Exosomal microRNA-199b-5p as a potential circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15161-e15161 ◽  
Author(s):  
Dong Won Baek ◽  
Kyung Hwa Kim ◽  
Byung Woog Kang ◽  
Hye Jin Kim ◽  
Soo Yeon Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Serum Samples ◽  
Pathologic Stage ◽  
Tissue Specimens ◽  
Response Group

e15161 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision has become the standard treatment for locally advanced rectal cancer (LARC). However, the effect of CRT varies from complete response to complete resistance, and predicting response to CRT have not been well characterized yet. Previous studies have shown the potential of micro-RNA (miRNA) based approaches to enhance tumor radiation response. Accordingly, the present study attempted to identify biomarkers to predict response for preoperative CRT using comprehensive miRNA analysis in patients with LARC. Methods: This study included 65 rectal cancer tissues and 90 serum samples from patients who diagnosed with LACR and received preoperative CRT at Kyungpook National University Chilgok Hospital. Tissue specimens and serum samples were collected before CRT to evaluate the biologic differences between the good CRT response group and the poor CRT response group. For discovery of specific miRNAs, 800 miRNAs were analyzed using NanoString in 30 rectal cancer tissues. Thereafter, a total of 65 tissues, and 90 serum samples were investigated using real-time PCR for validation. Results: The median age was 59 years (range, 30-82), and the ratio of male to female was 3.05 to 1. The pathologic stages after preoperative CRT were as follows: pathologic complete response (n=13, 14.4%), pathologic stage I (n=13, 14.4%), pathologic stage II (n=27, 30.0%), pathologic stage III (n=28, 31.1%), and pathologic stage IV (n=9, 10.0%). In the discovery set, 16 target miRNAs were detected. In the validation set with tissue specimens, expression of 3 miRNAs (miR-199a/b-3p ( p=0.032), miR-199a-5p ( p=0.023), miR-199b-5p ( p=0.005)) was significantly upregulated which was associated with better response of CRT. Moreover, among the 3 candidate miRNAs, miR-199b-5p level was significantly upregulated in serum, and it was also found to be related with better response of CRT in LARC (pathologic stage 0/I versus II/III/IV, p=0.027). Conclusions: In the present study, high level of exosomal miR-199b-5p was associated with better response, suggesting it to be a promising non-invasive biomarker to predict response of CRT in patients with LARC. Accordingly, specific miRNAs can be predictive biomarker or therapeutic target to overcome radiotherapy resistance in LARC with a functional study.

scholarly journals Road to organ preservation in locally advanced rectal cancer

2017 ◽  
Vol 145 (7-8) ◽  
pp. 415-420
Author(s):  
Milica Nestorovic ◽  
Goran Stanojevic ◽  
Branko Brankovic
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Operative Management ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Pathological Examination ◽  
Diagnostic Tools ◽  
Non Operative Management

Introduction. In the past 20 years there has been significant change in the treatment of rectal cancer, especially in terms of multimodal approach. Surgery is, at least for now, the mainstay treatment for resectable rectal cancer. Preoperative chemoradiotherapy is, regardless of its modality, short or long course, different chemotherapeutic regiments, widely recommended for locally advanced rectal cancer. After neoadjuvant treatment, 15?27% of patients experience pathological complete response (pCR). These patients could benefit from non-operative management, thus avoiding potential surgical complications and possible reduction in the quality of life. Unfortunately, one cannot precisely define, while omitting surgery, which patients have pCR. For this reason Habr-Gama, a pioneer in the ?watch-and-wait? strategy, developed a new endpoint for non-operative management ? clinical complete response. To measure the response, in the absence of pathological examination, same diagnostic tools are used as in initial staging, but none is reliable enough to be used alone. This article is focusing on critical points in the reassessment of response to preoperative chemoradiotherapy for advanced rectal cancer, which is mandatory for appropriate selection of patients who might benefit from non-operative management.

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.

scholarly journals Efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for locally advanced rectal cancer

2020 ◽  
Author(s):  
Nobuki Imano ◽  
Yuji Murakami ◽  
Katsumaro Kubo ◽  
Daisuke Kawahara ◽  
Yuki Takeuchi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Clinical Results ◽  
Tumor Stage ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Grade 3

Abstract Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2–3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m2/day, was orally administered during radiotherapy. A total dose of 45–50.4 Gy was delivered in 25–28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6–10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients.

The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy

2020 ◽  
Vol 26 (7) ◽  
pp. 1611-1620
Author(s):  
Abdullah Sakin ◽  
Suleyman Sahin ◽  
Nilay Sengul Samanci ◽  
Nurgul Yasar ◽  
Cumhur Demir ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Relapse Free Survival ◽  
Free Survival

Purpose The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Methods Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows – TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. Results Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25–87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%–92.3%, 74.7%–79.4%, and 55.7%–55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17–6.77), 0.39 (0.18–0.83), respectively). Conclusion This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.

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