S. A. Roberts

Stage-for-stage comparison of definitive chemoradiotherapy, surgery alone and neoadjuvant chemotherapy for oesophageal carcinoma†‡

Definitive chemoradiotherapy (dCRT) has been proposed as an alternative therapy for selected patients with oesophageal cancer. The aim of this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant chemotherapy followed by surgery (CS) in patients with oesophageal cancer.

Prospective comparison of endosonography, computed tomography, and histopathological stage of junctional oesophagogastric cancer

AIMS To assess the strength of agreement between the perceived preoperative stage of Siewert II (oesophagogastric junction) and Siewert III (proximal gastric tumours) as determined by computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with histopathological stage. METHODS Forty-four patients with Siewert II (n=18) and III (n=26) adenocarcinomas of the oesophagogastric junction underwent preoperative CT at their local hospitals followed by specialist EUS, and the strengths of the agreement between the radiological stages and the histopathological stages were determined by the weighted Kappa statistic (Kw). RESULTS Kw for Siewert II T and N stages was 0.491 (p=0.016) and 0.4 (p=0.087) for CT compared with 0.852 (p=0.0001) and 1 (p=0.0001) for EUS. Kw for Siewert III T and N stages was 0.181 (p=0.206) and 0.121 (p=0.376) for CT compared with 0.173 (p=0.195) and 0.263 (p=0.031) for EUS. CONCLUSION Siewert II tumour T and N stages were more accurately predicted by EUS than CT, but Siewert III tumour T and N stages were more difficult to assess, arguably because of anatomical constraints at the oesophagogastric junction. CT and EUS are complimentary techniques, and these results highlight the importance of multidisciplinary discussion in planning treatment.

Prospective cohort comparison of neoadjuvant chemoradiotherapy versus chemotherapy in patients with oesophageal cancer

Chemotherapy and chemoradiotherapy are common neoadjuvant treatments for resectable T3 N0–1 M0 oesophageal carcinoma. The aim of this study was to compare the outcomes of these therapies in consecutive cohorts of patients.

Prognostic significance of the endoscopic ultrasound defined lymph node metastasis count in esophageal cancer.

The key prognostic factor which predicts outcome after esophagectomy for cancer is the number of malignant lymph node metastases, but data regarding the accuracy of endoscopic ultrasound (EUS) in determining and predicting the metastatic lymph node count preoperatively are limited. The aim of this study was to assess the prognostic significance of EUS defined lymph node metastasis count (eLNMC) in patients diagnosed with esophageal cancer. Two hundred and sixty-seven consecutive patients (median age 63 years, 187 months) underwent specialist EUS followed by stage directed multidisciplinary treatment (183 esophagectomy [64 neoadjuvant chemotherapy, 19 neoadjuvant chemoradiotherapy], 79 definitive chemoradiotherapy, and 5 palliative therapy). The eLNMC was subdivided into four groups (0, 1, 2 to 4, >4) and the primary measure of outcome was survival. Survival was related to EUS tumor (T) stage (P < 0.0001), EUS node (N) stage (P < 0.0001), EUS tumor length (p < 0.0001), and eLNMC (P < 0.0001). Multivariable analysis revealed EUS tumor length (hazard ratio [HR] 1.071, 95% CI 1.008-1.138, P= 0.027) and eLNMC (HR 1.302, 95% CI 1.133-1.496, P= 0.0001) to be significantly and independently associated with survival. Median and 2-year survival for patients with 0, 1, 2-4, and >4 lymph node metastases were: 44 months and 71%, 36 months and 59%, 24 months and 50%, and 17 months and 32%, respectively. The total number of EUS defined lymph node metastases was an important and significant prognostic indicator.

Propensity score analysis of oesophageal cancer treatment with surgery or definitive chemoradiotherapy

The role of treatments involving surgery versus definitive chemoradiotherapy (dCRT) for oesophageal cancer remains controversial.

Stage for Stage Comparison of Recurrence Patterns after Definitive Chemoradiotherapy or Surgery for Oesophageal Carcinoma

AIMS Definitive chemoradiotherapy (dCRT) has been advocated as an alternative treatment for oesophageal carcinoma, but received criticism for perceived poorer locoregional disease control when compared with surgery. The aim of this study was to determine the relative incidence and pattern of oesophageal carcinoma recurrence after dCRT and surgery in patients receiving stage-directed therapy with curative intent. MATERIALS AND METHODS In total, 623 consecutive patients with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were studied. The primary outcome measure was disease-free survival, adjusted for baseline differences in gender, age and histological cell type. RESULTS Three hundred and eleven patients deemed unsuitable for surgery on the grounds of performance status (n = 137), bulky local disease (n = 121) or personal choice (n = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy). Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In contrast, distant metastases were more common after surgery than after dCRT (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage-related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6 versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710). CONCLUSIONS These findings provide further support for a randomised trial of dCRT versus surgery in both oesophageal squamous cell carcinoma and adenocarcinoma.

