For children with cancer who have relapsed, cancer genomic analyses can help make more accurate diagnoses, find appropriate therapy and delay disease progression. This is shown by the results of the INFORM study, in which the benefits of molecular precision oncology in children were systematically determined for the first time worldwide.
Every year, about 2000 children in Germany are newly diagnosed with cancer. Because cancer is comparatively rare in children, they also have far fewer innovative treatment options available to them than adults. New approaches such as targeted drugs and cancer immunotherapy, which have already been used successfully against some cancers in adults, hardly exist specifically for children. “Modern therapeutic approaches for children are urgently needed, however,” explains Olaf Witt, director at the Hopp Children’s Tumor Center Heidelberg (KiTZ), who is leading the INFORM study. Olaf Witt is also a pediatric oncologist at Heidelberg University Hospital (UKHD) and heads the Clinical Cooperation Unit Pediatric Oncology at DKFZ. “About one-fifth of young cancer patients cannot be cured because the usual standard therapies do not work when they relapse,” Witt says.
The INFORM (INdividualized therapy FOr Relapsed Malignancies in childhood) trial, launched in 2015, aims to give these children a second chance. In the event of a relapse, physicians and scientists are looking for molecular targets that could open up more effective treatment options tailored to tumor biology. The results of the long-term follow-up, now published in the journal Cancer Discovery, show the benefits of cancer genomic analyses for young sufferers. Together with physicians from the UKHD and scientists from the DKFZ as well as colleagues from the professional society GPOH, the team at the KiTZ developed an algorithm with which they classified the suitability of molecular alterations in a tumor as a therapeutic target in seven categories ranging from “very suitable” to “unsuitable”. For example, genetic alterations in the tumor that represent biological targets that can be directly attacked by active agents and for which there are already approved drugs or ongoing clinical trials were classified as very suitable. The treating pediatric oncologists at the 72 centers in eight European countries were then able to use this information to make treatment decisions.
“In total, we were able to identify genetic targets that are in principle treatable in 225 of the 519 patients,” explains KiTZ scientist and pediatric oncologist Cornelis van Tilburg, first author of the study. “In 42 of the 519 patients, we were able to classify the target structures as ‘very suitable.'” Half of these patients then received targeted cancer therapy, such as in a clinical trial, on the recommendation of their treating physician. Compared to all other patients, this doubled the time without cancer progression. In eight percent, the exact form of the tumor could also be determined on the basis of the genome analysis. In addition, 39 of the patients were found to have a familial genetic predisposition to the cancer, which was incorporated into counseling and screening programs for families. KiTZ Director Stefan Pfister, department head at DKFZ and pediatric oncologist at UKHD, sees the results of the study as a first important step in showing that some of those affected can benefit from modern cancer genome analyses. “Ideally, however, molecular diagnoses should not be used as a last hope only in the event of a relapse,” he said. In most of the young cancer patients, the disease is very advanced by then. If patients at particularly high risk of relapse could be offered a therapy tailored to them at an earlier stage, they would most likely be much more effective.”
To make the best use of precision oncology in children, he said, there is a particular lack of clinical trials of new drugs specifically for children. The DKFZ/NCT/DKTK MASTER cancer genome sequencing program for adults, the latest results of which were also recently published in the scientific journal “Cancer Discovery”, also shows how great the difference is to adult oncology. Already 18 percent of the patients enrolled in the MASTER program receive therapy recommendations for which the compatibility of target structure and drug for the tumor disease at hand has already been tested in several clinical trials and which are therefore more reliable. “We are still very far away from such figures in pediatric oncology,” emphasizes Stefan Pfister.
Source: German Cancer Research Center
Original publication: Cornelis M. van Tilburg, Elke Pfaff, Kristian W. Pajtler, Karin P.S. Langenberg et al The pediatric precision oncology INFORM registry: clinical outcome and benefit for patients with very high-evidence targets. In: Cancer Discovery (online publication August 09, 2021).
