Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Variables | Test Cohort (n = 1931) | Validation Cohort (n = 1085) | ||||
---|---|---|---|---|---|---|
N (%) | Missing (%) | N (%) | Missing (%) | p-Value * | ||
Age (continuous; years; median + IQR) | 59 (44.7–70) | 45 (2.3) | 61 (47–74) | 0 (0.0) | <0.0001 | |
Gender | Male | 1038 (53.8) | 0 (0.0) | 615 (56.7) | 0 (0.0) | 0.121 |
Female | 893 (46.2) | 470 (43.3) | ||||
Tumor Location | Upper Extremity | 520 (26.9) | 1 (0.05) | 312 (28.8) | 0 (0.0) | 0.285 |
Lower Extremity | 1410 (73.1) | 773 (71.2) | ||||
Depth | Epifascial | 518 (26.9) | 2 (0.1) | 291 (26.8) | 0 (0.0) | 0.984 |
Subfascial | 1411 (73.1) | 794 (73.2) | ||||
Tumor Size (continuous; cm; median + IQR) | 7 (4–11) | 30 (1.6) | 7.5 (5–12) | 5 (0.5) | 0.026 | |
Histology | Myxoid liposarcoma | 222 (11.6) | 16 (0.8) | 111 (10.2) | 0 (0.0) | <0.0001 |
MPNST | 83 (4.3) | 43 (4.0) | ||||
Myxofibrosarcoma | 451(23.6) | 104 (9.6) | ||||
Synovial Sarcoma | 174 (9.1) | 79 (7.3) | ||||
UPS | 325 (17.0) | 375 (34.6) | ||||
Angiosarcoma/Vascular Sarcoma | 22 (1.1) | 20 (1.8) | ||||
Dedifferentiated/Pleomorphic Liposarcoma | 141 (7.4) | 85 (7.8) | ||||
Leiomyosarcoma | 221 (11.5) | 118 (10.9) | ||||
Others | 276 (14.4) | 150 (13.8) | ||||
Grading | G2 | 719 (37.8) | 30 (1.6) | 382 (35.8) | 19 (1.8) | 0.282 |
G3 | 1182 (62.2) | 684 (64.2) | ||||
Margins | R0 | 1494 (77.4) | 0 (0.0) | 768 (70.8) | 0 (0.0) | <0.0001 |
R1/2 | 437 (22.6) | 317 (29.2) | ||||
CTX | No | 1408 (73.0) | 1 (0. 05) | 1039 (95.8) | 0 (0.0) | <0.0001 |
Neoadjuvant | 262 (13.6) | 40 (3.7) | ||||
Adjuvant | 209 (10.8) | 6 (0.6) | ||||
Neoadjuvant + Adjuvant | 51 (2.6) | 0 (0.0) | ||||
RTX | No | 619 (32.9) | 50 (2.6) | 335 (30.9) | 0 (0.0) | <0.0001 |
Neoadjuvant | 303 (16.1) | 460 (42.4) | ||||
Adjuvant | 956 (50.8) | 275 (25.4) | ||||
Neoadjuvant + Adjuvant | 3 (0.2) | 15 (1.4) | ||||
Follow-up (continuous; months; median + IQR) | 50 (23.3–95) | 11 (0.6) | 56 (21–91) | 0 (0.0) | 0.254 |
Variables | Coefficient | 95%-CI | p-value | ||
---|---|---|---|---|---|
Lower | Upper | ||||
Local Recurrence | |||||
Gender | Male | 1 | 0.011 | ||
Female | 0.698 | 0.529 | 0.921 | ||
Grading | G2 | 1 | 0.199 | ||
G3 | 0.816 | 0.598 | 1.113 | ||
Tumor size | 1.026 | 1.004 | 1.049 | 0.019 | |
Margins | R0 | 1 | <0.001 | ||
R1/R2 | 2.761 | 2.021 | 3.774 | ||
Histology | Myxoid Liposarcoma | 1 | |||
MPNST | 4.227 | 1.837 | 9.729 | 0.001 | |
Myxofibrosarcoma | 4.156 | 2.056 | 8.400 | <0.001 | |
Synovial Sarcoma | 3.116 | 1.429 | 7.014 | 0.005 | |
UPS | 3.373 | 1.620 | 7.025 | 0.001 | |
Angiosarcoma/Vascular Sarcoma | 3.316 | 0.981 | 12.341 | 0.074 | |
Dedifferentiated/Pleomorphic Liposarcoma | 1.727 | 0.719 | 4.143 | 0.221 | |