Prognostic Significance of Age in the Radical Treatment of Oesophageal Cancer with Surgery or Chemoradiotherapy: a Prospective Observational Cohort Study

AIMS To compare the outcomes of stage-directed surgical therapy and chemoradiotherapy (CRT) for oesophageal cancer and to determine if a significant age-treatment interaction exists to guide therapy. MATERIALS AND METHODS Five hundred and eight consecutive patients with oesophageal cancer suitable for radical treatment based on radiological stage and performance status were studied (275 surgery; 93 surgery alone, 131 neoadjuvant chemotherapy, 51 neoadjuvant CRT and 233 definitive CRT). The primary measure of outcome was survival. RESULTS Thirty-day mortality rates and 2-year survival after surgery and CRT in patients<70 years were 2.4 and 57.5%, respectively, compared with 0 (P=0.207) and 47.3% (P=0.011), respectively. Thirty-day mortality rates and 2-year survival after surgery and CRT in patients>or=70 years were 7.0 and 45.1%, respectively, compared with 0 (P=0.029) and 46.3% (P=0.992), respectively. Multivariate analysis including only surgical patients in the model revealed three factors to be independently and significantly associated with survival; endoscopic ultrasound (EUS) T stage (P=0.033), EUS lymph node metastasis count (>or=2 versus 0: hazard ratio 1.67, 95% confidence interval 1.06-2.92, P=0.026), and age>or=70 years (hazard ratio 1.51, 95% confidence interval 1.05-2.16, P=0.025). CONCLUSION Overall survival for patients treated with surgery was strongly age dependent around the age of 70 years, and patients>or=70 years with oesophageal cancer should be aware that outcomes after CRT are similar to those after surgery.

N-staging of oesophageal and junctional carcinoma: is there still a role for EUS in patients staged N0 at PET/CT?

AIM To assess whether separate endoscopic ultrasound (EUS) lymph node (N)-staging is still of prognostic value in those staged node negative (N0) at combined positron-emission tomography/computed tomography (PET/CT) in patients with oesophageal cancer (OC). MATERIALS AND METHODS One hundred and seventeen consecutive patients [median age 67 years; 88 male; 98 cases of adenocarcinoma, 19 cases of squamous cell carcinoma (SCC)] staged as N0 at PET/CT underwent EUS to record tumour (T)- and N-stage. The patients were subsequently separated into two groups: EUS N0 (n = 78) and EUS N+ (n = 39). Survival analysis using Kaplan-Meier and Coxs proportional hazard methods was performed. Primary outcome was overall survival from diagnosis. RESULTS EUS N-stage and EUS N0 versus EUS N+ (p = 0.005 and p = 0.001, respectively) were found to be significantly and independently associated with survival in two models of multivariate analysis, in patients staged N0 at PET/CT. EUS T-stage was significantly associated with survival on univariate analysis. CONCLUSION EUS N-staging still has prognostic value in patients staged N0 at PET/CT. There is a significant difference in survival between EUS N0 and positive nodal EUS status in those staged N0 at PET/CT, suggesting PET/CT is unreliable for local staging. PET/CT and EUS continue to have complimentary roles in OC staging.

Influence of a Regional Centralised Upper Gastrointestinal Cancer Service Model on Patient Safety, Quality of Care and Survival

AIMS The aim of this study was to determine outcomes of a reconfigured centralised upper gastrointestinal (UGI) cancer service model, allied to an enhanced recovery programme, when compared with historical controls in a UK cancer network. MATERIALS AND METHODS Details of 606 consecutive patients diagnosed with UGI cancer were collected prospectively and outcomes before (n = 251) and after (n = 355) centralisation compared. Primary outcome measures were rates of curative treatment intent, operative morbidity, length of hospital stay and survival. RESULTS The rate of curative treatment intent increased from 21 to 36% after centralisation (P < 0.0001). Operative morbidity (mortality) and length of hospital stay before and after centralisation were 40% (2.5%) and 16 days, compared with 45% (2.4%) and 13 days, respectively (P = 0.024). The median and 1 year survival (all patients) improved from 8.7 months and 39.0% to 10.8 months and 46.8%, respectively, after centralisation (P = 0.032). On multivariate analysis, age (hazard ratio 1.894, 95% confidence interval 0.743-4.781, P < 0.0001), centralisation (hazard ratio 0.809, 95% confidence interval 0.668-0.979, P = 0.03) and overall radiological TNM stage (hazard ratio 3.905, 95% confidence interval 1.413-11.270, P < 0.0001) were independently associated with survival. CONCLUSION These outcomes confirm the patient safety, quality of care and survival improvements achievable by compliance with National Health Service Improving Outcomes Guidance.

Development and validation of a prognostic model incorporating texture analysis derived from standardised segmentation of pet in patients with oesophageal cancer

ObjectivesThis retrospective cohort study developed a prognostic model incorporating PET texture analysis in patients with oesophageal cancer (OC). Internal validation of the model was performed.MethodsConsecutive OC patients (n = 403) were chronologically separated into development (n = 302, September 2010-September 2014, median age = 67.0, males = 227, adenocarcinomas = 237) and validation cohorts (n = 101, September 2014-July 2015, median age = 69.0, males = 78, adenocarcinomas = 79). Texture metrics were obtained using a machine-learning algorithm for automatic PET segmentation. A Cox regression model including age, radiological stage, treatment and 16 texture metrics was developed. Patients were stratified into quartiles according to a prognostic score derived from the model. A p-value < 0.05 was considered statistically significant. Primary outcome was overall survival (OS).ResultsSix variables were significantly and independently associated with OS: age [HR =1.02 (95% CI 1.01-1.04), p < 0.001], radiological stage [1.49 (1.20-1.84), p < 0.001], treatment [0.34 (0.24–0.47), p < 0.001], log(TLG) [5.74 (1.44–22.83), p = 0.013], log(Histogram Energy) [0.27 (0.10–0.74), p = 0.011] and Histogram Kurtosis [1.22 (1.04–1.44), p = 0.017]. The prognostic score demonstrated significant differences in OS between quartiles in both the development (X2 143.14, df 3, p < 0.001) and validation cohorts (X2 20.621, df 3, p < 0.001).ConclusionsThis prognostic model can risk stratify patients and demonstrates the additional benefit of PET texture analysis in OC staging.Key points• PET texture analysis adds prognostic value to oesophageal cancer staging.• Texture metrics are independently and significantly associated with overall survival.• A prognostic model including texture analysis can help risk stratify patients.