Transition from esophagectomy to endoscopic therapy for early esophageal cancer.

BACKGROUND: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET). METHODS: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs. RESULTS: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient). CONCLUSION: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy.

Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial.

BACKGROUND: There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer. METHODS: A prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery. RESULTS: Comparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1-3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed. CONCLUSION: The results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic. TRIAL REGISTRATION NUMBER: NCT03626610.

The role of surgery after prolonged primary chemotherapy for advanced oesophageal adenocarcinoma.

BACKGROUND: Most patients presenting with oesophageal cancer do so with advanced disease not suitable for surgery. However, there are examples of encouraging survival following surgery in highly selected patients who respond well to chemotherapy. METHODS: This was a retrospective cohort study of patients who presented with advanced but nonvisceral metastatic oesophageal cancer. Consecutive patients on a prolonged primary chemotherapy pathway who underwent surgical resection following a favourable response to chemotherapy were included. Survival and recurrence rates were analysed using Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 57 patients included in the cohort operated between 2007 and 2015, the overall median survival was 44 months and the 5-year survival was 42%. Prechemotherapy cN0/cN1 (HR: 0.27, 95% CI: 0.12-0.62) conferred an independent survival advantage compared to cN2 and cN3 disease. Poor differentiation (HR: 2.46, 95% CI: 1.11-5.42), R1 resection (HR: 2.43, 95% CI: 1.14-5.19) and advanced nodal status (HR: 3.28, 95% CI: 1.44-7.47) predicted worse survival on univariable analysis. Poor differentiation (HR: 3.93, 95% CI: 1.62-9.56) was independently associated with poor survival when adjusted for other variables. CONCLUSION: Patients who present with advanced inoperable oesophageal cancer who have a favourable response to chemotherapy represent a limited group of patients who may benefit from surgery.

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.

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.

Analysis of outcomes of a transoral circular stapled anastomosis following major upper gastrointestinal cancer resection.

BACKGROUND: Esophageal anastomoses performed following esophagectomy and total gastrectomy are technically challenging with a significant risk of anastomotic leak. A safe, reliable, and easy anastomotic technique is required to improve patient outcomes and reduce morbidity. METHOD: This paper analyses 328 consecutive patients who underwent transoral circular stapled esophageal anastomosis (ORVIL™) from a prospectively collected single-center database between December 2011 and February 2019. RESULTS: Two hundred and twenty-seven esophagectomies and 101 gastrectomies were performed using OrVil™ anastomoses. The mean patient age was 63.7 years. Of 328 consecutive OrVil™-based anastomoses, there were 10 clinically significant anastomotic leaks requiring radiological or operative intervention (3.05%). Twenty-eight (8.54%) patients developed anastomotic stricture, all of which were successfully treated with endoscopic balloon dilatation (a median of 1 dilatation was required per patient). CONCLUSION: The OrVil™ anastomotic technique is reliable and safe to perform. This is the largest reported series of the OrVil™ anastomotic technique to date. Leak rates and anastomotic dilations were similar to other reported series. Based on our experience, we consider the use of the OrVil™ device for reconstruction after major upper GI resection to be safe and reliable.

The Influence of Comorbidity on Health-Related Quality of Life After Esophageal Cancer Surgery.

BACKGROUND: Esophageal cancer surgery reduces patients' health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients. METHODS: This prospective cohort study included esophageal cancer patients having undergone curatively intended esophagectomy at St Thomas' Hospital London in 2011-2015. Clinical data were collected from patient reports and medical records. Well-validated cancer-specific and esophageal cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25) were used to assess HRQoL before and 6 months after esophagectomy. Number of comorbidities, American Society of Anesthesiologists physical status classification (ASA), and specific comorbidities were analyzed in relation to HRQoL aspects using multivariable linear regression models. Mean score differences with 95% confidence intervals were adjusted for potential confounders. RESULTS: Among 136 patients, those with three or more comorbidities at the time of surgery had poorer global quality of life and physical function and more fatigue compared with those with no comorbidity. Patients with ASA III-IV reported more problems with the above HRQoL aspects and worse social function and pain compared with those with ASA I-II. Cardiac comorbidity was associated with worse global quality of life and dyspnea, while pulmonary comorbidities were related to coughing. Patients assessed both before and 6 months after surgery (n = 80) deteriorated in most HRQoL aspects regardless of comorbidity status, but patients with several comorbidities had worse physical function and fatigue and more trouble with coughing compared with those with fewer comorbidities. CONCLUSION: Comorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL.

