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Correspondence |
Medulloblastoma is a primitive neuronal tumour, usually arising in childhood. It is characterized by its propensity for spread via the cerebrospinal fluid (CSF). Treatment is by surgical resection followed by craniospinal radiotherapy (CSRT) and adjuvant chemotherapy. CSRT is one of the most complex radiotherapy (RT) techniques planned in most oncology departments [1]. We report a case of medulloblastoma which highlights the need for better resources for RT departments in the UK in order to accommodate patients requiring complex planning within a short time frame, such as required for CSRT.
A 10-year-old boy presented with headaches and vomiting. CT and MR scans revealed a cerebellar tumour. He had a radiologically confirmed complete macroscopic resection of the tumour and histology confirmed medulloblastoma.
He had a normal MR scan of the supratentorial area and spine and no evidence of tumour cells on cytospin of CSF from lumbar puncture. He was planned to receive CSRT and a boost to the posterior fossa with weekly vincristine during RT, followed by eight courses of chemotherapy with cisplatin, vincristine and CCNU given 6-weekly.
During preparation for CSRT planning, he developed more headaches. A CT scan 33 days after surgery suggested recurrence. When he was about to commence CSRT his symptoms deteriorated. An MR scan performed 21 days after the CT demonstrated definite evidence of tumour progression within the surgical bed.
Following his recurrence he had a further complete resection and commenced CSRT 34.2 Gy in 19 fractions followed by 21.6 Gy to the posterior fossa, giving a total dose of 55.8 Gy to the posterior fossa. 6 weeks after the completion of RT he commenced chemotherapy. However, when he was due to receive his third course of chemotherapy he became unwell with nausea, vomiting and back pain. MR scan at that stage revealed extensive leptomeningeal relapse. He was given palliative treatment and died 8 months after initial presentation.
Tumour volumes on the sequential CT and MRI data sets were measured using the Volume Viewer package on an Advantage Workstation (GE Medical Systems, Erlangen, Germany). Image slices were loaded into the package and the tumour volume manually segmented by drawing a region of interest around the tumour in each slice. The software's volume algorithm was used to calculate the volume of the segmented tumour.
The two volume measurements were 3.88 cm3, and 3 weeks later 32.55 cm3. The volume doubling time (Td) was 6.84 days, [Using the formula: Td=t2 x log 2/(log VB–log VA), where Td=volume doubling time, VA=Initial tumour volume and VB=Tumour volume after t2 days].
It is generally recommended that children with medulloblastoma should be treated by "immediate" RT. This should commence as soon as feasible after surgery. However, in the European PNET-3 study [2] which recruited patients between 1992 and 2000, where 58.1% of patients were from the UK or Ireland, only 13.5% of patients could commence RT within 28 days, and for 31.5% of patients the surgery to RT interval was greater than 42 days. Extended waiting times are still experienced in many RT departments in the UK. A recently published national audit [3] has reported that a greater proportion of patients waited an unacceptably long time for RT in 2003 compared with 1998.
There is only limited information available on the doubling time for patients with medulloblastoma. Since patients are managed by surgical resection, there is generally no opportunity to observe the rate of tumour growth on sequential scans. However, sequential scans are occasionally available, allowing an estimate of Td.
In a series reported from the University of California, San Francisco [4], 26 patients had BUdR (bromo-deoxyuridine) labelling index performed to estimate the potential doubling time (Tpot). This was relatively short, 25–82 h. In three cases sequential CT scans were available in order to estimate the actual volume doubling time (Td). In these three cases the Td values were 20.7 days (Tpot=56 h), 24.4 days (Tpot=82 h) and 23.8 days (Tpot=25 h). The significantly lower values for Tpot compared with Td reflect a high cell loss factor for medulloblastoma. In an earlier series, the mean Td estimated from sequential CT scans for 3 medulloblastomas was 19.8 days [5].
In the case reported here the volume doubling time was estimated from scans using two different modalities, i.e. initially CT and subsequently MR, and the introduction of some inaccuracy in the estimation cannot be excluded. However the Td is significantly shorter than that reported in the other series. Because of the paucity of information on the growth rate of medulloblastomas it is not clear what range of Td these tumours may exhibit. It is likely that this doubling time represents the shorter end of the range. To concur with this the clinical course of his disease was aggressive, with tumour progression during adjuvant chemotherapy.
RT departments in the UK need to be better resourced in order to cope with the sudden need to accommodate a child with medulloblastoma requiring timely treatment with complex planning. In the European PNET-4 randomized study of conventionally fractionated compared with hyperfractionated RT for children with medulloblastoma, recently opened in the UK, the requirement is for RT to start preferably with 4 weeks and no later than 40 days after surgery.
In the case reported here the volume doubling time was significantly shorter than previously reported cases, and this was associated with a very poor clinical outcome, and for this patient tumour doubling time was probably at the shorter end of the range. However this case underlines the need for better resources for UK radiotherapy departments in order to provide the flexibility to accommodate patients requiring complex planning within a short time frame, such as required for CSRT.
Yours etc.,
Departments of 1 Medical Physics and 2 Clinical Oncology, Cookridge Hospital, Leeds, LS16 6QB, UK
Received for publication June 13, 2005. Accepted for publication June 15, 2005.
References
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