Biological Characterisation of High Risk CHildhood Cancer in Children, Adolescents and Young Adults (MICCHADO)

Methodology:

Prospective, multicentric, open, non-randomised, non-therapeutic, interventional study

To identify and characterise:

* meaningful molecular genetic alterations,
* meaningful immunological features of high risk childhood, adolescents and young adult cancers, at diagnosis, during patient treatment and follow-up (time dimension).

Eligibility Criteria:
Inclusion Criteria:

1. Inclusion within 3 months after diagnosis
2. Availability of a cryopreserved tumour sample (primary and/or metastatic and/or lymph nodes) or peripheral blood or bone marrow samples (if invasion more than 30% of lymphoblasts) for leukaemias, obtained at the time of diagnosis during a routine procedure
3. Availability of a formalin-fixed paraffin-embedded (FFPE) tumour sample (primary and/or metastasis and/or lymph nodes), obtained at the time of diagnosis during a routine procedure (except for leukaemia patients)
4. Age: ≤ 25 years at diagnosis
5. Written patient informed consent, or parents or legal representative written informed consent and assent of the child and the adolescent
6. Compulsory affiliation to a social security scheme

   Additional inclusion criteria for the study:

   To avoid multiple sampling for children, adolescents and young adults with cancer, patients already included or to be included in a study with similar analyses and/or objectives might also be included in MICCHADO study and in this case, samples or data might be exchanged on a collaborative basis.

   Cohort 1:
   * High risk neuroblastoma:

     - Any type of neuroblastoma with MYCN amplification, except INSS stage 1

     - Stage 4 neuroblastoma in children older than one year at diagnosis
   * High risk rhabdomyosarcoma:

     * Foxo1 rearrangement any stage;
     * and / or N1 ;
     * and / or metastatic rhabdomyosarcoma
   * High risk Ewing sarcoma:

     * Metastatic Ewing sarcoma family of tumours (ESFT)
     * Localised inoperable Ewing sarcoma with primary tumours ≥ 200 ml
   * High risk osteosarcoma:

     - Metastatic osteosarcoma

     - Localised inoperable osteosarcoma
   * High risk leukaemia:

     * Secondary acute myeloid leukaemia
     * Biphenotypic acute leukaemia

   Cohort 2:

   • Extra cerebral or cerebral high risk tumours including:
   * other metastatic sarcomas,
   * other rare high risk cancers,
   * high risk renal tumours with surgery after an initial chemotherapy
   * rhabdoid brain tumours (AT/RT) and extra cerebral rhabdoid tumours
   * high risk or metastatic cancers of unclear histological diagnosis • Lymphoblastic leukaemia with high MRD at Day 78 (time point 2) • Very high risk T-cells acute lymphoblastic leukaemia:
   * MRD ≥ 10-2 at the end of the induction ;
   * or MRD ≥ 10-3 at Day 78

   Cohort 3:

   Children, adolescents and young adults, with low/intermediate risk cancers belonging to the following types:

   • Neuroblastoma:

   - Localised, without MYCN amplification
   * Localised, INSS stage 1, with MYCN amplification
   * Stage 4s, in infants (younger than one year at diagnosis), without MYCN amplification

     • Rhabdomyosarcoma:
   * Localised, without Foxo1 rearrangement

     • ESFT:
   * All non-high risk localised ESFT • Osteosarcoma:
   * All non-high risk localised osteosarcoma

   Exclusion Criteria:

   Main non-inclusion Criteria common to all study cohorts:

1) Age: patients \> 25 years old at diagnosis 2) Absence of patient or parents or legal representative written informed consent 3) Patient for whom follow-up by the investigating centre does not appear feasible