Article Figures & Data
Figures
- Figure 1.
A, patients by tumor type (total n = 1,181). *Gastrointestinal tumors (N = 392) include colon (185); pancreas (61); rectum (46); esophagus (26); appendix (18); small Intestine (14); gastric (12); hepatocellular (11); cholangiocarcinoma (8); anus (6); cholangiocarcinoma and hepatocellular (2); peritoneum (2); and liver, NOS (1), **Others (N = 336) include melanoma (83); thyroid (82); sarcoma (52); lymphoma (19); hematologic other (19); endocrine (16); cancer of unknown primary (16); neuroendocrine (15); non-melanoma skin (15); CNS tumors (12); and mycosis fungoides (7). B, type of phase I trial.
- Figure 2.
A, Kaplan–Meier survival curve for overall survival in 1,181 patients. Ticks represent patients still alive and hence censored at last follow-up. B, Kaplan–Meier survival curve for the 5 risk groups based on MDACC score (n = 1,153 patients for whom all baseline data points were available). Ticks represent patients still alive and hence censored at last follow-up. C, Kaplan–Meier survival curve for the 4 risk groups based on RMH score (n = 1,169 patients for whom all baseline data points were available). Ticks represent patients still alive and hence censored at last follow-up.
- Figure 3.
Proposed algorithm to assign patients to 1 of the 5 risk groups that predict survival characterized by summing the number of risk factors present at the time of first visit to the phase I clinic. All risk factors carry equal weight.
Tables
- Table 1.
Univariate analysis of survival in 1,181 patients by characteristics at first visit to phase I clinic
N (%) Number of deaths Median survival, mo (95% CI) Survival rate (1 y), % Variables 1,181 795 10.0 (9.1–10.9) 44 P Age, y ≤60 660 (55.9) 434 10.9 (9.7–12.1) 46 0.125 >60 521 (44.1) 361 9.1 (8.1–10.1) 41 Sex Female 594 (50.3) 392 10.1 (8.8–11.2) 44 0.86 Male 587 (49.7) 403 9.8 (8.5–11.4) 44 Tumor classification Breast 112 (9.5) 83 8.3 (6.6–10.8) 35 <0.0001 Gastrointestinal 392 (33.2) 310 7.4 (6.6–8.1) 30 Genitourinary 110 (9.3) 67 12.8 (9.6–17.5) 54 Gynecologic 82 (6.9) 55 8.3 (6.8–11.0) 35 Lung/thoracic/head and neck 149 (12.6) 81 15.5 (12.2–23.1) 59 Others 336 (28.5) 199 15.5 (12.0–18.3) 55 ECOG PSa 0 369 (31.2) 234 13.8 (11.6–17.1) 54 <0.0001 1 705 (59.7) 470 9.1 (8.0–10.3) 41 2 83 (7.0) 68 4.1 (3.5–6.6) 26 3 7 (0.6) 7 3.1 (2.9, NA) 29 Liver metastases No 683 (57.8) 413 12.8 (11.3–15.2) 52 <0.0001 Yes 498 (42.2) 382 7.6 (6.6–8.4) 33 History of thromboembolism No 991 (83.9) 656 10.8 (9.7–11.7) 46 0.0005 Yes 190 (16.1) 139 7.7 (6.2–9.5) 33 Platelets,a K/UL <140 112 (9.5) 84 8.3 (6.8–12.7) 39 <0.0001 140–440 928 (78.6) 603 10.5 (9.6–11.8) 46 >440 136 (11.5) 106 7.9 (6.3–10.1) 32 Albumin,a g/dL ≥3.5 1,041 (88.1) 684 10.9 (10.1–12.0) 47 <0.0001 <3.5 133 (11.3) 107 5.4 (3.9–6.8) 20 Number of prior therapies 0 66 (5.6) 25 25.3 (22.8 to NA) 81 <0.0001 1 113 (9.6) 65 16.9 (14.6–25.4) 62 2 192 (16.3) 125 9.2 (7.7–12.0) 42 3 201 (17.0) 132 9.4 (7.8–11.5) 42 4 187 (15.8) 137 9.0 (7.5–10.8) 37 5+ 422 (35.7) 311 8.3 (7.5–9.7) 38 Prior radiation No 593 (50.2) 390 10.7 (9.5–12.4) 46 0.028 Yes 588 (49.8) 405 9.2 (8.1–10.7) 42 Prior surgery No 293 (24.8) 202 9.9 (8.1–11.4) 43 0.3253 Yes 888 (75.2) 593 10.1 (8.8–11.3) 44 Number of metastatic sites ≤2 734 (62.2) 457 12.4 (10.9–14.6) 51 <0.0001 >2 447 (37.8) 338 7.4 (6.7–8.1) 31 LDH,a IU/L ≤618 755 (63.9) 449 14.0 (12.4–16.0) 55 <0.0001 >618 419 (35.5) 343 6.8 (6.1–7.4) 24 RMH scorea 0 and 1 908 (76.9) 573 12.3 (11.2–13.8) 51 <0.0001 >1 261 (22.1) 216 5.5 (4.8–6.6) 19 Abbreviation: PS, performance status.
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↵aBaseline data at first visit to phase I clinic were not available for all patients for variables including: ECOG PS (17 patients), platelets (5 patients), albumin (7 patients), LDH (7 patients), and RMH score (12 patients).
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- Table 2.
