[Truncated abstract] Clinical and pathological predictors of survival for stage II and III colon cancer patients treated with or without chemotherapy: a population-based study. Aim: Using a population-based cohort of colorectal cancer (CRC), the major aims of this study were to: 1. Identify clinico-pathological markers that can be used to define a subset of stage II colon cancer patients with excellent prognosis and who therefore do not require referral for adjuvant chemotherapy; 2. Investigate whether there is a survival benefit from the use of adjuvant chemotherapy in a population-based cohort of stage II colon cancer; 3. Investigate stage III colon cancer patients for evidence of predictive markers for response to 5FU chemotherapy; 4. Investigate CRC for age-related differences in clinico-pathological and molecular features. Hypotheses to be tested: 1. A subset of good prognosis stage II colon cancers can be defined using routine pathological markers; 2. Females colon cancer patients gain more survival advantage from 5FU chemotherapy than males; 3. Tumours from young CRC patients have different molecular characteristics to those from older patients; 4. The underlying molecular characteristics of tumour can impact upon the response to 5FU chemotherapy. Methods: The study cohort consisted of 5,971 cases diagnosed between 1993 and 2003 representing over 90% of the CRCs diagnosed in the state of Western Australia. Results: The major findings of this translational research into colon cancer can be summarized as follows: The morphological features of serosal and vascular invasion allow for prognostic stratification of stage II colon cancer into "good" and "poor" prognosis groups. Good prognosis patients can confidently be spared adjuvant chemotherapy, however greater effort should be directed towards ensuring that more poor prognosis patients are referred for chemotherapy. Evidence was obtained for a survival advantage from the use of 5FU chemotherapy in stage II colon cancer patients, particularly women and those with poor prognosis features. Completion of chemotherapy confers a survival advantage, whereas failure to complete regimens results in a survival disadvantage, when compared with patients treated by surgery alone. This was observed for both stage II and III colon cancers. The factors associated with a survival advantage from the use of chemotherapy in stage III colon cancer were patient age more than 55 years, female gender, perforation and lymphocytic response. The age, site and sex distribution of CRCs revealed in this study provides further evidence for two major pathways of colorectal tumourigenesis. The CIN 7 pathway is predominant in distal tumours from young males, while the CIMP+ is predominant in proximal tumours from older females. Conclusions: Population based studies are an important component of translational research. In part, they allow for auditing of disease management in a population. Guideline verification and analysis of the reasons for lack of adherence to guidelines is integral to improving the management of a disease. Laboratory-based research that is linked to clinical databases allows elucidation of the mechanisms of the disease and the response to treatments.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2007|