Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Literature Search Results and Study Characteristics
2.2. Study Quality Assessment
2.3. Pathological Complete Response Rates
2.4. Disease-Free and Overall Survival
2.5. R0 Resection Rates
2.6. Grade 3–4 Adverse Events
3. Discussion
4. Materials and Methods
4.1. Search Strategy and Study Identification
4.2. Selection Criteria and Data Extraction
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Study | Year | Study Design | N | Treatment Arms | RT Dose (Gys) | N | pCR | DFS (%) | HR (95% CI) | OS (%) | HR (95% CI) | Median Follow-Up (m) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Fernandez-Martos C (GCR-3) NCT-00421824. | 2010 | Randomized phase II | 108 | • CRT→Sx→XELOX • XELOX x 4→CRT→Sx | 50.4 | 52 56 | 13.5 14.3 | 64 62 | 0.99 | 78 75 | 2.01 (0.69–5.85) | 69 |
Marechal R EudraCT 2006-006646-34 | 2012 | Randomized phase II | 57 | • CRT(5FU)→Sx • FOLFOX x 2→CRT(5FU)→Sx | 45 | 28 29 | 28 25 | NR | - | NR | - | NR |
Borg C (INOVA) NCT 00865189 | 2014 | Randomized phase II | 91 | • CRT (5FU-Bev)→Sx • FOLFOX+Bevx2→CRT (5FU-Bev)→Sx | 45 | 45 46 | 11.4 23.8 | NR | - | NR | - | NR |
Bujko K NCT-00833131 | 2016 | Phase III | 515 | • CRT→ Sx • SCRT→FOLFOX x3→Sx | 50.4 25 | 254 261 | 12 16 | 52 53 | 0.96 (0.75–1.24) | 65 73 | 0.73 (0.53–1.01) | 35 |
Moore J (WAIT) ACTRN-12611000339954 | 2017 | Randomized phase II | 49 | • CRT→Sx • CRT→5FU x 3→Sx | 45 + 5.4 Boost | 24 25 | 25 16 | NR | - | NR | - | NR |
Kim SY NCT-01952951 | 2018 | Randomized phase II | 108 | • CRT→Sx • CRT→XELOX x 2→Sx | 50.4 | 55 53 | 5.8 13.6 | NR | - | NR | - | NR |
Conroy T PRODIGE-23 NCT-01804790 | 2020 | Phase III | 461 | • CRT→Sx→ FOLFOX x 12 • FOLFIRINOX x6→ CRT→Sx→FOLFOX x 6 | 50.4 | 230 231 | 12.1 27.8 | 68.5 75.7 | 0.69 (p = 0.03) | 87.7 90.8 | 0.65 (0.40–1.05) | 46.5 |
Bahadoer R RAPIDO NCT-01804790 | 2020 | Phase III | 912 | • CRT→Sx→ CT x 6m • SCRT→XELOX x6/FOLFOX x9→Sx | 50.4 25 | 450 462 | 14.3 28.4 | 69.6 76.3 | 0.75 (0.60–0.96) | 88.8 89.1 | 0.92 (0.67–1.25) | 54 |
Study | Year | n | Arm | T4 n (%) | N+ n (%) | N2 n (%) | CRM+ n (%) | Location | ||
---|---|---|---|---|---|---|---|---|---|---|
Low n (%) | Mid n (%) | Upper n (%) | ||||||||
Fernandez-Martos C (GCR-3) | 2010 | 108 | Std: 52 Exp: 56 | 3 (5.8) 7 (12.5) | NR | NR | 5 (9.6) 0 (0.0) | 12 (23) 18 (32) | NR | NR |
Marechal R | 2012 | 57 | Std: 29 Exp: 28 | 3 (10.3) 2 (7.1) | 25 (86.2) 26 (92.8) | NR | NR | 13 (44.9) 11 (39.3) | 9 (31.0) 13 (46.4) | 7 (24.1) 4 (14.3) |
Borg C (INOVA) | 2014 | 91 | Std: 45 Exp: 46 | 0 (0.0) 0 (0.0) | 37 (82.2) 34 (73.9) | 5 (11.1) 9 (19.6) | NR | 18 (40.0) 18 (39.1) | 27 (60.0) 28 (60.9) | 0 (0.0) 0 (0.0) |
Bujko K | 2016 | 515 | Std: 254 Exp: 261 | 163 (64.2) 165 (63.2) | NR | NR | NR | 138 (54.3) 148 (56.7) | 99 (39.0) 106 (40.6) | 16 (6.3) 7 (2.7) |
Moore J (WAIT) | 2017 | 49 | Std: 24 Exp: 25 | 1 (4.2) 5 (20.0) | 22 (91.7) 25 (100) | 19 (76.0) 15 (62.5) | 15 (60.0) 12 (50.0) | NR | ||
Kim SY | 2018 | 108 | Std: 55 Exp: 53 | 10 (18.2) 9 (17.0) | 51 (92.7) 49 (92.4) | NR | 16 (29.1) 14 (26.4) | NR | ||
Conroy T (PRODIGE23) | 2020 | 461 | Std: 230 Exp: 231 | 35 (15.2) 41 (17.7) | 207 (90.0) 206 (89.2) | NR | 64 (27.8) 60 (26.0) | 83 (36.1) 87 (37.7) | 118 (51.3) 114 (49.3) | 29 (12.6) 30 (13.0) |
Badahoer R (RAPIDO) | 2020 | 912 | Std: 450 Exp: 462 | 137 (30.4) 147 (31.8) | NR | 295 (65.6) 302 (65.3) | 271 (60.2) 285 (60.7) | 114 (25.8) 103 (22.4) | 148 (33.6) 180 (39.1) | 21 (4.8) 32 (6.9) |
TOTAL | - | 2301 | 728 (31.6) | 682 (89.1) | 645 (61.3) | 742 (45.3) | 763 (43.6) | 842 (48.1) | 146 (8.3) |
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Riesco-Martinez, M.C.; Fernandez-Martos, C.; Gravalos-Castro, C.; Espinosa-Olarte, P.; La Salvia, A.; Robles-Diaz, L.; Modrego-Sanchez, A.; Garcia-Carbonero, R. Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials. Cancers 2020, 12, 3655. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123655
Riesco-Martinez MC, Fernandez-Martos C, Gravalos-Castro C, Espinosa-Olarte P, La Salvia A, Robles-Diaz L, Modrego-Sanchez A, Garcia-Carbonero R. Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials. Cancers. 2020; 12(12):3655. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123655
Chicago/Turabian StyleRiesco-Martinez, Maria C., Carlos Fernandez-Martos, Cristina Gravalos-Castro, Paula Espinosa-Olarte, Anna La Salvia, Luis Robles-Diaz, Andrea Modrego-Sanchez, and Rocio Garcia-Carbonero. 2020. "Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials" Cancers 12, no. 12: 3655. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123655