ASCO 2020: Results from the INFORM Registry, A Step Towards Personalized Therapy in Pediatric Cancer

By T. Chakraborty, Ph.D.

The “INdividualized Therapy FOr Relapsed Malignancies in Childhood” (INFORM) registry aims to create a personalized database for progressive or refractory pediatric cancer patients. Dr. Cornelis M. van Tilburg from the Hopp Children’s Cancer Center presented some clinical outcomes and subgroup analysis from the registry at the ASCO virtual meeting.

Every year approximately 16,000 children are diagnosed with cancer before their 19th birthday in the US. Currently, estimates suggest that one in 285 children will be diagnosed with pediatric cancer, making it a huge socio-economic burden. With advancements in treatments, survival rates have increased, but pediatric cancer is still the second most common cause of death among children. Despite the high overall cure rate among children as compared to adult patients, cancer relapse is a major hindrance with only a 10% cure rate.

The INFORM Consortium

The INFORM consortium is an initiative of the German Cancer Research Center (DFKZ) and Heidelberg University Hospital, Germany. The aim of this registry is to molecularly characterize tumor samples of all pediatric patients with relapsed cancer or high-risk refractory disease for which no therapy is available and then provide a personalized list of targets for treatment.

Next-generation sequencing technology was be applied to all individual tumor samples following which an expert group of pediatric oncologists, biologists, bioinformaticians, and pharmacologists identify key molecular targets depending on the druggability, specificity, and reliability of the target. The list of targets is then presented to the physician who can make a decision on the treatment paradigm. The targets are made available within 4 weeks making it a feasible option for personalized medicine approach.

The major aim of this registry is to have an infrastructure developed for future clinical trials that focus on personalized pediatric cancer. The primary objectives include establishing a pipeline for tissue submission, analysis, assessing individual risks, and identifying clinically relevant targets for personalized therapy. Besides, it also aims to maintain a database of response rate, overall survival, and progression-free survival rates of patients who were subjected to the therapy [2].

Updates from ASCO 2020

In his presentation, Dr. Cornelis M. van Tilburg mentioned that currently, 72 centers from eight different countries within Europe are participating in the development of the INFORM registry. The group investigated the tumor profiles from 526 affected children out of the 1300 enrolled participants. In order to identify targets and match them with the right drug, the tumor samples were analyzed by several means including whole-exome sequencing (WES), Low coverage whole genome sequencing (lcWGS), RNA sequencing (RNA-Seq), RNA expression array and DNA-methylation.

Based on these analyses, 146 out of the 526 children received targeted treatment. Among them, 20 had a very high priority target (mostly ALK, BRAF, and NRAS mutations and MET and NTRK-fusions). Physicians used the algorithm developed by the INFORM registry and identified 40 children (7.8%) who were predisposed to cancer. In addition, methylation analysis provided a diagnosis refinement in 8% of CNS tumors. Furthermore, patients receiving high-level priority target drugs had a longer progression-free survival (204.5 days) compared to all others (114 days) suggesting that precision pediatric medicine in a real-world setting is a possibility.

This approach can not only be used for personalized treatments but also to offer diagnostic information about probable predisposition towards cancer development. Finally, Dr. Tilburg concluded that there is an urgent need to develop biomarker-based personalized treatment in pediatric cancer and combining the current platform with further molecular and functional analysis like proteomics, this may be the future of personalized cancer therapy in children.

Editor: Rajaneesh K. Gopinath, Ph.D.

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References

1. https://www.acco.org/wp-content/uploads/2014/11/ACS-Special-Report-2014.pdf
2. https://www.dkfz.de/en/inform/protocol-synopsis.html
3. https://meetinglibrary.asco.org/record/185853/abstract

Author

Tulip Chakraborty