Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study

Abstract

The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001–2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.

Surveillance imaging for high‐grade childhood brain tumors: What to do 10 years after completion of treatment?

“…Tumor recurrence rate was between 18.7‐40% . No relapse occurred more than 10 years after diagnosis.…”

“…The longest documented latency period was 7.9 years in a patient with standard risk MB. 7 The proportion of late relapse, arbitrarily defined as >5 years from diagnosis, is mentioned in two publications and is 8% and 7% . According to Sabel et al.…”

“…According to Sabel et al. and Perreault et al., 69% and 46% of all recurrences were asymptomatic and detected by surveillance magnetic resonance imaging (MRI) …”

“…Secondary brain tumors were detected in 0.1‐4.1% of former brain tumor patients. The histologies of all 19 cerebral SMN are available . Hereof 79% are high‐grade lesions (HGG and PNET), 15% are meningioma, and 5% are pilocytic astrocytoma.…”

“…Hereof 79% are high‐grade lesions (HGG and PNET), 15% are meningioma, and 5% are pilocytic astrocytoma. Time to detection of SMN is available in five studies, ranging from 2.4 years (PNET) to 10.3 years (HGG) . Time to detection of low‐grade tumors is available in two cases and is 6.5 years (pilocytic astrocytoma) and 10.2 years (meningioma) .…”