Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study

Figures & data

Figure 1. Subgroup analysis flow chart.

Table 1. Patient characteristics.

	Analysis population
	All patients (N = 455)	All eligible patients (N = 310)
Characteristics	n (%)	n (%)
Treatment
Doxorubicin	228 (50.1)	156 (50.3)
Doxorubicin + ifosfamide	227 (49.9)	154 (49.7)
Gender
Male	217 (47.7)	148 (47.7)
Female	238 (52.3)	162 (52.3)
Age
<40 years	112 (24.6)	73 (23.5)
40–49 years	148 (32.5)	94 (30.3)
≥50 years	195 (42.9)	143 (46.1)
PS
0	252 (55.4)	176 (56.8)
1	201 (44.2)	134 (43.2)
2	2 (0.4)	0 (0.0)
Time since initial diagnosis
<3 months	156 (34.3)	95 (30.6)
3–12 months	128 (28.1)	96 (31.0)
>12 months	171 (37.6)	119 (38.4)
Tumor grade (central review)
I	18 (4.0)	0 (0.0)
II	131 (28.8)	128 (41.3)
III	190 (41.8)	182 (58.7)
Not assessed/unknown	116 (25.5)	0 (0.0)
Histological subtype (central review)
Liposarcoma	34 (7.5)	25 (8.1)
Leiomyosarcoma	85 (18.7)	74 (23.9)
Synovial sarcoma	54 (11.9)	52 (16.8)
UPS	58 (12.7)	55 (17.7)
Other	117 (25.7)	104 (33.5)
Not a sarcoma	6 (1.3)	0 (0.0)
Missing	101 (22.2)	0 (0.0)
Primary tumor site involved	214 (47.0)	133 (42.9)
Liver metastases	80 (17.6)	53 (17.1)
Lung metastases	310 (68.1)	227 (73.2)
Bone metastases	65 (14.3)	44 (14.2)
Other sites of metastases	270 (59.3)	185 (59.7)

Table 2. Prognostic factors for best overall response (CR + PR): multivariate analysis stratified by treatment.

		Full multivariate model		Reduced model stepwise selection
Parameter	Levels	OR (95% CI)	p value	OR (95% CI)	p value
Gender	Male	1.00	.231
	Female	1.46 (0.78, 2.73)
Age	<40 years	1.00	.653
	40–49 years	1.20 (0.51, 2.82)
	≥50 years	0.85 (0.36, 2.03)
PS	0	1.00	.992
	1	1.00 (0.54, 1.83)
Time since initial diagnosis	<3 months	1.00	.782
	3–12 months	0.75 (0.33, 1.73)
	>12 months	0.91 (0.40, 2.04)
Histological grade (central review)	II	1.00	.287
	III	1.41 (0.75, 2.65)
Histological subtype (central review)	Liposarcoma	1.00	.007	1.00	.014
	Leiomyosarcoma	0.15 (0.05, 0.50)		0.21 (0.08, 0.64)
	Synovial sarcoma	0.20 (0.06, 0.64)		0.30 (0.11, 0.84)
	UPS	0.21 (0.07, 0.65)		0.29 (0.10, 0.81)
	Other	0.14 (0.05, 0.40)		0.19 (0.07, 0.50)
Primary tumor site involved	No	1.00	.098
	Yes	0.55 (0.27, 1.12)
Liver metastases	No	1.00	.177
	Yes	0.52 (0.20, 1.34)
Lung metastases	No	1.00	.138
	Yes	1.86 (0.82, 4.23)
Bone metastases	No	1.00	.361
	Yes	1.50 (0.63, 3.59)
Other sites of metastases	No	1.00	.034	1.00	.006
	Yes	0.51 (0.28, 0.95)		0.42 (0.23, 0.78)

(CR + PR) = (complete response + partial response).

p values < .05 are highlighted in bold.

Table 3. Prognostic factor analysis for OS: multivariate analysis stratified by treatment.

		Full multivariate model		Reduced model stepwise selection
Parameter	Levels	HR (95% CI)	p value	HR (95% CI)	p value
Gender	Male	1.00	.058
	Female	0.78 (0.60, 1.01)
Age	<40 years	1.00	.553
	40–49 years	1.15 (0.79, 1.68)
	≥50 years	1.23 (0.85, 1.79)
PS	0	1.00	.013
	1	1.39 (1.07, 1.80)
Time since initial diagnosis	<3 months	1.00	.020
	3–12 months	1.43 (1.02, 2.00)
	>12 months	0.96 (0.68, 1.34)
Histological grade (central review)	II	1.00	.257
	III	1.16 (0.90, 1.50)
Histological subtype (central review)	Liposarcoma	1.00	.281
	Leiomyosarcoma	1.80 (1.04, 3.12)
	Synovial sarcoma	1.58 (0.88, 2.82)
	UPS	1.77 (1.02, 3.09)
	Other	1.72 (1.03, 2.88)
Primary tumor site involved	No	1.00	.999
	Yes	1.00 (0.74, 1.34)
Liver metastases	No	1.00	.294
	Yes	1.20 (0.85, 1.70)
Lung metastases	No	1.00	.838
	Yes	1.03 (0.77, 1.39)
Bone metastases	No	1.00	.046	1.00	.003
	Yes	1.45 (1.01, 2.09)		1.56 (1.16, 2.09)
Other sites of metastases	No	1.00	.344
	Yes	1.13 (0.87, 1.47)

p values < .05 are highlighted in bold.

Figure 2. Interaction of histological subtype with treatment on OS (A: central pathology review; B: local pathology review).

Table 4. Interaction of histological subtype on response to treatment (A: local pathology assessment; B: central pathology assessment).

Histological subtype (local)	Total (N = 310),n (%)	Doxo responders (N = 22), n (row %)	Total (N = 156),n (column %)	DxIf responders (N = 44), n (row %)	Total (N = 154),n (column %)	OR (95% CI)
A
Liposarcoma	31 (10)	6 (37.5)	16 (10.3)	5 (33.3)	15 (9.7)	0.83 (0.19, 3.64)
Leiomyosarcoma	80 (26)	4 (10.5)	38 (24.4)	9 (21.4)	42 (27.3)	2.32 (0.65, 8.27)
Synovial sarcoma	50 (16)	3 (11.1)	27 (17.3)	10 (43.5)	23 (14.9)	6.15 (1.43, 26.39)
UPS	30 (10)	3 (16.7)	18 (11.5)	2 (16.7)	12 (7.8)	1.00 (0.14, 7.10)
Other	119 (38)	6 (10.5)	57 (36.5)	18 (29.0)	62 (40.3)	3.48 (1.27, 9.53)
B
Liposarcoma	25 (8)	7 (50.0)	14 (9.0)	5 (45.5)	11 (7.1)	0.83 (0.17, 4.06)
Leiomyosarcoma	74 (24)	4 (12.5)	32 (20.5)	8 (19.0)	42 (27.3)	1.65 (0.45, 6.05)
Synovial sarcoma	52 (17)	4 (16.0)	25 (16.0)	9 (33.3)	27 (17.5)	2.63 (0.69, 9.98)
UPS	55 (18)	2 (6.9)	29 (18.6)	11 (42.3)	26 (16.9)	9.90 (1.93, 50.7)
Other	104 (33)	5 (8.9)	56 (35.9)	11 (22.9)	48 (31.2)	3.03 (0.97, 9.47)