Pediatric cancer's genome may help in selecting treatment

Pediatric cancer's genome may help in selecting treatment ...

According to data from the international clinical trialMAPPYACTS, a journal of the American Association for Cancer Research, a genome sequencing of tumors from pediatric cancer patients experiencing a relapse enabled 107 patients to receive an appropriate matched therapy.

Pediatric cancers have a high rate of remission, with 85 percent of patients living five years or longer after diagnosis. Nevertheless, treatment options are limited if the cancer returns.

Selon M. Girgit Geoerger, a professor of pediatric clinical research at the Gustave Roussy Cancer Center in France, his aim was to genetically profile the patients tumors and utilize that to suggest a treatment. Are there molecular alterations that can be addressed with these newer medications?

Pediatric cancers are subjected to gene panel sequencing, where common cancer driver genes are sequenced to investigate mutations. Nonetheless, this information may provide valuable insights about how the tumor operates, although it is not often used to guide treatment decisions. There aren''t a lot of trials currently testing targeted therapies in children, according to Geoerger.

Geoerger and his colleagues conducted a clinical trial in MAPPYACTS in order to prospectively recruit pediatric patients with relapsed cancers and perform extensive whole exome sequencing (WES) and/or RNA sequencing in order to establish a therapeutic suitable to each patient. 774 patients, 632 of them, were collected. A clinical molecular tumor board then reviewed the sequencing data from each patient.

If there was substantial evidence that a drug might effectively treat tumors harboring the mutation, mutations were considered potentially actionable. If any evidence indicates that a licensed or investigational druga drug in clinical trials might target the mutated protein or another member of the affected signaling pathway.

432 patients with potentially actionable alterations were identified by the clinical molecular tumor board, 107 of whom were then treated with a matched targeted therapy, either alone (57 percent), in combination with chemotherapy (37 percent), or in combination with another targeted therapy (11 percent). Notably, 42 percent of the ready for routine use mutations discovered in this study were previously unknown or had not been identified by previous diagnostics. Some of the cancers that developed ready for routine use mutations were tumors of the central nervous system, such

Because tests for these modifications do not exist, Geoerger claims, this is because they are not always used. It didnt mean an alteration could be found, rather that nobody looked for it, she claims.

Patients who received a personalized treatment received a response rate of 17 percent, with a 41 percent disease control rate. Among patients with alterations ready for routine use, all of whom received their treatment as a monotherapy, the objective response rate was 38 percent. Patients with potentially actionable mutations that were not available for routine use had a total response rate of 14 percent.

The researchers investigated the possibility of using circulating tumor DNA (ctDNA)fragments of tumor cell DNA that circulate in the bloodto identify targetable mutations. Although they did not make treatment decisions based on this arm of the study, they successfully performed WES on ctDNA from 128 patients with matched tumor WES and discovered 94 potentially actionable mutations, 35 of which were not detected by tumor WES.

Geoerger believes that liquid biopsies can encrypt some children from harmful procedures and enable the profiling of tumors that are difficult to biopsy or resect, such as those found in the central nervous system.

Geoerger believes that this research provides evidence for extensive genetic sequencing of pediatric cancers and the matching of patients'' tumor genetic profiles with targeted therapies and their combinations, as well as research that she and her colleagues are continuing in the concurrentAcSe-ESMARTtrial and the upcoming MAPPYACTS 2 trial.

According to Geoerger, our goal would be to have a sequencing panel for ready for routine use mutations and fusions. Nearly everyone should have that as part of their diagnostic setup.

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