The Prognostic Role of Pre-operative Positron Emission Tomography-Computed Tomography and Endoscopic Ultrasound Parameters in Oesophageal Adenocarcinoma.

Background: To evaluate the prognostic role of Positron Emission Tomography/Computed Tomography (PET/CT) and Endoscopic Ultrasound (EUS) performed before neoadjuvant chemotherapy (NAC) and surgery for oesophageal adenocarcinoma (OAC) patients, focusing on lymph node (LN) assessment. Methods: OAC patients treated in a single tertiary center during January 2008 until December 2014 were retrospectively studied. All patients had PET/CT and EUS before NAC and oesophagectomy. PET-FDG-avid local LNs and maximum standardized uptake value (SUVmax) of the primary tumour, EUS positive LNs and EUS tumour length were recorded. Univariate, multivariate and survival analyses were performed. Results: Following exclusions 151consecutive patients met the inclusion criteria, (median age 62 years). PET/CT and EUS sensitivity for local LNs metastasis was 39.2% and 88.6%, with specificities of 83.33% and 19.15% respectively. No overall survival (OS) difference was found between patients with PET/CT FDG-avid LNs and those with negative LNs (p=0.347). SUVmax uptake was divided into high and low (median cut-off value: 10) with no significant difference in OS between groups (p=0.141). EUS tumour length was not prognostic (OS, p=0.455). Conclusions: Initial LN staging in OA is inaccurate. Although PET/CT and EUS assessments may be complimentary, none independently predicted survival.

Patients' perspectives on opt-out consent for observational research: systematic review and focus group.

BACKGROUND:: observational research is increasingly important in clinical decision-making. Opt-out consent has been proposed as a more practical way to obtain participants' consent for such research. The authors evaluated patients' views on opt-out consent for observational research by identifying perceived benefits and barriers. METHODS:: following a systematic literature review of research on participants' perspectives on opt-out consent, a focus group interview was conducted with oncological patients and their family members. RESULTS:: the review identified 13 articles detailing perspectives on opt-out consent. Perceived advantages included benefitting medicine and future generations. These findings were confirmed in the focus group. The main reported barriers to opt-out consent are concerns regarding privacy and the sharing of data with third parties. Participants also demonstrated concerns on insufficient education on opt-out consent. CONCLUSION:: participants demonstrated willingness to participate in observational studies utilising opt-out consent. Special focus should be placed on outlining existing safeguards in research.

A longitudinal assessment of psychological distress after oesophageal cancer surgery.

BACKGROUND: Psychological distress is common among patients with oesophageal cancer. However, little is known about the course and predictors of psychological distress among patients treated with curative intent. Therefore, the aim of this study was to explore the prevalence, course and predictors of anxiety and depression in patients operated for oesophageal cancer, from prior to surgery to 12 months post-operatively. METHODS: A prospective cohort of patients with oesophageal cancer (n = 218) were recruited from one high-volume specialist oesophago-gastric treatment centre (St Thomas' Hospital, London, UK). Anxiety and depression were assessed prior to surgery, 6 and 12 months post-operatively. Mixed-effects modelling was performed to investigate changes over time and to estimate the association between clinical and socio-demographic predictor variables and anxiety and depression symptoms. RESULTS: The proportion of patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12 months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12-month follow-up. Anxiety symptoms remained stable over time whereas depression symptoms appeared to increase from pre-surgery to 6 months, levelling off between 6 and 12 months. Younger age, female sex, living alone and more severe self-reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety symptoms. In-hospital complications, greater limitations in activity status and more severe self-reported dysphagia were predictive of higher depression. CONCLUSIONS: Many patients report psychological distress during the first year following oesophageal cancer surgery. Whether improving the experience of swallowing difficulties may also reduce distress among these patients warrants further study.

A Role for Tumor Volume Assessment in Resectable Esophageal Cancer.

