Table 3.
Univariate and multivariate Cox models for overall and progression-free survival.
| n | Overall survival |
Progression-free survival |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Univariate models |
Multivariate model (n = 328) |
Univariate models |
Multivariate model (n = 328) |
||||||
| Hazard ratio (95% CI) | p-Value | Hazard ratio (95% CI) | p-Value | Hazard ratio (95% CI) | p-Value | Hazard ratio (95% CI) | p-Value | ||
| Year of randomisationa | |||||||||
| Each additional year from 1983 | 533 | 1.01 (0.98–1.03) | 0.599 | 1.02 (1.00–1.04) | 0.052 | ||||
| Collaborative group | 533 | ||||||||
| MRC | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| EORTC | 1.03 (0.78–1.35) | 0.856 | 0.53 (0.19–1.45) | 0.217 | 0.92 (0.72–1.18) | 0.529 | 0.50 (0.21–1.18) | 0.112 | |
| Geographical location | 533 | ||||||||
| UK/Ireland | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Mainland Europe | 1.09 (0.79–1.49) | 0.599 | 1.44 (0.49–4.24) | 0.510 | 0.91 (0.68–1.22) | 0.536 | 1.48 (0.57–3.89) | 0.422 | |
| Other | 1.02 (0.70–1.49) | 0.905 | 1.23 (0.52–2.94) | 0.638 | 0.93 (0.67–1.29) | 0.673 | 1.16 (0.55–2.41) | 0.697 | |
| Age group | 533 | ||||||||
| ⩽10 years | 1.00 | 1.00 | 1.00 | ||||||
| 11–15 years | 1.07 (0.72–1.61) | 0.730 | 1.08 (0.64–1.83) | 0.777 | 1.20 (0.85–1.71) | 0.305 | 1.30 (0.83–2.05) | 0.254 | |
| 16–20 years | 1.17 (0.78–1.75) | 0.448 | 1.27 (0.74–2.18) | 0.382 | 1.14 (0.80–1.64) | 0.471 | 1.24 (0.76–2.02) | 0.381 | |
| 21–25 years | 0.92 (0.53–1.61) | 0.772 | 0.75 (0.34–1.64) | 0.467 | 0.92 (0.56–1.51) | 0.748 | 0.87 (0.45–1.69) | 0.676 | |
| ⩾26 years | 1.53 (0.87–2.67) | 0.136 | 2.03 (0.97–4.24) | 0.061 | 1.22 (0.72–2.06) | 0.468 | 1.29 (0.61–2.69) | 0.505 | |
| Gender | 530 | ||||||||
| Male | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Female | 0.73 (0.55–0.97) | 0.028 | 0.68 (0.45–1.01) | 0.054 | 0.82 (0.64–1.04) | 0.101 | 0.80 (0.57–1.12) | 0.189 | |
| Site of tumoura | 529 | ||||||||
| Femur | 1.00 | 1.00 | |||||||
| Tibia | 0.68 (0.49–0.96) | 0.026 | 0.69 (0.51–0.93) | 0.014 | |||||
| Fibula | 0.94 (0.52–1.70) | 0.842 | 0.92 (0.54–1.56) | 0.749 | |||||
| Humerus | 1.57 (1.07–2.32) | 0.023 | 1.81 (1.27–2.57) | 0.001 | |||||
| Other | 0.53 (0.13–2.14) | 0.371 | 0.66 (0.21–2.06) | 0.471 | |||||
| Location of tumour | 527 | ||||||||
| Proximal | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Distal | 0.54 (0.39–0.75) | <0.001 | 0.45 (0.28–0.71) | 0.001 | 0.49 (0.36–0.66) | <0.001 | 0.34 (0.23–0.52) | <0.001 | |
| Type of osteosarcoma | 500 | ||||||||
| Common-type | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Chondroblastic | 1.13 (0.73–1.74) | 0.575 | 0.75 (0.42–1.36) | 0.343 | 1.38 (0.96–1.99) | 0.081 | 0.87 (0.54–1.40) | 0.575 | |
| Fibroblastic | 1.16 (0.72–1.89) | 0.545 | 1.49 (0.78–2.86) | 0.226 | 1.11 (0.71–1.76) | 0.643 | 1.61 (0.88–2.95) | 0.119 | |
| Anaplastic | 0.84 (0.37–1.91) | 0.682 | 0.39 (0.12–1.34) | 0.137 | 0.74 (0.35–1.58) | 0.435 | 0.32 (0.11–0.95) | 0.040 | |
| Telangiectatic | 1.23 (0.64–2.38) | 0.530 | 0.98 (0.45–2.17) | 0.967 | 0.84 (0.45–1.57) | 0.590 | 0.77 (0.37–1.63) | 0.500 | |
| Other | 1.77 (1.08–2.90) | 0.023 | 1.88 (1.01–3.50) | 0.046 | 1.64 (1.05–2.57) | 0.029 | 1.38 (0.78–2.42) | 0.265 | |
| Oral Mucositis | 518 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.75 (0.57–1.00) | 0.053 | 1.01 (0.67–1.53) | 0.946 | 0.70 (0.53–0.90) | 0.007 | 0.96 (0.66–1.38) | 0.809 | |
