Downstaging after preoperative chemoradiation as a prognostic marker for recurrence after curative surgery in locally advanced rectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14650-e14650
Author(s):  
Jieun Lee ◽  
Myung Ah Lee ◽  
Sang Woo Kim ◽  
Jun Ki Kim ◽  
Seong Taek Oh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Recurrence ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Oncologic Outcomes ◽  
Clinicopathologic Factors

e14650 Background: 5-fluorouracil (5-FU) based preoperative concurrent chemoradiation (CCRT) with surgery is the standard treatment for resectable rectal cancer. Chemotherapy after surgery improves local control, but there are some debates for the role in 5-FU based adjuvant chemotherapy. This study was aimed to analyze the tumor recurrence pattern in locally advanced rectal cancer, and the relationship between clinicopathologic factors with tumor recurrence. Methods: One hundred forty-nine patients with locally advanced rectal cancer, receiving preoperative 5-FU based CCRT (radiation dose: 5040 cGy) with total mesorectal excision (TME), followed by adjuvant 5-FU based chemotherapy were enrolled. Sex ratio was 95:54. Median age was 61 (range 37~83). Medical records were reviewed retrospectively. Clinicopathologic factors, oncologic outcomes (tumor recurrence, disease free survival (DFS)) were assessed. Results: Median follow-up duration was 25.3 months (range 5.2~66.2). Median DFS was 19.3 months (range 0~63.4). Thirty-five (23%) patients showed recurrence after surgery. Among tumor recurrence, 86% of patients were presented with distant metastases. Absence of T or N downstaging after 5-FU CCRT was significantly correlated with tumor recurrence (P=0.032 and P=0.011 by Fisher’s exact test, respectively) and longer DFS (P=0.003 and P<.001 by Kaplan-Meier survival curve, respectively). Lymphatic invasion, neural invasion after 5-FU CCRT showed correlation with recurrence (HR=6.37, 95% CI; 2.74-14.84, P<.001; HR=4.9, 95% CI; 1.85-12.97, P=0.002, respectively). In contrast, vascular invasion was not associated with tumor relapse after 5-FU CCRT followed by surgery. Conclusions: The absence of T or N downstaging, the presence of lymphatic or perineural invasion in pathology was associated with tumor recurrence. In spite of 5-FU based adjuvant chemotherapy, distant metastases were more prevalent. In patients with the possibility of distant metastases, more aggressive adjuvant chemotherapy-including platinum agents-should be considered.

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.

Nomograms for Predicting Local Recurrence, Distant Metastases, and Overall Survival for Patients With Locally Advanced Rectal Cancer on the Basis of European Randomized Clinical Trials

2011 ◽  
Vol 29 (23) ◽  
pp. 3163-3172 ◽  
Author(s):  
Vincenzo Valentini ◽  
Ruud G.P.M. van Stiphout ◽  
Guido Lammering ◽  
Maria Antonietta Gambacorta ◽  
Maria Cristina Barba ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Local Recurrence ◽  
External Validation ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Risk Groups ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusion The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up ( http://www.predictcancer.org ).

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.

Analysis of recurrence pattern and survival in locally advanced rectal cancer treated with neoadjuvant chemoradiation and surgery: 25 years of experience.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 744-744
Author(s):  
Javier A. Cienfuegos ◽  
Jorge Baixauli ◽  
Fernando Rotellar ◽  
Iosu Sola ◽  
Jorge Arredondo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathological Response ◽  
Upper Third

744 Background: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (CRT) followed by total mesorectal excision (TME). Despite the significant reduction (~ 40%) in local recurrence, the overall survival (OS) and disease free survival (DFS) remain stable during last decade. We aimed to study the pattern of recurrence and it’s relationship with clinico-pathological data in 356 patients with LARC treated with CRT and TME in last 25 years. Methods: From a total of 621 patients, 356 with LARC were analyzed. In 55 (15.4%) the tumor was localized in upper third, in 120 (33.7%) in middle third and in 181 (50.8%) in distal third. The median dose of radiotherapy for the 3 groups was between 47.5 - 48.52 Gy. Chemotherapy was based on 5-FU or capecitabine combined with oxaliplatin. Type of surgery, pathological response grade, circumferential resection margin, lymphovascular invasion, colloid response, local recurrence incidence, distal relapse, OS and DFS were analyzed. Results: The median interval between the end of CRT and surgery was 40 days. 52 low anterior resection were carried-out in upper third (94.5%), 112 (93.3%) in middle third and 92 (50.8%) in distal third. Four patients from the middle third (3.3%) underwent abdominoperineal resection and 72 (39.8%) in the distal location. No differences were observed in number of lymphoid nodes, vascular perineural invasion, and pathological response grade. A pathological complete response was assessed in 5 patients (9.1%) in upper third, in 12 (10%) in middle third, as well in 32 (17.7%) in distal third. Median follow-up of 187 months. The 5-10 year DFS for the 3 groups was 75%, 76%, and 69%, and 75%, 71%, and 66% respectively. The local recurrence rate was 3.6%, 4.2%, and 6.1%. The distal recurrence was more frequent in the lung, 10.9%, 16.7%, 23.8%, with tendency to be significant (p<0.007) in distal third. Conclusions: In spite of the good local control with the association of preoperative CRT and TME in treatment of LARC, the development of distant metastases, especially in distal third, gives rise to new therapeutics schemes. Further research is warranted as to the benefits of adjuvant chemotherapy.

