Schoot group

Dr. Schoot’s research group focuses on drug development for children and adolescents with solid tumours, with a particular emphasis on sarcomas. Clinical trial hypotheses are developed in close collaboration with preclinical scientists and are grounded in strong biological rationale. Trials are initiated and conducted through international collaborations such as the EpSSG and ITCC to accelerate access to innovative therapies.

OCTOPUS platform

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise a highly heterogeneous group of mesenchymal malignancies, accounting for approximately 4–5% of all childhood cancers. More than 50 distinct histological subtypes are included under the NRSTS umbrella, with a wide variability in clinical course and outcomes, ranging from highly favourable survival rates (approaching 100% in selected subtypes) to survival rates below 10-20%. Over the last decades, very few innovative clinical trials have been developed for children and adolescents with NRSTS, due to the rarity of tumour entities and the complexity of opening trials in ultra-rare diseases. Consequently, standard treatment for most NRSTS still relies on conventional chemotherapy, typically based on ifosfamide and/or doxorubicin in most histotypes, in combination with surgery and/or radiotherapy.

The master protocol ‘Optimising Combination Therapy fOr Paediatric, adolescent and yoUng adult patients with non-rhabdomyosarcoma soft tissue Sarcomas (OCTOPUS)’ is designed as an adaptive platform trial and will provide a flexible framework for the evaluation of multiple therapeutic strategies across different NRSTS subtypes. This platform trial is intended to overcome many of the hurdles in performing trials in ultra-rare diseases. As individual trials may take several years to open, the use of a master protocol offers a strategic advantage by enabling multiple sub-trials to be initiated sequentially or in parallel and a reliable structure for partnership with pharmaceutical companies

MyKids study

Molecular alterations, particularly chromosomal translocations, are common in soft tissue sarcoma (STS) and result in highly specific gene fusions characteristic for a particular histologic subtypes. For example, the translocation t(12;15)(p13;q25) leads to the ETV6-NTRK3 fusion in infantile fibrosarcoma. The identification of recurring genetic alterations has reduced the number of ‘undifferentiated/unclassified’ diagnoses, although some entities remain unclassified In approximately 10% of cases, molecular analysis leads to a revision of the initial histological diagnosis. In addition, ongoing discovery of novel transcripts continues to improve diagnostic precision and expand therapeutic options. Targeted therapies are increasingly guided by these molecular findings. For instance, NTRK inhibitors have largely replaced chemotherapy in ETV6-NTRK3-positive infantile fibrosarcoma due to superior outcomes. Other examples include imatinib for PDGFR-altered dermatofibrosarcoma protuberans (DFSP) and gastrointestinal stromal tumours (GIST).

The MyKids study aims to enhance understanding of molecular diagnostics in paediatric NRSTS and optimise treatment strategies by:
a) evaluating the clinical value of molecular profiling,
b) supporting personalised treatment decisions,
c) comparing molecular profiles with histological grading for prognostication,
d) developing tumour models for preclinical testing,
e) analysing circulating tumour DNA and cells through liquid biopsies, and
f) collecting post-treatment tissue to identify markers of disease progression.

ALK inhibitors

ALK is a tyrosine kinase encoded on chromosome 2 with a physiologic role in early brain development. Its oncogenic role was first identified in paediatric anaplastic large cell lymphoma (ALCL) approximately two decades ago. Since then, ALK inhibition has become an important therapeutic strategy, particularly in adult non-small cell lung cancer. ALK rearrangements also play a driving role in anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMT). ALK rearrangements are also key drivers in ALCL and inflammatory myofibroblastic tumours (IMT). Currently, two studies coordinated by the Princess Máxima Center are investigating ALK inhibitors: BrigaPED (brigatinib) and CRISP (crizotinib). These studies are conducted in close collaboration with pharmaceutical partners, with data collection aimed at supporting drug registration.