Background
Methods
Definition of standard chemotherapy and aggressive-approach chemotherapy
Data sources and identification of the study cohort
Statistical analysis
1) Definition and classification of explanatory variables
2) Analytical approach
Unadjusted comparison
Adjusted comparison-1: multiple Cox regression analysis
Adjusted comparison-2: propensity score analysis
Adjusted comparison-3: instrumental variable analysis
Results
Patient characteristics
Variables | No chemotherapy (n = 4,345) | Standard chemotherapy (n = 3,235) | Aggressive -approach chemotherapy (n = 299) | P-value | |||
---|---|---|---|---|---|---|---|
3 groups | No chemo-therapy vs. Chemo- therapy* | Standard chemotherapy vs. Aggressive -approach chemotherapy | |||||
Age at diagnosis, years | Median [IQR] | 73.0 [69.0-78.0] | 71.0 [68.0-74.0] | 70.0 [67.0-74.0] | < 0.001 | < 0.001 | 0.36 |
Gender, n (%) | Female | 1,938 (44.6) | 1,291 (39.9) | 108 (36.1) | < 0.001 | < 0.001 | 0.20 |
Male | 2,407 (55.4) | 1,944 (60.1) | 191 (63.9) | ||||
Charlson comorbidity index, n (%) | 0 | 3,123 (71.9) | 2,401 (74.2) | 226 (75.6) | < 0.001 | < 0.001 | 0.06 |
1 | 773 (17.8) | 576 (17.8) | 60 (20.1) | ||||
2 ≤ | 449 (10.3) | 258 (8.0) | 13 (4.4) | ||||
Race/Ethnicity, n (%) | non-Hispanic white | 3,551 (81.7) | 2,711 (83.8) | 254 (85.0) | 0.01 | 0.01 | 0.22 |
non-Hispanic black | 425 (9.8) | 248 (7.7) | 21 (7.0) | ||||
Hispanic or other | 369 (8.5) | 276 (8.5) | 24 (8.0) | ||||
Region of tumor registries, n (%) | Northeast | 672 (15.5) | 555 (17.2) | 51 (17.1) | < 0.01 | < 0.01 | 0.06 |
South | 228 (5.3) | 194 (6.0) | 28 (9.4) | ||||
Midwest | 1,426 (32.8) | 1,101 (34.0) | 86 (28.8) | ||||
West | 2019 (46.5) | 1385 (42.8) | 134 (44.8) | ||||
Urban residence, n (%) | Yes | 3,928 (90.4) | 2,973 (91.9) | 284 (95.0) | < 0.01 | < 0.01 | 0.06 |
No | 417 (9.6) | 262 (8.1) | 15 (5.0) | ||||
Socioeconomic status, n (%) | Highest quintile | 763 (17.6) | 682 (21.1) | 71 (23.8) | < 0.001 | < 0.001 | 0.85 |
Fourth quintile | 793 (18.3) | 673 (20.8) | 63 (21.1) | ||||
Third quintile | 866 (19.9) | 688 (21.3) | 59 (19.7) | ||||
Second quintile | 849 (19.5) | 635 (19.6) | 56 (18.7) | ||||
Lowest quintile | 1,074 (24.7) | 557 (17.2) | 50 (16.7) | ||||
Median income | Median [IQR] | 38,154 [29-152] | 41,205 [32-757] | 43,564 [32-179] | < 0.001 | < 0.001 | 0.28 |
Teaching hospital, n (%) | Yes | 2,110 (48.6) | 1,868 (57.7) | 163 (54.5) | < 0.001 | < 0.001 | 0.28 |
No | 2,235 (51.4) | 1,367 (42.3) | 136 (45.5) | ||||
Year of death, n (%) | 1991 | 365 (8.4) | 206 (6.4) | 18 (6.0) | < 0.001 | < 0.001 | 0.02 |
1992 | 576 (13.3) | 299 (9.2) | 22 (7.4) | ||||
1993 | 567 (13.1) | 340 (10.5) | 15 (5.0) | ||||
1994 | 581 (13.4) | 339 (10.5) | 33 (11.0) | ||||
1995 | 518 (11.9) | 372 (11.5) | 33 (11.0) | ||||
1996 | 490 (11.3) | 424 (13.1) | 32 (10.7) | ||||
1997 | 442 (10.2) | 413 (12.8) | 46 (15.4) | ||||
1998 | 421 (9.7) | 421 (13.0) | 52 (17.4) | ||||
