Diagnosis and treatment for gastro-oesophageal cancer in England and Wales: analysis of the National Oesophago-Gastric Cancer Audit (NOGCA) database 2012-2020.

BACKGROUND: The National Oesophago-Gastric Cancer Audit (NOGCA) captures patient data from diagnosis to end of primary treatment for all patients with oesophagogastric (OG) cancer in England and Wales. This study assessed changes in patient characteristics, treatments received, and outcomes for OG cancer surgery for the period 2012-2020, and examined which factors may have led to changes in clinical outcomes over this time. METHODS: Patients diagnosed with OG cancer between April 2012 and March 2020 were included. Descriptive statistics were used to summarize patient demographics, disease site, type, and stage, patterns of care, and outcomes over time. The treatment variables of unit case volume, surgical approach, and neoadjuvant therapy were included. Regression models were used to examine associations between surgical outcomes (duration of stay and mortality), and patient and treatment variables. RESULTS: In total, 83 393 patients diagnosed with OG cancer during the study period were included. Patient demographics and cancer stage at diagnosis showed little change over time. Altogether, 17 650 patients underwent surgery as part of radical treatment. These patients had increasingly more advanced cancers, and a greater likelihood of pre-existing comorbidity in more recent years. Significant decreases in mortality rates and duration of stay were noted, along with improvements in oncological outcomes (nodal yields and margin positivity rates). Following adjustment for patient and treatment variables, increasing audit year and trust volume were associated, respectively, with improved postoperative outcomes: lower 30-day mortality (odds ratio (OR) 0.93 (95 per cent c.i. 0.88 to 0.98) and OR 0.99 (95 per cent c.i. 0.99-0.99)) and lower 90-day mortality (OR 0.94 (95 per cent c.i. 0.91 to 0.98) and OR 0.99 (95 per cent c.i. 0.99-0.99)), and a reduction in duration of postoperative stay (incidence rate ratio (IRR) 0.98 (95 per cent c.i. 0.97 to 0.98) and IRR 0.99 (95 per cent c.i. 0.99 to 0.99)). CONCLUSION: Outcomes of OG cancer surgery have improved over time, despite little evidence of improvements in early diagnosis. The underlying drivers for improvements in outcome are multifactorial

The impact of postoperative chemotherapy on survival for oesophagogastric adenocarcinoma after preoperative chemotherapy and surgery

Background: perioperative chemotherapy is widely used in the treatment of oesophagogastric adenocarcinoma (OGAC) with a substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of patients, reflecting uncertainty among clinicians about its benefit and poor postoperative patient fitness. This study estimated the effect of postoperative chemotherapy after surgery for OGAC using a large population-based data set.Methods: patients with adenocarcinoma of the oesophagus, gastro-oesophageal junction or stomach diagnosed between 2012 and 2018, who underwent preoperative chemotherapy followed by surgery, were identified from a national-level audit in England and Wales. Postoperative therapy was defined as the receipt of systemic chemotherapy within 90 days of surgery. The effectiveness of postoperative chemotherapy compared with observation was estimated using inverse propensity treatment weighting.Results: postoperative chemotherapy was given to 1593 of 4139 patients (38.5 per cent) included in the study. Almost all patients received platinum-based triplet regimens (4004 patients, 96.7 per cent), with FLOT used in 3.3 per cent. Patients who received postoperative chemotherapy were younger, with a lower ASA grade, and were less likely to have surgical complications, with similar tumour characteristics. After weighting, the median survival time after postoperative chemotherapy was 62.7 months compared with 50.4 months without chemotherapy (hazard ratio 0.84, 95 per cent c.i. 0.77 to 0.94; P = 0.001).Conclusion: this study has shown that postoperative chemotherapy improves overall survival in patients with OGAC treated with preoperative chemotherapy and surgery

AUGIS Surv-G: Prediction of long-term survival after gastrectomy using Random Survival Forests

Background: no well validated and contemporaneous tools for personalised prognostication of gastric adenocarcinoma exist. This study aimed to derive and validate a prognostic model for overall survival after surgery for gastric adenocarcinoma using a large national dataset and a non-linear Random Survival Forest (RSF) methodology.Patients and methods: national audit data from England and Wales were used to identify patients who underwent a potentially curative gastrectomy for adenocarcinoma of the stomach. A total of 2931 patients were included and 29 clinical and pathological variables considered for their impact on survival. A RSF was then trained and validated internally using bootstrapping with calibration and discrimination (time dependent AUC) assessed.Results: the median survival of the cohort was 69 months, with a 5-year survival of 53.2%. Ten variables were found to significantly influence survival and included in the final model, with the most important being lymph node positivity, pT stage and achieving an R0 resection. Patient characteristics including ASA grade and age were also influential. On validation the model achieved excellent performance with a five-year tAUC of 0.80 (95%CI 0.78-0.82) and good agreement between observed and predicted survival probabilities. A wide spread of predictions for three- (14.8-98.3%, IQR 43.2-84.4%) and five-year (9.4-96.1%, IQR 31.7-73.8%) survival were seen.Conclusions: a prognostic model for survival after a potentially curative resection for gastric adenocarcinoma was derived and exhibited excellent discrimination and calibration of predictions. After appropriate external validation, it could provide utility in both prognostication for patients and for benchmarking of treatment responses

Phytotoxicity of four photosystem II herbicides to tropical seagrasses

Coastal waters of the Great Barrier Reef (GBR) are contaminated with agricultural pesticides, including the photosystem II (PSII) herbicides which are the most frequently detected at the highest concentrations. Designed to control weeds, these herbicides are equally potent towards non-target marine species, and the close proximity of seagrass meadows to flood plumes has raised concerns that seagrasses may be the species most threatened by herbicides from runoff. While previous work has identified effects of PSII herbicides on the photophysiology, growth and mortality in seagrass, there is little comparative quantitative toxicity data for seagrass. Here we applied standard ecotoxicology protocols to quantify the concentrations of four priority PSII herbicides that inhibit photochemistry by 10, 20 and 50% (IC, IC and IC) over 72 h in two common seagrass species from the GBR lagoon. The photosystems of seagrasses Zostera muelleri and Halodule uninervis were shown to be generally more sensitive to the PSII herbicides Diuron, Atrazine, Hexazinone and Tebuthiuron than corals and tropical microalgae. The herbicides caused rapid inhibition of effective quantum yield ({increment}F/F′), indicating reduced photosynthesis and maximum effective yields (F/F) corresponding to chronic damage to PSII. The PSII herbicide concentrations which affected photosynthesis have been exceeded in the GBR lagoon and all of the herbicides inhibited photosynthesis at concentrations lower than current marine park guidelines. There is a strong likelihood that the impacts of light limitation from flood plumes and reduced photosynthesis from PSII herbicides exported in the same waters would combine to affect seagrass productivity. Given that PSII herbicides have been demonstrated to affect seagrass at environmental concentrations, we suggest that revision of environmental guidelines and further efforts to reduce PSII herbicide concentrations in floodwaters may both help protect seagrass meadows of the GBR from further decline