CinCSeq and Histiotrak: Advancing Cancer Care
A growing number of pediatric hematology/oncology specialists rely on the Molecular and Genomic Pathology Services (MGPS) Laboratory at Cincinnati Children’s to help them diagnose, treat and monitor patients with cancer and cancer-like conditions.
Below, Somak Roy, MD, and Jennifer Picarsic, MD, discuss CinCSeq, a new comprehensive next-generation sequencing (NGS) cancer panel for histiocytic and pediatric neoplasms, and Histiotrak, a liquid biopsy molecular test to monitor treatment response in patients with Langerhans cell histiocytosis (LCH).
Dr. Roy, who is the director of Molecular Pathology at Cincinnati Children’s and an international leader in the field, developed the tests in collaboration with Picarsic.
What are the distinctive features of CinCSeq?
Dr. Roy: CinCSeq analyzes blood, tissue and bone marrow specimens with as little as 300 tumor cells to identify genetic drivers of cancer. The test covers 531 DNA and 184 RNA cancer-related genes and pinpoints clinically actionable genetic alterations that traditional testing methods may miss. Our average turnaround time is seven to 10 business days, significantly faster than what might be expected for send-out lab testing. Dr. Picarsic and I provide interpretation and consultation to clinical teams at Cincinnati Children’s as well as clinicians and pathologists at outside institutions, as needed.
How did you select the 531 genes?
It was a meticulous process that involved putting together a list of actionable and potentially actionable cancer-related genes based on a combination of published literature, consensus guidelines and expert opinion. This was a collaborative effort between faculty in oncology, bone marrow transplant, anatomic pathology and molecular pathology at Cincinnati Children’s. The probability of the test missing a genetic alteration associated with a pediatric or young adult cancer is quite small, but the team will continue to re-evaluate our panel as new alterations are found.
Tell us about Histiotrak, which looks for mutations in one specific gene, BRAF V600E.
Dr. Picarsic: We chose to target the BRAF V600E mutation because it is the most common and aggressive genetic mutation found in LCH. So far, physicians from 30 hospitals across 15 states have ordered this test to monitor circulating mutated cells or the LCH equivalent of minimal residual disease (MRD). The turnaround time is three to four days.
Histiotrak is so sensitive that it can detect a single tumor cell in the background of 50 thousand normal cells. We’ve had instances where a traditional test performed elsewhere was negative, but a subsequent Histiotrak test detected mutant cells that are still contributing to disease and the inflammatory process. Physicians can use the results to determine whether the patient is in molecular remission and plan treatment accordingly.
Why the emphasis on Langerhans cell histiocytosis, since the standard of care is chemotherapy?
Dr. Picarsic: Our colleague and clinical director of the Histiocytosis Center, Ashish Kumar, MD, PhD, developed a novel protocol that uses targeted kinase inhibitors such as trametinib and dabrafenib to target gene mutations that cause LCH, including BRAF V600E. Since 2016, Dr. Kumar has used the protocol on more than 50 LCH patients with a 100% response rate. Additionally, under Dr. Kumar’s leadership, the Histiocytosis Center at Cincinnati Children’s recently opened a phase II trial of the MEK inhibitor mirdametinib to determine if it will improve treatment efficacy and reduce side effects in patients with LCH or other histiocytic disorders. We developed Histiotrak to support Dr. Kumar’s work and made the test widely available in 2021. He participates in our consultation service from hematology/oncology specialists who order Histiotrak and have additional questions about the results or recommended next steps.
Currently, Histiotrak is a qualitative test. The report indicated whether the sample was positive, negative or suspicious for a BRAF V600E mutation. Soon, the test will be available as a quantitative test (i.e., results will estimate the amount of mutated tumor cells present in the blood).
Dr. Roy: We are refining Histiotrak and exploring new actionable genetic mutations. The test is part of our comprehensive offerings at Cincinnati Children’s Histiocytosis Center for heme/oncology specialists who are treating children and young adults with LCH. We offer end-to-end services, from expert pathology interpretation with diagnostic immunostaining and molecular MRD testing, to expertise in inhibitor therapy. Our team’s pathology, molecular science and clinical expertise is an excellent resource for doctors who treat this challenging disease.
(Published January 2024)
