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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 . 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
letters and contacting responsible clinicians on the
telephone.
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
( ).
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 ). 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 . 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
R0/M0 -> Maintenance-CX
age 3 yrs or progress
OP -> -> Radiotherapy
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.
B. Timmermann et al. / Radiotherapy and Oncology 77 (2005) 278–285 279