Leiomyosarcoma | 2.779 | 1.294 | 5.966 | 0.009 | |
Others | 2.385 | 1.123 | 5.065 | 0.024 | |
Neoadjuvant RTX | No | 1 | <0.001 | ||
Yes | 0.298 | 0.178 | 0.494 | ||
Adjuvant RTX | No | 1 | 0.001 | ||
Yes | 0.603 | 0.447 | 0.814 | ||
Adjuvant CTX | No | 1 | 0.008 | ||
Yes | 1.711 | 1.154 | 2.538 | ||
Restricted cubic spline 1 | 2.104 | 1.851 | 2.392 | <0.001 | |
Restricted cubic spline 2 | 1.332 | 1.230 | 1.442 | <0.001 | |
Restricted cubic spline 3 | 0.980 | 0.937 | 1.026 | 0.391 | |
Restricted cubic spline for time-dependent effect of grading | 0.944 | 0.813 | 1.096 | 0.449 | |
Constant | 0.048 | 0.024 | 0.097 | <0.001 | |
Death | |||||
Gender | Male | 1 | 0.005 | ||
Female | 0.736 | 0.595 | 0.910 | ||
Grading | G2 | 1 | <0.001 | ||
G3 | 2.215 | 1.655 | 2.964 | ||
Tumor size | 1.065 | 1.048 | 1.081 | <0.001 | |
Margins | R0 | 1 | 0.296 | ||
R1/R2 | 1.153 | 0.883 | 1.057 | ||
Histology | Myxoid Liposarcoma | 1 | |||
MPNST | 1.205 | 0.664 | 2.187 | 0.540 | |
Myxofibrosarcoma | 1.208 | 0.795 | 1.836 | 0.375 | |
Synovial Sarcoma | 1.461 | 0.888 | 2.404 | 0.136 | |
UPS | 1.150 | 0.753 | 1.758 | 0.517 | |
Angiosarcoma/Vascular Sarcoma | 4.729 | 2.335 | 9.580 | <0.001 | |
Dedifferentiated/Pleomorphic Liposarcoma | 1.420 | 0.863 | 2.338 | 0.167 | |
Leiomyosarcoma | 2.154 | 1.402 | 3.309 | <0.001 | |
Others | 1.516 | 0.975 | 2.356 | 0.065 | |
Neoadjuvant RTX | No | 1 | 0.007 | ||
Yes | 1.543 | 1.127 | 2.111 | ||
Adjuvant RTX | No | 1 | 0.296 | ||
Yes | 1.145 | 0.888 | 1.476 | ||
Adjuvant CTX | No | 1 | 0.022 | ||
Yes | 0.679 | 0.488 | 0.946 | ||
Restricted cubic spline 1 | 4.220 | 3.393 | 5.250 | <0.001 | |
Restricted cubic spline 2 | 1.487 | 1.329 | 1.663 | <0.001 | |
Restricted cubic spline 3 | 0.965 | 0.921 | 1.011 | 0.139 | |
Restricted cubic spline for time-dependent effect of grading | 0.714 | 0.580 | 0.889 | 0.002 | |
Constant | 0.050 | 0.032 | 0.078 | <0.001 |
Coefficient | 95%-CI | p-Value | |||
---|---|---|---|---|---|
Lower | Upper | ||||
Distant Metastasis | |||||
Gender | Male | 1 | <0.001 | ||
Female | 0.720 | 0.605 | 0.857 | ||
Grading | G2 | 1 | <0.001 | ||
G3 | 1.737 | 1.412 | 2.136 | ||
Tumor size | 1.069 | 1.056 | 1.083 | <0.001 | |
Margins | R0 | 1 | 0.006 | ||
R1/R2 | 1.347 | 1.087 | 1.669 | ||
Histology | Myxoid Liposarcoma | 1 | |||
MPNST | 1.825 | 1.158 | 2.875 | 0.009 | |
Myxofibrosarcoma | 1.064 | 0.750 | 1.508 | 0.729 | |
Synovial Sarcoma | 1.986 | 1.343 | 3.976 | 0.001 | |
UPS | 1.445 | 1.033 | 2.022 | 0.032 | |
Angiosarcoma/Vascular Sarcoma | 2.016 | 1.022 | 3.797 | 0.043 | |
Dedifferentiated/Pleomorphic Liposarcoma | 1.209 | 0.786 | 1.861 | 0.387 | |
Leiomyosarcoma | 2.689 | 1.900 | 3.797 | <0.001 | |
Other | 1.835 | 1.293 | 2.604 | 0.001 | |
