Predictors of textbook outcome following oesophagogastric cancer surgery.

Textbook outcome (TO) is a composite measure representing an ideal perioperative course, which has been utilized to assess the quality of care in oesophagogastric cancer (OGC) surgery. We aim to determine TO rates among OGC patients in a UK tertiary center, investigate predictors of TO attainment, and evaluate the relationship between TO and survival. A retrospective analysis of a prospectively collected departmental database between 2006 and 2021 was conducted. Patients that underwent radical OGC surgery with curative intent were included. TO attainment required margin-negative resection, adequate lymphadenectomy, uncomplicated postoperative course, and no hospital readmission. Predictors of TO were investigated using multivariable logistic regression. The association between TO and survival was evaluated using Kaplan-Meier analysis and Cox regression modeling. In sum, 667 esophageal cancer and 312 gastric cancer patients were included. TO was achieved in 35.1% of esophagectomy patients and 51.3% of gastrectomy patients. Several factors were independently associated with a low likelihood of TO attainment: T3 stage (odds ratio (OR): 0.41, 95% confidence interval (CI) [0.22-0.79], p = 0.008) and T4 stage (OR:0.26, 95% CI [0.08-0.72], p = 0.013) in the esophagectomy cohort and high BMI (OR:0.93, 95% CI [0.88-0.98], p = 0.011) in the gastrectomy cohort. TO attainment was associated with greater overall survival and recurrence-free survival in esophagectomy and gastrectomy cohorts. TO is a relevant quality metric that can be utilized to compare surgical performance between centers and investigate patients at risk of TO failure. Enhancement of preoperative care measures can improve TO rates and, subsequently, long-term survival.

Assessing the impact of rurality on oesophagogastric cancer survival in the North-East of Scotland- a prospective population cohort study.

INTRODUCTION: Despite advances in oncology therapies and surgical techniques, survival from oesophagogastric cancer remains low. Poorer cancer outcomes and survival for rural dwellers is documented worldwide and has been an area of focus in Scotland since 2007 when changes to suspected cancer national referral guidelines and governmental mandates on delivering remote and rural healthcare occurred. Whether these changes in clinical practice has impacted upon upper gastrointestinal cancer remains unclear. METHODS: A prospective, single-centre observation study was performed. Data from the regional oesophagogastric cancer MDT between 2013 and 2019 were included. The Scottish Index of Multiple Deprivation 2020 tool provided a rurality code (1 or 2) based on patient postcode at time of referral. Survival outcomes for urban and rural patients were compared across demographic factors, disease factors and stage at presentation. RESULTS: A total of 1038 patients were included in this study. There was no significant difference between rural and urban groups in terms of sex of patient, age at diagnosis, cancer location, or tumour stage. Furthermore, no difference was identified between those commenced on a radical therapy with other treatment plans. Despite this, rurality predicted for an improved outcome on survival analysis (p = 0.012) and this was independent of other factors on multivariable analysis (HR = 0.78, 95%CI 0.66-0.98; p = 0.032). DISCUSSION: The difference in survival demonstrated here between urban and rural groups is not easily explained but may represent improvements to rural access to healthcare delivered as a result of Scottish Government reports.

Understanding Cancer Cachexia and Its Implications in Upper Gastrointestinal Cancers.

OPINION STATEMENT: Considerable advances in the investigation and management of oesophagogastric cancer have occurred over the last few decades. While the historically dismal prognosis associated with these diseases has improved, outcomes remain very poor. Cancer cachexia is an often neglected, yet critical, factor for this patient group. There is a persuasive argument that a lack of assessment and treatment of cachexia has limited progress in oesophagogastric cancer care. In the curative setting, the stage of the host (based on factors such as body composition, function, and inflammatory status), alongside tumour stage, has the potential to influence treatment efficacy. Phenotypical features of cachexia may decrease the survival benefit of (peri-operative) chemoradiotherapy, immunotherapy, or surgical resection in patients with potentially curative malignancy. Most patients with oesophagogastric cancer unfortunately present with disease which is not amenable, or is unlikely to respond, to these treatments. In the palliative setting, host factors can similarly impair results from systemic anti-cancer therapies, cause adverse symptoms, and reduce quality of life. To optimise treatment pathways and enhance patient outcomes, we must utilise this information during clinical decision-making. As our understanding of the genesis of cancer cachexia improves and more therapeutic options, ranging from basic (e.g. exercise and nutrition) to targeted (e.g. anti-IL1 α and anti-GDF-15), become available, there can be grounds for optimism. Cachexia can change from a hitherto neglected condition to an integral part of the oesophagogastric cancer treatment pathway.

