Outcome of Treatment for Osteosarcoma of the Extremities Over the Last 20 Years: Report from 11 Referral Centers in Japan


Characteristic

No. of patients

%

Entire population

529

100

Age, years; mean [SD]

20.0 [12.9]
 
 ≤12

134

25.3

 13–19

227

42.9

 20–39

121

22.9

 40–

47

8.9

Sex

 Male

326

61.6

 Female

203

38.4

Tumor size, cm: mean [SD]

9.6 [4.1]
 
 ≤8

237

44.8

 >8

292

55.2

Tumor site

 Distal extremitya

42

7.9

 Distal femur

251

47.4

 Proximal tibia/fibula

151

28.5

 Proximal humerus

47

8.9

 Proximal femur

38

7.2

Pathologic fracture

 No

489

92.4

 Yes

40

7.6

Histologic response (tumor necrotic rate, %)

 Grade 1 (<50)

133

25.1

 Grade 2 (50–89)

161

30.4

 Grade 3 (90–99)

169

31.9

 Grade 4 (100)

66

12.5

Type of surgery

 Limb salvage

420

79.4

 Amputation

71

13.4

 Unknown

38

7.2

Surgical margin

 Negative

193

36.5

 Positive

1

0.2

 Unknown

335

63.3


SD standard deviation

aThe distal extremity was defined as any location distal to the knee or elbow joint with the exception of the proximal tibia/fibula (i.e., the radius, ulna, distal tibia, or hand and foot)





4.3 Survival and Prognostic Factors


Distant metastasis and tumor-related death occurred in 194 patients and 106 patients, respectively. The data for metastasis-free survival (MFS) and overall survival (OAS) estimated using the Kaplan-Meier method are shown Fig. 4.1a, b. The 3-, 5-, and 10-year MFS rates and OAS rates for the 529 patients were 70 %, 64 %, and 62 % and 88 %, 83 %, and 77 %, respectively. The univariate associations of the various factors with the MFS and OAS rates determined using Kaplan-Meier plots are shown in Figs. 4.2a–g and 4.3a–g, respectively.

A323285_1_En_4_Fig1_HTML.gif


Fig. 4.1
Kaplan-Meier plots for the patients overall (MFS (a) and OAS (b))


A323285_1_En_4_Fig2a_HTML.gifA323285_1_En_4_Fig2b_HTML.gif


Fig. 4.2
Kaplan-Meier survival plots stratified by predictor variables on MFS: (a) age (≤12, 13–19, 20–39, ≥40 year), (b) sex, (c) tumor size (≤8 cm, >8 cm), (d) tumor site (distal extremity, distal femur, proximal tibia/fibula, proximal humerus, proximal femur), (e) pathologic fracture, (f) histologic response to preoperative chemotherapy, and (g) type of surgery (limb salvage, amputation)


A323285_1_En_4_Fig3a_HTML.gifA323285_1_En_4_Fig3b_HTML.gif


Fig. 4.3
Kaplan-Meier survival plots stratified by predictor variables on OAS: (a) age (≤12, 13–19, 20–39, ≥40 year), (b) sex, (c) tumor size (≤8 cm, >8 cm), (d) tumor site (distal extremity, distal femur, proximal tibia/fibula, proximal humerus, proximal femur), (e) pathologic fracture, (f) histologic response to preoperative chemotherapy, and (g) type of surgery (limb salvage, amputation)

Table 4.2 shows the univariate and multivariate Cox proportional hazard models for MFS and OAS. Multivariate analyses demonstrated significant associations between distant metastasis and a patient age of 13–19 years (hazard ratio [HR], 1.56; 95 % confidence interval [CI], 1.07–2.29; P = 0.022) or ≥40 years (HR, 2.13; 95 % CI, 1.26–3.59; P = 0.005), tumor size >8 cm (HR, 1.58; 95 % CI, 1.17–2.14; P = 0.003), tumor location in the proximal humerus (HR, 2.86; 95 % CI, 1.32–6.19; P = 0.008), presence of pathologic fracture (HR, 1.75; 95 % CI, 1.10–2.78; P = 0.018), and tumor necrotic rate (50–89 % (HR, 0.66; 95 % CI, 0.47–0.94; P = 0.021), 90–99 % (HR, 0.53; 95 % CI, 0.36–0.77; P = 0.001), and 100 % (HR, 0.36; 95 % CI, 0.20–0.65; P = 0.001)). Moreover, multivariate analyses demonstrated significant associations between tumor-related death and a patient age of 13–19 years (HR, 1.76; 95 % CI, 1.00–3.08; P = 0.048) or ≥40 years (HR, 3.91; 95 % CI, 1.96–7.78; P < 0.001), tumor size >8 cm (HR, 1.61; 95 % CI, 1.06–2.46; P = 0.026), tumor site (distal femur (HR, 8.48; 95 % CI, 1.17–61.68; P = 0.035), proximal tibia/fibula (HR, 10.94; 95 % CI, 1.49–80.32; P = 0.019), proximal humerus (HR, 9.42; 95 % CI, 1.20–73.89; P = 0.033), and proximal femur (HR, 14.07; 95 % CI, 1.83–108.16; P = 0.011)), presence of pathologic fracture (HR, 2.72; 95 % CI, 1.56–4.74; P < 0.001), and tumor necrotic rate (50–89 % (HR, 0.56; 95 % CI, 0.35–0.90; P = 0.015), 90–99 % (HR, 0.48; 95 % CI, 0.29–0.79; P = 0.004), and 100 % (HR, 0.30; 95 % CI, 0.13–0.68; P = 0.004)).


Table 4.2
Cox proportional hazards models for MFS and OAS





























































 
MFS
OAS

Univariate analysis
Multivariate analysis
Univariate analysis
Multivariate analysis

Hazard ratio
P value
Hazard ratio
P value
Hazard ratio
P value
Hazard ratio
P value

(95 % CI)
(95 % CI)
(95 % CI)
(95 % CI)

Age (year)

≤12
Reference
  
Reference
  
Reference
  
Reference
  

13–19
1.51 (1.04–2.21)
0.032
1.56 (1.07–2.29)
0.022
1.71 (0.98–2.97)
0.059
1.76 (1.00–3.08)
0.048

20–39
1.17 (0.75–1.82)

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Jun 4, 2017 | Posted by in ORTHOPEDIC | Comments Off on Outcome of Treatment for Osteosarcoma of the Extremities Over the Last 20 Years: Report from 11 Referral Centers in Japan

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