First-line chemotherapy prolongs survival in adults with medulloblastoma

First-line chemotherapy treatment appeared to significantly improve long-term survival among adults with medulloblastoma, according to a literature-based meta-analysis.

Medulloblastoma occurs in every 0.5 to one adult per million; however, only 75% of adult patients treated in clinical trials and of 64.9% in epidemiological studies survive 5 years with the disease.

Valid data on demographics, prognostic factors and therapy of patients with adult medulloblastoma is limited to retrospective studies.

There is a broad consensus that surgical resection followed by radiotherapy is the most effective modality of treatment; however, the role of chemotherapy in first-line treatment is controversial.

Dagmar Beier , MD, of the department of neurology at University of Southern Denmark, and colleagues conducted a meta-analysis of literature published from 1969 to 2013 to address the unanswered questions associated with adult medulloblastoma and to clarify the role of chemotherapy.

The primary endpoint of this study was the effect of chemotherapy.

Researchers identified 227 publications with 907 identifiable patients aged 15 to 88 years (mean, 29.1 years).

Estimated median OS of all patients reported was 65 months (95% CI, 54.6-75.3). Overall, 50.9% of patients achieved 5-year OS, which indicates a substantial improvement over the last 4 decades, the researchers wrote.

Median time from the onset of symptoms to diagnosis was 3 months (range, 0-48).

Signs of increased intracranial pressure appeared associated with better prognosis (estimated median OS = 57 months; 95% CI, 44–69), and symptoms indicating tumor manifestation in the brainstem or other parts of the central nervous system were associated with poorer survival (estimated median OS = 42 months; 95% CI, 24.5–59.4).

Researchers identified Chang-M stage at tumor recurrence as a new prognostic factor for OS, whereas metastases at initial diagnosis and desmoplastic/classic medulloblastoma did not appear associated with OS.

“A closer look at the survival curves showed that this difference was mainly due to the favorable survival of patients with local recurrence at the time-point of recurrence,” Beier and colleagues wrote.

Most patients received gross total (55%) or subtotal (40%) resection and radiotherapy (82%).

Patients who underwent gross total resection had a longer median OS (84 months; 95% CI, 68.5-99.5) than patients who underwent subtotal resection (48 months, 95% CI, 31.8-64.2) or biopsy (36 months, 95% CI, 0-84.2).

Patients who received first-line neoadjuvant chemotherapy survived significantly longer (median OS = 108 months, 95% CI, 68.6–148.4) than those who received only radiotherapy (mOS = 57 months, 95% CI, 39.6–74.4) and those who only received chemotherapy at tumor recurrence (mOS = 45 months, 95% CI, 30.9–59.1).

“This effect was not biased by the decade of treatment and was also seen in cases published after the year 2000,” Beier and colleagues wrote. “Importantly, only the survival of patients treated with neoadjuvant chemotherapy, but not the survival of patients treated with radiotherapy and chemotherapy at recurrence, plateaued, suggesting that neoadjuvant chemotherapy may improve long-term survival.”

Overall, 16% of patients died 5 years after initial diagnosis and late tumor recurrences occurred in 15.2% of all patients. When comparing all patients alive for more than 5 years after initial diagnosis with all patients who died within 5 years, chemotherapy increased the chance for long-term survival 180%. – by Kristie L. Kahl

Disclosure: The researchers report no relevant financial disclosures.