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Neoadjuvant Treatments For Resectable Rectal Cancer: A Network Meta-analysis

W. Zhong, Xiao-Jun Xue, Lianzhi Dai, R. Li, Kai Nie, Song Zhou
Published 2020 · Medicine

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Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.
This paper references
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Cochrane Bias (2011)
10.1200/JCO.2012.42.9597
Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04.
S. Ngan (2012)
A multicenter randomized controlled trial of mFOLFOX6 with or without radiation in neoadjuvant treatment of local advanced rectal cancer (FOWARC study): Preliminary results
Y Deng (2015)
10.1016/j.clcc.2019.07.001
Neoadjuvant Chemotherapy With mFOLFOXIRI Without Routine Use of Radiotherapy for Locally Advanced Rectal Cancer.
J. Zhang (2019)
A comparison of nonop‐ erative vs. preoperative radiotherapy in rectal carcinoma. A 10‐year randomized trial
JA Reis Neto (1989)
10.1002/jrsm.1058
Network meta-analysis, electrical networks and graph theory.
G. Rücker (2012)
Preoperative chemo‐ radiation vs radiation alone for stage II and III resectable rectal cancer: A meta‐analysis
T Latkauskas (2010)
10.1097/00000658-198811000-00011
Preoperative Radiotherapy as Adjuvant Treatment in Rectal Cancer: Final Results of a Randomized Study of the European Organization for Research and Treatment of Cancer (EORTC)
A. Gerard (1988)
Preoperative conven‐ tional chemoradiotherapy versus short‐course radiotherapy with delayed surgery for rectal cancer: Results of a randomized controlled trial
T Latkauskas (2016)
10.1002/sim.3767
Checking consistency in mixed treatment comparison meta-analysis.
S. Dias (2010)
10.1200/jco.2014.32.3_suppl.609
Preoperative radiotherapy combined with simultaneous chemotherapy with capecitabine plus oxaliplatin versus surgery alone: A single-centered, phase II study in patients with mid/low rectal cancer.
Fu-long Wang (2014)
10.1002/1097-0142(197506)35:6<1597::AID-CNCR2820350618>3.0.CO;2-S
Preoperative irradiation for carcinoma of the rectum and rectosigmoid colon: Report of a national veterans administration randomized study
B. Roswit (1975)
10.1007/S001040050487
[Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study].
S. Petersen (1998)
10.1200/JCO.2013.51.7904
Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial.
D. Schrag (2014)
10.3322/caac.21395
Colorectal cancer statistics, 2017
R. Siegel (2017)
Randomise d trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer
G Oates (1996)
10.1245/s10434-013-3198-9
Neoadjuvant Radiotherapy for Rectal Cancer: Meta-analysis of Randomized Controlled Trials
N. Rahbari (2013)
10.1016/j.jval.2011.04.002
Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1.
J. Jansen (2011)
eds): Cochrane handbook for systematic reviews of interventions, version 5.1.0
JPT Higgins (2011)
Trial 22921: Chemotherapy with preoperative radiotherapy in rectal cancer
Eortc Radiotherapy Group (2006)
Colorectal Cancer Study Group: The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: Long‐term follow‐up of a population‐based study
A Martling (2001)
Long‐term results of a randomized trial comparing preoperative short‐course radiotherapy with preop‐ erative conventionally fractionated chemoradiation for rectal cancer
K Bujko (2006)
10.1200/JCO.2006.06.7629
Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.
J. Gérard (2006)
The Stockholm I Trial of preoperative short term radiotherapy in operable rectal carcinoma - A prospective randomized trial. Invited commentary.
L. Påhlman (1995)
10.1007/BF02257783
Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma
P. J. Marsh (1994)
10.1186/s40880-015-0024-8
Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial
W. Fan (2015)
Randomise d trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer . Medical research council rectal cancer working party
S Petersen (1996)
Locally advanced rectal cancer: A comparison of management strategies
R Glynne‐Jones (2011)
Randomised trial of surgery alone versus radiotherapy followed by surgery for poten ‐ tially operable locally advanced rectal cancer . Medical research council rectal cancer working party
S Petersen (1996)
10.3109/00016485509120666
The study group.
G. H. Duvel (1980)
10.1007/BF02305759
Randomized study on preoperative radiotherapy in rectal carcinoma
B. Cedermark (2006)
10.1002/1097-0142(19860715)58:2<352::AID-CNCR2820580226>3.0.CO;2-D
Preoperative radiation and surgery for cancer of the rectum: Veterans administration surgical oncology group trial II
G. Higgins (1986)
10.1002/14651858.CD006041.pub3
Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer.
Laura de Caluwé (2013)
Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial.
W. Rider (1977)
