Predictive clinical model of tumor response after chemoradiation in rectal cancer

Abstract

Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: “good responders” (Mandard TRG1-2) and “poor responders” (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design. Conclusion: It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

“…EGFR expression is known to activate a cascade of multiple signaling pathways that enable tumor growth process [ 30 ]. Furthermore, high EGFR expression was identified to be associated with more aggressive disease, advanced tumor stage and increased risk of metastases [ 30 ]. In addition, high EGFR expression can predict results of radiochemotherapy [ 30 ].…”

“…Furthermore, high EGFR expression was identified to be associated with more aggressive disease, advanced tumor stage and increased risk of metastases [ 30 ]. In addition, high EGFR expression can predict results of radiochemotherapy [ 30 ]. The present study showed that ADCmax might be used as a surrogate marker for EGFR expression.…”

“…In every case, all histopathological parameters were estimated per two high power fields a 0.16 mm 2 . Immunhistochemical expression was semiautomatically estimated using ImageJ and overall stained areas were measured according to previous descriptions [ 30 , 37 ]. Finally, PD1- expression was estimated in PD1- positive and PD1-negative manually by stained cancer cells [ 17 ].…”

Outcomes prediction in pre-operative radiotherapy locally advanced rectal cancer: leucocyte assessment as immune biomarker

“…Patient characteristics (age, sex, WHO performance status, body mass index (BMI)), tumor histology and staging, radiotherapy characteristics, administered chemotherapy, complete sterilization of the operative specimen (ypCR), complete tumor resection (R0), local recurrence, progression-free survival (PFS) and overall survival (OS) were also studied. Regarding pathological response, the Mandard tumor regression grade (TRG) was also used [ 38 ], classifying patients into “good responders” (complete pathological response with no viable cancer cell (TRG1, i.e. ypCR) or almost complete pathological response with rare cancer cells that might be still viable (TRG2)) and into “poor responders” (Mandard TGR3-5).…”

Non Melanoma Skin Cancer Pathogenesis Overview

“…VEGF single-nucleotide polymorphisms (SNPs) can be detected in regulatory regions, affecting VEGF expression or activity [ 77 , 78 ]. VEGF polymorphisms have been previously reported in several carcinomas, including esophageal squamous cell carcinoma, and oral squamous cell carcinoma [ 78 , 79 , 80 ]. The VEGF gene −460 C>T polymorphism and −1154 G>A polymorphism have been reported as possible markers of prognosis in SCC [ 79 ].…”