Table 4. Mortality-related findings of meta-analyses on the association between time to cancer diagnosis and/or treatment and clinical outcomes, by cancer site/type and lag time interval.
| Cancer | Lag time interval | Findings | First author (year) | |||||
|---|---|---|---|---|---|---|---|---|
| Site | Type | Interval | Type | Comparison | Time range | Outcome measures* | Pooled risk estimate [95% CI](model type, heterogeneity statistics I2 or Ri) | |
| Blood | Smoldering multiple myeloma | T21 | Categorical | No distinct cut-off specified† | No range of lag times specified | Mortality | HR: 0.90 [0.72–1.12] (fixed-effects) | Zhao et al., 2019 |
| Brain | Glioblastoma | T30 | Continuous | Per 1-week increase | 12 to 53 days | Mortality | HR: 0.98 [0.90–1.08] (non-adjusted model) | Loureiro et al., 2016 |
| Breast | -- | T30 | Continuous | Per 1-month increase | 31 to 203 days | Mortality | RR: 0.99 [0.94–1.05] (fixed-effects) | Gupta et al., 2016 |
| -- | T32 | Continuous | Per 4-week increase | <21 days to >3 months | Mortality | HR: 1.15 [1.03–1.28] (random-effects, I2 = 75.4%) | Yu et al., 2013 | |
| Worsened DFS | HR: 1.16 [1.01–1.33] (fixed-effects) | |||||||
| -- | Continuous | Per 4-week increase | <21 days to >3 months | Mortality | RR: 1.04 [1.01–1.08] (fixed-effects) | Raphael et al., 2016 | ||
| RR: 1.08 [1.01–1.15] (random-effects, I2 = 60%) | ||||||||
| Worsened DFS | RR: 1.05 [1.01–1.08] (fixed-effects) | |||||||
| RR: 1.05 [1.01–1.10] (random-effects, I2 = 94.9%) | ||||||||
| -- | Continuous | Per 4-week increase | <21 days to >3 months | Mortality | HR: 1.13 [1.08–1.19] (random-effects, I2 = 78.9%) | Liu et al., 2017 | ||
| Worsened DFS | HR: 1.14 [1.05–1.24] (random-effects, I2 = 60.9%) | |||||||
| Colorectal | Rectal | T28 | Categorical | >4 vs. <4 weeks | 5 days to 8 weeks | Mortality | RR: 0.75 [0.53–1.07] (random-effects, I2 = 60%) | Wu et al., 2018 |
| Worsened DFS | RR: 0.78 [0.84–1.14] (fixed-effects) | |||||||
| Rectal | T29 | Categorical | >6–8 vs. <6–8 weeks |
4 to 14 weeks | Mortality | RR: 0.85 [0.50–1.43] (random-effects, I2 = 59%) | Petrelli et al., 2016 | |
| Worsened DFS | RR: 0.81 [0.58–1.12] (random-effects, I2 = 61%) | |||||||
| Rectal | Categorical | ≥8 vs. <8 weeks |
4 to 14 weeks | Mortality | RR: 0.98 [0.91–1.06] (random-effects, I2 = 42.4%) | Du et al., 2018 | ||
| Worsened DFS | RR: 1.04 [0.94–1.14] (random-effects, I2 = 46.7%) | |||||||
| Colorectal (Stage II/III) | T32 | Categorical | >8 vs. <8 weeks |
4 to 8+ weeks | Mortality | RR: 1.20 [1.15–1.26] (fixed-effects) | Des Guetz et al., 2010 | |
| Worsened RFS | RR: 0.98 [0.89–1.08] (fixed-effects) | |||||||
| Colorectal (Stage II/III) | Continuous | Per 4-week increase | 4 to >36 weeks | Mortality | HR: 1.14 [1.10–1.17] (fixed-effects) | Biagi et al., 2011 | ||
| DFS | HR: 1.14 [1.10–1.18] (fixed-effects) | |||||||
| Gastric | Categorical | >6–8 vs. <6–8 weeks |
<4 to >12 weeks | Mortality | HR: 1.20 [1.04–1.38] (fixed effects) | Petrelli et al., 2019 | ||
| HR: 1.41 [0.94–1.28] (random-effects, I2 = 90%) | ||||||||