1999 | 385 (8.9) | 421 (13.0) | 48 (16.1) | ||||
Death in the hospital, n (%) | Yes | 774 (17.8) | 812 (25.1) | 152 (50.8) | < 0.001 | < 0.001 | < 0.001 |
No | 3,571 (82.2) | 2,423 (74.9) | 147 (49.2) | ||||
ICU admission within 1 month of death, n (%) | Yes | 187 (4.3) | 213 (6.6) | 37 (12.4) | < 0.001 | < 0.001 | < 0.001 |
No | 4,158 (95.7) | 3,022 (93.4) | 262 (87.6) | ||||
More than 1 ER visit within 1 month of death, n (%) | Yes | 870 (20.0) | 857 (26.5) | 104 (34.8) | < 0.001 | < 0.001 | < 0.01 |
No | 3,475 (80.0) | 2,378 (73.5) | 195 (65.2) | ||||
Hospice admission, n (%) | None | 2,208 (50.8) | 1,668 (51.6) | 241 (80.6) | < 0.001 | < 0.001 | < 0.001 |
Three or fewer days | 156 (3.6) | 198 (6.1) | 25 (8.4) | ||||
Four or more days | 1,981 (45.6) | 1,369 (42.3) | 33 (11.0) |
Unadjusted outcomes
Adjusted outcomes
1) Results from Cox model
Variables | HR | (95%CI) | P-value | |
---|---|---|---|---|
Receipt of chemotherapy | No chemotherapy | 1.00 | - | - |
Standard chemotherapy | 0.80 | (0.76, 0.83) | < 0.001 | |
Aggressive-approach chemotherapy | 0.82 | (0.72, 0.92) | < 0.001 | |
Age at diagnosis | 65 | 1.00 | - | - |
Each increasing year | 1.01 | (1.00, 1.01) | < 0.001 | |
Gender | Female | 1.00 | - | - |
Male | 1.09 | (1.05, 1.14) | < 0.001 | |
Charlson comorbidity index | 0 | 1.00 | - | - |
1 | 1.16 | (1.09, 1.23) | < 0.001 | |
2 ≤ | 1.28 | (1.18, 1.38) | < 0.001 | |
Region of tumor registries | Northeast | 1.00 | - | - |
South | - | - | n.s. | |
Midwest | - | - | n.s. | |
West | 1.08 | (1.03, 1.13) | < 0.001 | |
Socioeconomic status | Lowest quintile | 1.00 | - | - |
Each increasing quintile | - | - | n.s. | |
Teaching hospital | No | 1.00 | - | - |
Yes | - | - | n.s. | |
Year of death | 1991 | 1.00 | - | - |
1992 | 1.11 | (1.04, 1.19) | < 0.01 | |
1993 | - | - | n.s. | |
1994 | - | - | n.s. | |
1995 | - | - | n.s. | |
1996 | - | - | n.s. | |
1997 | - | - | n.s. | |
1998 | 0.91 | (0.84, 0.97) | < 0.01 | |
1999 | 0.89 | (0.82, 0.96) | < 0.01 |
2) Results from propensity score analyses
Analysis | Variables | HR | (95%CI) | P-value |
---|---|---|---|---|
Stratified analysis | ||||
Lowest quintile of PS* | No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.82 | (0.73, 0.93) | < 0.01 | |
Second quintile of PS | No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.77 | (0.69, 0.85) | < 0.001 | |
Third quintile of PS | No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.81 | (0.74, 0.90) | < 0.001 | |
Fourth quintile of PS | No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.85 | (0.77, 0.93) | < 0.01 | |
Highest quintile of PS†
| No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.73 | (0.66, 0.81) | < 0.001 | |
Multiple Cox regression adjustment using the PS | No chemotherapy | 1.00 | - | - |
Chemotherapy | 0.76 | (0.71, 0.82) | < 0.001 |
Analysis | Variables | HR | (95%CI) | P-value |
---|---|---|---|---|
Stratified analysis | ||||
