scholarly journals Prognostic significance of clinical and pathological stages on locally advanced rectal carcinoma after neoadjuvant chemoradiotherapy

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Bixiu Wen ◽  
Luning Zhang ◽  
Chengtao Wang ◽  
Rong Huang ◽  
Haihua Peng ◽  
...  
2016 ◽  
Vol 63 (1) ◽  
pp. 59-73
Author(s):  
M. Micev ◽  
M. Micev-Cosic ◽  
Djikic Rom ◽  
M. Andrejevic ◽  
M. Dimic-Cumic ◽  
...  

Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by radical surgical resection is the mainstay of curative therapy in the management of patients with locally advanced (stage II and III) rectal carcinoma in order to reduce local recurrence and improve survival following surgery for rectal cancer. A brief survey of histopathological tumor regression grading (TRG) systems, other histomorphological and immunohistochemical findings and their clinical implications were reported including authors? experience. Possible diagnostic pitfalls are discussed specially on complete tumour regression (pCR), differentiation downstaging and downsizing and other aspects of standard histopathological examination and RT-induced histologic changes, including morphological, immunohistochemical and molecular transdifferentiation of tumour cells. Some of these histopathological parameters have to be considered when auditing rectal cancer resections and identifying prognostic factors


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 624-624
Author(s):  
Erika B. Ruiz Garcia ◽  
Gilberto Lopez-Rosas ◽  
Cesar Lopez-Camarillo ◽  
Silvio Namendys-Silva ◽  
Leonardo Lino-Silva ◽  
...  

624 Background: Neoadjuvant chemoradiotherapy (nCRT) follow by surgery, as treatment for locally advanced rectal carcinoma (LARC), has improve local disease control, increase of complete pathological response (cPR) and preserve anal sphincter. cPR is associated with better prognosis. CRT act mainly through induction of DNA damage. MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at post-transcriptional level. miRNAs are involved in the regulation of DNA damage/repair mechanism. Our goal was to measure expression of miRNAs involved in DNA damage/repair genes and correlated with cPR. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 20 Mexican patients with LARC treated with nCRT at National Cancer Institute of Mexico between 2010-2013. Treatment response was evaluated with Ryan Classification. Ten patients had cPR (Ryan Grade 0) meanwhile other 10 poor response (Ryan Grade 3). RNA extraction was done with RNeasy FFPE (Qiagen) Kit. RNA concentration and purity was assessed using NanoDrop 2000 Spectrophotometer. miRNAs expression were evaluated by real-time polymerase chain reaction (PCR) analysis with TaqMan Probes from Applied Biosystems. Statistical analysis was carried out with IBM SPSS Statistics 22.0. Differential expression between the two groups was performed with Chi square test. Results: There wasn’tsignificant difference betweenclinical/demographic features between the 2 groups. All patients received CRT at a total dose of 4500 cGy of pelvic irradiation, concomitantly with fluoropyrimidine. Surgical treatment was performed 14 weeks after completion of nCRT. The 2 miRNAs (188-5p and 590-5p) was overexpressed in the cPR group vs poor response group (p = 0.011 and p = 0.057, respectively). Conclusions: We evaluated the expression of miR590-5p and miR188-5p because they are related to DNA repair genes such as: MSH2, ERCC3, BRCC3 and XRCC5. We found overexpression in both miRNAs. Even though miR590 5p didn't reach statistical significance this maybe because of simple size.Our results now are been analyzed with a biological and functional genes network platform: Ingenuity Pathway Analysis.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 55-55
Author(s):  
Po Kuei Hsu ◽  
Teh-Ying Chou ◽  

55 Background: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer. However, its efficacy is limited in non-responders and there is no reliable clinical parameter in predicting treatment response. We aim to identify chemoradiation-resistant cancers and avoid unnecessary treatments in non-responders with mutation analysis. Methods: Genomic DNA was extracted from diagnostic biopsy specimens of 20 patients (10 with good and 10 with poor response) with esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and esophagectomy. Using next-generation sequencing, we screened mutation hotspots in 46 cancer-related genes (Ion AmpliSeq Cancer Panel). Potential predictive genetic variations were validated in another cohort of patients. Chemoradiotherapy response was based on pathological evaluation of surgically resected specimens. The prognostic significance of genetic variations was evaluated with Cox regression survival analysis. Results: In the first cohort, we discovered PIK3CA H1047R and STK11 F354L as potential targets to predict chemoradiation resistance. Next, we investigate these genetic variations in another 54 patients. Altogether, 18.9% (14/74) and 6.8% (5/74) of patients had PIK3CA H1047R and STK11 F354L, respectively. In patients with poor response to chemoradiotherapy, 45.8% (11/24) had either PIK3CA H1047R or STK11 F354L; compared to 12.0% (6/50) in patients with good response ( p = 0.001). In other words, 64.7% of patients with either one genetic variation responded poorly to chemoradiotherapy. In survival analysis, the 5-yr survival rates were 7.7% and 43.7% in patients with either one genetic variation and those without, respectively ( p = 0.003). In multivariable analysis, the presence of either one genetic variation was a significant prognostic factor for overall survival (Hazard ratio: 2.43, 95% confidence interval: 1.195-4.944, p= 0.014). Conclusions: PIK3CA H1047R and STK11 F354L mutations are associated with poor response to neoadjuvant chemoradiotherapy and worse prognosis in esophageal cancer. It may potentially be biomarkers to guide treatment decisions.


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