Statin Use After Colorectal Cancer Diagnosis and Survival: A Population-Based Cohort Study
Abstract
Purpose
Patients and Methods
Results
Conclusion
Introduction
Patients and Methods
Data Source
Study Design
Exposure Data
Covariates
Statistical Analysis
Results
Patient Cohort
Characteristic | Statin Use After Diagnosis | |||
---|---|---|---|---|
Ever Used No. of Patients/% | Never Used No. of Patients/% | |||
Year of diagnosis | ||||
1998-2000 | 317 | 12 | 961 | 19 |
2001-2003 | 665 | 25 | 1,294 | 26 |
2004-2006 | 816 | 31 | 1,341 | 27 |
2007-2009 | 864 | 32 | 1,399 | 28 |
Age at diagnosis, years | ||||
< 50 | 37 | 1 | 364 | 7 |
50-59 | 233 | 9 | 848 | 17 |
60-69 | 850 | 32 | 1,216 | 24 |
70-79 | 1,077 | 40 | 1,584 | 32 |
80-89 | 452 | 17 | 911 | 18 |
≥ 90 | 13 | 0 | 72 | 1 |
Men | 1,650 | 62 | 2,586 | 52 |
Stage | ||||
1 | 550 | 21 | 772 | 15 |
2 | 1,154 | 43 | 2,090 | 42 |
3 | 958 | 36 | 2,133 | 43 |
Grade | ||||
Well | 175 | 7 | 274 | 5 |
Moderate | 2,000 | 75 | 3,639 | 73 |
Poor | 319 | 12 | 760 | 15 |
Missing | 168 | 6 | 322 | 6 |
Treatment within 6 months of cancer diagnosis | 2,548 | 96 | 4,791 | 96 |
Surgery | ||||
Chemotherapy | 660 | 25 | 1,619 | 32 |
Radiotherapy | 297 | 11 | 610 | 12 |
Smoking status before cancer diagnosis | ||||
Nonsmoker | 1,157 | 43 | 2,332 | 47 |
Former smoker | 966 | 36 | 1,208 | 24 |
Current smoker | 289 | 11 | 644 | 13 |
Missing | 250 | 9 | 811 | 16 |
Alcohol consumption before diagnosis | ||||
Never | 316 | 12 | 588 | 12 |
Ever | 1,787 | 67 | 2,943 | 59 |
Missing | 559 | 21 | 1,464 | 29 |
BMI before diagnosis, kg/m2 | 27.6 | 4.7 | 26.1 | 4.6 |
Mean | ||||
SD | ||||
Underweight (< 18.5) | 22 | 1 | 85 | 2 |
Normal (18.5 to 25) | 662 | 25 | 1,485 | 30 |
Overweight (25-30) | 999 | 38 | 1,480 | 30 |
Obese (> 30) | 589 | 22 | 616 | 12 |
Missing | 390 | 15 | 1,329 | 27 |
Deprivation quintile | ||||
First (least deprived) | 635 | 24 | 1,358 | 27 |
Second | 619 | 23 | 1,266 | 25 |
Third | 575 | 22 | 999 | 20 |
Fourth | 490 | 18 | 840 | 17 |
Fifth (most deprived) | 339 | 13 | 523 | 10 |
Missing | 4 | 0 | 9 | 0 |
Comorbidity before cancer diagnosis | ||||
Cerebrovascular disease | 251 | 9 | 172 | 3 |
Chronic pulmonary disease | 453 | 17 | 764 | 15 |
Congestive heart disease | 120 | 5 | 137 | 3 |
Diabetes | 607 | 23 | 213 | 4 |
Myocardial infarction | 320 | 12 | 82 | 2 |
Peptic ulcer disease | 178 | 7 | 239 | 5 |
Peripheral vascular disease | 172 | 6 | 102 | 2 |
Renal disease | 218 | 8 | 146 | 3 |
Medication after diagnosis | ||||
Low-dose aspirin use (in exposure period) | 1,646 | 62 | 898 | 18 |
ACE use (in exposure period) | 1,445 | 54 | 977 | 20 |
