Medical Policy: 02.04.52
Original Effective Date: July 2015
Reviewed: June 2021
Revised: June 2021
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This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Topographic genotyping is referred to as integrated molecular pathology, is a type of quantitative genetic mutational analysis. Interspace Diagnostics has created two topographic tests, PancraGEN and BarreGEN which combines genetic testing with pathology services, such as sample preparation, genetic testing and interpretation of the results by a pathologist. These tests are proposed as adjunctive tools when a definitive pathologic diagnosis or prognosis is inconclusive.
The PathFinderTG is a patented topographic genotyping test platform that combines anatomic pathology with quantitative genetic mutational analysis. Interpace Diagnostics acquired RedPath Integrated Pathology and has since cultivated and developed the PancraGEN and BarreGEN molecular pathology panels on the PathFinderTG platform.
PancraGEN is a proprietary integrated molecular pathology test that assesses the cumulative DNA mutations in key oncogenes and tumor suppressor genes associated with pancreatic cancer. PancraGEN can help assess risk of malignancy in patients with pancreatic cysts and enhance diagnostic tools such as EUS imaging, CEA, cytology and other risk factors by providing more information for use in management decisions for surveillance versus surgical intervention.
Specimen type utilized is aspirated pancreatic cyst fluid and PancraGEN identifies the following:
The PancraGEN molecular panel using PathFinderTG also provides risk stratification of patient’s pancreaticobiliary sample by integrating clinical features and the following test components:
The PacraGEN report categorizes patients into four group according to their risk (benign, statistically indolent, statistically higher- risk or aggressive) and provides either the probability of benign disease over 3 years or the probability of high-grade dysplasia/carcinoma.
BarreGEN (esophageal cancer risk classifier) is a molecular based assay that helps resolve the risk of progression of Barrett’s Esophagus (BE) to esophageal cancer.
Barrett’s esophagus (BE) is a precancerous condition typically caused by gastroesophageal reflux disease (GERD) and is a major risk for esophageal cancer. Other risks for Barrett’s esophagus (BE) include age, male sex, white race, obesity, tobacco use, and family history of GERD, BE or esophageal cancer. While individuals with BE are at higher risk of esophageal cancer, progression to cancer is uncommon. Roughly, only 0.5% people with BE develop cancer each year. While uncommon there is a potential for the progression of cellular changes that can lead to esophageal cancer. BarreGEN is utilized to help identify Barrett’s esophagus (BE) patients at higher risk of esophageal cancer.
Triaging patients according to their risk of future progression to esophageal cancer would help to limit unnecessary repeat endoscopies in patients with low risk and justify more aggressive management in patients with higher risk, perhaps even supporting early means of cancer prevention such as ablation. However, differentiating the presence and stage of dysplasia remains a challenge for pathologists, resulting in high inter-observer variability in diagnosing the level of dysplasia and the associated risk of esophageal cancer.
BarreGEN is a molecular based assay conducted using tissue biopsy sample that quantifies the mutational load (ML) in esophageal specimens obtained from patients with BE. ML provides a measure of cumulative genomic instability (DNA damage). In looking at key genomic loci 1p (CMM1, L-myc), 3p (VHL, HoGG1), 5q (MCC, APC), 9p (CDKN2A), 10q (PTEN, MXI1), 17p (TP53), 17q (RNF43, NME1), 18q (SMAD4, DCC), 21q (TFF1, PSEN2) and 22q (NF2) in patients with BE and assessing DNA damage in tumor suppressor genes associated with progression to HGD and esophageal cancer, the risk of more advanced disease can be determined. The use of BarreGEN purports this testing assists the physicians understanding if dysplasia is present or if there is a risk for developing dysplasia or cancer in the future, which assists in treatment management decisions for cancer preventative treatments such as ablation or provide justification for when such treatments may not be necessary.
Currently, there is insufficient evidence in the published, peer-reviewed, scientific literature to demonstrate that topographic genotyping using PancraGEN or BarreGEN is an effective method to aid in the diagnosis or management of individuals with pancreatic cysts or Barrett’s esophagus (BE) when other testing methods, such as endoscopic ultrasound and microscopic analysis and staining, fail or are inconclusive. There is a lack of peer-reviewed evidence demonstrating that the use of topographic genotyping in the diagnosis and management of individuals with pancreatic cysts or Barrett’s esophagus (BE) results in improved clinical outcomes. The evidence is insufficient to determine the effects of this technology on net health outcomes.
This current NCCN guideline does not include any information regarding the use of topographic genotyping (PancraGEN).
This current NCCN guideline does not include any information regarding the use of topographic genotyping (BarreGEN).
The American Gastroenterological Association guidelines have no recommendations for the use of topographic genotyping for evaluating pancreatic cysts.
The American Society of Gastrointestinal Endoscopy guideline (2016) states Molecular analysis (which requires only 200 mL of fluid) may be most useful in small cysts with nondiagnostic cytology, equivocal cyst fluid CEA results, or when insufficient fluid is present for CEA testing. However, additional research is needed to determine the precise role molecular analysis of cyst fluid will play in evaluating pancreatic cystic lesions.
The College (2018) published guidelines on the diagnosis and management of pancreatic cysts. The guidelines stated that the evidence for the use of molecular biomarkers for identifying high-grade dysplasia or pancreatic cancer is insufficient to recommend their routine use. However, molecular markers may help identify intraductal papillary mucinous neoplasms and mucinous cystic neoplasms in cases with an unclear diagnosis and if results are likely to change the management (conditional recommendation; very low quality evidence).
Topographic genotyping are laboratory-developed tests under the Clinical Laboratory Improvement Amendments (CLIA) and do not require approval by the U.S. Food and Drug Administration for clinical use.
See Related Medical Policy
02.01.23 Treatment of GERD and Barrett’s Esophagus
Topographic genotyping using the PathfinderTG system is considered investigational for all indications including, but not limited to the following, because the evidence is insufficient to determine the effects of this technology on net health outcomes:
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