| Colorectal | Mortality | HR: 1.27 [1.21–1.33] (fixed-effects) | ||||||
| HR: 1.27 [1.25–1.28] (random-effects, I2 = 70%) | ||||||||
| Pancreatic | Mortality | HR: 1.00 [1.00–1.01] (fixed-effects) | ||||||
| Head and neck | -- | T1 | Categorical | No distinct cut-off specified | 30 to 60 days | Mortality | RR: 1.54 [1.21–1.94] (fixed-effects) | Seoane et al., 2012 |
| RR: 1.67 [0.88–3.19] (random-effects, Ri = 0.85) | ||||||||
| T2 | Categorical | No distinct cut-off specified | 72 days | Mortality | RR: 2.72 [1.45–5.09] (fixed-effects) | |||
| RR: 3.17 [1.12–9.00] (random-effects, Ri = 0.61) | ||||||||
| T4 | Categorical | No distinct cut-off specified | 108 to 180 days | Mortality | RR: 1.04 [1.01–1.07] (fixed-effects) | |||
| RR: 1.04 [1.01–1.07] (random-effects, Ri = 0.00) | ||||||||
| T11 | Categorical | No distinct cut-off specified | 21 to 106 days | Mortality | RR: 1.34 [1.00–1.78] (fixed-effects) | |||
| RR: 1.32 [0.66–2.66] (random-effects, Ri = 0.82) | ||||||||
| T1, T2, T4, T11 | Categorical | No distinct cut-off specified | 21 to 180 days | Mortality | RR: 1.05 [1.02–1.07] (fixed-effects) | |||
| RR: 1.34 [1.12–1.61] (random-effects, Ri = 0.95) | ||||||||
| Oral | T2 | Categorical | No distinct cut-off specified | >1 month | Mortality | RR: 2.48 [1.39–4.42] (fixed-effects) | Seoane et al., 2016 | |
| RR: 2.48 [1.39–4.42] (random-effects, Ri = 0.00) | ||||||||
| T1, T2, T4, T11 | Categorical | No distinct cut-off specified | >30 to >45 days | Mortality | RR: 1.02 [0.93–1.12] (fixed-effects) | |||
| RR: 1.35 [0.84–2.18] (random-effects, Ri = 0.94) | ||||||||
| Esophageal | T29 | Categorical | >7–8 vs. ≤7–8 weeks |
≤46 to >64 days | Mortality, 2 years |
OR: 1.40 [1.09–1.80] (fixed-effects) | Lin et al., 2016 | |
| Mortality, 5 years |
OR: 1.14 [0.84–1.54] (fixed-effects) | |||||||
| Ovarian | -- | T32 | Categorical | No distinct cut-off specified | <15 days to >12 weeks | Mortality | HR: 1.18 [1.06–1.32] (random-effects, I2 = 17.6%) | Liu et al., 2017 |
| Continuous | Per 1-week increase | Mortality | HR: 1.04 [1.00–1.09] (random-effects, I2 = 9.05%) | |||||
| -- | Categorical | No distinct cut-off specified | 19 to 42 days | Mortality, 3 years | OR: 1.06 [0.90–1.24] (random-effects, I2 = 64.3%) | Usón et al., 2017 | ||
Significant pooled risk estimates are bolded.
-- indicates that cancer type not specified or applicable to the site.
*
Response variables of interest indicate the directionality of the pooled risk estimate (e.g., RR >1 associated with greater risk of mortality among patients with lag time intervals to cancer care endpoint greater than the lag time cut-off considered by the meta-analysis).
†
Meta-analyses utilized the ‘early’ and ‘deferred’ lag time interval definitions in included studies without standardization of lag time cut-offs.
CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; I2, heterogeneity; OR, odds ratio; RFS, recurrence-free survival; Ri, proportion of total variance due to between-study variance; RR, risk ratio; SMD, standardized mean difference.