Metformin use (in exposure period) | 550 | 21 | 148 | 3 |
Association Between Statin Use and Survival
Medication Use After Diagnosis | Cancer-Specific Mortality | All Patients | Person Years | Unadjusted HR (n = 7,657) | 95% CI | P | Adjusted HR* (n = 7,657) | 95% CI | P | Fully Adjusted HR† (n = 6,178) | 95% CI | P |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Statin nonuser | 1,337 | 4,995 | 21,770 | 1.00 | — | 1.00 | — | 1.00 | — | |||
Statin user‡ | 346 | 2,662 | 9,047 | 0.72 | 0.64 to 0.81 | < .001 | 0.68 | 0.59 to 0.79 | < .001 | 0.71 | 0.61 to 0.84 | < .001 |
Statin user, 1 to 11 prescriptions§ | 158 | 745 | 3,373 | 0.70 | 0.59 to 0.83 | < .001 | 0.69 | 0.57 to 0.82 | < .001 | 0.73 | 0.60 to 0.88 | < .001 |
Statin user ≥ 12 prescriptions§ | 188 | 1,917 | 5,672 | 0.73 | 0.63 to 0.86 | < .001 | 0.71 | 0.60 to 0.85 | < .001 | 0.70 | 0.57 to 0.85 | < .001 |
Statin user 1 to 365 DDD§ | 170 | 687 | 3,257 | 0.79 | 0.68 to 0.93 | .005 | 0.76 | 0.64 to 0.90 | .002 | 0.79 | 0.65 to 0.95 | .01 |
Statin user ≥ 365 DDD§ | 176 | 1,975 | 5,789 | 0.65 | 0.56 to 0.77 | < .001 | 0.65 | 0.54 to 0.78 | < .001 | 0.64 | 0.53 to 0.79 | < .001 |
Medication Use After Diagnosis | All-Cause Mortality | All Patients | Person Years | Unadjusted HR (n = 7,657) | 95% CI | P | Adjusted HR* (n = 7,657) | 95% CI | P | Fully Adjusted HR† (n = 6,178) | 95% CI | P |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Statin nonuser | 1,963 | 4,995 | 21,770 | 1.00 | 1.00 | 1.00 | ||||||
Statin user‡ | 678 | 2,662 | 9,046 | 0.88 | 0.81 to 0.96 | .006 | 0.72 | 0.65 to 0.80 | < .001 | 0.75 | 0.66 to 0.84 | < .001 |
Statin user, 1 to 11 prescriptions§ | 269 | 745 | 3,373 | 0.85 | 0.74 to 0.96 | .01 | 0.73 | 0.63 to 0.84 | < .001 | 0.74 | 0.64 to 0.87 | < .001 |
Statin user, ≥ 12 prescriptions§ | 409 | 1,917 | 5,672 | 0.91 | 0.82 to 1.02 | .10 | 0.74 | 0.65 to 0.84 | < .001 | 0.75 | 0.65 to 0.86 | < .001 |
Statin user, 1 to 365 DDD§ | 281 | 687 | 3,257 | 0.92 | 0.82 to 1.05 | .22 | 0.77 | 0.67 to 0.88 | < .001 | 0.78 | 0.68 to 0.91 | .001 |
Statin user, ≥ 365 DDD§ | 397 | 1,975 | 5,789 | 0.86 | 0.76 to 0.96 | .01 | 0.71 | 0.62 to 0.81 | < .001 | 0.72 | 0.62 to 0.83 | < .001 |
Sensitivity/Secondary Analyses
Analysis | Users | Nonusers | Unadjusted | Fully Adjusteda | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Cancer-Specific Mortality | All Patients | Person Years | Cancer-Specific Mortality | All Patients | Person Years | HR | 95% CI | P | HR | 95% CI | P | |
Statin users v nonusers, after diagnosis | ||||||||||||
Main analysis | 346 | 2,662 | 9,047 | 1,337 | 4,995 | 21,770 | 0.72 | 0.64 to 0.81 | < .001 | 0.71 | 0.61 to 0.84 | < .001 |
