Clinical and Biological Factors Related to Survival in Patients with Rectal Cancer

Sammanfattning: Rectal cancer is a common malignancy within the gastrointestinal tract. Despite the advances in diagnosis and treatment of rectal cancer patients during the last decades, there are still many patients who die from their disease. In order to personalise the therapy and optimise the clinical outcomes, it is important to identify factors that have an impact on survival of rectal cancer patients. Therefore, the overall aim of this thesis was to identify clinical and biological factors that were related to survival in patients with rectal cancer.  Paper I aimed to evaluate the impact of statins on survival in older and younger patients with rectal cancer. The study included 238 older patients (≥70 years) and 227 younger patients (<70 years) from the southeast healthcare region of Sweden. The patients were classified as statin users if they used any type of statins at the time of the cancer diagnosis. In the older group, statin users had better cancer-specific survival, disease-free survival, and overall survival compared with non-users. No such association was present in the younger group.  Paper II aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients. The study included 173 patients from the region Ostergotland of Sweden who underwent a CT colonography at the time of diagnosis. Skeletal muscle index (SMI) and visceral adipose tissue area (VAT) were quantified at the level of the third lumbar vertebral body, using the CT colonography acquired at the time of diagnosis. The patients were divided into a low or high SMI group, and a low or high VAT group. Low SMI was related to worse survival compared to high SMI in all the patients. High VAT was related to better survival in men with low or middle rectal cancer, while high VAT was related to worse survival in women with low or middle rectal cancer. Paper III aimed to evaluate the prognostic value of SPARCL1 expression in patients with rectal cancer with a focus on radiotherapy (RT). The study included 138 patients with rectal cancer who participated in the Swedish Rectal Cancer Trial. Of those, 63 patients underwent both preoperative RT and surgery, while 75 patients had surgery alone. SPARCL1 expression was determined by immunohistochemistry. Strong SPARCL1 expression was related to better overall survival compared to weak SPARCL1 expression in patients with stage III disease who received RT, but not in patients with stage III disease who did not receive RT. Moreover, SPARCL1 expression was increased in primary tumours with RT compared to tumours without RT.  In summary, statin use was related to improved survival in older patients with rectal cancer. CT-measured body composition parameters provided useful information for determining the prognosis of rectal cancer patients. SPARCL1 was identified as a potential prognostic biomarker in rectal cancer patients who received preoperative RT. Conclusively, the results of this thesis indicate that statin drugs, CT-measured body composition and SPARCL1 are factors related to survival in patients with rectal cancer. The evidence may benefit patients by more accurate estimating of their prognosis, personalised treatment and improved clinical outcomes.