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Radiation therapy alone or in combination with chemotherapy has lead to improved outcomes in the management of rectal cancer patients. Many studies have demonstrated that for locally advanced rectal cancer, preoperative chemoradiation (CRT) significantly improves local control, reduces toxicity profiles and the risk of disease recurrence (HabrGama, Perez et al. 2004), (Kapiteijn, Marijnen et al. 2001), (Frileux, Burdy et al. 2007), (Horisberger, Hofheinz et al. 2008), (Krook, Moertel et al. 1991), (Sauer, Becker et al. 2004). Highly radiosensitive cancers completely regress, leading to improved survival. A histology tumor grading system is used to determine the success of radiation prior to surgery. This is called a tumor regression grade (TRG). Originally described for oesophageal tumors, the TRG system has been adapted to rectal cancer (Mandard, Dalibard et al. 1994). Regression grading stratifies response based on the biological effect of radiation on tumors, dividing it into five different grades based on the ratio of fibrosis to tumor where TRG1: no residual cancer; TRG2: rare residual cancer cells; TRG3 fibrosis outgrowing residual cancer; TRG4: residual cancer outgrowing fibrosis and TRG 5: absence of regressive changes. This TRG scoring system is extremely valuable as it can highlight those tumors demonstrating large variation in biological response to radiation not undergoing a T stage change (Bouzourene, Bosman et al. 2002). In a paper by Ryan et al, they have revised the 5 point TRG system into a 3 point where grade 1 indicates a complete response, grade 2 a partial response and grade 3 no response (Ryan, Gibbons et al. 2005). Currently, only approximately 25% of patients who receive CRT treatment obtain a complete pathological response (Valentini, Coco et al. 2002; Sauer, Becker et al. 2004). Disease free survival in these patients is improved with a reduce rate of local recurrence However, up to 75% of patients receive a treatment that achieves little or no benefit and an increased risk of second cancers has been documented within or adjacent to the irradiated volume (Birgisson, Pahlman et al. 2005). The broad and unpredictable response to tumor of patients with rectal cancer treated with preoperative chemoradiotherapeutic interventions shows that our understanding of the molecular events leading to radioresistance in patients affected with this malignancy is limited. This variation is thought to depend on tumor size but also on the biological properties of individual tumors. It is important to understand what factors within the tumor predict high sensitivity to the new-adjuvant regimen and what determines resistance, as this information may allow tailor-made individualization of therapy. Classification of

Tumor Markers of Neo-Adjuvant Chemo-Radiation Response in Rectal Cancer