Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: An analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998

Figures & data

Table I.  Patients’ characteristics and cumulative probability of 5-year Disease Free Survival (DFS).

	Patients Number (596)	5-year DFS (%)	P
Male	379 (63.6%)	51.2	0.004
Female	217 (36.4%)	60.3
≤13 years	264 (44.3%)	62.5	0.001
>13 years	332 (55.7%)	48.2
Extremity tumors	375 (62.9%)	58.1	0.07
Axile tumors	221 (37.1%)	48.2
Normal Serum LDH	371 (64.1%)	59.6	0.0001
Elevated Serum LDH (*)	193 (33.3%)	40.4
Volume ≤150 ml	265 (44.4%)	59.7	0.02
Volume >150 ml (§)	199 (33.3%)	51.3

(*) Data not available in 32 patients.

(§) Data not available in 132 patients.

Table II.  Chemotherapy protocols for ESFT at our Institution between 1972 and 1999.

REA-1 (1972-1978: 84 patients)
(VAC)×10+(VC)×32	V = 1mg/m^2; A = 50 mg/m^2; C = 800 mg/m^2
REA-2 (1979-1982: 59 patients)
Induction (VAC/D)×3	V = 1.4 mg/m^2; A = 20 mg/m^2; C = 500 mg/m^2; D = 250 mg/m^2
Maintenance (V/Ac-V/A-V/C)×6	Ac = 15 mcg/kg
REN-1 (1983-1988: 108 patients)
Induction (VAC/V)×3	V = 1.5 mg/m^2 (Top: 2 mg), TD = 36 mg/m^2 (Top. 48 mg), A = 60 mg/m^2;
	TD = 480 mg/m^2; C = 1200 mg/m^2; TD = 10800 mg/m^2
Maintenance (VC-VA-VAc)×6 cycles (*);	Ac = 1.5 mg/m^2 (Top: 2 mg); TD = 9 mg/m^2 (Top 12 mg)
REN-2 (1988-1991: 82 patients)
Induction (VAC/V)×2	V = 1.5 mg/m^2 (Top 2 mg); TD = 18 mg/m^2 (Top: 24 mg); A = 80 mg/m^2;
	TD = 400 mg/m^2; C = 1200 mg/m^2; TD = 8400 mg/m^2
Maintenance (VAC-VIAc)×3-(EI-VCAc)×2-EI	I = 9 g/m^2; TD = 54 mg/m^2; E = 500 mg/m^2; TD = 1500 mg/m^2
REN-3 (1992-1999: 263 patients)
Induction (VAC/V-VAcI/V-VAC/V)	V = 1.5 mg/m^2 (Top: 2 mg); TD = 18 mg/m^2 (Top: 24 mg); A = 80 mg/m^2; TD = 400 mg/m^2;
	C = 1200 mg/m^2; TD = 7200 mg/m^2
Maintenance (VAC-VAcI)×2-VAC-(EI-VCAc)×2-EI	I = 9 g/m^2; TD = 54 mg/m^2; E = 500 mg/m^2; TD = 1500 mg/m^2

(*) In the last cycle A was omitted; V = Vincristine; A = Adriamycin; C = Cyclophosphamide; D = dacarbazine; Ac = Actinomycin D; I = Ifosfamide; E = Etoposide; TD = Total dose.

Table III.  Local recurrence according to local treatment and surgical margins.

Local treatment	Radical margins	Wide margins	Marginal Margins	Intralesional margins	Total
Surgery	0/6	13/175 (7.5%)	4/18	0/0	17/199
Surgery + radiotherapy	0/0	9/106 (8.4%)	8/48 (16.6%)	3/9 (22.2%)	20/163 (12.2%)

Table IV.  5-year Disease Free Survival (DFS) according to treatment features (579 patients)*.

	Number of Patients (%)	5-year DFS (%)	P
Local Treatment
Surgery	194 (33.5%)	64.9	0.00005
Radiotherapy	224 (38.7%)	37.0
Surgery + RxT	161 (27.6%)	49.7
Histological response to chemo §
Grade III	107 (38.2%)	79.8	0.00005
Grade II	71 (25.8%)	65.7
Grade I	100 (36.0%)	36.7
Chemotherapy protocol
REA-1	80 (13.8%)	26.2	0.0005
REA-2	57 (9.8%)	40.3
REN-1	106 (18.3%)	39.6
REN-2	80 (13.8%)	50.0
REN-3	256 (44.2%)	63.7
Number of drugs per protocol
3 drugs	80 (13.8%)	26.2	0.00005
4 drugs	163 (28.2%)	39.9
6 drugs	336 (58.0%)	60.4

*4 patients who died of chemotherapy toxicity and 13 who developed a second neoplasm were not considered.

§Data available for 278 patients: 137 patients had adjuvant chemotherapy and 164 who received a neoadjuvant treatment lacked information on necrosis.

Table V.  Type of local treatment by tumor site (579 patients)*.

Tumor site	Number of cases	treated by radiotherapy (%)	treated by surgery (%)	treated by surgery + radiotherapy (%)
EXTREMITY	363
Femur	131	32.2	51.9	15.9
Tibia	94	33.0	53.2	13.8
Fibula	55	9.1	30.9	60.0
Humerus	47	29.8	44.7	25.5
Foot	19	26.3	57.9	15.8
Radius	9	11.1	55.6	33.3
Ulna	5	—	20.0	80.0
Hand	3	33.3	66.7	—
AXILE BONES	216
Pelvis	112	77.7	63.2	16.1
Scapula	37	16.2	10.8	73.0
Ribs	20	5.0	30.0	65.0
Spine	20	80.0	—	20.0
Sacrum	13	84.6	—	15.4
Clavicle	8	12.5	25.0	62.5
Mandible	5	40.0	—	60.0
Sternum	1	100	—	—

*4 patients who died of chemotherapy toxicity and 13 who developed a second neoplasm were not considered.

Table VI.  Multivariate Cox Regression Analysis with Backward Wald Statistics Method (579 Patients).

Variable	Odd-ratio	95% C.I.	Wald test (P)
Local treatment
Surgery	1.75	1.28–2.39
Radiotherapy	1		0.05
Surgery + radiotherapy	1.44	1.02–2.03
Gender
Male	1.34	1.04–1.74	0.03
Female	1
Age
≤ 13 years	1
> 13 years	1.54	1.19–1.98	0.0008
Serum LDH
Normal	1
Elevated	2.2	1.76–2.87	0.0005
Number of drugs
3	1.9	1.38–2.65
4	1.47	1.12–1.93	0.06
6	1

Table VII.  Multivariate Cox Regression Analysis with Backward Wald Statistics Method (278 Patients)*.

Variable	Odd-ratio	95% C.I.	Wald test (P)
Histologic response
Grade III	1
Grade II	2.38	1.22–4.62	0.0005
Grade I	5.1	2.9–9
Tumor volume
≤ 150 ml	1		0.0004
> 150 ml	2.19	1.4–3.39
Age
≤ 13 years	1
> 13 years	2.01	1.27–1.19	0.003
Serum LDH
Normal	1
Elevated	2.2	1.76–2.87	0.0005

*Patients who lacked data on histologic response to chemotherapy and/or tumor volume were not considered in this analysis.