BACKGROUND: Esophageal cancer has a poor prognosis, and many patients undergoing surgery have a low chance of cure. Imaging studies suggest that tumor volume is prognostic. The study aimed to evaluate pathological tumor volume (PTV) as a prognostic variable in esophageal cancer. METHODS: This single-center cohort study included 283 patients who underwent esophageal cancer resections between 2000 and 2012. PTVs were obtained from pathological measurements using a validated volume formula. The prognostic value of PTV was analyzed using multivariable regression models, adjusting for age, tumor grade, tumor (T) stage, nodal stage, lymphovascular invasion, resection margin, resection type, and chemotherapy response, which provided hazard ratios (HRs) with 95 % confidence intervals (CIs). Primary outcomes were time to death and time to recurrence. Secondary outcomes were margin involvement and lymph node positivity. Correlation analysis was performed between imaging and PTVs. RESULTS: On unadjusted analysis, increasing PTV was associated with worse overall mortality (HR 2.30, 95 % CI 1.41-3.73) and disease recurrence (HR 1.87, 95 % CI 1.14-3.07). Adjusted analysis demonstrated worse overall mortality with increasing PTV but reached significance in only one subgroup (HR 1.70, 95 % CI 1.09-2.38). PTV was an independent predictor of margin involvement (OR 2.28, 95 % CI 1.02-5.13) and lymph node-positive status (OR 2.77, 95 % CI 1.23-6.28). Correlation analyses demonstrated significant positive correlation between computed tomography (CT) software and formula tumor volumes (r = 0.927, p < 0.0001), CT and positron emission tomography tumor volumes (r = 0.547, p < 0.0001), and CT and PTVs (r = 0.310, p < 0.001). CONCLUSIONS: Tumor volume may predict survival, margin status, and lymph node positivity after surgery for esophageal cancer.

The Impact of COVID-19 on Clinical Nurse Specialists and Patients With Cancer: A Pan-Specialty Cross-sectional Survey.

PURPOSE/AIMS: Uptake and delivery of cancer services across the United Kingdom have been significantly impacted by the COVID-19 pandemic. This study aimed to understand the impact of the pandemic on the working practices of clinical nurse specialists and their patient interactions across different cancer specialties. DESIGN: We performed a cross-sectional survey exploring nurses' experiences of delivering care during the pandemic, as well as their perceptions of the concerns that cancer patients were experiencing. METHODS: Clinical nurse specialists working in London cancer services were invited to complete an online questionnaire. Nurses' experiences and their perceptions of patients' concerns were analyzed descriptively. RESULTS: Fifty-four nurses participated. Almost half had been redeployed to other clinical areas during the pandemic (n = 19). COVID-19 discussions added 5 to 10 minutes on average to most consultations, with nurses either working longer/unpaid hours (34%) or spending less time talking to patients about cancer (39%) to deal with this. Approximately 50% of nurses would have liked additional information and support from their hospital. CONCLUSIONS: Clinical nurse specialist time and resources have been stretched during the COVID-19 pandemic. Hospitals need to work with nursing staff to ensure the specific information needs of cancer patients are being met.

Endoscopic tumour morphology impacts survival in adenocarcinoma of the oesophagus.

BACKGROUND: Prognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative survival. METHODS: Patients with endoscopic descriptions of tumours were identified from the prospectively managed databases including the OCCAMS database. Tumours were classified as exophytic, ulcerating or stenosing. Kaplan Meier survival analysis and multivariable Cox regression analyses were performed to determine hazard ratios (HR) with 95% confidence intervals. RESULTS: 262 patients with oesophageal adenocarcinoma undergoing potentially curative resection were pooled from St Thomas' Hospital (161) and the OCCAMS database (101). There were 70 ulcerating, 114 exophytic and 78 stenosing oesophageal adenocarcinomas. Initial tumour staging was similar across all groups (T3/4 tumours 71.4%, 70.2%, 74.4%). Median survival was 55 months, 51 months and 36 months respectively (p < 0.001). Rates of lymphovascular invasion (P = 0.0176), pathological nodal status (P = 0.0195) and pathological T stage (P = 0.0007) increased from ulcerating to exophytic to stenosing lesions. Resection margin positivity was 21.4% in ulcerating tumours compared to 54% in stenosing tumours (p < 0.001). When compared to stenosing lesions, exophytic and ulcerating lesions demonstrated a significant survival advantage on multivariable analysis (HR 0.56 95% CI 0.31-0.93, HR 0.42 95% CI 0.21-0.82). CONCLUSION: This study demonstrates that endoscopic morphology may be an important pre-treatment prognostic factor in oesophageal cancer. Ulcerating, exophytic and stenosing tumours may represent different pathological processes and tumour biology.

Extent of Lymphadenectomy and Prognosis After Esophageal Cancer Surgery.

IMPORTANCE: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. CONCLUSIONS AND RELEVANCE: This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.

Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction.

PURPOSE: Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. METHODS: We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. RESULTS: Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. CONCLUSION: The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.