Original ArticleAn Evaluation of Conformal and Intensity-modulated Radiotherapy in Whole Ventricular Radiotherapy for Localised Primary Intracranial Germinomas
Introduction
Central nervous system germ cell tumours (CNS GCTs) are primary tumours occurring predominantly in the second decade of life. They are the intracranial counterpart of tumours arising in the gonads and other extracranial sites, and are derived from totipotential primordial germ cells. Histopathologically and clinically they are subdivided into germinomas and non-germinomatous GCTs [1]. Due to the embryological origin, CNS GCTs primarily involve midline structures such as the pineal gland and/or the suprasellar region.
The management of localised germinomas is controversial. Since the 1970s craniospinal radiotherapy followed by a boost to the primary tumour area was perceived as the standard of care. In patients with localised and disseminated disease (M1–M3) craniospinal irradiation achieved a 5-year disease-free survival of up to 97% with an average of 90% at 10 years 2, 3, 4, 5, 6, 7.
Advances in neuroradiology, neurosurgical techniques and postoperative care allow for routine histopathological verification rather than relying on a ‘radiosensitivity’ test. This means to clinically establish the diagnosis of non-biopsied, radiologically suspected tumours of the pineal gland or suprasellar area as a germinoma by showing on repeat imaging a significant reduction in size after a primary radiation dose of 20 Gy. With increasing understanding of the natural history and confidence in the staging of germinomas as localised or disseminated, clinicians started to treat localised germinoma patients with reduced volume irradiation, usually in a non-prospective manner and achieving similar cure rates [8]. Another driving force for using reduced volume irradiation was instigated in the 1980s and 1990s as the consequences of craniospinal irradiation and their effect on the quality of life of survivors began to become apparent. Concerns of large volume radiotherapy originated predominantly from experiences in the treatment of other paediatric primary CNS tumours, such as medulloblastomas (receiving doses of 35 Gy to the cranio spinal axis (CSA) followed by a boost to 54–55 Gy to the posterior fossa using a two-dimensional planned parallel pair), and in patients given radiotheraphy for acute lymphoblastic leukaemia (ALL) (24–30 Gy either CSA or whole brain radiotherapy [WBRT]) 9, 10, 11, 12, 13, 14. However, the potential causative role in neurocognitive dysfunction of children with medulloblastomas who are on average significantly younger at the time of diagnosis than GCTs and of the intensive use of neurotoxic drugs such as methotrexate for ALL patients, render these patient populations different from the germinoma group. Rogers et al.[8] deduced from the available published research that whole ventricular radiotherapy (WVRT), followed by a boost to the primary tumour, in localised germinomas, is equivalent to craniospinal irradiation with respect to relapse-free survival and overall survival. WVRT as part of the curative treatment approach is at present considered the standard of care in patients with localised germinomas both in the Children Oncology Group (COG) and the forthcoming International Society of Paediatric Oncology study (SIOP CNS GCT 08), either as sole modality or as part of a combined modality approach.
The ventricles of the CNS have a complex shape with a number of concavities and are in close proximity to critical normal tissue structures. Intensity-modulated radiotherapy (IMRT) has shown technical advantages over conventionally planned three-dimensional radiotherapy, e.g. in head and neck, lung and prostate cancer [15]. The ability to better conform to the planning target volume (PTV) could improve the therapeutic ratio and reduce doses to organs at risk (OARs) and thus potentially decrease long-term toxicity. The aim of this study was to quantify the amount of normal tissue sparing that is achievable in WVRT using IMRT techniques compared with low- or medium-complexity non-IMRT methods.
Section snippets
Materials and Methods
Five patients with localised CNS GCTs for whom computed tomography and magnetic resonance imaging (MRI) scans for computed tomography–MRI co-registration were available, formed the basis of this planning study. The mean age at diagnosis was 15 years (range 6–21 years). The primary tumour location was suprasellar in two patients and pineal in three.
The Philips Pinnacle treatment planning system (version 6.2) was used. Manual computed tomography–MRI co-registration was made using bone and soft
Planning Target Volume Coverage
Examples of dose distributions are shown in Fig. 1 for three techniques representing low (PP), medium (3F and 4F) and high complexity (4FIMRT and 7FIMRT). PTV1 coverage was not statistically different between the techniques, although it was found to be more time consuming to achieve results with the IMRT methods, especially 4FIMRT (Table 1). Ninety-five per cent and 99% of PTV1 were covered by at least the 95 and 92% isodoses, respectively. However, for 4FIMRT on the patient with the largest PTV
Discussion
In localised germinomas, much effort was made in the past to show the safe reduction of the radiotherapy treatment volume from craniospinal irradiation. It seems that the previous gold standard of craniospinal irradiation is redundant in completely staged localised CNS germinomas [8]. Yet minimising the radiotherapy volume to focal irradiation of the primary tumour alone is probably a step too far as this is associated with unacceptably high relapse rates [8]. As the pathological pattern of
Conclusions
WVRT in localised completely staged CNS germinomas is becoming the standard of care in many centres across Europe and the USA and forms part of the basis of current COG and SIOP studies. Although we found small differences between the doses to OARs by the various techniques, a 7FIMRT plan for WVRT was shown to allow the greatest normal-brain sparing among those considered. Whether the technical advantage of highly complex radiotherapy with a modest reduction in mean doses to OARs can translate
Acknowledgements
Dr Mosleh-Shirazi was partially supported by the Royal Marsden Children's Cancer Unit Fund.
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Present address: Servizio di Radioterapia, Villa Maria Cecilia Hospital, via Corriera 1, 48010, Cotignola (RA), Italy.