Subgroup analyses | ||||||||||||
Colon cancer patients | 219 | 1,726 | 5,824 | 834 | 3,228 | 13,738 | 0.72 | 0.62 to 0.83 | < .001 | 0.76 | 0.62 to 0.92 | .006 |
Rectal cancer patients (including rectosigmoid junction) | 127 | 936 | 3,222 | 503 | 1,767 | 8,032 | 0.71 | 0.59 to 0.86 | .001 | 0.63 | 0.48 to 0.82 | .001 |
Excluding patients ≤ 50 years | 343 | 2,616 | 8,866 | 1,226 | 4,577 | 20,003 | 0.73 | 0.64 to 0.82 | < .001 | 0.74 | 0.63 to 0.86 | < .001 |
Sex | ||||||||||||
Men | 228 | 1,650 | 5,611 | 746 | 2,586 | 11,311 | 0.71 | 0.61 to 0.82 | < .001 | 0.64 | 0.52 to 0.78 | <0.001 |
Women | 118 | 1,012 | 3,435 | 591 | 2,409 | 10,459 | 0.71 | 0.58 to 0.86 | .001 | 0.85 | 0.66 to 1.09 | .19 |
Stage | ||||||||||||
1 | 23 | 550 | 1,980 | 72 | 772 | 4,160 | 0.69 | 0.43 to 1.11 | .13 | 0.79 | 0.39 to 1.60 | .52 |
2 | 108 | 1,154 | 4155 | 386 | 2,090 | 10,038 | 0.76 | 0.61 to 0.93 | .01 | 0.81 | 0.61 to 1.07 | .14 |
3 | 215 | 958 | 2,912 | 879 | 2,133 | 7,572 | 0.73 | 0.63 to 0.85 | < .001 | 0.69 | 0.57 to 0.84 | < .001 |
Surgically treated | 332 | 2,548 | 8,604 | 1,265 | 4791 | 20,976 | 0.73 | 0.65 to 0.83 | < .001 | 0.75 | 0.64 to 0.88 | <0.001 |
Diabetes before diagnosis | ||||||||||||
Yes | 86 | 2,055 | 2,040 | 79 | 4,782 | 928 | 0.57 | 0.42 to 0.77 | < .001 | 0.76 | 0.64 to 0.90 | .002 |
No | 260 | 607 | 7,006 | 1,258 | 213 | 20,842 | 0.73 | 0.64 to 0.83 | < .001 | 0.52 | 0.34 to 0.78 | .002 |
BMI before diagnosis, kg/m2 | ||||||||||||
≤ 25 | 98 | 684 | 2,300 | 399 | 1,570 | 6,889 | 0.86 | 0.69 to 1.08 | .19 | 0.85 | 0.64 to 1.13 | .26 |
> 25 | 199 | 1,588 | 5,437 | 547 | 2,096 | 9,207 | 0.69 | 0.59 to 0.81 | < .001 | 0.68 | 0.55 to 0.84 | < .001 |
Prediagnosis statin use | ||||||||||||
Nonusersb | 96 | 1,032 | 3,585 | 1,182 | 4,518 | 19,536 | 0.69 | 0.56 to 0.85 | .001 | 0.66 | 0.50 to 0.85 | .002 |
Usersb | 226 | 1,469 | 4,817 | 27 | 86 | 274 | 0.55 | 0.37 to 0.82 | .003 | 0.59 | 0.37 to 0.94 | .03 |
Sensitivity analyses: statin users v nonusers, after diagnosis | ||||||||||||
Adjusting for aspirin in categoriesc | 346 | 2,662 | 9,047 | 1,337 | 4,995 | 21,770 | 0.72 | 0.64 to 0.81 | < .001 | 0.71 | 0.61 to 0.84 | .001 |
Increasing lag to 1 year | 323 | 2,548 | 8,347 | 1,360 | 5,109 | 22,470 | 0.75 | 0.67 to 0.85 | < .001 | 0.77 | 0.66 to 0.90 | .001 |
Increasing lag to 2 yearsd | 204 | 2,139 | 5,987 | 860 | 4,470 | 17,704 | 0.83 | 0.71 to 0.97 | .02 | 0.84 | 0.69 to 1.02 | .09 |
Increasing lag to 2 years, user status based on ≥ 365 DDDsd | 77 | 1,361 | 3,281 | 987 | 5,248 | 20,411 | 0.72 | 0.56 to 0.91 | .01 | 0.75 | 0.56 to 0.99 | .04 |
