Background
Methods
Statistical Methods
Results
Baseline patient characteristics
Characteristic | Number | % | Median (range) | |
---|---|---|---|---|
Gender
| Male | 124 | 53 | |
Age
| Median (range) | 57 (21-88) | ||
Performance status
| ECOG 0 | 105 | 45 | |
ECOG 1 | 122 | 52 | ||
ECOG 2 | 6 | 3 | ||
No. of prior treatments
| 2 (0-14) | |||
0-2 | 135 | 58 | ||
≥ 3 | 98 | 42 | ||
Primary tumor site
| Gastrointestinal | 108 | 46 | |
Thoracic, Head & Neck | 58 | 25 | ||
Breast & Gynecological | 40 | 17 | ||
Urologic: Sarcoma: Other | 9: 5: 13 | 4:2:6 | ||
Type of trial
| Targeted agent alone | 89 | 38.2 | |
Cytotoxic agent alone | 8 | 3.4 | ||
Combined | 136 | 58.4 | ||
No. of metastatic sites
| 3 (1-4) | |||
Locoregional disease* | 20 | 9 | ||
1-2 sites | 138 | 59 | ||
> 2 sites | 75 | 32 | ||
Site of metastasis
| Liver | 121 | 52 | |
Lung | 129 | 55 | ||
Bone | 39 | 17 | ||
Baseline albumin
| 41 g/L (28-48 g/L) | |||
< 35 g/L | 8 | 3 | ||
≥ 35 g/L | 225 | 97 | ||
Baseline LDH
| 224 U/L (93-3132 U/L) | |||
Normal LDH | 142 | 61 | ||
Elevated LDH > ULN | 91 | 39 | ||
Baseline hemoglobin
| 12.5 g/dL (8.2-17.1 g/dL) | |||
< 12 g/dL | 90 | 39 | ||
≥ 12 g/dL | 143 | 61 | ||
Baseline WBC
| 7 × 109/L (2.3-20.7 × 109/L) | |||
≤ 10.5 × 109/L | 203 | 87 | ||
> 10.5 × 109/L | 30 | 13 | ||
Baseline platelets
| 264 × 109/L (106-832 × 109/L) | |||
≤ 400 × 109/L | 204 | 88 | ||
> 400 × 109/L | 29 | 12 |
Patient outcomes: Early mortality, overall survival, and response
Outcome | Number | % | Median (days) | 95% CI (days) | |
---|---|---|---|---|---|
90 day mortality
| Alive ≥ 90 days | 200 | 86 | ||
Alive < 90 days | 33 | 14 | |||
Overall survival
| 320 | 270-365 | |||
Response by RECIST
| Partial Response | 17/196 | 9 | ||
Stable Disease | 92/196 | 47 | |||
Progressive Disease | 87/196 | 44 | |||
Stable disease duration
| 0-3 months | 20/86 | 23 | ||
3-6 months | 46/86 | 54 | |||
> 6 months | 20/86 | 23 | |||
Stable disease duration
| 1-2 cycles | 13/90 | 15 | ||
3-4 cycles | 23/90 | 26 | |||
5-6 cycles | 29/90 | 32 | |||
> 6 cycles | 25/90 | 27 |
Baseline predictors of 90-day mortality
Univariate model | Multivariable model (stepwise) | |||||
---|---|---|---|---|---|---|
Odds Ratios | 95% CI | p-value | Odds Ratios | 95% CI | p-value | |
Male
| 1.42 | 0.67-3.01 | 0.36 | |||
Age ≥ 65 years old
| 0.54 | 0.21-1.38 | 0.21 | |||
Albumin < 35 g/L
| 11.73 | 2.66-51.78 | 0.01 | 8.24 | 1.75-38.81 | 0.008 |
LDH > ULN
| 1.81 | 0.86-3.79 | 0.12 | |||
Metastatic sites > 2
| 3.01 | 1.42-6.38 | 0.01 | 2.57 | 1.15-5.72 | 0.02 |
ECOG Performance Status > 0
| 7.40 | 2.51-21.81 | 0.01 | 6.23 | 2.06-18.83 | 0.001 |
Hemoglobin < 12 g/dL
| 2.47 | 1.167-5.21 | 0.02 | |||
WBC > 10.5 × 10
9
/L
| 2.59 | 1.04-6.44 | 0.04 | |||
Platelets > 400 × 10
9
/L
| 0.97 | 0.31-2.98 | 0.95 | |||
Lymphocytes < 0.7 × 10
9
/L
| 2.21 | 0.94-5.23 | 0.07 | |||
Lung metastases
| 2.04 | 0.92-4.51 | 0.08 | |||
Liver metastases
| 2.04 | 0.94-4.43 | 0.07 | |||
Bone metastases
| 1.41 | 0.57-3.53 | 0.46 | |||
Brain metastases