scholarly journals Conventional Pre-operative Chemoradiotherapy and Post-operative Adjuvant Chemotherapy with Induction Chemotherapy Followed by Chemoradiotherapy and Surgery in Locally Advanced Rectal Cancer

2012 ◽  
Vol 08 (01) ◽  
pp. 48
Author(s):  
Carlos Fernández-Martos ◽  
Rafael Estevan ◽  
Joan Maurel ◽  
◽  
◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
High Risk Population ◽  
Combined Modality Treatment

In locally advanced rectal cancer, pre-operative combined-modality treatment with 5-fluorouracil and radiation has become standard, as it improves locoregional control. However, to date, no improvement has been demonstrated in terms of survival outcomes. Phase III trials published in the past decade included clinically staged populations of heterogeneous risk, and one recurring finding was that there was poor adherence to the adjuvant chemotherapy treatment after surgery. No randomized studies have been able to show that the administration of adjuvant chemotherapy in patients undergoing pre-operative radiochemotherapy improves outcomes, compared to observation. One strategy to address this is to give upfront chemotherapy prior to pre-operative chemoradiotherapy. Compared with post-operative chemotherapy, the upfront strategy does not appear to improve pathological complete response, but it has been found to have a better toxicity profile, improve compliance with treatment, and provide greater exposure to systemic treatment. This can be important for patients at higher risk of distant disease relapse. Introducing a systemically active combination chemotherapy prior to chemoradiotherapy and surgery in an appropriately selected high-risk population may well be the next step in phase III testing in order to improve disease-free survival.

Adjuvant chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) in patients with locally advanced rectal cancer after preoperative chemoradiotherapy followed by surgery: A randomized phase II study (The ADORE).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3570-3570 ◽  
Author(s):  
Yong Sang Hong ◽  
Byung-Ho Nam ◽  
Kyung Hae Jung ◽  
Jae-Lyun Lee ◽  
Kyu-Pyo Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer

3570 Background: Preoperative chemoradiotherapy (Pre-CRT) with fluoropyrimidines (Fp) followed by surgery is one of the standard treatments for patients (pts) with locally advanced rectal cancer (LARC); however, the role of adjuvant chemotherapy is still controversial. The aim of this study is to investigate the efficacy of adjuvant FOLFOX for LARC pts who underwent Fp-based Pre-CRT and complete total mesorectal excision (TME). Methods: This randomised phase II study accrued LARC pts whose ypStage was II (ypT3-4/ypN0) or III (any ypT/ypN1-2) after Fp-based Pre-CRT followed by TME. Pts were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (5-FU 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 on D1, 5-FU bolus 400 mg/m2 on D1, 5-FU infusion 2400 mg/m2 for 46 hours q 2 weeks X 8 cycles). The primary endpoint was disease-free survival (DFS). Results: A total of 320 pts were randomly assigned (161 FL and 159 FOLFOX) between November 2008 and June 2012, the arms were balanced. By intent-to-treat analysis, estimated 2-year DFS rate was 82.0% in FOLFOX arm and 69.4% in FL arm (HR 0.46 [95% CI, 0.28-0.76], p=0.002) after the median follow-up duration of 22.5 months. The statistical improvements of DFS were maintained regardless of ypStage: 2-year DFS rate was 89.7% (FOLFOX) vs 76.4% (FL) in pts (n=122) with ypStage II (HR 0.32 [0.10-0.98], p=0.035), and 78.1% (FOLFOX) vs 64.4% (FL) in pts (n=198) with ypStage III (HR 0.49, [0.27-0.86], p=0.011). All grade leucopenia (32% vs 22%), neutropenia (70% vs 46%), thrombocytopenia (26% vs 2%) and sensory neuropathy (71% vs5%) were more frequently observed in FOLFOX arm; however, grade 3/4 adverse events (AE) were not different between arms. Conclusions: Adjuvant FOLFOX improved 2-year DFS relative to FL for LARC pts whose ypStage II or III after Fp-based Pre-CRT followed by TME. Significant AEs were not different between arms. The DFS results will be updated in the presentation. Clinical trial information: NCT00807911.

Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years

2012 ◽  
Vol 30 (16) ◽  
pp. 1926-1933 ◽  
Author(s):  
Rolf Sauer ◽  
Torsten Liersch ◽  
Susanne Merkel ◽  
Rainer Fietkau ◽  
Werner Hohenberger ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Cumulative Incidence ◽  
Working Group ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Purpose Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. Patients and Methods A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival. Results Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival. Conclusion There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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