Genetic Sequencing May Impact Treatment for Children With Rare, Aggressive Cancers
For children with rare, aggressive, and advanced cancer, precision medicine may help doctors determine their best treatment options, a new study found. Using information from a patient's entire genome helped to suggest personalized treatment options for nearly half of children with cancer and led to specific treatment changes in one-quarter of these patients, according to researchers at the University of Michigan Comprehensive Cancer Center and C.S. Mott Children's Hospital (Mott).
Sequencing Those With Relapsed or Rare Disease
The study is based on a program implemented at Mott in 2012 called Peds-MiOncoSeq, which includes sequencing the tumor's DNA and RNA as well as normal DNA from children and young adults with cancer that has relapsed or that is rare. Results from the first 102 patients enrolled were published by Mody et al in the Journal of the American Medical Association (JAMA).
“We found that for some children with rare, difficult-to-treat, and aggressive cancers, this technology can dramatically change the course of their treatment,” said Rajen Mody, MD, MS, a pediatric oncologist at Mott.
“We have made significant strides in cancer treatment, but for some kids, especially those with metastatic or relapsed disease, even the most advanced, proven therapies have not been able to improve their outcome. Our approach in precision oncology showed its greatest promise in these difficult to treat patients—80% of our study patients had relapsed or refractory disease, and those are the ones who benefited most from our study.”
Sequencing Findings
Overall, 46% of patients had an actionable finding: a specific genetic anomaly that is the target of an approved or experimental drug; a change in diagnosis; or genetic counseling for inherited cancer risk that could affect the patient or the whole family. Further, 25% of patients went on to receive a study recommended novel therapy, which resulted in 10% of patients achieving a partial or complete remission lasting 6 months or longer.
“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time. These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient,” said Arul Chinnaiyan, MD, PhD, Director of the Michigan Center for Translational Pathology.
In addition, researchers also found 10% of patients had an inherited cancer risk potentially impacting multiple family members. Those patients and their families were offered genetic counseling. Four of the nine families had no notable family history to suggest an inherited risk, and they would not otherwise have been referred for genetic counseling.
Future Procedures and Costs of Sequencing
As part of the program, all sequencing results were discussed at a precision medicine tumor board, which included pediatric and adult oncologists, genetics specialists, pathologists, bioinformatics specialists, and genetic counselors, among others. This group discussed all results and assessed the feasibility of pursuing treatment options based on the genomic findings.
The cost of sequencing was approximately $6,000 per patient and was covered under the research protocol. Patients in the study did not pay for sequencing. Researchers expect to see sequencing costs decrease over time, as the technology improves and competition increases. In addition, it took researchers about 7 to 8 weeks to report the sequencing results to treating physicians and families.
“These are early days and the full promise of precision medicine is yet to be fully realized,” cautioned Dr. Mody. “We need better targeted therapies designed for children, and turnaround time for sequencing needs to be less than 2 weeks for it to be a regular part of a patient's treatment plan.”
“The earlier we can carry out the sequencing, the better chance of identifying the right therapy before the [patients] develop resistance to therapies we could predict wouldn't work. We hope to make it commonplace for patients to have a molecular blueprint of their tumor to guide treatment choices,” Dr. Chinnaiyan said.
To see a video explaining the Peds-MiOncoSeq program, click here.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