| Grades 3–4 | 0.38 (0.25–0.57) | <0.001 | 0.51 (0.29–0.91) | 0.023 | 0.48 (0.34–0.68) | <0.001 | 0.61 (0.37–0.99) | 0.046 | |
| Nausea and vomiting | 519 | ||||||||
| Grade 0 | 1.00 | 1.00 | |||||||
| Grades 1–2 | 0.60 (0.31–1.16) | 0.129 | 0.37 (0.16–0.85) | 0.020 | 0.55 (0.30–1.00) | 0.049 | 0.35 (0.16–0.76) | 0.008 | |
| Grades 3–4 | 0.60 (0.31–1.14) | 0.117 | 0.53 (0.23–1.20) | 0.127 | 0.61 (0.34–1.10) | 0.103 | 0.49 (0.22–1.05) | 0.068 | |
| Infection | 517 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.84 (0.62–1.14) | 0.269 | 0.91 (0.58–1.42) | 0.666 | 0.90 (0.68–1.19) | 0.459 | 1.07 (0.72–1.60) | 0.733 | |
| Grades 3–4 | 0.71 (0.49–1.03) | 0.072 | 0.90 (0.52–1.56) | 0.715 | 0.85 (0.62 –1.17) | 0.313 | 1.44 (0.89–2.32) | 0.135 | |
| Cardiac | 518 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.84 (0.52–1.36) | 0.481 | 0.85 (0.44–1.68) | 0.648 | 0.99 (0.66–1.49) | 0.959 | 1.44 (0.83–2.48) | 0.193 | |
| Grades 3–4 | 0.71 (0.18–2.90) | 0.636 | 1.02 (0.13–8.07) | 0.988 | 0.67 (0.21–2.12) | 0.501 | 1.04 (0.23–4.65) | 0.958 | |
| Neurological | 517 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.51 (0.31–0.85) | 0.010 | 0.81 (0.43–1.52) | 0.513 | 0.45 (0.28–0.72) | 0.001 | 0.56 (0.32–0.99) | 0.044 | |
| Grades 3–4 | 1.73 (0.24–12.42) | 0.587 | 0.71 (0.07–7.63) | 0.780 | 3.75 (0.52–27.22) | 0.192 | 2.16 (0.21–22.72) | 0.520 | |
| Leucopenia | 437 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.88 (0.48–1.62) | 0.678 | 0.86 (0.35–2.12) | 0.741 | 0.76 (0.44–1.30) | 0.309 | 0.67 (0.31–1.44) | 0.304 | |
| Grades 3–4 | 0.60 (0.35–1.03) | 0.063 | 0.82 (0.33–2.00) | 0.662 | 0.56 (0.35–0.89) | 0.014 | 0.66 (0.31–1.38) | 0.267 | |
| Thrombocytopenia | 437 | ||||||||
| Grade 0 | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Grades 1–2 | 0.56 (0.37–0.84) | 0.005 | 0.49 (0.27–0.87) | 0.016 | 0.58 (0.41–0.83) | 0.003 | 0.50 (0.30–0.83) | 0.008 | |
| Grades 3–4 | 0.59 (0.42–0.83) | 0.003 | 0.63 (0.36–1.13) | 0.119 | 0.59 (0.43–0.80) | 0.001 | 0.58 (0.35–0.96) | 0.035 | |
| Histological responseb | 351 | ||||||||
| Poor | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Good | 0.42 (0.28–0.62) | <0.001 | 0.42 (0.27–0.65) | <0.001 | 0.38 (0.27–0.54) | <0.001 | 0.36 (0.25–0.54) | <0.001 | |
| Surgery typeb | 506 | ||||||||
| Amputation | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Limb salvage | 0.80 (0.59–1.07) | 0.130 | 0.81 (0.51–1.28) | 0.367 | 0.84 (0.65–1.10) | 0.214 | 0.84 (0.55–1.27) | 0.407 | |
| Timeliness of surgeryb | 505 | ||||||||
| On-time | 1.00 | 1.00 | 1.00 | 1.00 | |||||
| Early | 1.67 (0.98–2.87) | 0.060 | 0.91 (0.28–3.01) | 0.878 | 1.61 (0.96–2.70) | 0.070 | 0.77 (0.25–2.41) | 0.654 | |
| Late | 0.89 (0.67–1.18) | 0.416 | 0.97 (0.67–1.41) | 0.886 | 1.00 (0.78–1.29) | 0.981 | 1.01 (0.73–1.40) | 0.972 | |
Models stratified by trial (except for year of randomisation in univariate models). Toxicity grade = maximum recorded over all cycles for each category. Location of tumour: proximal = proximal humerus/femur; distal = all other sites. Surgery type: amputation includes rotationplasty and disarticulation. Timeliness of surgery: on-time = between 3 d earlier and 10 d later than specified in protocol; early = more than 3 d earlier than specified; late = more than 10 d later than specified.
a
Not included in multivariate model due to overlap with other variables.
b
Timed from date of surgery (includes multivariate model).