Outcome and prognostic factors of desmoplastic medulloblastoma treated within a multidisciplinary treatment concept

Abstract

Background: Desmoplasia in medulloblastoma is often diagnosed in adult patients and was repeatedly associated with improved results. Today, all medulloblastoma patients receive intensive multimodal treatment including surgery, radiotherapy and chemotherapy. This study was set up to investigate treatment outcome and prognostic factors after radiation therapy in patients with desmoplastic medulloblastomas.

Methods: Twenty patients treated for desmoplastic medulloblastoma in the Department of Radiation Oncology at the University of Heidelberg between 1984 and 2007 were included. Data were collected retrospectively. Tumor resection was performed in all patients. All patients underwent postsurgical radiotherapy (RT). Two patients underwent whole brain radiotherapy (WBRT), and 18 patients received craniospinal irradiation (CSI). In all patients, an additional boost was delivered to the posterior fossa. The median dose to the whole brain and the craniospinal axis was 35.2 Gray (Gy), and 54.4 Gy to the posterior fossa. Fourteen patients received chemotherapy, including seven who were treated with combined radiochemotherapy and twelve who received adjuvant chemotherapy. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method.

Results: Median follow-up was 59 months. Overall (OS), local (LPFS) and distant progression-free survival (DPFS) was 80%, 71.2%, and 83.3% at 60 months. Patients who suffered from local or distant relapses had significantly worse outcome. Five patients died from recurrent medulloblastoma. Treatment-associated toxicity was acceptable.

Conclusions: Multimodal approaches with surgical resection followed by chemoirradiation achieved high response rates with long OS in desmoplastic medulloblastoma patients. Staging parameters expected to predict for poor prognosis did not significantly influence outcome. However, success of any first line regimen had strong impact on disease control, and remission was achieved in no patient with relapsing disease. Multimodal concepts must be evaluated in further clinical trials.

Figure 1

Neuropathological diagnosis of desmoplastic medulloblastoma. A: Rarefied nodules of reduced cellularity surrounded by densely packed hyperchromatic cells (100× magnification; HE-staining). B: Dense intercellular reticulin and nodular reticulin-free zones (200× magnification; TP-staining).

Figure 2

Event-free Survival: EFS was 90.0% at 12 months, 85.0% at 24 months, 68.3% at 60 months and 54.9% at 120 months (Kaplan-Meier, n = 20).

Figure 3

Overall survival: OS was 94,4% at 12 months, 88,9% at 24 months, 80% at 60 months and 54,9% at 120 months (Kaplan-Meier, n = 20).

Figure 4

Local progression-free survival. LPFS was 94,7% at 12 months, 83,9% at 24 months, 71,2% at 60 months, and 59,9% at 120 months (Kaplan-Meier, n = 20).

Figure 5

Distant progression-free survival. DPFS was 93,3% after 36 months and 83,3% after 60 months with no further recurrences after 43 months (Kaplan-Meier, n = 20).

Figure 6

Local progression-free survival with adjuvant radiotherapy versus radiochemotherapy (RCHT; concomitant and adjuvant chemotherapy). The addition of chemotherapy achieves favourable, but not yet significant results for local progression-free survival (p = 0.19).