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.

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 Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II)

2019 ◽  
Vol 25 (1) ◽  
pp. 118-125 ◽  
Author(s):  
Norifumi Hattori ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Toshisada Aiba ◽  
Kiyoshi Ishigure ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Treatment Compliance ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Ii ◽  
R0 Resection

Abstract Objective This multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer. Methods Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1–14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety. Results A total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57–86%) and 96% (95% CI 80–99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively. Conclusion CapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

Comparison of Two Neoadjuvant Chemoradiotherapy Regimens for Locally Advanced Rectal Cancer: Results of the Phase III Trial ACCORD 12/0405-Prodige 2

2010 ◽  
Vol 28 (10) ◽  
pp. 1638-1644 ◽  
Author(s):  
Jean-Pierre Gérard ◽  
David Azria ◽  
Sophie Gourgou-Bourgade ◽  
Isabelle Martel-Laffay ◽  
Christophe Hennequin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Conservative Surgery ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Neoadjuvant Radiotherapy ◽  
Operative Specimen ◽  
To Receive

Purpose Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. Patients and Methods We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). Results Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). Conclusion The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.

Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA4008-CRA4008 ◽  
Author(s):  
C. Aschele ◽  
C. Pinto ◽  
S. Cordio ◽  
G. Rosati ◽  
A. Tagliagambe ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Anal Verge ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathologic Response ◽  
Phase Iii ◽  
Local Tumor ◽  
Phase Iii Trial

CRA4008 Background: Oxaliplatin (OXA) enhances the efficacy of FU-based chemotherapy in colon cancer. This randomized phase III trial investigated the effect of adding OXA to preoperative (preop) FU-based pelvic chemoradiation (CRT) in patients (pts) with locally-advanced rectal cancer. Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or lymphnode involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq × 6) (Arm B). Surgery was scheduled 6–8 weeks after completing CRT. Overall survival was the primary endpoint. A protocol-planned analysis of local tumor response to preop treatment (secondary end-point) is the object of this report. Results: 747 pts from 41 Italian centers were randomized between 12/2003 and 8/2008 (arm A/B: 379/368). Pretreatment characteristics in arm A/B: median age 63/62 years; male:female 2:1; median distance from anal verge 6 cm; T4 16/14%, N+ 63/65%. Overall grade 3–4 toxicity rates on treated pts (mainly diarrhoea) were 8% and 24% (arm A/B, p<0.001). 96/90% of pts (arm A/B) received > 90% of the planned RT. 82% of Arm B pts had > 5 oxa courses. 358/342 pts (arm A/B) had surgery at a median of 52/53 days from the end of CRT, 14 pts in each arm were not operated (progression 8, death 5, other/unknown 15) and surgery data are not yet available for 19 pts. Pathologic response data analyzed on the randomized population are reported in the table . Conclusions: The addition of weekly OXA to standard FU-based preop CRT significantly increases toxicity without affecting local tumor response. The reduced pathologic M+ rate suggests a potential effect on distant micrometastases. Longer follow-up is needed to assess the impact on efficacy endpoints. [Table: see text] No significant financial relationships to disclose.

Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging–Defined, Locally Advanced Rectal Cancer: Grupo Cáncer de Recto 3 Study

2010 ◽  
Vol 28 (5) ◽  
pp. 859-865 ◽  
Author(s):  
Carlos Fernández-Martos ◽  
Carles Pericay ◽  
Jorge Aparicio ◽  
Antonieta Salud ◽  
MariaJose Safont ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Randomized Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
R0 Resection ◽  
Concomitant Chemoradiotherapy

Purpose The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. Patients and Methods A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A—preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. Conclusion Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

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.

scholarly journals Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD

2021 ◽  
Vol 39 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Alexander Stein ◽  
Eric Van Cutsem ◽  
Timothy Price ◽  
Ralf D. Hofheinz ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anal Verge ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Site Location ◽  
Intention To Treat

PURPOSE The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

scholarly journals Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002)

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingwen Wang ◽  
Yun Guan ◽  
Weilie Gu ◽  
Senxiang Yan ◽  
Juying Zhou ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Concomitant Boost ◽  
The Impact ◽  
To Receive ◽  
Incision Healing

Abstract Background This study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer. Methods Patients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint. Results From February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups (P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control (P = 0.856), disease-free survival (P = 0.349) and overall survival (P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis. Conclusions A concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations. Trial registration NCT01064999 (ClinicalTrials.gov).

Nodal status after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer: Prognostic evaluation of number of resected lymph nodes (LNs), metastatic resected LNs, and LN ratio in the National Cancer Institute of Brazil.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14568-e14568
Author(s):  
Fernando Meton Vieira ◽  
Rodrigo Otavio Araujo ◽  
Ana Paula Victorino ◽  
Maria de Lourdes Oliveira ◽  
Carlos G. M. Ferreira
Keyword(s):  
Rectal Cancer ◽  
Strong Predictor ◽  
Anal Verge ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Categorical Variables ◽  
Rank Test ◽  
Time Interval

e14568 Background: For accurate colon cancer staging, 12 or more LNs must be resected. However, in rectal cancer, preoperative CRT can decrease the number of evaluable LNs, and the cutoff for a minimum number of LNs retrieved is unclear, as well as the prognostic value of LN ratio. Methods: We evaluated all locally advanced rectal cancer that received CRT followed by standard surgery (TME) from 2002 to 2009. External radiotherapy consisted of 45 to 50.4 Gy in 5 weeks and concomitant chemotherapy was bolus 5-Fu/LV. Pre-treatment staging included abdominal and pelvic CTs, chest RXs, CEA, and physical examination. Clinical data was collected from medical records and surgical specimens were pathologically evaluated accordingly to Quirke's method. LN ratio was defined as the ratio of the number of positive LN and total number of LN examined. Kaplan-Meier overall survival (OS) and disease free survival (DFS) curves were obtained and compared using the Long-rank test. Categorical variables were assessed using Fish's exact test. Results: Of 202 patients included, 125 (62%) were low rectal cancers (5cm or less from anal verge). Surgery was performed in a mean time interval from CRT of 3.95 months (0.28-24), and the type of resection was a low anterior resection in 139 (64%) and abdominoperineal resection in 63 (36%). Only 42.5% received postoperative chemoterapy. LN metastasis at the vascular stump level were more frequent in cancers lying more than 5 cm above the anal verge (p=0.02). Median number of LNs found in the specimens was 12 (0-56). The number of resected LNs had no impact in prognosis within the cutoff levels of 7 or 12, neither when considering only ypN0 cases. A LN Ratio >0.15 was found in 33% of our patients, and associated to a decrease in OS (p<0.001) and DFS (p=0.01), and was the only variable associated to distant metastasis (p=0.048). Conclusions: Positive LNs after CRT severely impaired prognosis in patients treated with rectal cancer. A prognostic cutoff value for LN dissection were not achieved, but a LN ratio >0.15 seems to be a strong predictor of recurrence and cancer related death.

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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