Surgery for LGA
- This is the treatment of choice for most cases if feasible.
- The 5-year survival rate is between 95-100% for complete resection alone.
- Cerebellar tumors are generally low-grade pilocytic, thus making complete resection possible in 90%.
- Low-grade tumors have low recurrence rates after complete surgical resection.
5-year progression-free survival is observed in:
- 92% of children following gross total resection
- 95-100% for JPA’s and gangliomas
- 80% for diffuse astrocytomas.
Recurrence rate is also specific to the location of the tumor. This may be related to the extent of possible resection.
- 50-60% of children with diencephalic tumors progress
- 80-90% of tumors in the cerebellum or cerebral hemispheres do not recur.
The main determinants for a successful resection are:
- Small tumor size
- Readily accessible location
- Well-circumscribed pilocytic astrocytoma, DNET or ganglioglioma histology.
The surgical approach depends on the site of tumor origin:
- Tumors may not be resectable because they are located near eloquent cerebral areas and the potential for negative neurological side effects associated with damage to normal tissues
- Diencephalic tumors - surgery may be limited to stereotactic biopsy, cyst decompression, and ventriculoperitoneal shunts.
- Cerebellar tumors very amenable to resection
When an incompletely resected tumor is asymptomatic and limited in volume, the child is generally followed until progression is documented through imaging or neurologic findings.
Not all incompletely resected tumors progress.
Chemotherapy for low grade tumors
Complete surgical resection of low grade astrocytomas is optimal and can be curative therapy when feasible.
Unfortunately young children (< 5 years) have a higher incidence of unresectable astrocytomas and consequently worse progression free and overall survival.
Almost 50% of astrocytomas in children < 5y are midline, thalamic or diencephalic compared to only 15% in older children. This group of children may benefit from an initial approach that involves chemotherapy, as radiation therapy (RT) may need to be delayed due to young age and unacceptable neurocognitive sequelae.
Children who may benefit from the addition of chemotherapy to their treatment regimen are those with recurrent, progressive or disseminated disease.
Typically chemotherapy results in disease stabilization or partial radiographic response, but complete response to chemotherapy is unusual.
Chemotherapy regimens for low grade astrocytomas:
Carboplatin and vincristine: This combination of drugs given weekly has shown demonstrable benefit. A multi-institutional study revealed that 62% of newly diagnosed children and 50% of children with recurrent disease following RT had an objective response; with another ~30% who had stabilization of disease. Overall 3 year progression free survival (PFS) was 68%, with a significantly higher PFS in children < 5 years.
Children’s Oncology Group (COG) randomized phase III trial, COG-A9952 was designed to compare standard weekly vincristine / carboplatin with a combination of thioguanine, lomustine (CCNU), procarbazine and vincristine in children < 10 years. Children with NF1 were treated only on the carboplatin and vincristine arm.
Follow up is not sufficiently mature for conclusions at this point. However, combined overall survival and event free survival, with a median follow up of 5y, is 87% and 41% respectively. This supports the concept that although chemotherapy is beneficial, it is typically not curative.
Radiation therapy (RT) for low grade astrocytomas
Remains controversial for low grade astrocytomas. However, RT may be used alone for hypothalamic and chiasmatic tumors and can result in prolonged progression-free survival.
Post-operative RT for incompletely resected low grade gliomas in the pediatric population may give improved progression free survival but no change in overall survival.
In one retrospective study, post operative RT after incomplete resection did not delay first progression in children with residual pilocytic astrocytoma (PA).
Indications for RT:
- Surgical resection is not possible without very significant morbidity
- Progression on second or third line chemotherapy
- Neurologic symptom relief
- Tumor progression with increase in size of residual disease
- More aggressive histological subtype
RT can often be effective in achieving tumor control, but:
- Efficacy must be balanced with potential toxicities
- Severity of toxicity depends on many factors such as anatomic location, tumor volume, and patient age
- RT is associated with significant long term morbidity in children:
- Cognitive disability
- Increased risk of second malignant neoplasm
- RT is also possibly linked with late anaplastic changes in patients with previous low grade tumors
The goal of RT is to treat the tumor and spare the surrounding normal brain. This can be achieved in most cases by using 3D conformal RT. Using multiple RT beams it is possible to treat the tumor with an even dose throughout (homogenous dose distribution).
Radiation Therapy (RT) Guidelines for low grade glioma:
- A mask is made for immobilization and the placement of reference marks.
- CT scan for RT planning is then done with the patient in the mask.
- Contrast-enhanced pre and post operative MRI used to define clinical target volumes.
- Fusion image registration software is used to identify GTV on MR and transfer that image to the CT planning scan.
- A typical total dose would be 54 Gy in 30 fractions (180 cGy size fractions).
Different treatment volumes are defined:
GTV = Gross tumor volume = All areas of enhancement seen on a PREoperative MR scan
Planning with CT-MRI co-registration. The best sequences to use are:
T1 plus gadolinium for JPA
T2 FLAIR for grade II astrocytoma
CTV = Clinical target volume. Which is the GTV expanded to cover any areas of microscopic disease extension
PTV = Planning target volume = Volume further expanded to cover any amount of variability in set up. The PTV should be encompassed within the 95% isodose surface.
For low grade gliomas
CTV = GTV + 5mm = CTV
PTV = CTV + 3 to 5mm.
Dose for low grade gliomas:
There is little dose-response data available for pediatric astrocytomas.
- Adult low-grade gliomas have shown no clear benefit with dosages greater than 45 Gy.
- Planned national trials on children use doses between 50-54 Gy.
- Generally children over the age of 2 years receive 50-54 Gy using 150 to 180 cGy per fraction.
- Efforts are made to delay RT in children under 3 years, usually through preliminary use of chemotherapy. When RT is needed, 45-50 Gy is usually given to a small volume.
For small low grade gliomas – especially in the region of the optic chiasm stereotactic RT is often appropriate.