Medulloblastoma in adults: treatment results and prognostic factors
Abacioglu U, International Journal of Radiation Oncology*Biology*Physics 01 November 2002 (Vol. 54, Issue 3, Pages 855-860)
 

To investigate the treatment outcome and prognostic factors of adult medulloblastoma patients who received postoperative craniospinal irradiation (RT). Between 1983 and 2000, 30 adult patients (17 men and 13 women, age ≥16 years, median 27, range 1645) underwent postoperative RT. The median duration of symptoms was 2 months (range 19). The tumor location was lateral in 16 (53%). A desmoplastic variant was seen in 12 (40%). Tumor resection was complete in 20 (67%) and incomplete in 10 (33%). All patients received craniospinal RT. The median dose to the whole brain was 40 Gy (range 3651), to the posterior fossa 54 Gy (range 4956), and to the spinal axis 36 Gy (range 2440). The median interval between surgery and the start of RT was 31 days (range 1269), and the median duration of RT was 45 days (range 3489). Ten patients (33%) received adjuvant chemotherapy. The median follow-up was 51 months (range 5215).

The 5- and 8-year overall survival and disease-free survival rates were 65% and 51% and 63% and 50%, respectively. Twelve patients (40%) developed relapse, with a median follow-up of 51 months. The posterior fossa was the most common site of relapse (6 patients). The median time to relapse was 26 months (range 478). Fifty percent of the relapses occurred after 2 years, 17% after 5 years. In univariate analysis, M stage and the interval between surgery and the start of RT were significant prognostic factors for disease-free survival. At 5 years, 70% of M0 patients were estimated to be disease-free, but none of the 3 M3 patients reached 5 years without recurrence (p = 0.0002). The 5-year disease-free survival rate for the patients whose interval between surgery and the start of RT was <3 weeks, between 3 and 6 weeks, and >6 weeks was 0%, 85%, and 75%, respectively (p = 0.002). The 5-year posterior fossa control rate for patients who received ≥54 Gy or <54 Gy to the posterior fossa was 91% and 33%, respectively (p = 0.05).

Conclusion: The survival results for medulloblastomas in adults compare favorably with those in children. However, late relapses, lateral tumor location, and desmoplastic histologic features are more frequent in adults. Spinal seeding at presentation is a poor prognostic factor for disease-free survival. A minimal dose of 54 Gy to the posterior fossa is essential for adequate tumor control. The interval between surgery and the start of RT, which was found to be a significant prognostic factor, is an interesting issue that requires further study.

Discussion  

The adult presentation of medulloblastoma is an infrequent disease entity that shows both similarities and discrepancies with its pediatric counterpart. Adult medulloblastoma differs mainly in the incidence of more laterally located tumors and more desmoplastic histologic findings compared with pediatric tumors. In the current study, a lateral location was observed in 53% and desmoplastic histologic features in 40% of the patients. In previous adult medulloblastoma series, the incidence of a lateral location was reported to be 2971% and that of desmoplastic histologic features 2550%. Park reported an incidence of 7% lateral tumors and 18% desmoplastic variant in 144 children with medulloblastoma.

The 5-year survival rate in this study compares favorably with both pediatric and adult medulloblastoma series. In well-documented retrospective adult medulloblastoma series reporting results of 13147 patients, the 5-year overall survival rate ranged between 40% and 84% and the disease-free survival rate between 32% and 63%. In the current study, the disease-free survival rate was 63% at 5 years, but had decreased to 50% by 8 years. One-half of the recurrences were after 2 years, contrary to pediatric patients whose tumors recur mostly in the first 2 years.

Spinal seeding at presentation, although not very common, is one of the most important prognostic factors for recurrence. In the current study, only 3 patients had evidence of spinal metastases at diagnosis, and all had recurrence despite adequate postoperative treatment. This result is consistent with other adult medulloblastoma series.

The RT dose to the posterior fossa appeared to be a significant prognostic factor for posterior fossa control in the current study, similar to other studies in both pediatric and adult populations. A radiation dose of 54 Gy is suggested as the threshold dose for postoperative effectiveness. Higher radiation doses ≤72 Gy, fractionated, twice daily have not revealed superior control.

Usually, the aim is to keep the interval between surgery and RT as short as possible, taking into account operative scar tissue healing in all postoperative oncologic situations. The studies investigating this factor have not been able to show a detrimental effect of a delay in treatment results for medulloblastoma. In a study from the University of Florida, prolongation of the overall RT treatment time adversely affected the treatment results, but the interval between surgery and the start of RT had no effect on the treatment results for the pediatric medulloblastoma patients. In the study by Jenkin from Saudi Arabia in which 16% of 173 patients were >14 years old, no significant differences in outcome were found when the variables of the time from the first resection to the first day of RT (<25 vs. ≥25 days) and the duration of any interruption of RT in excess of 7 days were evaluated. In our study, patients with a shorter interval between surgery and RT (≤3 weeks) were found to have a worse prognosis compared with patients with medium and longer intervals (36 and ≥6 weeks). It is difficult to draw a definitive conclusion with these results, because no biologic explanation was found and the patient numbers were small. It may be only a coincidence, but needs further investigation.

One-third of our patients received adjuvant chemotherapy. Although no definite scheme or criteria were present for this group, we were not able to show any benefit by adding chemotherapy. Additionally, it is difficult to draw any conclusions from previous reports to show any advantage. The most prominent useful effect of adjuvant chemotherapy was shown in the study from the Royal Marsden Hospital. Patients treated with megavoltage RT and chemotherapy had a 5-year survival rate of 76% compared with 37% after RT alone. However, as they stated, other factors were present that could have contributed to the better survival such as a higher posterior fossa dose, earlier spinal RT, and more total or subtotal resection in the patients who received chemotherapy.

Conclusion  

Surgery and postoperative craniospinal RT are the mainstay treatments for adult medulloblastoma patients. Long-term follow-up is necessary, because late recurrences are not rare. Spinal seeding at presentation is a poor prognostic factor for recurrence. The posterior fossa radiation dose must be kept at a minimum of 54 Gy for adequate control. The interval between surgery and the start of RT is an interesting issue that requires further study. The role of adjuvant chemotherapy needs further investigation in prospective multi-institutional studies.