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 current COG investigational study for high risk disease is ANBL0532
The aim of this study is to improve event free survival for children with high-risk neuroblastoma. The study assesses the value of tandem, or dual-cycle, stem cell transplant (HSCT) in therapy. After transplant, local RT is given and the dose is increased to reduce the risk of local relapse.
Neuroblastoma patients receiving 2100 cGy in 150 cGy fractions after incomplete resection of the primary tumor have a local control rate of just over 80% at 5 years. The aim of ANBL0532 is to improve this. The RT outline for this protocol is as follows:
RT Guidelines:
RT is given following myelo-ablative stem cell transplant (no earlier than 28 days post transplant but within 42 days is best).
Dose:
After gross total resection:
- Primary site is always given RT on this protocol
- The dose is 2160 cGy in 12 fractions with no boost.
After incomplete surgical resection:
- RT dose is 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 is given to the post-induction chemotherapy, pre-operative primary tumor volume.
- Boost follows of 1440 cGy to the gross residual volume.
- Total dose is 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 moves to space previously occupied by the tumor, the normal structure doesn'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 is used. Portals should be 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 is not always evenly irradiated as in Wilms - in the long term scoliosis due to uneven spinal growth is 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 will NOT be given RT
- Persistent active metastatic disease is 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 |
|
Off study, the total dose of radiotherapy for high risk neuroblastoma is generally 2100 - 2160 cGy.
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.
