early and localized to the pancreas, a surgical resection can lead to an improved 5-year survival rate — up to 44%. Late development of symptoms and lack of validated biomarkers or a cost-effective screening strategy have been the main obstacles to early detection. Currently, screening is aimed at individuals with genetically identified mutations or familial risk for pancreatic cancer.
Previous research has shown us that new-onset diabetes can serve as a potential clue to early diagnosis of pancreatic cancer.
In this current retrospective analysis of a large cancer registry, the researchers found substantial loss of visceral and adipose fat in the 6 months preceding pancreatic cancer diagnosis and highlight the onset of sarcopenia and osteopenia as markers of change in body composition months before cancer diagnosis. These results underscore the catabolic state, aggressive behavior and late diagnosis of pancreatic cancer.
Study findings have advanced our understanding of changes in metabolic and body composition preceding pancreatic cancer. Until the availability of a reliable, population-based, biomarker-guided screening strategy, further validation of study results will help define risk and development of models directed toward early detection.
Collapse
Click Here to Manage Email Alerts