The Stockholm I trial of preoperative short term radiotherapy in oper‐ able rectal carcinoma. A prospective randomized trial
B Cedermark (1995)
Preoperative radiation and surgery for
GA Higgins
10.1136/bmj.39489.470347.AD
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations
G. Guyatt (2008)
10.1002/9780470712184.CH8
Assessing Risk of Bias in Included Studies
J. P. Higgins (2008)
10.1002/1097-0142(19901201)66:11<2286::AID-CNCR2820661106>3.0.CO;2-T
Low‐dose preoperative radiation postpones recurrences in operable rectal cancer: Results of a randomized multicenter trial in western norway
O. Dahl (1990)
10.1136/bmj.38937.646400.55
Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study
G. Brown (2006)
10.1111/j.1463-1318.2009.02015.x
Preoperative chemoradiation vs radiation alone for stage II and III resectable rectal cancer: a meta‐analysis
T. Latkauskas (2010)
10.7150/jca.7988
Early Detection of Colorectal Cancer Recurrence in Patients Undergoing Surgery with Curative Intent: Current Status and Challenges
P. E. Young (2014)
10.1186/1745-6215-8-16
Practical methods for incorporating summary time-to-event data into meta-analysis
J. Tierney (2007)
10.1016/S0140-6736(96)05348-2
Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer
Medical Research Council Rectal Cancer Working Party (1996)
Stockholm Colorectal Cancer Study Group: The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: Long-term follow-up of a population-based study
(2001)
Network meta‐analysis for indirect treatment compar‐ isons
T Lumley (2002)
10.1016/j.jclinepi.2010.03.016
Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.
G. Salanti (2011)
10.1002/1097-0142(19950501)75:9<2269::AID-CNCR2820750913>3.0.CO;2-I
The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma
B. Cedermark (1995)
10.1016/0197-2456(86)90046-2
Meta-analysis in clinical trials.
R. Dersimonian (1986)
10.1186/s12885-016-2959-9
Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial
T. Latkauskas (2016)
10.1001/JAMA.1976.03270110017009
Preoperative Radiotherapy for colorectal Cancer
G. Higgins (1975)
10.1016/S0140-6736(86)91510-2
RECURRENCE AND SURVIVAL AFTER TOTAL MESORECTAL EXCISION FOR RECTAL CANCER
R. Heald (1986)
10.1001/ARCHSURG.133.8.894
Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997.
R. Heald (1998)
10.1056/NEJMOA060829
Chemotherapy with preoperative radiotherapy in rectal cancer.
J. Bosset (2006)
10.1002/bjs.1800690906
A trial of preoperative radiotherapy in the management of operable rectal cancer
(1982)
Colorectal cancer statistics
R L Siegel (2017)
10.1007/springerreference_178671
National comprehensive cancer network.
F. Detterbeck (2013)
10.1002/9780470712184
Cochrane Handbook for Systematic Reviews of Interventions
J. P. Higgins (2019)
10.1200/JCO.2005.02.113
Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921.
J. Bosset (2005)
10.1002/14651858.CD002102.PUB2
Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma.
R. Wong (2007)
10.1002/BJS.1800710107
The evaluation of low dose pre‐operative X‐ray therapy in the management of operable rectal cancer; results of a randomly controlled trial
W. Duncan (1984)
10.1056/NEJM199704033361402
Improved survival with preoperative radiotherapy in resectable rectal cancer.
B. Cedermark (1997)
10.1002/SIM.1201
Network meta-analysis for indirect treatment comparisons.
T. Lumley (2002)
10.1136/bmj.g5630
A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis
M. Puhan (2014)
10.1097/00042737-200110000-00028
[Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer].
U. Tiefenbacher (2001)
10.1001/JAMA.284.8.1008
Preoperative radiotherapy for resectable rectal cancer: A meta-analysis.
C. Cammà (2000)
10.1136/pmj.78.922.473
Management of colorectal cancer
A. Leslie (2002)
10.1002/bjs.5506
Long‐term results of a randomized trial comparing preoperative short‐course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer
K. Bujko (2006)
A comparison of nonoperative vs. preoperative radiotherapy in rectal carcinoma. A 10‐year randomized trial
JA Reis Neto (1989)
eds): Cochrane handbook for systematic reviews of interventions, version
J PTHiggins (2011)
EORTC Radiotherapy Group Trial 22921: Chemotherapy with preoperative radiotherapy in rectal cancer
JF Bosset (2006)
10.1097/00000658-200106000-00007
Neoadjuvant Chemoradiation for Rectal Cancer: Analysis of Clinical Outcomes From a 13-Year Institutional Experience
M. Onaitis (2001)
10.1016/S1470-2045(11)70097-3
Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.
W. van Gijn (2011)
10.1016/0959-8049(94)00312-S
Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure.
P. Goldberg (1994)
10.1080/10618600.1998.10474787
General methods for monitoring convergence of iterative simulations
S. Brooks (1998)
10.1136/bmj.d5928
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
J. P. Higgins (2011)



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