Table 1.
Overview of included randomized controlled trials sorted by year of the end of enrollment.
| Lorvidhaya [14] |
Dueňas- González [13] |
Kim [15] |
Tangjitgamol [16] |
Mileshkin OUTBACK [17] |
|
|---|---|---|---|---|---|
| Year of publication | 2003 | 2012 | 2008 | 2019 | 2021 |
| Country | Thailand | Multiple a | Korea | Thailand | Multiple b |
| Outcomes | |||||
| The main result favors ACT | no | yes | no | no | no |
| Overall survival (HR) | 1.41 c | 0.68 | 0.92 c | 1.42 | 0.90 |
| (95% CI) | (0.79; 2.16) | (0.49; 0.95) | (0.53; 1.59) | (0.81; 2.49) | (0.70; 1.17) |
| Randomization | Stratified e | Minimization d | Stratified f | Stratified g | Stratified h |
| Concealed allocation | no | yes | no | not clear/yes | no |
| Masking/blinding | no | no | no | outcome ass | no |
| Patients | |||||
| Number of patients randomized | 230/233 | 259/256 | 78/77 | 130/129 | 461/465 |
| Enrollment (start-end year) | 1988–1994 | 2002–2004 | 1998–2005 | 2015–2017 | 2011–2017 |
| Duration of enrollment (years) | 6 | 2 | 7 | 2 | 6 |
| Patient median age (years) | 50/48 i | 45/46 | 58/57 | 49/50 | 46/45 |
| Range of patient age (years) | <65 | 22–68/18–70 | 36–75/34–73 | 23–68/26–68 j | 21–99/22–88 |
| Disease | |||||
| Stage (%) | |||||
| IB1 (all node+), IB2, IIA | 0/0 | 0/0 | 0/0 | 0/0 | 33/33 |
| IIB | 43/50 | 62/61 | 67/75 | 65/62 | 43/43 |
| IIIA | 1/1 | <1/<1 | 6/3 | 1/3 | 0/0 |
| IIIB | 55/49 | 36/37 | 22/17 | 31/35 | 24/24 k |
| IVA | 0/0 | 2/2 | 5/5 | 3/0 | - |
| Median tumor diameter (cm) | n.a. | 6/6 | 5/5 l | 5/5 | 5/5 |
| Histology (%) | |||||
| Squamous cell carcinoma | 90/88 | 93/94 m | 96/95 | 77/76 | 83/79 |
| Adenocarcinoma | 6/9 | 7/6 | 3/3 | 20/22 | 15/17 |
| Adenosquamous carcinoma | 1/0 | - | 1/3 | 2/2 | 3/4 |
| Small-cell carcinoma | 3/3 | - | 0/0 | 0/0 | 0/0 |
| Positive pelvic lymph nodes | yes | n.a. | yes | yes | yes |
| Para-aortic lymph nodes >1 cm | yes | no n | no | no | no |
| Previous chemotherapy or RT | no | no | no | yes o | yes p |
| Intervention (%) | |||||
| Completed CCRT | 95 | n.a. | 73 | 80 | 83 |
| Received at least one ACT dose | n.a. | 86 | n.a. | 77 | 78 |
| Completed CCRT + ACT | 92 | 77 | 65 | 65 | 62 |
| CCRT in control arm (cycle × DRUG mg/m2 or AUC) |
2 × MIT 10 2 × FU 300 mg/day |
6 × CIS 40 | 6 × CIS 30 | 6 × CIS 40 | 5 × CIS 40 |
| CCRT in ACT arm | 2 × MIT 10 2 × FU 300 mg/day |
6 × CIS 40 6 × GEM 125 |
2 × CIS 20 2 × FU 1000 |
6 × CIS 40 | 5 × CIS 40 |
| ACT protocol | 3 × FU 200 mg/day | 2 × CIS 50 2 × GEM 1000 |
1 × CIS 20 1 × FU 1000 |
3 × PAC 175 3 × CAR 5 |
4 × PAC 155 4 × CAR 5 |
| Follow-up | |||||
| Median follow-up (months) q | 89 | 46 | 39 | 27 | 60 |
Data are presented in CCRT + ACT arm/in control CCRT only arm if not stated otherwise. Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; CCRT, concurrent chemoradiation; ACT, adjuvant (consolidation) chemotherapy; RT, radiotherapy; n.a., not available; CIS, cisplatin; GEM, gemcitabine; FU, fluorouracil; PAC, paclitaxel; CAR, carboplatin; A, AUC; MIT, mitomycin C. a Mexico, Argentina, India, Panama, Bosnia and Herzegovina, Peru, Thailand, Pakistan, Australia; b Australia, New Zealand, USA, Saudi Arabia, Canada, China, Singapore; c HR was calculated by Parmar [37] and Tierney [38] methods; d Minimization using Pocock and Simon algorithm [39], balancing disease stage (IIB vs. III-IVA), tumor diameter (<5 cm vs. ≥5 cm), study center (not clear, probably 9 that is one per country), radiation equipment (cobalt-60 vs. linear accelerator), age (<55 vs. ≥55 years); e Stratified for six study centers; f Stratified for tumor stage; g Mixed block with stratification for disease stage (IIV vs. III-IVA) and histopathology (squamous vs. adenocarcinoma or adenosquamous carcinoma); h Stratified for nodal status, participating site, FIGO stage, age, planned extended-field radiotherapy; i Mean instead of median; j Interquartile range instead of range; k Including IIIB and IVA; l Estimated from categories (≤4; 4.1–6; 6.1–8; ≥8.1) weighted by frequencies; m Including squamous cell, poorly differentiated and adeno/squamous carcinoma; n Para-aortic lymph nodes >1 cm were exclusion criteria, but 2.3% in ACT arm and 4.7% in CCRT alone arm had at least one; o Previous chemotherapy was not an exclusion criterion, but all patients had newly diagnosed cervical cancer, so the previous chemotherapy/radiotherapy were allowed only for other cancers; p However, not for cervical cancer; q Rounded down to the last full month.