Predicting response to neoadjuvant chemotherapy in patients with oesophageal adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. METHODS: A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1-3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. RESULTS: Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02-3.62; p = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49-34.36; p = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05-7.04; p = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02-0.13; p = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. CONCLUSION: This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins.

BACKGROUND: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins. METHODS: This was a retrospective collaborative cohort study combining two prospectively collected UK institutional databases of patients with oesophageal adenocarcinoma. Multivariable Cox regression and propensity matched analyses were used to compare overall and recurrence-free survival according to the adjuvant treatment. RESULTS: Of 374 patients with clear resection margins, 221 patients (59%) had no adjuvant treatment, 137 patients (37%) had adjuvant chemotherapy and 16 patients (4%) had adjuvant chemoradiotherapy. For patients who had received NAC (290, 76%), when adjuvant chemotherapy was compared to no adjuvant treatment, hazard ratios (HRs) favoured adjuvant chemotherapy but did not reach independent significance (overall survival [OS] HR 0.65 95% confidence interval [CI] 0.40-1.06; p .0.087). Responders to NAC (Mandard 1-3) were seemingly more likely to demonstrate a survival benefit from adjuvant chemotherapy (HR 0.42 95% CI 0.15-1.11; p .1.081). CONCLUSIONS: Although no independent survival benefit was observed, the point estimates favoured adjuvant treatment, predominantly in patients with chemo-responsive tumours.