Functional MRI for quantitative treatment response prediction in locally advanced rectal cancer

71 Background: Although many efforts to predict treatment response of concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) have been made, no molecular has proved to be a robust biomarker. Methods: We performed mass spectrometry-based quantitative proteomic analysis of pretreatment Formalin-fixed, Paraffin-embedded (FFPE) biopsy samples of 13 patients with LARC, who were treated with CCRT followed by curative surgery. Based on pathologic report of surgical specimens, we divided thirteen patients as two response groups: complete response (CR) and non-complete response (nCR) groups. Results: A total of 3,637 proteins were identified and 498 proteins were confirmed as expressed at significantly different levels (DEPs; differently expressed proteins) between these two groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were also performed: the result showed that up-regulated DEPs enriched in biological processes (BP) were significantly different between two groups; immune response, cell migration & motility, protein transport in CR group; amide/peptide biosynthetic process, translation, posttranscriptional regulation of gene expression and detoxification in nCR group. To identify the best classifier to evaluate predictive power of signatures, we employed for different machine learning algorithms to classify samples between CR and nCR groups. As a result, we identified the predictive relevance of dual oxidase 2 (DUOX2) as the strongest predictive biomarker. Conclusions: This study identified a new biomarker, DUOX2, applicable to discrimination between CR and nCR after NACRT for LARC. To our knowledge, the present study provides the first identification of a clinical biomarker for response prediction based on in-depth proteomics and machine learning algorithms.

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Tumor necrosis as prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.722 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 722-722

Author(s):

Ji Han Jung ◽

Hyung Jin Kim ◽

Ho Jung An ◽

Sung Whan Kim ◽

Hyun Min Cho ◽

...

Keyword(s):

Rectal Cancer ◽

Treatment Response ◽

Tumor Necrosis ◽

Cox Regression ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Tissue Response ◽

Response Factor ◽

Pathologic Stage

722 Background: Association between treatment response on the basis of pathologic stage evaluated after radical tumor resection and patient prognosis was well established. The object of this study is that tumor necrosis factor after CRT is also important as treatment response. Methods: A total of 243 patients with locally advanced rectal cancer that underwent neoadjuvant CRT was included. Three treatment response groups were classified by their pathologic stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified by tissue pathologic results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). Results: Overall survival (OS) and recurrence free survival (RFS) rate at 3 years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR were 83.7%, 75.9%, and 69.7%, respectively (p<0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p<0.001). The 3-year OS rates of the CNR, INR, and PNR were 83.7%, 80.6%, and 61.8%, respectively (p<0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p<0.001). When compared to CTR / CNR, PTR / PNR was strongly related to an increased risk of recurrence (hazard ratio, 5.53; 95% CI, 2.01 to 15.23 / 6.37; 95% CI, 2.29 to 17.74) respectively in the univariate Cox regression. Therefore in the two models using multivariate Cox regression, both PTR and PNR were strongly associated to RFS and OS compared with CTR and CNR. Conclusions: The tissue response factor to neoadjuvant CRT is one surrogate marker for recurrence and oncologic outcomes and almost as important as the treatment response factor in rectal cancer patients treated with neo-adjuvant CRT.

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