Timing to achieve the best recurrence-free survival after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: experience in a large-volume center in China

2021 ◽  
Author(s):  
Xiaojie Wang ◽  
Zhifang Zheng ◽  
Heyuan Zhu ◽  
Qian Yu ◽  
Shenghui Huang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Large Volume ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cancer Experience

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 results of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Comparative efficiency of hypofractionation and classical fractionation schedules

2020 ◽  
Vol 10 (2) ◽  
pp. 19-27
Author(s):  
A. S. Abdujapparov ◽  
S. I. Tkachev ◽  
V. A. Aliev ◽  
D. S. Romanov ◽  
J. M. Madyarov ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Main Group ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

Objective: comparison of the effectiveness of the results of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer using classical and hypofractionated schedule of radiation therapy.Materials and methods. This study is based on a retrospective analysis of a database of patients with locally advanced rectal cancer (T3C–D, positive circumferential resection margin or T4) who underwent a prolonged course of neoadjuvant chemoradiotherapy followed by surgery. The patients were divided into two groups: the first (main) group, 71 patients who received a course of chemoradiotherapy in hypofractionation schedule as part of neoadjuvant treatment (4 Gy × 40 Gy, 3 fractions per week) in combination with chemotherapy with capecitabine 1650 mg / m2 in two doses on weekdays. The second group (control group) included 79 patients who treated with long-course chemoradiotherapy in the classic fractionation mode (2 Gy × 50–58 Gy, 5 fractions per week) in combination with chemotherapy with capecitabine 1650 mg / m2 in two doses on weekdays. In the preoperative period, along with chemoradiotherapy, 4–8 courses of the systemic chemotherapy in the CapOx mode was used. The primary endpoint of this study was pathological complete response. Secondary endpoints included the seve rity of early radiation and hematological toxicity, the incidence of local recurrence, distant metastases, overall and disease-free survival. Results. The study included 150 patients. The overall frequency of acute radiation toxicity of grade III–IV was 5.6 % in the main group and 8.9 % in the control group (p = 0.658), from them hematological toxicity – 2.82 % and 7.6 %, respectively (p = 0.350), skin and pelvic organ toxicity – 2.82 % and 1.3 %, respectively (p = 0.926). Complete pathological response of III degree in the groups achieved 22.5 % and 19 %, respectively (p = 0.593), grade IV – 18.3 % and 15.2 %, respectively (p = 0.829). In the main and control groups, 4.2 % and 3.8 % of local recurrence were registered, respectively (p = 0.954; hazard ratio (HR) 1.05; 95 % confidence interval (CI) 0.21–5.22). The median time of disease-free survival was 39.4 months. The three-year disease-free survival in the main group was 73.2 % and in the control group 64.6 %, respectively (p = 0.353; HR 0.79; 95 % CI 0.42–1.35). The three-year overall survival in the main and control groups were 84.5 % and 82.3 %, respectively (p = 0.743; HR 0.87; 95 % CI 0.39–1.92). Conclusions. The hypofractionation schedule can be considered as an alternative and not inferior to the standard dose fractionation regimen in a prolonged course of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. 

scholarly journals Neoadjuvant Chemoradiotherapy in the Downstaging of Locally Advanced Rectal Cancer and its Impact on Progression–Free Survival

2020 ◽  
Vol 18 (1) ◽  
pp. 39-44
Author(s):  
Tatjana Neško ◽  
Arvils Neško ◽  
Elīna Sīviņa ◽  
Gunta Purkalne
Keyword(s):  
Rectal Cancer ◽  
Vascular Invasion ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Free Survival ◽  
The Impact

