PATTERNS OF FAILURE IN CHILDREN WITH MEDULLOBLASTOMA - EFFECTS OF PREIRRADIATION CHEMOTHERAPY

Purpose: To evaluate the effects of preirradiation chemotherapy on pat terns of failure in children with medulloblastoma. Methods and Materia ls: Fifty-three patients (pts) with medulloblastoma were given preirra diation chemotherapy as initial postoperative treatment at St. Jude Ch ildren's Research Hospital from November 1984 to September 1993. Patie nts less than or equal to 3 years of age (a = 23) received chemotherap y (CH) with delayed craniospinal irradiation (CSI). Children greater t han or equal to 3 years with more advanced disease (T3b-T4, M+ or meas urable residual after resection) were given CH followed by CSI (30 pat ients). Chemotherapy regimen depended on protocol, but usually include d cis-or carboplatin and etoposide, +/- cyclophosphamide and vincristi ne. Results: Actuarial overall survival and event-free survival rates are 60% (95% confidence interval [41,79]) and 37% [19,55] at 5 years. Children less than or equal to 3 at diagnosis: six of 23 pts completed CH,without progression and received consolidative CSI; all six are al ive with no evidence of disease (NED) at 2.4-9.1 years. Seventeen pati ents progressed during CH and were then given CSI. Sites of progressio n during CH were posterior fossa (PF) in II patients, neuraxis (NEUR) in 4, and PF+NEUR in 2. Following CSI, 7 patients are alive NED at 2.0 -8.6 years; 10 patients died of progressive disease. Eleven patients h ad MO disease at diagnosis; 8 (73%) progressed during CH, 3 in the neu raxis. Children greater than or equal to 3 at diagnosis: 20 of 30 pati ents completed pre-CSI CH without progression; 15 are alive NED at 1.3 -9.2 years, and 5 showed post-CSI progression in the PF (a = 3), in th e NEUR (a = I) and in bone marrow (a = 1). Ten of the 30 (33%) patient s progressed on CH (6 in NEUR, 4 in PF); 5 are alive and NED or with s table disease. Seventeen patients had MO disease at diagnosis; 3 out o f 17 (18%) progressed during CEI, 2 in NEUR and 1 in an extraneural si te. In the total group of 30 patients, II have had disease recurrence after completion of XRT. The actuarial rate of failure was 23 +/- 9% f or the patients less than or equal to 3 years of age and 21 +/- 8% for the older children when evaluated at 4 months after diagnosis (at the completion of chemotherapy in the older children but during the ongoi ng chemotherapy in the younger children). Conclusions: In patients pre senting with MO disease and receiving pre-CSI chemotherapy, the risk o f neuraxis progression seems to increase with duration of chemotherapy . The sites of progression during preirradiation chemotherapy are near ly equally divided between posterior fossa and other neuraxis sites. C SI salvage of patients progressing on chemotherapy is possible in appr oximately 50% of patients. Following CSI, neuraxis progression is more frequent than posterior fossa relapse. (C) 1997 Elsevier Science Inc.