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.

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: First results of the PETACC-6 randomized phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3531-3531 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Karin Haustermans ◽  
Timothy Jay Price ◽  
Bernard Nordlinger ◽  
Ralf Hofheinz ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anal Verge ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Treatment Compliance ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
R0 Resection ◽  
To Receive

3531 Background: The PETACC-6 trial investigates whether the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer. We present results of the early secondary endpoints. Methods: Between 11/2008 and 09/2011, patients with rectal cancer within 12 cm from the anal verge, T3/4 and/or node-positive, with no evidence of metastatic disease and considered either resectable at the time of entry or expected to become resectable after preoperative CRT, were randomly assigned to receive 5 weeks of preoperative CRT (45 Gy in 25 fractions) with capecitabine (825 mg/m² twice daily), followed by 6 cycles of adjuvant CT with capecitabine (1000 mg/m2twice daily/days 1-15 every three weeks) (arm 1) or to receive the same regimen with the addition of oxaliplatin before (50 mg/m²/days 1, 8, 15, 22, 29) and after surgery (130 mg/m²/day 1, every three weeks) (arm 2). Additional RT before surgery (5.4 Gy/days 36-38) using the same fields or as a boost with capecitabine was an option. Primary endpoint is DFS. Results: 1094 patients were randomized (547 in each arm). 98% and 92% of patients, respectively, received at least 45 Gy of preoperative RT in arm 1 and arm 2. More than 90% of full dose concurrent CT was delivered in 91% and 63% of patients, respectively, in arm 1 and arm 2. Preoperative grade 3/4 toxicity occurred in 15.1% of patients in arm 1 vs. 36.7% in arm 2; 1 vs. 3 patients died before surgery. R0 resection rate was 92.0% in arm 1 and 86.3% in arm 2. The pCR rate (ypT0N0) was equal in both arms with 11.3% in arm 1 and 13.3% in arm 2 (p=0.31). The anal sphincter was preserved in 70% vs. 65% (p=0.09) in arm 1 and 2. Postoperative complications were not different between arms (38% vs. 41%; 5 vs. 4 patients died following surgery). Definitive numbers will be presented at the congress. Conclusions: The addition of oxaliplatin to preoperative fluoropyrimidine-based CRT led to decreased treatment compliance and increased toxicity, but did not improve surgical outcome. Clinical trial information: NCT00766155.

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.

Ten fractions of preoperative radiotherapy for advanced rectal cancer: Is it a new protocol to follow?

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 439-439
Author(s):  
J. Gu
Keyword(s):  
Rectal Cancer ◽  
Preoperative Radiotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Free Survival ◽  
Short Course ◽  
Disease Free

439 Background: This study is a retrospective analysis to investigate the efficiency of short-course preoperative radiotherapy following standardized total mesorectal excision (TME) for locally advanced rectal cancer. Methods: Clinical data of locally advanced mid-low rectal cancer who received TME in Beijing Cancer Hospital from 2001 to 2005 were collected retrospectively. Survival analysis was performed between patients who had TME following short-course preoperative radiotherapy (biological equivalent dose: 36Gy) or TME alone at the corresponding period. Results: Two hundred and sixty-three patients were eligible for analysis including 101 patients who received TME plus preoperative radiotherapy (PRT group) and 162 patients with TME alone (TME group). The occurrence of TNM downstaging in PRT group was 49.5%, including five percent who had complete response. The local reccurence rate was 4% in PRT group and 8.4% in TME group, with statistically different (p=0.04). An significant improved 5-year overall survival and disease-free survival was obtained in PRT group comparing with TME group (77.2% vs. 69.8%, p=0.04; 76.2% vs. 67.3%, p=0.03). Conclusions: Improved local control and survival benefits could be achieved by short-course preoperative radiotherapy on the basis of standardized TME for locally advanced rectal cancer. No significant financial relationships to disclose.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: Final results of PRODIGE 23 phase III trial, a UNICANCER GI trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
Thierry Conroy ◽  
Najib Lamfichekh ◽  
Pierre-Luc Etienne ◽  
Emmanuel Rio ◽  
Eric FRANCOIS ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Anal Verge ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Surgical Morbidity ◽  
Free Survival