Multivariate analysis of survival by independent predictors, including the RMH score variables (LDH, number of metastatic sites >2, and albumin) individually and then by including the RMH score by itself as a single variable
Risk factors RR for death (95% CI) P Albumin < 3.5 g/dLa 1.66 (1.34–2.05) <0.0001 Number of metastatic sites > 2a 1.34 (1.16–1.55) 0.0001 LDH > 618 IU/La,b 1.78 (1.53–2.06) <0.0001 Gastrointestinal tumor type 1.55 (1.34–1.80) <0.0001 ECOG PS ≥ 1 1.32 (1.13–1.55) 0.0004 Platelets > 440 K/UL 1.35 (1.10–1.67) 0.0047 Number of prior therapies ≥ 3 1.33 (1.13–1.57) 0.0007 RMH score as single variable RMH score > 1 1.97 (1.67–2.32) <0.0001 Gastrointestinal tumor type 1.65 (1.43–1.92) <0.0001 ECOG PS ≥ 1 1.33 (1.13–1.55) 0.0004 Platelet > 440 K/UL 1.43 (1.16–1.76) 0.0008 Number of prior therapies ≥ 3 1.43 (1.21–1.68) <0.0001 - Table 3.
Internal validation study of independent predictors of survival
Variables RR for death (95% CI) P Training data (randomly selected 50% of patients) Albumin < 3.5 g/dL 1.58 (1.16–2.15) 0.0035 Number of metastatic sites > 2 1.42 (1.15–1.75) 0.0012 LDH > 618 IU/L 1.74 (1.40–2.15) <0.0001 Gastrointestinal tumor type 1.68 (1.36–2.07) <0.0001 ECOG PS ≥ 1 1.32 (1.05–1.66) 0.0160 Platelet > 440 K/UL 1.40 (1.05–1.88) 0.0230 Prior treatment ≥ 3 1.40 (1.10–1.78) 0.0063 Validation data (the remaining 50% of patients) Albumin < 3.5 g/dL 1.69 (1.25–2.29) 0.0006 Number of metastatic sites > 2 1.26 (1.03–1.55) 0.0260 LDH > 618 IU/L 1.83 (1.48–2.27) <0.0001 Gastrointestinal tumor type 1.42 (1.15–1.76) 0.0010 ECOG PS ≥ 1 1.32 (1.07–1.64) 0.0110 Platelet > 440 K/ULa 1.35 (0.99–1.84) 0.0540 Prior treatment ≥ 3a 1.23 (0.98–1.55) 0.0730 Abbreviations: PS, performance status; RR, relative risk.
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↵aElevated platelet levels (>440 K/UL) and ≥3 prior therapies are not statistically significant in the validation set and are therefore not included in our prognostic score.
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Supplementary Data
Files in this Data Supplement:
- Supplementary Figure 1A - PDF file, 95KB, Kaplan - Meier survival curves by albumin levels (n=1,174 patients for whom albumin levels were available). Median survival is 10.9 months (95% CI: 10.1 - 12.0) for albumin <3.5 g/dL, and 5.4 months (95% CI: 3.9 - 6.8) for albumin ≥3.5 g/dL (Log-rank p-value <0.0001).
- Supplementary Figure 1B - PDF file, 94KB, Kaplan - Meier survival curves by LDH levels (n=1,174 patients for whom LDH levels were available). Median survival is 14.0 months (95% CI: 12.4 - 16.0) for LDH ≤618 IU/L, and 6.8 months (95% CI: 6.1 - 7.4) for LDH >618 IU/L (Log-rank p-value <0.0001).
- Supplementary Figure 1C - PDF file, 97KB, Kaplan - Meier survival curves by number of metastatic sites (n=1,181 patients). Median survival is 12.4 months (95% CI: 10.9 - 14.6) for ≤2 metastatic sites, and 7.4 months (95% CI: 6.7 - 8.1) for >2 metastatic sites (Log-rank p-value <0.0001).
- Supplementary Figure 1D - PDF file, 95KB, Kaplan - Meier survival curves by ECOG performance status (0 versus 1+) (n=1,164 patients for whom ECOG performance status was available). Median survival is 13.8 months (95% CI: 11.6 - 17.1) for ECOG performance status=0, and 8.3 months (95% CI: 7.7 - 9.5) for ECOG performance status ≥1 (Log-rank p-value <0.0001).
- Supplementary Figure 1E - PDF file, 97KB, Kaplan - Meier survival curves by tumor type (gastrointestinal versus non-gastrointestinal) (n=1, 181 patients). Median survival is 12.2 months (95% CI: 10.9 - 14.0) for non-gastrointestinal tumors, and 7.4 months (95% CI: 6.6 - 8.1) for the gastrointestinal tumor (Log-rank p-value <0.0001).
- Supplementary Figure 2A - PDF file, 96KB, Kaplan - Meier survival curves by dichotomized MDACC score (n=1,153 patients for whom all baseline data points were available). Median survival is 13.7months (95% CI: 12.1 - 15.5) for MDACC score ≤2, and 5.7 months (95% CI: 6.3 - 7.4) for MDACC score >2 (Log-rank p-value<0.0001).
- Supplementary Figure 2B - PDF file, 90KB, Kaplan - Meier survival curves by dichotomized RMH score (n=1,169 patients for whom RMH score was available). Median survival is 12.3 months (95% CI: 11.2 - 13.8) for RMH score ≤1, and 5.5 months (95% CI: 4.8 - 6.6) for RMH score >1 (Log-rank p-value <0.0001).
- Supplementary Table 1 - PDF file, 72KB, Comparison of prognostic models: the MDACC score vs. the RMH score showing number of patients by variable (p<0.00001).
Volume 18, Issue 10