Neoadjuvant RTX | No | 1 | 0.005 | ||
Yes | 1.351 | 1.097 | 1.663 | ||
Restricted cubic spline 1 | 2.928 | 2.591 | 3.308 | <0.001 | |
Restricted cubic spline 2 | 1.458 | 1.374 | 1.547 | <0.001 | |
Restricted cubic spline 3 | 0.965 | 0.926 | 1.006 | 0.096 | |
Restricted cubic spline 4 | 1.040 | 1.020 | 1.062 | <0.001 | |
Restricted cubic spline 5 | 0.995 | 0.982 | 1.008 | 0.427 | |
Restricted cubic spline for time-dependent effect of grading | 0.723 | 0.640 | 0.817 | <0.001 | |
Constant | 0.108 | 0.078 | 0.149 | <0.001 | |
Death | |||||
Gender | Male | 1 | 0.864 | ||
Female | 0.968 | 0.666 | 1.407 | ||
Grading | G2 | 1 | 0.018 | ||
G3 | 1.873 | 1.116 | 3.145 | ||
Tumor size | 1.023 | 0.997 | 1.050 | 0.087 | |
Margins | R0 | 1 | 0.198 | ||
R1/R2 | 1.378 | 0.846 | 2.244 | ||
Histology | Myxoid Liposarcoma | 1 | |||
MPNST | 2.506 | 0.844 | 7.442 | 0.098 | |
Myxofibrosarcoma | 3.136 | 1.325 | 7.418 | 0.009 | |
Synovial Sarcoma | 0.600 | 0.150 | 2.416 | 0.472 | |
UPS | 1.781 | 0.714 | 4.443 | 0.216 | |
Angiosarcoma/Vascular Sarcoma | 11.165 * | 3.507 * | 35.542 * | <0.001 * | |
Dedifferentiated/Pleomorphic Liposarcoma | 3.331 | 1.259 | 8.812 | 0.015 | |
Leiomyosarcoma | 1.798 | 0.675 | 4.782 | 0.241 | |
Other | 2.408 | 0.963 | 4.782 | 0.060 | |
Neoadjuvant RTX | No | 1 | 0.048 | ||
Yes | 0.541 | 0.295 | 0.993 | ||
Restricted cubic spline 1 | 3.604 | 2.494 | 5.211 | <0.001 | |
Restricted cubic spline 2 | 1.270 | 1.060 | 1.523 | 0.010 | |
Restricted cubic spline 3 | 0.952 | 0.863 | 1.049 | 0.316 | |
Restricted cubic spline 4 | 0.953 | 0.908 | 1.001 | 0.057 | |
Restricted cubic spline 5 | 0.974 | 0.569 | 1.199 | 0.097 | |
Restricted cubic spline for time-dependent effect of grading | 0.826 | 0.569 | 1.199 | 0.314 | |
Constant | 0.010 | 0.004 | 0.025 | <0.001 |
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Smolle, M.A.; van de Sande, M.; Callegaro, D.; Wunder, J.; Hayes, A.; Leitner, L.; Bergovec, M.; Tunn, P.-U.; van Praag, V.; Fiocco, M.; et al. Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models. Cancers 2020, 12, 47. https://doi.org/10.3390/cancers12010047
Smolle MA, van de Sande M, Callegaro D, Wunder J, Hayes A, Leitner L, Bergovec M, Tunn P-U, van Praag V, Fiocco M, et al. Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models. Cancers. 2020; 12(1):47. https://doi.org/10.3390/cancers12010047
Chicago/Turabian StyleSmolle, Maria Anna, Michiel van de Sande, Dario Callegaro, Jay Wunder, Andrew Hayes, Lukas Leitner, Marko Bergovec, Per-Ulf Tunn, Veroniek van Praag, Marta Fiocco, and et al. 2020. "Individualizing Follow-Up Strategies in High-Grade Soft Tissue Sarcoma with Flexible Parametric Competing Risk Regression Models" Cancers 12, no. 1: 47. https://doi.org/10.3390/cancers12010047