ctDNA Could Detect Post-Transplant Cancer Early

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More evidence for the biomarker circulating tumor DNA (ctDNA) as a means to test for the presence of a rare, but deadly cancer in organ transplant recipients was presented at the International Society for Heart and Lung Transplantation meeting held in Orlando last week.

The study showed that screening for ctDNA could lead to earlier diagnosis and better management of post-transplant lymphoproliferative disorder (PTLD), an aggressive form of cancer that often affects two to 10 percent of heart transplant recipients within five years of the transplant. PTLD has vague symptoms like fatigue, weight loss and night sweats.  So, diagnosis is often delayed, and death rates are high.

“It’s heartbreaking when a patient almost dies of end-stage heart disease, only to get cancer. We hope this work can go a long way in impacting survival rates for organ transplant recipients,” according to a statement issued by the study’s lead author Kiran Khush, M.D.

About 50 percent of PTLD is caused by the Epstein-Barr virus (EBV), but monitoring for EBV does not reliably predict who will develop lymphoma. 

Using Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) on tumor tissue from PTLD and other lymphomas, researchers developed a PTLD mutation panel with over 300 genes commonly mutated in humans and associated with PTLD and EBV.

Including an array of mutations allows the test to be more specific for PTLD mutations.

The study included stored blood samples from heart and lung transplant patients who developed PTLD.

Results showed that ctDNA was identifiable in all patients who developed PTLD, and that ctDNA was found as early as one-and-a-half years before clinical diagnosis.

Levels of ctDNA correlated with EBV titers in EBV positive cancer. Both ctDNA levels and EBV titers rose before diagnosis, and both fell with response to treatment. That suggests measuring ctDNA may be helpful for monitoring response to treatment.

“PTLD patients have detectable ctDNA prior to clinical diagnosis. Development of screening tools utilizing such as ctDNA would facilitate early detection of PTLD in the transplant population, and would enable us to monitor response to therapy,” the authors concluded.

Researchers hope to partner with other transplant centers worldwide to continue the development of this test.  They also plan to develop noninvasive tests to improve early detection of lung, colorectal and other common cancers among transplant recipients.

REFERENCES
Khush K, Soo J, Schroers-Martin J, et al. “Early detection of post-transplant lymphoproliferative disorder using circulating tumor DNA.” Session BSTR Basic and Translational Research. Presented April 3, 2019 at the 39th annual meeting of the International Society for Heart & Lung Transplantation. Orlando, Florida.