The current low risk COG research study (ARST 0331) attempts to maximize long-term failure-free survival and minimize short and long-term toxicity, particulary infertility and secondary malignancy related to cyclophosphamide exposure.
- Two subsets (A and B) have been defined within the low risk category (see risk category page), both with excellent overall survival on IRS-III and IV studies (~95%).
- In ARST 0331, a lower dose of cyclophosphamide (4.8 g/m2 total cumulative dose) is given with vincristine plus dactinomycin and radiation therapy to areas of residual tumor to patients in each of the two subsets. The duration of therapy is 22 weeks for patients in Subset A and 46 weeks in Subset B.
Embryonal/ Botryoid/ Spindle cell Tumors
Stage 1, Clinical Group I |
No radiotherapy |
Stage 1, Clinical Group II N0 |
Conventional RT - 3600 cGy |
Stage 1, Clinical Group II, N1 |
Conventional RT – 4140 cGy |
Stage 1, Clinical Group III |
Conventional RT – 4500 cGy (orbit only) |
Stage 1, Clinical Group III |
Conventional RT– 5040 cGy (non-orbit) |
Stage 2, Clinical Group I |
No radiotherapy |
Stage 2, Clinical Group II, N0 |
Conventional RT - 3600 cGy |
Stage 3, Clinical Group I |
No radiotherapy |
Stage 3, Clinical Group II, N0 |
Conventional RT - 3600 cGy |
Stage 3, Clinical Group II, N1 |
Conventional RT – 4140 cGy |
All radiotherapy is given in 180 cGy fractions.
RADIOTHERAPY
GTV = Gross tumor volume
- Pre-treatment visible and/or palpable disease
- Determined by physical examination, operative surgical findings, CT or MR (T1 sequence).
- This includes any clinically involved lymph nodes. Initial GTV does not change based on any surgical resection or chemotherapy response.
CTV = Clinical Target Volume
- CTV = GTV + 1.0 cm (but not extending outside of the patient).
- For some sites, the definition of CTV is modified to account for specific anatomic barriers to tumor spread.
- CTV will always include the entire draining lymph nodes chain if the regional nodes are clinically or pathologically involved with tumor.
NB. Patients with Clinical Group III disease who do not have a second look operation may have a second CTV and PTV defined for a “cone down”boost.
- These patients will receive a total dose of 50.4 Gy.
- However, if they have a radiographic response to induction chemotherapy, then a cone down boost will be given after a dose of 36.0 Gy.
- This boost volume will be defined as having a CTV of the original GTV at the time of diagnosis plus a margin of 0.5 cm.
PTV = Planning Target Volume
- PTV = CTV plus an institution specific margin to account for day to day setup variation ( depends on ability to immobilize the patient and physiologic motion).
- For many patients, this margin will be 5 mm.
- For patients who are to receive a cone down boost a second PTV will be defined after a dose of 36.0 Gy, based upon the cone down
- The biopsy site and surgical scar should always be included in the XRT volume.
- Nodal areas are irradiated if they are clinically positive or biopsy positive. Prophylactic nodal XRT for uninvolved nodes (NO) is not advised.
- Radiotherapy usually starts at week 13.
- Vincristine chemotherapy is given concurrent with radiotherapy. Dactinomycin is given at week 13 just before starting radiotherapy, but is withheld during RT.
- The prescription point for the PTV is at or near the center of the volume.
- For multi-convergent beams, the prescription point is at the intersection of the beam axes' isocenter.
- All patients with gross residual disease (Clinical Group III) in a favorable site(Stage 1), except most patients with orbital , should be reassessed for a second-look operation and attempt at resection at week 13 if possible.
- All patients with initial nodal involvement (N1) must receive radiotherapy regardless of response to induction therapy and second look operation. Radiation dose to gross nodal disease after initial resection is 5040 cGy. This may be reduced to 4140 cGy if there is only microscopic residual.
