RT is an important part of therapy for these tumors in children older than 3 - 5 years.
These tumors are radiosensitive (evidence from retrospective studies).
RT is generally used in children older than 3 years of age17
- Treatment to large volumes of the developing brain to a moderately high dose is likely to result in severe long-term neurocognitive problems.
There is debate about the dose, timing and target volume, but the current recommendations for RT in children over 3 years old are:
- Combination of 24 Gy to 36 Gy to the entire craniospinal axis (CSA RT) plus a boost to the site of the primary tumor to a total dose of 54 Gy17,18
Some important knowledge regarding the role of RT in supratentorial PNET treatment comes from the German HIT 88/89 and HIT 91 trials13.
HIT 88/89 trial:
- Patients were treated postoperatively with pre-RT chemotherapy (ifosfamide, etoposide, methotrexate, cisplatin, cytarabine)
- Chemotherapy was given starting 14 days after surgery
- External beam RT then followed 4 weeks after chemotherapy
HIT 91 trial:
- RT given 3 weeks following surgery
- Maintenance chemotherapy (cisplatin, vincristine, lomustine) given 6 weeks after finishing RT
All patients were treated with fractionated RT to the CSA (3520 cGy to CSA with additional boost to the supratentorial tumor of 20 Gy).
Results of HIT trial:
Immediate RT followed by maintenance chemotherapy was better than delaying RT with pre-RT chemotherapy (with an increased rate of early progression 22% in the pre-chemo RT group versus 4% in the immediate RT group).
Dose and volume of RT significant prognostic factor:
- Progression free survival decreased if there were major protocol violations in the way RT as given23
- Protocol violations were defined as:
- CSA RT dose less than 35 Gy
- Local tumor boost dose less than 54 Gy
- No CSA RT was given
- No RT was performed
Effectiveness of RT16:
Study of 15 children under18 years old with non-pineal supratentorial PNETs
Initial treatment with surgery and chemotherapy was given to all patients
RT delivered as follows:
- Up front (initial) RT in 5 patients
- RT given at time of progression in 5 patients
- No RT in 5 patients
All patients receiving upfront RT were alive without any evidence of disease at a follow up averaging 4 years
Another retrospective SIOP/UKSSCG PNET-3 study looked at the effectiveness of RT alone compared to pre-RT chemotherapy (alternating cycles of vincristine, etoposide, carboplatin and vincristine, etoposide and cyclophosphamide) for adjuvant treatment
RT was delivered in standard fractionated format
CSA RT dose of 35 Gy in 21 daily fractions, followed by a boost of 20 Gy to the primary tumor in 12 fractions (total dose was 55 Gy to the primary tumor)18
- No significant improvement for event free survival
- This study supports the importance of RT in the treatment of supratentorial PNETs.
Radiation Therapy details (for children older than 3 - 5 years):
- RT should start within 31 days of surgery
- Craniospinal RT (CSA RT) should start first followed by a boost to the primary tumor site
- CTV = entire craniospinal axis
- PTV = Institutionally defined margin for daily set up error. Usually 0.3 cm to 0.5 cm (but may be more for craniospinal RT)
The recommended dose is 36 Gy in 180 cGy fractions
Boost to primary tumor:
- GTV includes all gross residual tumor and/or the walls of the resection cavity at the primary site based on initial imaging (contrast enhanced MR scan) showing extent of original tumor prior to surgery and should also include residual disease after surgery.
- CTV = GTV + margin for microscopic residual disease
- CTV = GTV + 1 cm
- Margin may be reduced to 0.5 cm to allow for sparing of critical structures (e.g. total dose to the optic chiasm and both optic nerves should not exceed 50.4 Gy).
- PTV = 0.3 cm to 0.5 cm margin around the CTV to account for day-to-day set up variation.
The recommended total dose to a supratentorial primary tumor is either 54 Gy or 55.8 Gy in 180 cGy (this includes both the CSA RT as well as the boost).
Patients with M3 disease (spinal metastatic deposits visible on MR scan) should be given boosts to metastatic deposits.
- CTV margin for boosting metastatic deposits = 0.5 to 1.0 cm encompassing the lesion within the anatomic compartment.
- PTV = CTV + 0.3 to 0.5 cm margin.
Recommended total dose for:
- Diffuse (gross disease visible on MR) spinal diseae = 39.6 Gy to the whole spine
- Focal metastatic disease above the termination of the spine = 45 Gy
- Focal metastatic disease below the termination of the spine = 50.4 Gy