4007 Background: PRODIGE 23 investigated the role of neoadjuvant mFOLFIRINOX before preoperative (preop) chemoradiation (CRT), with TME-surgery and adjuvant chemotherapy (CT) in resectable locally advanced rectal cancer. Methods: PRODIGE 23 is a phase III multicenter randomized clinical trial. Eligible pts had cT3 or cT4, M0 rectal adenocarcinomas <15 cm from the anal verge, age 18-75 years, and WHO PS ≤1. Randomization was stratified by center, T stage, N status, tumor location, and perirectal fat extramural extension. Primary endpoint was 3-yr disease-free survival (DFS). Main secondary endpoints were ypT0N0 rate, overall survival (OS) and metastasis-free survival (MFS). 460 pts were required to observe 136 events to show a gain in 3-year DFS from 75% to 85% (HR=0.56) with a 2-sided α=0.05 and 90% power. HR and 95% CI were estimated by a stratified Cox proportional hazard model. Arm A pts received preop CRT (50 Gy, 2 Gy/fraction [fr]; 25 fr + capecitabine), surgery, then adjuvant CT for 6 months (mos). Arm B pts received 6 cycles of mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 180 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) every 14 days, followed by the same preop CRT, surgery and 3 mos of adjuvant CT. Adjuvant CT consisted of mFOLFOX6 or capecitabine, depending on the centre’s choice for all pts. Imaging work-up, operative and pathology reports were centrally reviewed. Results: (ITT) Between 6/2012 and 6/2017, 230 and 231 pts were randomly assigned in Arm A/B, respectively by 35 participating centers. Pts characteristics were well balanced. Neoadjuvant mFOLFIRINOX and CRT in both arms were well tolerated. Compliance to CRT and to adjuvant CT was not hampered by neoadjuvant CT. Surgical morbidity did not differ between the 2 arms. The ypT0N0 rate was 11.7 vs 27.5% in Arm A/B (p<0.001). Median follow-up was 46.5 mos. 136 DFS events was reported. 3-yr DFS was significantly increased in arm B (HR 0.69, 95% CI 0.49-0.97, p=0.034): 68.5% (CI: 61.9-74.2) vs 75.7% (CI: 69.4-80.8) in arm A/B. The subgroup analysis showed no evidence of heterogeneity of the effect size of treatment on DFS. 3-yr MFS was also significantly higher in arm B: 71.7 in arm A vs 78.8% (HR 0.64, CI 0.44-0.93, p<0.02) in arm B. 3-yr OS was 87.7 vs 90.8% (HR 0.65, CI 0.40-1.05, p=0.077) in arm A/B, with 54.2% of the pts with recurrence being alive. Conclusions: Neoadjuvant mFOLFIRINOX plus CRT is safe, and significantly increased ypCR rate, DFS and MFS. OS data are not mature. Clinical trial information: NCT01804790 .

scholarly journals Prognostic impact of acellular mucin pools towards the patients with locally advanced rectal cancer achieving pathological complete response after preoperative chemoradiotherapy

2020 ◽  
Vol 13 ◽  
pp. 175628482091125
Author(s):  
Lin Zhang ◽  
Huajie Guan ◽  
Qiuyun Luo ◽  
Lifang Yuan ◽  
Yulan Mao ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Prognostic Impact

Background: To date, the prognostic significance of acellular mucin pools in tumors from patients with locally advanced rectal cancer (LARC) undergoing preoperative chemoradiotherapy (CRT) and subsequently obtaining pathological complete response (pCR) has not been well determined. Our current study aimed to explore the prognostic impact on these patients of acellular mucin pools. Methods: We collected clinical data from 117 consecutive LARC patients who achieved pCR after preoperative CRT and then underwent radical resection. Two groups of patients were generated, according to the presence or absence of acellular mucin pools. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared between the two groups of patients. Results: A total of 27 (23.1%) patients presented with acellular mucin pools. At a median follow-up period of 64 months, patients with acellular mucin pool showed a 5-year DFS rate (96.3% versus 83.7%, p = 0.110) and 5-year OS rate (100% versus 87.5%, p = 0.054) statistically similar to those of patients without acellular mucin pools. In univariable and multivariable Cox regression analyses, the presence of acellular mucin pools was not determined as an independent risk factor for DFS [hazard ratio (HR): 0.222; 95% confidence interval (CI): 0.029–1.864; p = 0.145] or OS (HR: 0.033; 95% CI: 0.000–9.620; p = 0.238). Conclusions: Acellular mucin pools had no significant prognostic impact on LARC patients showing pCR after preoperative CRT.

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.

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