paediatrics Brussels 17

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letters and contacting responsible clinicians on the telephone.

trial to evaluate delaying or omitting radiation therapy by administering intensive chemotherapy after surgery in very young children with malignant brain tumors. The aim was to reduce potential injury of the developing central nervous system. The study plan was tested in the Pilot trial HIT-SKK 87 from March 1987 to October 1992 and continued in HIT (HirnTumor; in English: ‘braintumour’)-SKK (Sa¨uglinge und KleinKinder; English ‘infants and babies’) 92 trial until December 1997. Patient eligibility Children younger than 3 years of age with newly diagnosed malignant brain tumors were accrued to the study. Several German and Austrian institutes participated. Diagnosis was made by the institutional pathologist accord- ing to the World Health Organization classification of brain tumors [24] . Central review for histology was also rec- ommended. The subgroup of patients with an anaplastic ependymoma was included in the present analysis only. Evaluation of disease Prior to surgery, computed tomography or magnetic resonance imaging scans of the brain and entire spine were recommended. Repetition of imaging was obtained after surgery and every 10 weeks during the therapy course. Neurological examinations and evaluation of cerebrospinal fluid were also advocated. After completion of therapy, neuroradiologic imaging was performed every 6 months. Evaluation of toxicity and quality of life At the beginning of the protocol, no prospective standardized tests for evaluation of radiotherapy toxicity and late effects were implemented. However, data about late toxicity were collected by the Department of Radio- oncology, University of Tu¨bingen, Germany, by sending

Treatment protocol

Surgery Maximum achievable resection was recommended, with- out risking major impairment. Confirmation of histological diagnosis was mandatory. Extent of resection, either subtotal or complete, was estimated from the operative report and postoperative imaging. Chemotherapy Two to 4 weeks after surgery, all children received chemotherapy according to the HIT-SKK 87 or 92 trial ( Fig. 1 ). HIT-SKK 87 Low risk patients (complete resection, no dissemination of disease) received maintenance chemotherapy until radio- therapy at the age of 3 years or progression. High risk patients (subtotal resection, metastatic disease), as well as children between age of 2.5 and 3.0, received induction chemotherapy after surgery given in two cycles ( Fig. 2 ). Subsequently, maintenance chemotherapy followed until radiotherapy was initiated at the age of three. If there was progression or recurrence, chemotherapy was interrupted and radiotherapy was given immediately. HIT-SKK 92 Three cycles of postoperative chemotherapy were given with intervals of 3 weeks ( Fig. 2 ). If there was complete remission, no radiotherapy was recommended. If there was progression or tumor recurrence before 18 months of age, an

HIT-SKK 87

Maintenance-CX

->

R0/M0

age 3 yrs or progress

-> Radiotherapy

OP ->

R+/M+ or -> Induction-CX

-> Maintenance-CX

age 2.5-3.0 yrs.

HIT-SKK 92

-> CR

-> End of Therapy

OP ->

Postoperative Chemotherapy

-> PR/SD/PD ; age <18 months ->

Experimental CX

age >18 months ->

Radiotherapy

Fig. 1. Treatment schema.