Jan Johansson

Standard time-to-surgery after neoadjuvant chemoradiotherapy for esophageal cancer has historically been 4–6 weeks. Observational studies have suggested improved oncological outcomes and health-related quality of life in patients after prolonged time-to-surgery. This study aimed to investigate whether prolonged time-to-surgery is associated with improved health-related quality of life compared to the standard interval. This study is a secondary endpoint analysis within the NeoRes II trial, in which patients with locally advanced resectable esophageal cancer were randomized to either standard time-to-surgery (4–6 weeks) or prolonged time-to-surgery (10–12 weeks). The primary endpoints have been reported previously. Health-related quality of life was assessed using the EORTC QLQ-C30 and QLQ-OG25 questionnaires at time of diagnosis, preoperatively, and at 6-months and 1–5 years postoperatively. A total of 249 patients were randomized of whom 192 were available for health-related quality of life analyses, with 97 (51%) assigned to standard time-to-surgery and 95 (49%) to prolonged time-to-surgery. The groups were well-matched regarding baseline characteristics. Preoperatively, within a week of the day of surgery, patients in the prolonged time-to-surgery group reported better global quality of life, improved physical functioning, and less fatigue, coughing, dysphagia, odynophagia, pain, discomfort, and weight loss compared to those in the standard time-to-surgery group. These benefits were observed at 6 months postoperatively, but not thereafter during follow-up, where no significant differences were observed. Although prolonged time-to-surgery was associated with better preoperative health-related quality of life, no such benefits were observed postoperatively. In addition, the results from the primary endpoint analysis suggested that longer time-to-surgery was associated with worse oncological outcomes. This, together with the results of the current sub-study, strongly supports that the standard time-to-surgery of 4–6 weeks should be recommended after neoadjuvant chemoradiotherapy for esophageal cancer.

Summary: Multidisciplinary team meetings (MDTs) are recommended for patients with esophageal cancer. Improved staging, timeliness to surgery and better adherence to guidelines have been attributed to MDTs, but there are few studies published on the MDTs’ effect on survival. All patients with esophageal cancer in Sweden between 2006 and 2018 were grouped according to whether they had been discussed at an MDT as part of their clinical pathway. Factors affecting group allocation were explored with multivariable logistic regression, and the impact of MDT on survival was studied with Cox-regression and the Kaplan–Meier estimator. Of 6837 included patients, 1338 patients (20%) were not discussed at an MDT. Advanced age (80–90 years; odds ratio [OR] 0.25, 0.16–0.42 (95% confidence interval)) and clinical stage IVb (OR 0.65, 0.43–0.98) decreased the probability of being presented at an MDT, whereas high education level (OR 1.31, 1.02–1.67), being married (OR 1.20, 1.01–1.43), squamous histology (OR 1.50, 1.22–1.84) and later year of diagnosis (OR 1.33, 1.29–1.37 per year) increased the probability of an MDT. In multivariable adjusted analysis, MDT discussion was associated with improved survival (hazard ratios 0.72, 0.66–0.78) and median survival increased from 4.5 to 10.7 months. MDTs were associated with improved survival for esophageal cancer patients. Elderly patients with advanced disease and poor socioeconomic status were less likely to be presented at an MDT, but had clear survival-benefits if they were discussed in a multidisciplinary setting.

Oesophagectomy for cancer of the oesophagus carries significant morbidity and mortality. Ninety-day mortality and anastomosis leakage are critical early postoperative problems traditionally analysed through logistic regression. In this study, we challenge traditional logistic regression models to predict results with new explainable AI (XAI) models. We used the Swedish National Quality Register for Oesophageal and Gastric Cancer (NREV) to perform traditional multivariable logistic regression and XAI. The 90-day mortality was 6.0%, while anastomosis leakage was present in 12.4%. The XAI models yielded an area under the curve (AUC) of 0.91 for 90-day mortality (as compared with 0.84 for logistic regression). For anastomosis leakage, the AUC was 0.84 using XAI (0.74 using logistic regression). We show that age (mortality increases sharply after 55 years) and body mass index (BMI) (lowest mortality for BMI 30 kg/m ² ) are important survival factors. Additionally, we show that surgery time (minimum anastomosis leakage for a surgery time of 200 min to sharply increase to a maximum at 375 min) and BMI (the lower the BMI, the less anastomosis leakage) are important factors for anastomosis leakage. The surgical understanding of anastomosis leakage and mortality after oesophagectomy is advanced by judiciously applying XAI to structured data. Our nationwide oesophagectomy data contains significant nonlinear relationships. With the help of XAI, we extract personalised knowledge, bringing oesophagus surgery one step closer to personalised medicine.

Accumulating evidence suggests a survival benefit after curative oesophageal cancer surgery in women compared with men. The aim of this study was to explore sex disparities in survival after surgery with curative intent in patients with oesophageal cancer. This was a population-based cohort study, including all patients with oesophageal or gastric cancer who underwent surgery with a curative intent between 2006 and 2017 in Sweden. Female versus male mortality rate ratio (MRR) and excess mortality rate ratio (EMRR) were used as measures of survival. Two different parametric models were designed to account for potential confounders. Patients with gastric cancer were used as a comparison group as no differences in survival between sexes were expected among these patients. A total of 1301 patients underwent resection for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. Women had a lower EMRR (0.76, 95 per cent c.i. 0.58 to 1.01, P = 0.056; 0.52, 95 per cent c.i. 0.32 to 0.84, P = 0.007 respectively) in both histological subtypes. The effect was more profound in early clinical stages, in patients receiving neoadjuvant treatment, and without postoperative complications. No sex-related difference was observed in survival of patients with gastric cancer. Women undergoing resection for oesophageal carcinoma have better survival compared with men.

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64–1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41–0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21–4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

The Swedish National Register for Esophageal and Gastric cancer was launched in 2006 and contains data with adequate national coverage and of high internal validity on patients diagnosed with these tumors. The aim of this study was to describe the evolution of esophageal and gastric cancer care as reflected in a population-based clinical registry. The study population was 12,242 patients (6,926 with esophageal and gastroesophageal junction (GEJ) cancers and 5,316 with gastric cancers) diagnosed between 2007 and 2016. Treatment strategies, short- and long-term mortality, gender aspects, and centralization were investigated. Neoadjuvant oncological treatment became increasingly prevalent during the study period. Resection rates for both esophageal/GEJ and gastric cancers decreased from 29.4% to 26.0% (P = 0.022) and from 38.8% to 33.3% (P = 0.002), respectively. A marked reduction in the number of hospitals performing esophageal and gastric cancer surgery was noted. In gastric cancer patients, an improvement in 30-day mortality from 4.2% to 1.6% (P = 0.005) was evident. Overall 5-year survival after esophageal resection was 38.9%, being higher among women compared to men (47.5 vs. 36.6%; P < 0.001), whereas no gender difference was seen in gastric cancer. During the recent decade, the analyses based on the Swedish National Register for Esophageal and Gastric cancer database demonstrated significant improvements in several important quality indicators of care for patients with esophagogastric cancers. The Swedish National Register for Esophageal and Gastric cancer offers an instrument not only for the control and endorsement of quality of care but also a unique tool for population-based clinical research.