April 13, 2015

Tumor DNA in Blood Reveals Lymphoma Progression

At a Glance

  • Using an advanced genetic test, researchers were able to detect diffuse large B-cell lymphoma (DLBCL) in blood serum before it could be seen on CT scans.
  • The technique could improve disease monitoring and reduce the need for multiple CT scans, lowering both costs and exposure to radiation.
Illustration of the lymphatic system. Lymphoma is cancer that begins in the lymphatic system, which is part of the immune system. The system includes a network of lymph vessels that carry fluid containing infection-fighting white blood cells.pixologicstudio/iStock

DLBCL is the most common type of lymphoma — cancer that arises in the lymphatic system, where infection-fighting cells are made. DLBCL is usually curable, but it recurs in up to 40% of patients and is then often incurable. Because of the risk of recurrence, patients are monitored for up to 5 years after disease remission.

Currently, CT or PET scans are used to monitor patients during and after treatment. Repeated imaging tests pose both a potential health risk from radiation exposure and a financial burden. Relapses of DLBCL also most likely occur due to residual disease below levels that imaging can detect. For these reasons, researchers have been searching for better monitoring techniques.

Past studies have shown that tumor cells can be detected in blood and bone marrow by searching for tumor-specific gene sequences. However, DLBCL has fewer circulating tumor cells relative to many other cancers. A research team led by Dr. Wyndham Wilson at NIH’s National Cancer Institute (NCI) tested next-generation sequencing to assess whether cell-free circulating tumor DNA (ctDNA) from DLBCL could be detected in blood serum and used to monitor the disease.

The researchers did a retrospective analysis of DLBCL patients who received treatment according to standard protocols in clinical trials between May 1993 and December 2013. Serum samples were collected before treatment, during treatment, and for many years afterward. CT scans were done at the same time as the blood testing as part of standard surveillance. The participants were followed for a median of 11 years after completion of therapy. Reults appeared online on April 2, 2015, in Lancet Oncology.

Among 107 patients who achieved complete remission, those who developed detectable ctDNA during surveillance were over 200 times more likely to have disease progression than those who had no detectable ctDNA. The researchers also found that ctDNA monitoring could detect cancer recurrence a median of 3.5 months before clinical evidence of disease. In addition, the ctDNA test was able to identify patients at high risk of treatment failure during treatment, a strategy known as interim monitoring.

“Even with frequent CT imaging, administered for a median of 11 times per patient in our study, early disease detection was suboptimal. Indeed, a recent study suggested that surveillance CT scans might be no better than an up-to-date patient history and physical exams, supporting the need for more effective monitoring technologies,” Wilson says.

The results suggest that ctDNA monitoring could be used to improve outcomes for patients with DLBCL. Early disease detection based on ctDNA might also be used to precisely monitor the effects of novel therapies.

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Reference: Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Lancet Oncol. 2015 Apr 1. pii: S1470-2045(15)70106-3. doi: 10.1016/S1470-2045(15)70106-3. [Epub ahead of print]. PMID: 25842160.

Funding: NIH’s National Cancer Institute (NCI) and Adaptive Biotechnologies.