scholarly journals Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 663-671 ◽  
Author(s):  
Jeanne Tie ◽  
Joshua D Cohen ◽  
Yuxuan Wang ◽  
Lu Li ◽  
Michael Christie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Recurrence Free Survival ◽  
Plasma Samples ◽  
Free Survival ◽  
Ctdna Analysis ◽  
Circulating Tumour Dna

ObjectiveFor patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.DesignWe enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4–10 weeks after surgery. Somatic mutations in individual patient’s tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results.ResultsWe analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001).ConclusionPostoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

scholarly journals Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

2020 ◽  
Author(s):  
Lucrezia D’Alimonte ◽  
Quoc Riccardo Bao ◽  
Gaya Spolverato ◽  
Giulia Capelli ◽  
Paola Del Bianco ◽  
...  
Keyword(s):  
Local Excision ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Recurrence Free Survival ◽  
Long Term Outcomes ◽  
Relapse Free Survival ◽  
Free Survival

Abstract Background Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy. Methods Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan–Meier method. The rate of patients with rectum preserved and without stoma were also calculated. Results Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25–82) years. At baseline, the following clinical stages were found: cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32–166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76–93) and 79% (95% CI 66–87), 89% (95% CI 78–94) and 82% (95% CI 66–91), both 91% (95% CI 81–96), and 90% (95% CI 80–95) and 86% (95% CI 73–93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free. Conclusion In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

scholarly journals Systematic Review: Adjuvant Chemotherapy for Locally Advanced Rectal Cancer with respect to Stage of Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Ii ◽  
Stage Iii ◽  
Free Survival ◽  
Disease Free

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.

Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: First results of the German CAO/ARO/AIO-04 randomized phase III trial.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA3505-LBA3505 ◽  
Author(s):  
C. Roedel ◽  
H. Becker ◽  
R. Fietkau ◽  
U. Graeven ◽  
W. Hohenberger ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Free Survival ◽  
Disease Free

LBA3505 Background: The German CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), surgery, and postoperative chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. With this approach local relapse rates are below 10%. The development of distant metastasis is the predominant mode of failure. Integrating more effective systemic treatment into combined modality therapy was the goal of CAO/ARO/AIO-04. Methods: Between 7/2006-2/2010, patients with rectal cancer within 12 cm from the anal verge and clinical evidence of perirectal fat or lymph node involvement were randomly assigned to receive preoperative CRT, surgery, and adjuvant chemotherapy with 5-FU according to CAO/ARO/AIO-94 (arm 1), or preoperative CRT (50.4 Gy in 28 fractions) with 5-FU (250 mg/m2/days 1-14 and 22-35) and oxaliplatin (50 mg/m2/days 1, 8, 22, 29), surgery, and 8 cycles of adjuvant chemotherapy according to modified FOLFOX6 regimen (arm 2). Disease-free survival was the primary endpoint. We present early secondary endpoints, including acute toxicity, treatment compliance, and pCR-rates. Results: 637 patients were randomly assigned to arm 1 and 628 to arm 2. Full dose preoperative RT and full dose concurrent chemotherapy was delivered in 97% and 74% of patients in both arms, respectively. Preoperative grade 3/4 toxicity occurred in 21.6% in arm 1 and in 22.9% in arm 2. The R0-resection rate was 95.4% in both arms, and abdominoperineal resections were limited to 11.9% and 12.2% in arms 1 and 2, respectively. Overall postoperative complications were not different between both arms (21.0% and 21.9%). The pCR rate (ypT0N0) was 13.1% in arm 1 and 17.6% in arm 2 (p = 0.033, Cochran-Mantel-Haenszel Chi-Squared Test without continuity correction for conditional independence of pCR rate in the two treatment arms in each stratum). Conclusions: Inclusion of oxaliplatin to 5-FU based CRT was well tolerated and associated with increased pCR-rates compared with 5-FU-CRT alone. Longer follow-up is necessary to evaluate the primary endpoint, disease-free survival.

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