Neoadjuvant chemoradiation for locally advanced rectal cancer with fluoropyrimidine alone or intensified with oxaliplatin: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 678-678 ◽  
Author(s):  
Ashlie Nadler ◽  
Elizabeth Handorf ◽  
Elin R. Sigurdson ◽  
Joshua E. Meyer ◽  
Crystal Shereen Denlinger ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Resection Margin ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Significant Heterogeneity ◽  
Short Term ◽  
Grade 3

678 Background: Improved outcomes have been demonstrated with the use of neoadjuvant fluoropyrimidine-based chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer. The addition of oxaliplatin in the adjuvant setting has also resulted in improved disease-free survival (DFS). A meta-analysis was performed to evaluate DFS and overall survival (OS) with the addition of oxaliplatin to standard neoadjuvant chemoradiation for locally advanced rectal cancer. Methods: A systematic literature review was performed. Randomized-controlled trials (RCTs) comparing the addition of oxaliplatin in the neoadjuvant setting (oxaliplatin group) to fluoropyrimidine-based chemoradiation (standard group) were included. The primary outcomes were DFS and OS; secondary outcomes were short-term surgical results, morbidity, and mortality. Results were combined using meta-analysis via linear mixed-effects models. Calculations were performed using R. Results: Of 73 studies identified, 4 reported DFS (n=3829) and 3 reported OS (n=2680). There was no difference in DFS between the standard and oxaliplatin groups amongst RCTs [HR 0.90 (0.64-1.26), p=0.5313]. There was no difference in OS [HR 0.93 (0.59-1.47), p=0.9894]. There was no significant heterogeneity between RCTs for primary outcomes. There was also no difference in pathologic complete response rate [OR 0.93 (0.77-1.14), p=0.4923), resection margin (R0) status [OR 1.01 (0.59-1.72), p=0.9846], circumferential resection margin status [OR 0.84 (0.50-1.41), p=0.5079], sphincter saving surgery rate [OR 0.87 (0.74-1.03), p=0.1103], grade 3-4 toxicity [OR 1.60 (0.88-2.92), p=0.1251], and 60-day mortality [OR 1.27 (0.50-3.25), p=0.6148]. There was significant heterogeneity between RCTs for R0 status, circumferential margin status, and grade 3-4 toxicity. Adjuvant treatment varied across studies. Conclusions: There are no short-term or long-term survival benefits with the addition of oxaliplatin to fluoropyrimidine-based chemoradiation in the neoadjuvant setting for locally advanced rectal cancer.

Outcomes of Neoadjuvant Chemotherapy without Radiation for Rectal Cancer

2015 ◽  
Vol 32 (4) ◽  
pp. 275-283 ◽  
Author(s):  
Takuya Matsumoto ◽  
Suguru Hasegawa ◽  
Masazumi Zaima ◽  
Naoya Inoue ◽  
Yoshiharu Sakai
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Short Term ◽  
Group 2 ◽  
Grade 3

Aim: The efficacy of neoadjuvant chemotherapy without radiation (NAC) in the treatment of rectal cancer remains unclear. This retrospective study was aimed at determining the pathological complete response rate and short-term outcomes of NAC in patients with locally advanced rectal cancer. Patients and Methods: We collected data on 159 consecutive patients treated for rectal cancer (cT3/cT4a, cN+, and cM0 status) at five tertiary referral hospitals between 2005 and 2010. Pathological complete response (pCR) and safety were assessed as the main outcomes in 124 eligible patients comprising 15 who received NAC (NAC group) and 109 who received no neoadjuvant chemotherapy (non-NAC group). Results: In the NAC group, 2 patients (13.3%) achieved a pCR (95% confidence interval: 1.7-40.5%) and 3 patients (20%) experienced grade 3/4 adverse events. No significant differences were found between the NAC and non-NAC groups in terms of short-term outcomes, including R0 proportion (100 vs. 96.3%, p = 0.45) and postoperative grade 3/4 complications (13.3 vs. 18.4%, p = 0.63). Conclusions: Neoadjuvant systemic chemotherapy without radiation appears to be safe, without worsening short-term outcomes, in patients with locally advanced rectal cancer. A further study is needed to verify these findings in larger samples.