Lowest quintile of PS* | Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 1.32 | (0.90, 1.92) | 0.15 | |
Second quintile of PS | Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 1.30 | (0.98, 1.72) | 0.07 | |
Third quintile of PS | Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 1.22 | (0.81, 1.84) | 0.35 | |
Fourth quintile of PS | Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 1.21 | (0.94, 1.56) | 0.14 | |
Highest quintile of PS†
| Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 0.85 | (0.68, 1.07) | 0.16 | |
Multiple Cox regression adjustment using the PS | Standard chemotherapy | 1.00 | - | - |
Aggressive-approach chemotherapy | 1.21 | (1.00, 1.48) | 0.05 |
3) Results from instrumental variable analysis
Model | Patient population | Variable used for classification | Variables | Lowest quintile | Second quintile | Third quintile | Fourth quintile | Highest quintile | Instrumental variable estimate |
---|---|---|---|---|---|---|---|---|---|
1 | All patients (n = 7,879) | Prevalence of "chemotherapy" | Number of patients* | 1,492 | 1,388 | 1,439 | 1,255 | 2,139 | |
Chemotherapy recipients, %†
| 30.8 | 43.4 | 47.5 | 49.8 | 52.3 | ||||
Aggressive-approach chemotherapy recipients, %†
| 2.2 | 3.2 | 4.2 | 5.1 | 4.4 | ||||
Age at diagnosis, years | 73.0 | 73.3 | 72.8 | 73.3 | 72.8 | ||||
Female, % | 42.2 | 41.7 | 42.6 | 48.3 | 39.8 | ||||
non-Hispanic white, % | 83.7 | 85.4 | 88.1 | 71.9 | 82.8 | ||||
Socioeconomic status, mean quintile | 2.9 | 2.8 | 3.0 | 3.1 | 3.0 | ||||
Without comorbidity, % | 78.2 | 73.7 | 74.5 | 69.8 | 69.1 | ||||
Survival at 1 year after diagnosis, %‡
| 21.7 ± 1.1 | 23.5 ± 1.1 | 22.2 ± 1.1 | 21.7 ± 1.2 | 23.7 ± 0.9 | 6.7% (95%CI: -6.6, 19.9) | |||
Survival at 2 years after diagnosis, %‡
| 5.6 ± 0.6 | 6.7 ± 0.7 | 6.1 ± 0.6 | 4.8 ± 0.6 | 6.8 ± 0.5 | 1.7% (95%CI: -5.9, 9.3) | |||
Hazard Ratio (95%CI)§
| 1.0 | 0.94 (0.87, 1.01) | 0.96 (0.89, 1.03) | 1.04 (0.96, 1.12) | 0.93 (0.87, 0.99) | ||||
2 | Chemotherapy recipients (n = 3,534) | Prevalence of "aggressive-approach chemotherapy" | Number of patients||
| 453 | 136 | 990 | 619 | 614 | |
Chemotherapy recipients, % | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | ||||
Aggressive-approach chemotherapy recipients, %†
| 4.6 | 6.6 | 7.7 | 10.3 | 12.1 | ||||
Age at diagnosis, years | 71.7 | 71.7 | 71.1 | 71.7 | 71.9 | ||||
Female, % | 43.7 | 44.1 | 38.6 | 41.7 | 43.3 | ||||
non-Hispanic white, % | 89.0 | 83.8 | 84.6 | 86.0 | 74.8 | ||||
Socioeconomic status, mean quintile | 3.0 | 3.3 | 3.2 | 3.2 | 3.2 | ||||
Without comorbidity, % | 73.5 | 78.7 | 70.6 | 79.2 | 68.2 | ||||
Survival at 1 year after diagnosis, %‡
| 30.5 ± 2.2 | 29.4 ± 3.9 | 26.0 ± 1.4 | 26.3 ± 1.8 | 27.9 ± 1.8 | -53.5% (95%CI: -124.1, 17.2) | |||
Survival at 2 years after diagnosis, %‡
| 8.4 ± 1.3 | 8.1 ± 2.3 | 7.4 ± 0.8 | 6.5 ± 1.0 | 6.2 ± 1.0 | -35.1% (95%CI: -76.9, 6.6) | |||
Hazard Ratio (95%CI)§
| 1.0 | 1.05 (0.87, 1.28) | 1.07 (0.96, 1.20) | 1.11 (0.98, 1.25) | 1.11 (0.99, 1.26) |