Ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors are brain tumors that are relatively common in children, but rare in adults. In this study, IKNL researcher Vincent Ho and colleagues established incidence, treatment and survival patterns for these brain tumors in adult patients (≥18 years) over a 30-year period (1989-2018). They thus provide basic information for (inter)national standard treatment protocols and thus for further improvement of care.
To obtain this basic information, the researchers analyzed data from 1,384 ependymomas, 454 pilocytic astrocytomas, 205 medulloblastomas and 112 intracranial germ cell tumors from the Dutch Cancer Registry (NKR). For each tumor type, they reported trends in incidence, major treatments, and patient survival. The crude survival was calculated using the Kaplan-Meier method and the relative survival rates were estimated using the Pohar-Perme method.
‘The landscape of brain tumors is changing rapidly, thanks to the molecular developments of recent years. Epidemiological studies such as these are needed to (partly) determine whether improved diagnostics will translate into better outcomes for patients in the long run.’ – researcher Vincent Ho
Increasing incidence and survival in ependymones
Incidence and survival rates generally remained stable for pilocytic astrocytomas, medulloblastomas and germ cell tumors. Increasing incidence was observed for spinal ependymomas, most commonly for myxopapillary ependymomas. Survival improved over time for grade II ependymomas.
Varying treatment patterns
The operations for all tumor types in most cases involved a resection, in which as much tumor material as possible is removed. More than 87% of all patients underwent resection, with the exception of patients with germ cell tumors, especially germinomas, for which only 28% of patients underwent resection. Treatment patterns varied over time, especially in surgery for ependymomas and for chemotherapy and radiation in medulloblastomas and germinomas.
- Despite increased use over time, a quarter of patients with a anaplastisch ependymoom no radiation. The reasons for this are largely unclear. Perhaps these patients were in too bad a condition to undergo radiotherapy or a complete resection would have been expected to be sufficient treatment, as evidence for the efficacy of radiation was found to be inconclusive. In any case, a more thorough evaluation requires more detailed data, for example on the functional status of patients.
- The majority of patients with pilocytair astrocytomen underwent resection, while a minority received radiotherapy as part of primary treatment (9.7%). The resection rate increased from 68.9% in the period 1989-1993 to 88.9% in 1994-1998, after which it remained stable above 80%. After 1999, no improvement in survival was observed for people with this type of tumor.
- When treating medulloblastomen in adults, the growing number of patients receiving chemotherapy, usually in addition to radiation (craniospinal radiation), deserves attention. Particularly between 2010 and 2018, the national treatment protocol recommended that systemic treatment be reserved primarily for high-risk patients in the first place, while after 2018 all medulloblastoma patients received adjuvant chemotherapy. About 1 in 10 patients did not receive radiation therapy, which is presumably due to their relatively poorer performance status or disease stage.
- Radiation is the main primary treatment for germinomas, the largest group of intracranial germ cell tumors. From 1994-1998 to 2004-2008, an increasing proportion of patients were treated with a combination of radiation therapy and chemotherapy. In front of non-germinomatous tumors except teratomas, combined radiation and chemotherapy was added to the treatment arsenal from 1999. Patient survival seemed to fluctuate over time: for both germinomas and non-germinomas, the five-year survival was lower in the 1999-2008 period. Nevertheless, the proportion of patients receiving chemotherapy in the interim period 2004-2008 appears to be remarkably high. This may have been related to initiatives, in children but probably also in adults, to replace radiation therapy doses and volumes with chemotherapy to reduce long-term adverse effects. Because treatments with only chemotherapy or chemotherapy combined with focal radiotherapy appeared to give less good results, they switched to more extensive radiation. Treatment patterns for non-germinomas proved more difficult to evaluate due to the low number of cases. While patients with teratomas generally only undergo resection of their tumor, chemotherapy and/or radiation were added in the majority of other patients. Although the results obtained in (mostly) pediatric patients suggest that craniospinal radiotherapy can be avoided for localized disease, the combined treatment is considered standard treatment for metastases.
Treatment protocols needed to improve patient outcomes
Due to the rarity and complex biology of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors in adults, there is a need for standard treatment protocols. Interpretation of scientific studies is complicated by the considerable changes that are taking place in the diagnosis of brain tumors. This study provides information for evaluating such changes and for monitoring patient outcomes over time.
Ho VK, Gijtenbeek AJ, Wagemakers M, Taal W, van Linde ME, Swaak-Kragten AT, Kurt E, van der Weide HL, Wesseling P, de Vos FY, Bromberg JE Rare central nervous system tumors in adults: a population-based study of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors. Neurooncol Adv. 2022 Apr 22;4(1):vdac062. doi: 10.1093/noajnl/vdac062.