Thromboembolism and neoadjuvant chemoradiation for rectal cancer
AuthorSmart, Philip James
AffiliationSurgery (St Vincent's)
Surgery (Austin & Northern Health)
Access StatusThis item is currently not available from this repository
© 2015 Dr. Philip James Smart
Thromboembolism (TE) is one of the leading causes of morbidity and mortality in cancer, is an independent predictor of reduced survival, and the overall rate of TE in cancer patients is increasing. Assessing the TE risk of an individual patient at a given time point and the benefit of thromboprophylaxis (TP) can be complex, involving widely variable TE rates according to tumour related factors (such as cancer subtype and disease stage), as well as patient and treatment related factors. Some, such as surgery and hospitalisation are well recognised and appropriately targeted with mechanical and pharmacological thromboprophylaxis (TP) strategies backed by Level I evidence. There is evidence that TP after hospital discharge following surgery (extended TP) is also beneficial. Recently, subgroups such as those with metastases receiving palliative chemotherapy have been shown to be at equally high risk, and also benefit from primary TP. Both chemotherapy and central venous access devices (CVAD) have been shown to be independently associated with development of TE. In addition, early studies examining neoadjuvant radiotherapy (nRT) in rectal cancer reported higher rates of TE however this finding was not repeated in subsequent studies using modern radiotherapy techniques. Extrapolating these findings raises the question of TE risk and the potential benefit of TP during neoadjuvant radiotherapy (nRT) or chemoradiotherapy (nCRT) for rectal cancer. This thesis explores the current evidence and contemporary guidelines concerning TE risk during nCRT, demonstrating considerable uncertainty and a lack of robust data. Randomised trials examining nCRT in rectal cancer are systematically reviewed to determine rates of TE, demonstrating a failure to capture TE events due to inadequate complication reporting frameworks. Existing attitudes and prescribing practices of specialist rectal cancer surgeons are surveyed, as well as barriers to TP prescribing. Issues of equipoise, ownership and logistical problems with outpatient TP prescribing were identified. The historical TE rate and epidemiology over a prolonged follow-up period in rectal cancer patients, as well as the relationship to nCRT is examined at both Peter MacCallum Cancer Centre in Australia and the Cleveland Clinic in the United States. These studies demonstrated that most TE events occurred in patients with metastatic disease receiving ambulatory palliative chemotherapy, and that the overall rate of TE in patients treated with nCRT was not elevated over those patients who had surgery alone. Finally, a prospective study of thrombogenic biomarkers in patients with rectal cancer was undertaken demonstrating significant coagulation abnormalities in colorectal cancer patients at baseline, but no major alteration during neoadjuvant chemoradiation. Marked and prolonged procoagluant abnormalities were demonstrated in the post-operative phase. Thus the current literature, attitudes of treating clinicians, historical rates, as well as candidate biomarkers for prospective TE risk were examined in nCRT for rectal cancer for the first time, identifying future potential research questions aimed at reducing this common complication of cancer care.
Keywordsrectal cancer; chemoradiation; thromboembolism
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