Statin user status based on ≥ 36 prescriptions | 44 | 868 | 2,053 | 1,639 | 6,789 | 28,764 | 0.74 | 0.54 to 1.01 | .06 | 0.72 | 0.50 to 1.03 | .08 |
Available BMI before diagnosis (adjusted for diagnosis)e | 297 | 2,272 | 7,738 | 946 | 3,666 | 16,096 | 0.74 | 0.65 to 0.85 | < .001 | 0.74 | 0.62 to 0.87 | < .001 |
Not restricted to stage 1 to 3 (or known stage)f | 562 | 3,478 | 11,392 | 2,162 | 6,879 | 27,563 | 0.75 | 0.69 to 0.83 | < .001 | 0.71 | 0.63 to 0.79 | < .001 |
Based on first year after diagnosisg | 275 | 1,698 | 5,742 | 1,408 | 5,959 | 25,074 | 0.76 | 0.66 to 0.86 | < .001 | 0.78 | 0.66 to 0.92 | .004 |
Propensity score matched analysish | 165 | 1,020 | 3,671 | 214 | 1,020 | 3,330 | 0.72 | 0.58 to 0.88 | .001 | |||
Prediagnostic statin use | ||||||||||||
Statin users v nonusers before diagnosisi | 1,018 | 2,990 | 8,899 | 4,473 | 11,036 | 37,553 | 0.85 | 0.79 to 0.90 | < .001 | 0.86 | 0.79 to 0.93 | <.001 |
Year of diagnosis before 2006 | 416 | 1,128 | 4,514 | 3,172 | 7,266 | 28,615 | 0.80 | 0.73 to 0.89 | < .001 | 0.81 | 0.72 to 0.92 | .001 |
Available BMI before diagnosis (and adjusted for diagnosis)j | 927 | 2,674 | 7,934 | 3,086 | 7,957 | 28,045 | 0.92 | 0.86 to 0.99 | .03 | 0.91 | 0.83 to 0.99 | .03 |
Discussion
Acknowledgment
The JCO Exclusive series features interviews with authors of recent JCO and JOP Original Reports
JCO Exclusive Coverage is a new series of articles on ASCO.org that are designed to provide quick insight and additional author perspectives on select studies recently published in Journal of Clinical Oncology and Journal of Oncology Practice. Based on interviews conducted with the lead or corresponding researchers behind JCO and JOP Original Reports, Exclusive Coverage articles convey the authors’ thoughts on their study's key points and significance for clinical practice. The articles are written in an accessible style designed for quick reading.
To read story: Statins May Reduce Death Among Patients With Colorectal Cancer
The JCO Exclusive Coverage series features interviews with authors
of recent JCO and JOP Original Reports
JCO Exclusive Coverage is a new series of articles on ASCO.org that are designed to provide quick insight and additional author perspectives on select studies recently published in Journal of Clinical Oncology and Journal of Oncology Practice. Based on interviews conducted with the lead or corresponding researchers behind JCO and JOP Original Reports, Exclusive Coverage articles convey the authors' thoughts on their study's key points and significance for clinical practice. The articles are written in an accessible style designed for quick reading.