Is there a benefit of oxaliplatin in neoadjuvant treatment of locally advanced rectal cancer? An updated meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4098-4098
Author(s):  
Gaetan Des Guetz ◽  
Thierry Landre ◽  
Anne Larrouy ◽  
Yves Panis ◽  
Jean F. Morere ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Cochrane Library ◽  
Perioperative Chemotherapy ◽  
Grade 3

4098 Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until December 2019, we searched PubMed, the Cochrane Library. We also search for relevant ASCO conferences. Primary endpoint was Disease-Free-Survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of 7 Randomized Clinical Trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6 and STAR-01) with 5782 stage II or III rectal cancer patients were analysed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone regimen. Compared with 5FU-based regimen group, OXP-based regimen group improved DFS (HR = 0.90, 95% CI: 0.81−0.99, P = 0.03) and increased pathologic Complete Response (OR = 1.21, 95% CI: 1.07−1.37, P = 0.002). Patients treated with OXP-regimen had significantly less metastatic disease (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering Adverse Events (AEs), there was more grade 3-4 diarrhoea with OXP (OR = 2.41, 95% CI: 1.74−3.32, P < 0.00001). However, there were no significant differences grade 3-4 haematologic AEs (OR = 1.16, 95% CI: 0.87−1.57, P = 0.31). Conclusions: Combining oxaliplatin with capecitabine or 5FU in preoperative chemoradiotherapy or perioperative chemotherapy seems beneficial significantly and improved DFS. It remains necessary to identify which patients benefit most from the addition of oxaliplatin.

Evaluation of Dworak grading system as a prognostic indicator after neoadjuvant chemoradiotherapy in rectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15053-e15053
Author(s):  
Rebecca Buecker ◽  
Hansen Torsten ◽  
Frank Hartmann ◽  
Ulrich Schafer
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
Resection Margin ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Regression Grading ◽  
N Stage ◽  
Grade 3

e15053 Background: The objective of this study was to assess the prognostic role of Tumor Regression Grading (TRG) according to the Dworak system on progression free survival (PFS) after chemoradiotherapy (CRT) in locally advanced rectal cancer. Methods: In total, 159 patients with locally advanced rectal cancer who underwent neoadjuvant CRT from January 2007 and December 2016 were enrolled. PFS (any relapse after surgery) was tested against TRG (Dworak grade 1+2 versus Dworak grade 3+4) and other potential risk factors (age, gender, pre- and postoperative T-stage, pre- and postoperative N-stage, grading, lymph invasion, vessel invasion, chemotherapy regime, resection margin, treatment delay). Risk factors with a highly significant influence (p < 0.01) in the univariate Kaplan-Meier (KM) estimation were tested for independence using the multivariate cox regression model. Results: With a mean follow-up of 42.5 months, 5 years and 10 years estimated PFS for all patients was 60.1% and 49.1% respectively. Estimation of 5 years and 10 years PFS was 49.7% and 45.5% for TRG Dworak grade 1+2 (n = 109) and 83.8% and 67% respectively for TRG Dworak grade 3+4 (n = 50). This difference was highly significant (p < 0.001). Other highly significant risk factors were postoperative N-stage (negative versus positive), lymph invasion (L0 versus L1), and resection margin (R0 versus R1/2). In the multivariate analysis, only TRG and post-op N-stage were identified as independent risk factors for PFS. Conclusions: In this analysis, Dworak Tumor Regression Grading appears to be a prognostic marker for oncologic outcomes in locally advanced rectal carcinoma patients treated with neoadjuvant CRT.

scholarly journals Is There a Benefit of Oxaliplatin in Combination with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer? An Updated Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6035
Author(s):  
Gaëtan Des Guetz ◽  
Thierry Landre ◽  
Marc A. Bollet ◽  
Muriel Mathonnet ◽  
Laurent Quéro
Keyword(s):  
Rectal Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Long Term Results ◽  
Cochrane Library ◽  
Metastatic Progression ◽  
Grade 3

Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81–0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07–1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3–4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74–3.32, p < 0.00001). However, there were no significant differences grade 3–4 hematologic AEs (OR = 1.16, 95% CI: 0.87–1.57, p = 0.31). Conclusions: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

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