ABSTRACT
Background: A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods: Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results: A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion: The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.
Antecedentes: Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínicopatológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía. Métodos: Se realizó un análisis multivariable de las características clínicopatológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap. Resultados: Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,396,01) y un estadio clínico T avanzado (T34) (OR 2,93, i.c. del 95% 1,039,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,438,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,680,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09). Conclusión: La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.
Subject(s)
Adenocarcinoma/therapy , Esophageal Neoplasms/therapy , Esophagectomy , Margins of Excision , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Chemotherapy, Adjuvant/methods , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagus/diagnostic imaging , Esophagus/pathology , Esophagus/surgery , Feasibility Studies , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Predictive Value of Tests , Preoperative Period , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment , Tomography, X-Ray Computed , Tumor BurdenABSTRACT
BACKGROUND: Weight loss is a cardinal symptom of oesophageal cancer and is often continued after surgery. High body mass index (BMI) is a strong risk factor for oesophageal adenocarcinoma. This study aimed to assess the impact of pre- and post-operative weight loss and BMI on long-term mortality after resection for oesophageal cancer. METHODS: This prospective and nationwide cohort study included 390 patients, operated on for oesophageal cancer in Sweden in 2001-2005 with follow-up until 2016, who responded to a questionnaire on weight history 6 months after surgery. Multivariable Cox proportional hazard models provided hazard ratios (HRs) and 95% confidence intervals (95% CIs) of mortality while adjusting for several prognostic factors, including tumour stage. RESULTS: Compared to weight stable patients, pre-surgery weight loss indicated increased HRs of overall all-cause mortality (HR = 1.32, 95% CI 0.94-1.86) and disease-specific mortality (HR = 1.36, 95% CI 0.93-1.98). Patients with >20% weight loss post-surgery had worse overall all-cause mortality (HR = 1.71, 95% CI 1.01-2.88) and disease-specific mortality (HR = 2.20, 95% CI 1.24-3.89). Compared to patients with normal BMI, decreased HRs were indicated for patients who were obese at the time of surgery (overall all-cause mortality HR 0.87 95% CI, 0.58-1.31 and disease-specific mortality HR = 0.89, 95% CI 0.57-1.40), while patients with BMI ≤19.9 at 6 months post-surgery had increased all-cause mortality (HR = 1.41, 95% CI 1.03-1.95) and disease-specific mortality (HR = 1.55, 95% CI 1.09-2.21). CONCLUSION: Post-operative weight loss and low BMI at 6 months post-surgery are independent markers of poor prognosis in patients who undergo surgery for oesophageal cancer.