Read the story: Statins May Reduce Death Among Patients With Colorectal Cancer
Authors' Disclosures of Potential Conflicts of Interest
References
Appendix
Medication Use After Diagnosis | Cancer-Specific Mortality | All Patients | Person Years | Unadjusted HR (n = 7,657) | 95% CI | P | Adjusted HR* (n = 7,657) | 95% CI | P | Fully Adjusted HR† (n = 6,178) | 95% CI | P |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Simvastatin use | ||||||||||||
No | 1,445 | 5,544 | 24,145 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 238 | 2,113 | 6,670 | 0.71 | 0.62 to 0.81 | < .001 | 0.71 | 0.61 to 0.83 | < .001 | 0.72 | 0.61 to 0.85 | < .001 |
Atorvastatin use | ||||||||||||
No | 1,575 | 6,907 | 27,914 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 108 | 750 | 2,903 | 0.77 | 0.64 to 0.94 | .01 | 0.81 | 0.66 to 0.99 | .04 | 0.91 | 0.73 to 1.13 | .38 |
Pravastatin | ||||||||||||
No | 1,661 | 7,474 | 30,165 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 22 | 183 | 652 | 0.76 | 0.50 to 1.16 | .20 | 0.80 | 0.52 to 1.22 | .29 | 0.79 | 0.50 to 1.23 | .29 |
Rosuvastatin | ||||||||||||
No | 1,674 | 7,549 | 30,445 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 9 | 108 | 372 | 0.57 | 0.29 to 1.09 | .09 | 0.57 | 0.30 to 1.11 | .10 | 0.49 | 0.22 to 1.10 | .08 |
Fluvastatin | ||||||||||||
No | 1,675 | 7,622 | 30,630 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 8 | 35 | 186 | 1.01 | 0.50 to 2.01 | .99 | 1.00 | 0.50 to 2.01 | .99 | 1.23 | 0.58 to 2.61 | .59 |
Medication Use After Diagnosis | All-Cause Mortality | All Patients | Person Years | Unadjusted HR (n = 7,657) | 95% CI | P | Adjusted HR* (n = 7,657) | 95% CI | P | Fully Adjusted HR† (n = 6,178) | 95% CI | P |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Simvastatin | ||||||||||||
No | 2,149 | 5,544 | 24,146 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 492 | 2,113 | 6,670 | 0.89 | 0.81 to 0.98 | .02 | 0.77 | 0.69 to 0.86 | < .001 | 0.79 | 0.70 to 0.90 | < .001 |
Atorvastatin | ||||||||||||
No | 2,438 | 6,907 | 27,914 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 203 | 750 | 2902 | 0.86 | 0.74 to 0.99 | .04 | 0.80 | 0.69 to 0.93 | .004 | 0.84 | 0.72 to 099 | .04 |
Pravastatin | ||||||||||||
No | 2,601 | 7,474 | 30,165 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 40 | 183 | 652 | 0.78 | 0.57 to 1.06 | .11 | 0.71 | 0.52 to 0.97 | .03 | 0.65 | 0.46 to 0.91 | .01 |
Rosuvastatin | ||||||||||||
No | 2,621 | 7,549 | 30,445 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 20 | 108 | 372 | 0.69 | 0.45 to 1.08 | .10 | 0.65 | 0.42 to 1.00 | .05 | 0.61 | 0.36 to 1.01 | .06 |
Fluvastatin | ||||||||||||
No | 2,628 | 7,622 | 30,630 | 1.00 | 1.00 | 1.00 | ||||||
Yes‡ | 13 | 35 | 186 | 0.90 | 0.52 to 1.55 | .70 | 0.82 | 0.47 to 1.42 | .48 | 1.00 | 0.57 to 1.78 | .99 |
Medication Usage After Diagnosis | Cancer-Specific Mortality | All Patients | Person Years | Unadjusted HR | 95% CI | P | Fully Adjusted HR* | 95% CI | P |
---|---|---|---|---|---|---|---|---|---|
No aspirin and no statin use | 1,122 | 4,097 | 18,310 | 1.00 | — | 1.00 | — | ||
Aspirin use, but no statin use | 215 | 898 | 3,460 | 1.11 | 0.95 to 1.28 | .18 | 1.06 | 0.90 to 1.27 | .49 |
