Prof. Dr. med. Martin Stanulla
Medizinische Hochschule Hannover
The evolution of treatment in pediatric cancer - from no treatment to individualized approaches
After the end of World War II, the discovery of cytotoxic substances led to development of the first systematic clinical approaches to malignant diseases – the true birth of cancer chemotherapy. In 1948, the report of a 3-months remission in ten of 16 children with leukemia undergoing folate monotherapy documents the first successful chemotherapy for childhood leukemia. In 1956 the first successful treatment of a solid tumor by antifolates was reported. It took another ten years until combination chemotherapy was developed which resulted in the first long-term remissions of pediatric leukemia. During the next decades, continuous optimization of polychemo- and radiation therapy in parallel with improved clinical and biological characterization of pediatric cancers led to more refined risk-adapted treatment stratification. This allowed to better balance the risk of disease recurrence and therapy-related toxic side-effects and resulted in growing survival rates. In more recent years, supported by the enormous technical progress in sequencing technologies, biological characterization at both tumor and host levels progressed towards truly personalized genomics which currently results into “super-stratified” treatment approaches. From now on, the challenge will be to integrate the growing complexity of comprehensive data at different biological levels with clinical data and to decipher those pathways integral to malignant disease and treatment response. Keeping in mind an ever growing number of new substances entering the drug market for malignant diseases, it will be difficult to evaluate the results of integrated efforts in context of numerous new drugs and their combinations in classical clinical trial structures. Therefore, innovative computational and mathematical tools will be needed to allow the transition from “super-stratified” to truly individualized pediatric cancer medicine.