Table 3.

COG AREN0321, AREN0532, and AREN0533 Treatment Approach

Stage	Histology	Other Clinical or Biologic Factor	LOH 1p and 16q	Chemotherapy	XRT
I	Favorable	Age < 2 years and tumor < 550 g	Any	None	None
		Age ≥ 2 years or tumor ≥ 550 g	No	AV × 19 weeks	None
		Age ≥ 2 years or tumor ≥ 550 g	Yes	AVD × 25 weeks	None
	Focal anaplasia	Any	Any	AVD × 25 weeks	10.8 Gy flank
	Diffuse anaplasia	Any	Any	AVD × 25 weeks	10.8 Gy flank
II	Favorable	Any	No	AV × 19 weeks	None
			Yes	AVD × 25 weeks	None
	Focal anaplasia	Any	Any	AVD × 25 weeks	10.8 Gy flank
	Diffuse anaplasia	Any	Any	VDCBE × 30 weeks	10.8 Gy flank
III	Favorable	Any	No	AVD × 25 weeks	10.8 Gy flank/abdomen; 10.8-Gy boost for gross disease
			Yes	VDACE × 31 weeks
	Focal anaplasia	Any	Any	AVD × 25 weeks	10.8 Gy flank/abdomen; 10.8-Gy boost for gross disease
	Diffuse anaplasia	Any	Any	VDCBE × 30 weeks	20 Gy flank/abdomen; 10.8-Gy boost for gross disease
IV	Favorable	Week 6 lung nodule CR	No	AVD × 25 weeks	No lung XRT
		Week 6 lung nodule CR	Yes	VDACE × 31 weeks	12 Gy lung*
		Week 6 lung nodule no CR	Any	VDACE × 31 weeks	12 Gy lung*
	Focal anaplasia	Any	Any	VDCBE × 30 weeks	12 Gy lung*
	Diffuse anaplasia	Any	Any	VDCBEI × 36 weeks†	12 Gy lung*

Abbreviations: AV, dactinomycin/vincristine; AVD, dactinomycin/vincristine/doxorubicin (cumulative doxorubicin dose, 150 mg/m²); COG, Children's Oncology Group; CR, complete response; VDACE, vincristine/doxorubicin/dactinomycin/cyclophosphamide/etoposide (cumulative doxorubicin dose, 195 mg/m²); VDCBE, vincristine/doxorubicin/carboplatin/cyclophosphamide/etoposide; VDCBEI, vincristine/doxorubicin/carboplatin/cyclophosphamide/etoposide/irinotecan (cumulative doxorubicin, dose 225 mg/m²); XRT, radiation therapy.

^*Metastatic sites other than lung were also irradiated; XRT dose varied according to metastatic site.

^†Patients with stage IV disease received vincristine/irinotecan only if a response was seen after 6 weeks of phase II window therapy.