Pediatric Cancers• Embryonal tumours of the CNS account for approximately 20-30% of all cancers seen in children less than 15 years of age . ▫ Medulloblastomas are one of the most common subtypes (approx. 18% ).• Incidences of medulloblastomas: ▫ Occur in a higher ratio of boys than girls ▫ Median age group of 6- to 8- years with diagnosed cases decreasing with age (Fig. 1). Figure 1. Age-dependent frequency of the most common pediatric brain tumours in %. (Rickert, 2001)
Medulloblastomas • Medulloblastomas is a highly malignant tumour of undifferentiated primitive neuroectodermal (PNET) originating in the posterior fossa. • Classification of medulloblastoma tumors : ▫ classical medulloblastoma ▫ desmoplastic/nodular medulloblastoma ▫ medulloblastoma with extensive Figure 2. Saggital section of a T1 weighted MRI nodularity scan showing a medulloblastoma arising from the inferior cerebellar vermis. B. Contrast enhanced ▫ anaplastic medulloblastoma characteristic of medulloblastomas, seen with ▫ large cell medulloblastoma gadolinium-ehanced T1 weighted MRI scan. (Tomlinson, 1992)
Clinical Presentation • Medulloblastomas show pattern of infiltration from the cerebellum to surrounding structures. • Symptoms are reflective of cerebellar function and location. ▫ Unsteadiness and poor coordination ▫ Raised intracranial pressure from obstructive hydrocephalus . • Secondary symptoms : ▫ Vomiting ▫ Diplopia ▫ Ataxia ▫ Papilledema • Patients with wide spread disease present with more severe symptoms: ▫ Spinal cord compression ▫ seizures
Diagnosis & StagingDiagnosis:• Magnetic resonance imaging (MRI)• CT scan• Post-surgery biopsy• Magnetic resonance spectroscopyStaging:Chang’s staging system for medulloblastomas is utilised: ▫ Characterised by tumor size (T) and extent of tumor spread (M).
Staging• T1 describes tumors less than 3 cm, invading the fourth ventricle or cerebellar hemisphere• T2 indicates tumors greater than 3 cm, involving one adjacent structure• T3a defines tumors greater than 3 cm involving two adjacent structures• T3b tumors exhibit features of T3a lesions but originate from or invade the floor of the fourth ventricle• T4 tumors are greater than 3 cm and extends through the aqueduct• M0: No evidence of metastasis• M1: Tumor cells found in cerebrospinal fluid• M2: Tumor beyond primary site but still within the brain• M3: Tumor dessimination of seeds in spine area• M4: Tumor spread to areas outside the CNS
Treatment• The treatment of medulloblastomas is conducted with a multi-modality approach incorporating surgery, radiation therapy and chemotherapy.• Surgery: ▫ Primary source of treatment• Radiation Therapy (RT): ▫ Administered post-operatively ▫ Restricted to patient over three years of age due to harmful effects of radiation on the immature nervous system. ▫ Role of RT defined by patient risk group (average and high).• Chemotherapy: ▫ Primary impact of multi-agent chemotherapeutic approaches on children under three years of age ▫ Decreases the use of high dose radiation therapy to the neuraxis.
Simulation • Prone • Customized foam body cradle and plastic mask for face and shoulders (Fig. 3). • Head position with the chin extended
Planning• Pre- and postoperative magnetic resonance images fused with the planning CT scan.Cranial Treatment Volume:• The treatment fields are comprised of the primary tumour site and the cerebrospinal pathways.• Beam arrangement: An opposed lateral Figure 4. Patient treated with tumour bed technique utilising 6MV photons beams. intensity modulated radiation therapy (IMRT) boost. Prescription dose of 32Gy. Tumour bedIMRT Planning: (red), PTV (purple). (Paulino, 2010)• Five non-coplanar 6-MV photon fields• Utilises dynamic multi-leaf collimators• Inverse planning software
Radiation Therapy Radiation therapy regime • Standard-risk patients: 18Gy- 23Gy to CSI and boost to posterior fossa to 36Gy and/or tumor bed to 54- 55.8Gy. • • High-risk patients: 36-39.6Gy to CSI and posterior fossa boost to 45 Gy and/or TB boost to 55.8 Gy. IMRT vs. Conventional radiotherapy • The use of an IMRT boost for medulloblastoma has reported lower levels of ototoxicity ▫ 47% of IMRT patients showed no hearing loss ▫ 82% of patients receiving conventional therapy developed ototoxicity.
Craniospinal Irradiation • Conventionally patients receiving cerebrospinal irradiation (CSI) are treated with: • A single posterior photon beam which are matched at the cranial junction (Fig. 5). • The treatment volume includes the entire spine with at least a 1 cm margin. Figure 5. The gap plane is defined at midline, at the level where the spine photons are observed. (Phillips, 2004)
Craniospinal Irradiation Electrons: • Large CSI dose is reported to have negative effects on growth and development later in life. • Electron beams as an alternative to limit the exit dose from the spine field. • Organs at risk from the exit beam : ▫ Heart, thyroid, breast, gastrointestinal tract and lungs and bone marrow • Electron energy ranged from 15 to 21 MeV • Moving junction at cranial/spine field Figure 6. Shows the moving junction over the three junctions day cycle. The lower electron field has a separate insert made for each day of the cycle, to maintain the gap with the upper electrons, and keep the lower level constant. (Phillips, 2004)
Organs at RiskOrgan at Risk Dose ToleranceOptic chiasm 45 GyOptic nerve 45GyBrainstem 54GyLenses 8GyCochlea V55<5Cochlea (IMRT) 40% of boost dose
Side Effects & ManagementAcute Toxicity Side Effect ManagementNausea Antiemetic prior to treatmentSkin ulcerations Topical creams/ dressingPituitary gland failure hormone substitutionchronic neuropathy• Late Toxicities: ▫ Neurocognitive impairment, hearing loss, endocrine dysfunction and skeletal growth retardation.
Reflection• Medulloblastomas is an embryonal tumour with a high incidence in children aged <15 years.• The treatment is conducted with a multi-modality approach incorporating surgery, radiation therapy and chemotherapy.• Treatment modality is heavily dependent on tumour staging and risk group categorization.• Advancements in technology have provided a wide arrange of treatment options to improve survival and reduce the long-term side effects.• Due to the vulnerable developmental stage of patients the effect of radiation therapy in the long term neurological effects must be observed.
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