Low doses of fractionated radiotherapy with total doses in the range of 15 - 30 Gy have been shown to reduce the risk of local recurrence.
High Risk Disease
The COG investigational study for high risk disease was ANBL0532 and this study is now closed to accrual.
The aim of this study was to improve event free survival for children with high-risk neuroblastoma. The study assessed the value of tandem, or dual-cycle, stem cell transplant (HSCT) in therapy. After transplant, local RT was given and the dose was increased to reduce the risk of local relapse.
Neuroblastoma patients receiving 2100 cGy in 150 cGy fractions after incomplete resection of the primary tumor had a local control rate of just over 80% at 5 years. The aim of ANBL0532 was to improve this. The RT outline for this protocol was as follows:
RT Guidelines:
RT given following myelo-ablative stem cell transplant (no earlier than 28 days post transplant but within 42 days recommended).
Dose:
After gross total resection:
- Primary site was always given RT on this protocol
- The dose was 2160 cGy in 12 fractions with no boost.
After incomplete surgical resection:
- RT dose was 2160 cGy in 12 fractions (180 cGy per fraction) plus a boost of 1440 cGy in 8 fractions to areas of gross residual disease.
- 2160 cGy was given to the post-induction chemotherapy, pre-operative primary tumor volume.
- Boost followed of 1440 cGy to the gross residual volume.
- Total dose was 3600 cGy in 20 fractions.
RT given to the primary tumor and metastatic sites.
GTV = tumor volume before attempted surgical resection (on CT, MRI, and/or MIBG scans). Not the prechemotherapy volume or the post-surgical volume. Uninvolved LNs not included.
Boost GTV volume = Gross-residual disease after surgical resection. Sometimes disease can extend into a body cavity (for example lung) or displace a normal structure. If after surgery the normal structure moved to space previously occupied by the tumor, the normal structure didn't have to be included in the GTV (as long as it was not infiltrated by disease).
CTV = Clinical Target Volume = GTV with a 1.5 cm margin.
PTV = Planning Target Volume = CTV + a margin for set up error or patient movement (depends on immobilization methods and patient cooperation)
- Should be at least 0.5 cm
- 3D conformal technique used with 4, 6 or 10 MV photons
- Use wedges, compensators to make the dose distribution more uniform
- Entire PTV should be encompassed within the 95% isodose surface
- No more than 10% of the PTV should receive greater than 110% of the prescription dose (evaluated by DVH)
Often a 3 field technique was used. Portals were designed as far as possible to:
- Spare the kidneys &/ remaining kidney
- Spare liver to prevent veno-occlusive disease
- Because sparing the kidney is a priority, the vertebral body was not always evenly irradiated as in Wilms - in the long term scoliosis due to uneven spinal growth can be more of a problem in these patients
Metastatic sites
- Given RT if persistent active disease (MIBG positive) on the pre-HSCT evaluation (after 6 cycles of induction chemotherapy)
- If negative on the pre-HSCT scans would NOT be given RT
- Persistent active metastatic disease was given RT concurrently with primary site
- Dose of 2160 cGy given in 12 fractions
Tolerances/Dose Modifications for different sites of spread:
| Tolerances | Liver:
|
Kidney
|
|
Peritoneal Cavity If diffusely involved by metastatic disease |
If entire peritoneal cavity must be given RT
|
Thorax |
|
Bone Mets |
|
It would be reasonable to continue to use these study guidelines in the treatment of pediatric NBL.
Radiotherapy can be used to treat emergencies such as:
- Cord compression
- Tracheal compression
- Expanding retro-orbital tumor
- Imminent bone fracture
- Rapidly enlarging liver
However there is evidence that prompt treatment with chemotherapy is also very effective in these situations.
