In locally advanced rectal cancer the pathological complete response (pCR) to neoadjuvant chemoradiation therapy (nCRT) is associated with a favourable long-term prognosis. The identification of markers predictive of response to therapy would therefore optimise treatment by allowing personalised therapy. It has been shown that the genetic profile of the patient could influence the activation of the immune system in combination with chemoradiation therapy in targeting tumour cells. In addition, genetic features of molecular pathways correlated with response to chemoradiotherapy, may in turn affect the probability of a good response to treatment in these patients, but also the occurrence of adverse events. The main objective of the study is to define the role of genetic markers related to immune system activation and other molecular pathways in predicting the complete pathological response to preoperative chemoradiation therapy in patients with locally advanced rectal cancer.
histologically confirmed diagnosis of primary resectable LARC;
confirmed absence of distant metastases;
≥18 years old;
stage of disease T3-T4 and N0-N2;
evidence of secondary tumour
inadequate liver function (bilirubin >1.5 times the normal range, ALT and AST >2 times the normal range);
inadequate renal function (creatinine >1.5 times the upper limit of normal range);
Major concomitant systemic diseases that contraindicate surgery;
Patients with a histologically confirmed diagnosis of primary resectable LARC
Cohort
Prospective
Not listed
Defining the predictive role of rare (MAF<1%) and very rare genetic variants (MAF<0.1%) in the SMAD3 and IL-17F genes, implicated in nCRT-mediated activation of the immune system on the pathological tumour response to nCRT in LARC.
Relation between rare and very rare genetic variants and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval
Plasma levels of IL-17F and SMAD3 proteins during treatment to be correlated with the genetic characteristics
Mean difference between subgroup of patients with different genetics characteristics
Plasma levels of IL-17F and SMAD3 proteins during treatment and tumour response
Relation between plasma levels of IL-17F and SMAD3 proteins and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval
Plasma levels of IL-17F and SMAD3 proteins during treatment and prognosis of the tumour.
Relation between plasma levels of IL-17F and SMAD3 and disease-free survival (DFS) defined as time between enrollment and objective tumor progression using Kaplan Meyer method
Identify further genetic markers of pathological tumour response
Relation between selected genetic markers and pathological tumour response will be assessed with logistic regression analysis and data will be reported as odds ratio and relative confidence interval
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