| 6.22 | 0.38-101.94 | 0.22 | |||
Lymph node metastases
| 2.16 | 1.02-4.54 | 0.04 | |||
Peritoneal metastases
| 0.76 | 0.28-2.10 | 0.60 | |||
Prior treatments ≥ 3
| 0.76 | 0.35-1.64 | 0.48 |
Test Characteristic | PMHI | RMI |
---|---|---|
Score ≥ 2 in multivariate analysis
| OR 7.24 (95% CI: 2.91-18.02), p < 0.0001 | OR 1.08 (95% CI: 0.41-2.89), p = 0.88 |
Sensitivity
| 61% | 36% |
Specificity
| 83% | 85% |
Positive likelihood ratio
| 3.57 | 2.42 |
False positive rate
| 14.6% | 12.9% |
False negative rate
| 5.6% | 9.0% |
Area under curve (AUC)
| 0.782 | 0.696 |
Baseline predictors of overall survival
Univariate model | Multivariable model (stepwise) | ||||||
---|---|---|---|---|---|---|---|
Variables | Median OS (days) | 95% CI | p-value (Log-rank) | Hazard ratio | 95% CI | p-value | |
Gender
| Female | 365 | 276-501 | 0.05 | |||
Male | 270 | 204-346 | |||||
Age
| < 65 years | 325 | 271-400 | 0.81 | |||
≥ 65 years | 297 | 210-398 | |||||
Albumin
| ≥ 35 g/L | 325 | 271-365 | 0.02 | |||
< 35 g/L | 54 | 42-408 | |||||
LDH
| Normal | 366 | 320-501 | 0.001 | |||
Elevated | 210 | 147-276 | 1.75 | 1.24-2.46 | 0.001 | ||
No. of metastatic sites
| ≤ 2 | 358 | 299-446 | 0.0001 | |||
> 2 | 210 | 136-290 | 1.68 | 1.18-2.40 | 0.004 | ||
ECOG Performance Status
| 0 | 366 | 302-464 | 0.02 | |||
> 0 | 270 | 158-325 | 1.42 | 1.00-1.99 | 0.05 | ||
Hemoglobin
| ≥ 12 g/dL | 350 | 273-412 | 0.09 | |||
< 12 g/dL | 276 | 185-346 | |||||
WBC
| ≤ 10.5 × 109/L | 345 | 276-398 | 0.07 | |||
> 10.5 × 109/L | 236 | 103-352 | |||||
Platelets
| ≤ 400 × 109/L | 329 | 273-398 | 0.23 | |||
> 400 × 109/L | 261 | 137-352 | |||||
Lymphocytes
| ≥ 0.7 × 109/L | 346 | 290-400 | 0.04 | |||
< 0.7 × 109/L | 166 | 99-315 | |||||
Lung metastases
| No | 338 | 271-414 | 0.58 | |||
Yes | 302 | 223-365 | |||||
Liver metastases
| No | 366 | 297-501 | 0.01 | |||
Yes | 250 | 191-329 | |||||
Bone metastases
| No | 329 | 276-365 | 0.32 | |||
Yes | 261 | 135-433 | |||||
Brain
| No | 320 | 270-358 | 0.47 | |||
Yes | 269.5 | 40-499 | |||||
Peritoneal Mets
| No | 325 | 250-365 | 0.99 | |||
Yes | 315 | 257-474 | |||||
No. of prior treatments
| < 3 | 302 | 266-365 | 0.76 | |||
≥ 3 | 320 | 227-400 |
Overall Survival Predictors | Hazard Ratio | 95% CI | p-value |
---|---|---|---|
PMHI
| |||
Albumin < 35 g/L
| 1.99 | 0.86-4.58 | 0.11 |
> 2 metastatic sites
| 1.79 | 1.26-2.53 | 0.01 |
ECOG Performance Status > 0
| 1.36 | 0.96-1.91 | 0.08 |
RMI
| |||
Albumin < 35 g/L
| 1.94 | 0.84-4.48 | 0.12 |
> 2 metastatic sites
| 1.74 | 1.23-2.48 | 0.01 |
LDH > ULN
| 1.69 | 1.20-2.38 | 0.01 |
Risk Score | PMHI | RMI | ||||||
---|---|---|---|---|---|---|---|---|
No. | Dead | Censored | Median OS (95% CI) in days | No. | Dead | Censored | Median OS (95% CI) in days | |
Score 0
| 79 | 41 | 38 | 412 (329-515) | 104 | 55 | 49 | 400 (325-561) |
Score 1
| 100 | 58 | 42 | 320 (239-365) | 87 | 53 | 34 | 315 (205-366) |
Score 2
| 51 | 40 | 11 | 154 (87-270) | 39 | 31 | 8 | 137 (104-223) |
Score 3
| 3 | 3 | 0 | 54 (54-408)* | 3 | 3 | 0 | 54 (54-408)* |