Table 7. Randomized trials comparing postoperative CRT vs. postoperative CT—outcomes.
| Author | Year | N |
Planned sample size | FU |
OS |
DFS |
Local regional RFS |
Toxicity¶ |
Notes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CRT | CT | Median | CRT (95% CI) | CT (95% CI) | P | CRT (95% CI) | CT (95% CI) | P | CRT (95% CI) | CT (95% CI) | P | CRT | CT | P | ||||||||
| Kim (32) | 2012 | 46 | 44 | 140 To detect a 20% difference (from 30% CT to 50% CRT) in 5 years DFS, with power 80%, one-sided alpha 0.05 |
86.7 months [60-117] | 5-year: 65.2% (51.4-79) | 5-year: 54.6% (39.8-69.3) | 0.67 | 5-year: 60.9% (36.8-75) | 5-year: 50% (35.2-64.8) | 0.25 | 5-year: 84.4% (72.7-96.1) | 5-year: 62.7% (47.6-77.7) | 0.04 | ≥ Grade 3 GI: 17.4% | ≥ Grade 3 GI: 11% | NS | Study closed after accrual of 90 patients over 4 years due to slow accrual | ||||
| ≥ Grade 3 hemorrhage: 19.6% | ≥ Grade 3 hemorrhage: 25% | NS | Subgroup analysis suggests stage III patients benefited more | |||||||||||||||||||
| Lee (33) (ARTIST) | 2012 | 230 | 228 | 448 To detect a HR 1.45 of DFS (from recurrence rate of 23% CT vs. 16% CRT) with power of 80% and two-sided alpha of 0.05 |
53.2 months [37-77] | NA | NA | NA | 3-year: 78% | 3-year: 74% | 0.09 | 3-year: 95% | 3-year: 92% | 0.35 | Treatment modifications: 35%, death*: 1 | Treatment modifications: 52%, death*: 1 | – | Final analysis was scheduled for when 227 events has occurred. The actual analysis was done when 127 events has occurred due to the lower event rate (due to the lower event rate as a result of large % of stage Ib/II patients) Subgroup analysis suggest N+ patients benefited more |
||||
| Yu (34) | 2012 | 34 | 34 | NA | NA (all patients completed 3 years FU) | 3-year: 67.7% | 3-year: 44.1% | 0.04 | 3-year: 55.8% | 3-year: 29.4% | 0.02 | NA | NA | NA | Grade 1-2 anorexia: 74% | Grade 1-2 anorexia: 44% | <0.05 | |||||
| Grade 1-2 N+V: 82% | Grade 1-2 N+V: 74% | >0.05 | ||||||||||||||||||||
| Grade 1-2 neutropenia: 71% | Grade 1-2 neutropenia: 44% | <0.05 | ||||||||||||||||||||
| Zhu (35) | 2012 | 56 | 59 | NS (OS was primary endpoint) | 42.5 months (all patients alive completed 5 years FU) | 5-year: 48.4%, HR 1.24 (0.9-1.65) | 5-year: 41.8% | 0.1 | 5-year: 45.2%, HR 1.35 (1-1.78) | 5-year: 35.8% | 0.03 | 5-year: 15.60% | 5-year: 24.2% | 0.04 | ≥ Grade 3 vomit: 1.6% | ≥ Grade 3 vomit: 0 | – | |||||
| ≥ Grade 3 diarrhea: 1.6% | ≥ Grade 3 diarrhea: 0 | – | ||||||||||||||||||||
| ≥ Grade 3 leucopenia: 7.5% | ≥ Grade 3 leucopenia: 7.3% | – | ||||||||||||||||||||
| Bamias (36) | 2010 | 72 | 71 | 200 To detect an increase in survival of 20% (35% CT, 55% CRT), power of 80% and alpha 0.05 |
53.7 months (0.1-77.8) | 3-year: 57% | 3-year: 61% | NS | 3-year: 48% | 3-year: 51% | NS | – | – | – | ≥ Grade 3 febrile neutropenia: 7% | ≥ Grade 3 febrile neutropenia: 9% | NA | Study close after accrual of 147 over 3 years due to decreasing accrual | ||||
| ≥ Grade 3 diarrhea: 4% | ≥ Grade 3 diarrhea: 7% | – | ||||||||||||||||||||
| Kwon (37) | 2010 | 31 | 30 | 170 To detect a 20% increase in DFS (30% CT, 50% CRT, HR 1.7) with a power of 80% and two-sided alpha of 0.05 |
77.2 months (2.4-92.8) | 5-year: 70.1% | 5-year: 70% | NS | 5-year: 76.7% | 5-year: 59.1% | 0.2 | 5-year: 87.1% | 5-year: 76.7% | 0.4 | ≥ Grade 3 neutropenia: 48% | ≥ Grade 3 neutropenia: 17% | – | Study close after accrual of 61 over 2.5 years due to slow accrual | ||||
| ≥ Grade 3 diarrhea: 3.2% | ≥ Grade 3diarrhea: 0% | – | ||||||||||||||||||||
¶, not all side effects reported are included. Diarrhea, neutropenia and nausea and vomiting are preferentially presented, as they are typically the most common; *, one patient (CRT) died of neutropenic sepsis, one patient (CT) died of pneumonia. CRT, chemoradiotherapy; CT, chemotherapy; FU, 5-fluorouracil; OS, overall survival; CI, confidence interval; DFS, disease free survival; RFS, relapse free survival; GI, gastrointestinal; NS, not specified; HR, hazard ratio; NA, not available.