Abstract
BackgroundDespite advances in treatment strategies and improvements in overall survival rates, oesophageal cancer remains an important cause of cancer-related deaths worldwide. Oesophageal cancer is an aggressive disease and most patients present with locally advanced or metastatic disease. As a result, only a minority of patients are suitable for curative resection. Over the last two decades, UK practice has been influenced by numerous large clinical trials demonstrating the benefit of neoadjuvant treatment compared to surgery alone. The specific gains afforded by adjuvant treatment remain largely unknown and only approximately 50% of patients scheduled for post-operative treatment complete it, due to the accumulation of acquired therapeutic toxicities. This thesis examines the current role of neoadjuvant and adjuvant therapies in patients with oesophageal adenocarcinoma.
Aims and Methods
The main aim of this thesis was to assess patients with oesophageal adenocarcinoma as responders or non-responders in the context of the peri-operative treatment pathway. As the benefit of neoadjuvant treatment is well established, this thesis addresses the possibility of identifying clinical and radiological factors in relation to pathological response to neoadjuvant chemotherapy and if a combination of these factors could be used to predict chemoresponse. There is currently still a lack of evidence to support a clear benefit of adjuvant treatment in these patients. As such, this thesis addresses the potential survival benefit of adjuvant therapies in this group of patients, sub-classified and assessed based on surgical resection margin. This thesis comprises three main studies; one assessing neoadjuvant chemotherapy and two assessing adjuvant treatments in patients with oesophageal adenocarcinoma treated on a pre-determined, peri-operative pathway. A prospectively maintained, hospital-based operative database was used for all data collection. Adjuvant therapies were assessed using an ethically approved, collaborative database from two high-volume tertiary referral centres in the UK. Main outcomes for the studies included overall survival and time to recurrence in addition to recurrence patterns. A variety of statistical methods were employed across the studies including Kaplan-Meier survival analysis, Cox proportional hazards regression analysis, logistic regression analysis and receiver-operating characteristics (ROC) curve analysis.
Results
Analysis of patients in the neoadjuvant treatment study demonstrated that a decrease in radiological tumour volume, a ‘partial response’ RECIST score, a clinically improved dysphagia score and lymphovascular invasion all influenced pathological response to neoadjuvant chemotherapy. Additional ROC curve analysis supported the association between these factors and the pathological response to neoadjuvant chemotherapy. The main finding demonstrated in the adjuvant study assessing patients with positive resection margins (R1), was an overall survival and recurrence-free survival benefit of adjuvant chemoradiotherapy when compared with adjuvant chemotherapy. In those with clear resection margins (R0), no independent survival benefit was observed, however adjuvant treatment was favoured in those with chemoresponsive tumours.
Conclusion
In conclusion, this thesis has addressed the current role of neoadjuvant and adjuvant therapies in patients with oesophageal adenocarcinoma, classified as responders or non-responders, and in the context of overall and disease-free survival. This work has identified factors that can be used to pre-determine chemoresponse to neoadjuvant therapy and has highlighted the potential benefit of adjuvant chemoradiotherapy in margin-positive patients. These results can be utilised clinically to encourage a more individualised and tailored approach to the peri-operative pathway for oesophageal cancer patients.
| Date of Award | 1 Nov 2021 |
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| Original language | English |
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| Supervisor | Andrew Davies (Supervisor) & Jesper Lagergren (Supervisor) |