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.  

Background The association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy. Methods This retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography scans at the time of diagnosis were used to assess the skeletal muscle index (SMI) and the visceral adipose tissue area (VAT). The patients were divided into a low or high SMI group and a low or high VAT group according to previously defined cutoff values. Endpoints included cancer-specific survival (CSS) and overall survival (OS). Results In all patients, low SMI was associated with worse CSS (HR, 2.63; 95% CI, 1.35-5.12; P = 0.004) and OS (HR, 3.57; 95% CI, 2.01-6.34; P &lt; 0.001) compared to high SMI. The differences remained significant after adjusting for potential confounders (CSS: adjusted HR, 2.28; 95% CI, 1.13-4.58; P = 0.021; OS: adjusted HR, 3.17; 95% CI, 1.73-5.82; P &lt; 0.001). Low SMI was still related to a poor prognosis after stratifying by sex, tumour location, stage and radiotherapy (P &lt; 0.05). High VAT was associated with better CSS (HR, 0.31; 95% CI, 0.11-0.84; P = 0.022) and OS (HR, 0.40; 95% CI, 0.17-0.97; P = 0.044) compared to low VAT among men with rectal cancer &lt;= 10 cm from the anal verge. High VAT was associated with worse CSS (HR, 4.15; 95% CI, 1.10-15.66; P = 0.036) in women with rectal cancer &lt;= 10 cm from the anal verge. Conclusions Low SMI was associated with worse survival. High VAT predicted better survival in men but worse survival in women. The results suggest that CT-measured body composition is a useful tool for evaluating the prognosis of rectal cancer patients and demonstrate the need to include the sex and the tumour location in the analyses.

Purpose

The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.

Methods and Materials

The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.

Results

Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).

Conclusions

SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.