No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

Received 23 May 2008; received in revised form 17 June 2008; accepted 18 June 2008. published online 18 November 2008.

Purpose

Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997–2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation.

Methods and Materials

In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa (± carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible.

Results

Seventeen patients were treated: previous treatment included CSI of 19.5–36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11–93 months, with a median of 41 months.

Conclusions

Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few exceptions. A salvage therapy for medulloblastoma after CSI still needs to be sought.

Medulloblastoma, Relapse, Myeloablative Chemotherapy, Reirradiation

∗ Division of Pediatrics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

† Division of Radiotherapy, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

‡ Division of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

§ Division of Physics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

‖ Division of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

¶ Division of Transfusional, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

# Division of Cytogenetics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

∗∗ Division of Statistics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

†† Neurosurgery II, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

‡‡ Pediatric Neurosurgery Unit, San Raffaele Hospital, Milan, Italy

§§ Acquired Lesion Unit, Eugenio Medea Institute, Bosisio Parini, Italy

Reprint requests to: Maura Massimino, M.D., Pediatric Oncology Unit, Istituto Nazionale Tumori, Via Venezian, 1 20133 Milano, Italy. Tel: (+39) 022-390-2593-2588; Fax: (+39) 022-390-2648

Supported in part by the Associazione Italiano perla Ricerca Sul Cancro and Associazione Bianca Garavaglia (Busto Arsizio Varese).

Conflict of interest: none.

PII: S0360-3016(08)02972-6

doi:10.1016/j.ijrobp.2008.06.1930

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