No aspirin use, but statin use | 131 | 1,016 | 3,632 | 0.67 | 0.56 to 0.80 | < .001 | 0.70 | 0.57 to 0.86 | .001 |
Aspirin and statin use | 215 | 1,646 | 5,414 | 0.77 | 0.66 to 0.89 | < .001 | 0.78 | 0.65 to 0.94 | .009 |
Test for interaction between statin and aspirin use | .79 | .74 |
Characteristic | Statin-User Group | Propensity-Matched Control Group | ||
---|---|---|---|---|
No. of Patients | % | No. of Patients | % | |
Year of diagnosis | ||||
1998-2000 | 46 | 5 | 83 | 8 |
2001-2003 | 189 | 19 | 190 | 19 |
2004-2006 | 370 | 36 | 280 | 27 |
2007-2009 | 415 | 41 | 467 | 46 |
Age at diagnosis, years | ||||
< 50 | 11 | 1 | 34 | 3 |
50-59 | 81 | 8 | 99 | 10 |
60-69 | 318 | 31 | 238 | 23 |
70-79 | 429 | 42 | 371 | 36 |
80-89 | 175 | 17 | 257 | 25 |
≥ 90 | 6 | 1 | 21 | 2 |
Male sex | 602 | 59 | 589 | 58 |
Stage | ||||
1 | 180 | 18 | 173 | 17 |
2 | 431 | 42 | 421 | 41 |
3 | 409 | 40 | 426 | 42 |
Grade | ||||
Well | 58 | 6 | 50 | 5 |
Moderate | 818 | 80 | 820 | 80 |
Poor | 144 | 14 | 150 | 15 |
Treatment within 6 months of cancer diagnosis | ||||
Surgery | 978 | 96 | 966 | 95 |
Chemotherapy | 271 | 27 | 269 | 26 |
Radiotherapy | 106 | 10 | 129 | 13 |
Smoking status before cancer diagnosis | ||||
Nonsmoker | 505 | 49 | 486 | 48 |
Former smoker | 401 | 39 | 430 | 42 |
Current smoker | 114 | 11 | 104 | 10 |
Alcohol consumption before diagnosis | ||||
Never | 115 | 11 | 157 | 15 |
Ever | 737 | 72 | 674 | 66 |
Missing | 168 | 16 | 189 | 19 |
BMI before diagnosis, kg/m2 | ||||
Mean | 27.3 | 26.9 | ||
SD | 4.7 | 4.8 | ||
Underweight, < 18.5 | 13 | 1 | 20 | 2 |
Normal, 18.5 to 25 | 274 | 27 | 295 | 29 |
Overweight, 25-30 | 387 | 38 | 371 | 37 |
Obese, > 30 | 227 | 22 | 205 | 20 |
Missing | 119 | 12 | 129 | 13 |
Deprivation fifth | ||||
First (least deprived) | 252 | 25 | 254 | 25 |
Second | 228 | 22 | 227 | 22 |
Third | 214 | 21 | 225 | 22 |
Fourth | 196 | 19 | 185 | 18 |
Fifth (most deprived) | 130 | 13 | 129 | 13 |
Comorbidities before cancer diagnosis | ||||
Cerebrovascular disease | 98 | 10 | 96 | 9 |
Chronic pulmonary disease | 174 | 17 | 178 | 17 |
Congestive heart disease | 46 | 5 | 46 | 5 |
Diabetes | 192 | 19 | 200 | 20 |
Myocardial infarction | 77 | 8 | 88 | 9 |
Peptic ulcer disease | 70 | 7 | 75 | 7 |
Peripheral vascular disease | 62 | 6 | 65 | 6 |
Renal disease | 85 | 8 | 89 | 9 |
Medication after diagnosis in exposure period | ||||
Low-dose aspirin use | 422 | 41 | 448 | 44 |
ACE use | 308 | 30 | 340 | 33 |
Metformin use | 90 | 9 | 86 | 8 |
Statins After Diagnosis (No. of prescriptions) | Colorectal Cancer–Specific Deaths | Unadjusted OR | 95% CI | P | Adjusted OR* | 95% CI | P | |||
---|---|---|---|---|---|---|---|---|---|---|
No. of Cases | % | No. of Patients | % | |||||||
0 | 1,323 | 79.3 | 5,993 | 73.6 | 1.00 | Ref cat | 1.00 | Ref cat | ||
≥ 1 | 345 | 20.7 | 2,145 | 26.4 | 0.72 | 0.63 to 0.82 | < .001 | 0.73 | 0.60 to 0.88 | < .001 |
1-11 | 158 | 9.5 | 1,007 | 12.4 | 0.70 | 0.59 to 0.85 | < .001 | 0.76 | 0.61 to 0.95 | .02 |
≥ 12 | 187 | 11.2 | 1,138 | 14.0 | 0.73 | 0.61 to 0.87 | < .001 | 0.69 | 0.54 to 0.87 | .002 |
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Journal of Clinical Oncology 2014 32:28, 3177-3183
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