Table 4.
Univariable and multivariable Cox regression for all-cause mortality of patients with brain metastases present at the time of primary cancer diagnosis
| Univariable HR (95% CI) | P value | Multivariable HR (95% CI) | P value | |
|---|---|---|---|---|
| Age at BM diagnosis, years | ||||
| <70 | Ref | Ref | ||
| 70–72 | 1.01 (0.90–1.14) | 0.84 | 1.02 (0.90–1.15) | 0.81 |
| 73–76 | 1.09 (0.97–1.22) | 0.15 | 1.12 (0.99–1.25) | 0.06 |
| 77–81 | 1.16 (1.03–1.31) | 0.01 | 1.18 (1.05–1.33) | 0.008 |
| >81 | 1.70 (1.50–1.91) | <0.001 | 1.57 (1.39–1.78) | <0.001 |
| Sex | 0.02 | 0.005 | ||
| Male | Ref | Ref | ||
| Female | 0.91 (0.85–0.99) | 0.89 (0.82–0.97) | ||
| Race | ||||
| White | Ref | Ref | ||
| African American | 1.01 (0.88–1.16) | 0.91 | 0.86 (0.74–0.99) | 0.04 |
| Hispanic | 1.08 (0.91–1.29) | 0.39 | 0.96 (0.80–1.16) | 0.68 |
| Asian | 0.59 (0.49–0.72) | <0.001 | 0.60 (0.49–0.72) | <0.001 |
| Other/Unknown | 0.94 (0.54–1.61) | 0.81 | 1.08 (0.62–1.87) | 0.79 |
| Marital status at diagnosis | ||||
| Unmarried/single | Ref | Ref | ||
| Married/partnered | 0.81 (0.75–0.87) | <0.001 | 0.89 (0.82–0.97) | 0.005 |
| Unknown | 0.93 (0.74–1.16) | 0.51 | 1.06 (0.84–1.33) | 0.63 |
| Graduated from high school (per % increase) a | 0.99 (0.99–0.99) | <0.001 | 1.00 (0.99–1.00) | 0.55 |
| Household income (per 10K USD increase) a | 0.95 (0.94–0.97) | <0.001 | 0.97 (0.95–0.99) | 0.001 |
| Residence | <0.001 | 0.13 | ||
| Non-urban/ Unknown | Ref | Ref | ||
| Urban | 0.77 (0.69–0.87) | 0.90 (0.79–1.03) | ||
| Charlson comorbidity index b | ||||
| 0–2 | Ref | Ref | ||
| >2 | 1.33 (1.20–1.47) | <0.001 | 1.20 (1.08–1.34) | <0.001 |
| Unknown | 1.10 (0.89–1.36) | 0.36 | 0.97 (0.78–1.21) | 0.80 |
| Primary tumor site | ||||
| NSCLC | Ref | Ref | ||
| SCLC | 1.15 (1.03–1.27) | 0.01 | 1.03 (0.92–1.14) | 0.65 |
| Breast | 0.93 (0.73–1.19) | 0.56 | 0.98 (0.76–1.26) | 0.85 |
| Melanoma | 0.86 (0.70–1.06) | 0.16 | 0.96 (0.78–1.19) | 0.72 |
| Kidney | 1.35 (1.06–1.73) | 0.02 | 1.41 (1.10–1.81) | 0.007 |
| Colorectal | 0.91 (0.62–1.34) | 0.64 | 0.97 (0.66–1.44) | 0.89 |
| Esophagus | 0.57 (0.30–1.09) | 0.09 | 0.63 (0.32–1.22) | 0.17 |
| Esophagus*log(time)c | 1.60 (1.11–2.31) | 0.01 | 1.65 (1.12–2.41) | 0.01 |
| Ovarian | 0.57 (0.27–1.19) | 0.13 | 0.56 (0.27–1.19) | 0.13 |
| Type of managing hospital d | ||||
| Government and medical school‒associated | Ref | Ref | ||
| Government and not medical school‒associated | 1.25 (1.06–1.47) | 0.007 | 0.99 (0.84–1.17) | 0.87 |
| Non-government and medical school‒associated | 0.98 (0.87–1.09) | 0.70 | 1.00 (0.89–1.12) | 0.97 |
| Non-government and not medical school‒associated | 1.30 (1.14–1.47) | <0.001 | 1.18 (1.03–1.34) | 0.01 |
| Unknown | 2.85 (2.40–3.39) | <0.001 | 18.3 (4.50–74.20) | <0.001 |
| Urban hospital | ||||
| No | Ref | Ref | ||
| Yes | 0.91 (0.81–1.02) | 0.12 | 0.86 (0.75–0.97) | 0.02 |
| Unknown | 0.28 (0.24–0.33) | <0.001 | 0.10 (0.03–0.42) | 0.002 |
| Initial BM treatment strategy e | ||||
| Non-stereotactic brain-directed radiation | Ref | Ref | ||
| Stereotactic brain-directed radiation | 0.50 (0.44–0.57) | <0.001 | 0.52 (0.46–0.59) | <0.001 |
| Neurosurgical resection | 0.57 (0.51–0.65) | <0.001 | 0.56 (0.49–0.64) | <0.001 |
| Systemic therapy without local brain-directed therapyf | 0.75 (0.65–0.88) | <0.001 | 0.79 (0.68–0.93) | 0.004 |
| Other/noneg | 1.67 (1.52–1.84) | <0.001 | 1.45 (1.31–1.60) | <0.001 |
Abbreviations: BM, brain metastasis; CI, confidence interval; HR, hazard ratio; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer.
aZip-code level.
bExcluded diagnosis of metastatic cancer so as not to inflate all scores by 6 points.
cFor covariates with significant violations of the proportional hazards assumption, the interaction of the covariate with time (denoted by *) was included in the model.
dCovariates for medical school-associated hospital and government hospital were re-grouped in this manner due to high linkage between ‘unknown’ categories for these variables.
ePatients were considered recipients of a treatment if at least one of the relevant administrative codes (Table A1) was present within 1 month prior—2 months after BM diagnosis for brain-directed radiation or 1 month prior—1 month after BM diagnosis for neurosurgical resection.
fMay underestimate patients receiving systemic therapy given that data on receipt of oral systemic agents were only available for patients with Part D coverage.
gMay include patients who received systemic therapy but for whom this information was not captured by claims due to lack of Part D coverage.