SummaryIntroductionThe standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT) followed by radical surgery, which allows to reduce local recurrence, downsize the tumor and facilitate its R0 resection.Aim of the studyThe aim of this study was to evaluate the downstaging of LARC after NACRT and to assess the impact of downstaging on progression–free survival (PFS).Materials and methods65 patients diagnosed with LARC from 2012 to 2018, who received NACRT with subsequent radical surgery were identified in the Pauls Stradins Clinical University Hospital in Riga and included in this retrospective study. Average follow–up period was 31 months. Data were analysed with SPSS Statistics 22.0, Wilcoxon signed–rank test and Kaplan–Meier survival analysis were performed.ResultsOverall, 66.7% (n=40) of patients experienced a downstaging in response to NACRT, of which 37.5% (n=24, p=0.004) had a downstaging of T and 63.3% (n=38, p=0.0001) of N.12–month PFS was 87.8%, 24–month PFS – 66.1% and 3–year PFS – 62.7%, median PFS (mPFS) was not met. 3–year PFS of those patients treated with intravenous 5FU/LV boluses was significantly higher (76.5%) than those who received oral tegafur (45.6%, mPFS 32 months), p=0.038. 3–year PFS of patients with downstaged T was 85.9%, compared to 52.1% without it; mPFS not met, p=0.04. Similarly, 3–year PFS of patients with downstaged N was 71.5%, compared to 43.3% without it (mPFS 24 months), p=0.112. Lymphatic and vascular invasion were associated with significantly lower PFS compared to the patients with absent lymphatic and vascular invasion (p=0.0001 and p=0.014, respectively), while perineural invasion did not show any impact on PFS. Age at diagnosis, tumor location, type of surgery and adjuvant chemotherapy did not have a significant impact on PFS.ConclusionsResults confirm the efficacy of NACRT in LARC in the downstaging of T and N. Downstaging of LARC, intravenous chemotherapy and absence of lymphovascular invasion are associated with significantly increased PFS.

Neoadjuvant chemoradiotherapy with capecitabine in locally advanced rectal cancer: Analysis of prognostic factors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 92-92
Author(s):  
Jesus Romero ◽  
Sofía Sánchez ◽  
Arsenio Sánchez ◽  
Isabel Alonso ◽  
Raquel Benlloch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Factors ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Rank Test ◽  
Free Survival

92 Background: Capecitabine-based neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer (LARC). The objective of this retrospective study is to analyze overall survival (OS), local relapse free-survival (LRFS), distant metastases free-survival (DMFS) and prognostic factors. Methods: Between 2009 and 2018, 207 patients(p) with LARC has been treated in our hospital with neoadjuvant CRT. Clinical characteristics: Mean age: 65 y (41-87); male:129, female:78; TNM: cT2: 12p, cT3: 176p, cT4: 19p, cN0: 59p, cN1: 106p, cN2: 42p. Treatment: pelvic radiotherapy (45Gy, 1.8Gy/day) plus concomitant capecitabine (852mg/sqm/12h for 28 days). Surgery (mesorectal excision) was carried out 6-8 after the end of CRT. Statistics:Kaplan-Meier and Log-rank test. Results: Mean follow-up: 43 months. Downstaging:104/192 (54%). Pathological complete response:31/192 (16%). Sphincter preservation rate was 82%. Five-year OS, LRFS and DMFS were 89.9%, 93.3% and 81.7%, respectively. Factors predicting shorter 5-y OS were: cT4 (69% vs 91% and 91% for cT1 and CT2, respectively; p=0.027), pT3-4 (85% and 64% vs 100%, 100% and 98% for pT0, pT1 and pT2, respectively; p=0.008), pathological involved nodes (pN+) (77% vs 96%; p=0.001), perineural invasion (PNI) (78% vs 95%; p=0.041), LVI (p<0.001), Ryan 3 (p<0.001), resection margin R1 (67% vs 94% for R0; p<0.001), no pCR (p=0.027) and absence of downstaging (73% vs 97%; p=0.001). Factors associated with poor 5-y DMFS were:pT3-4 ( 70% and 0% vs 96%,88% and 98% for pT0,pT1 and pT2, respectively; p<0.001), pN+ (68% vs 88% for pN0: p<0.001), PNI (64% vs 85%; p=0.036), Ryan 3 (49% vs 96%, 85% and 85% for Ryan 0, 1 and 2, respectively; p<0.001), R1 (33% vs 86% for R0; p<0.001) and absence of downstaging (50% vs 71%; p<0.001). CTCAE 4.0 grade 3 toxicity: 1%. No grade 4 toxicity was seen. Conclusions: CRT with capecitabine provides high rates of survival and sphinter preservation with excellent tolerance. Patients with adverse pathological factors (pT4, pN+, PNI, Ryan 3, R1 and absence of downstaging) have a higher risk of distant metastasis and are more likely to benefit from adjuvant chemotherapy.

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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