A qualitative investigation of the supportive care experiences of people living with pancreatic and oesophagogastric cancer.

BACKGROUND: Pancreatic and oesophagogastric (OG) cancers have a dismal prognosis and high symptom burden, with supportive care forming an integral component of the care provided to patients. This study aimed to explore the supportive care experiences of patients and caregivers living with pancreatic and OG cancers in order to identify perceived opportunities for improvement. METHODS: Semi-structured individual interviews were conducted with people living with pancreatic and OG cancers, and their caregivers, across Victoria, Australia during 2020. Interviews were thematically analysed to identify common themes. RESULTS: Forty-one participants were interviewed, including 30 patients and 11 caregivers. Three overarching themes, each with multiple sub-themes, were identified: (i) inadequate support for symptoms and issues across the cancer journey (ii) caregiver's desire for greater support, and (iii) a multidisciplinary care team is the hallmark of a positive supportive care experience. Generally, those who had access to a cancer care coordinator and/or a palliative care team recounted more positive supportive care experiences. CONCLUSION: Unmet needs are prevalent across the pancreatic and OG cancer journey, with supportive care provided to varying levels of satisfaction. Greater awareness of and access to high-quality multidisciplinary support services is greatly desired by both patients with pancreatic and OG cancer and their caregivers.

Identifying outcomes reported in exercise interventions in oesophagogastric cancer survivors: a systematic review.

BACKGROUND: Research investigating exercise interventions in oesophagogastric cancer survivors is sparse, and the outcomes are varied. The aim of this systematic review is to identify the domains and outcomes reported in exercise interventions in oesophagogastric cancer survivors to be included in a Delphi study, with a view to informing the development of a core outcome set (COS). METHODS: EMBASE, PubMed, CINHAL, Cochrane Library, SCOPUS, and PEDro were searched up to March 2020 using a predefined search strategy. The outcomes identified during data extraction were categorised using the core areas outlined in the OMERACT Filter 2.0. RESULTS: Fourteen domains and 63 outcomes were identified. The most frequently reported outcomes were in the domains of quality of life using the EORTC-QLQ-C30 questionnaire and the relevant disease-specific modules (100%), exercise capacity/fitness/physical function (100%), anthropometrics (83.33%), physical activity (66.67%), and biomarker analysis (50%). CONCLUSION: This systematic review quantifies and describes the domains and outcomes examined in exercise interventions in oesophagogastric cancer survivors. Some inconsistency exists within the domains and outcomes used, and little attention was given to nutritional or economic endpoints. In order to develop a COS, a Delphi consensus process with key stakeholders is needed to identify the relevant domains and outcomes for inclusion.

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial.

BACKGROUND: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. METHODS: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed. DISCUSSION: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019.

A modified Delphi process to establish future research priorities in malignant oesophagogastric surgery.

BACKGROUND: With rapid advancement in the genomics of oesophagogastric (OG) cancer and raised expectations in clinical outcomes from patients and clinicians alike there is a clear need to determine the current research priorities in OG cancer surgery. The aim of our study was to use a modified Delphi process to determine the research priorities among OG cancer surgeons in the United Kingdom. METHODS: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high priority research questions. All questions submitted and subsequently ranked were analysed on an anonymised basis. RESULTS: In total, 427 questions were submitted in phase I and 75 with an OG cancer focus were taken forward for prioritisation in phase II. Phase III produced a final list of 12 high priority questions with an emphasis on tailored or personalised treatment strategies in OG cancer surgery. CONCLUSION: A modified Delphi process produced a list of 12 high priority research questions in OG cancer surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research across multiple centres.

Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study.

BACKGROUND: Survival rates for upper gastrointestinal (GI) cancer are poor since many are diagnosed at advanced stages. Fast track endoscopy has been introduced to prompt diagnosis for patients with alarm symptoms that could be indicative of upper GI cancer. However, these symptoms may represent benign conditions and little is known about the predictive values of alarm symptoms of upper GI cancer in the general population. METHODS: The study is a nationwide cohort study of 60,562 individuals aged 45 years or above randomly selected from the Danish general population. Participants were invited to complete a survey comprising of questions on several symptom experiences, including alarm symptoms for upper GI cancer within the past four weeks. The participants were asked about specific symptoms (repeated vomiting, difficulty swallowing, signs of upper GI bleeding or persistent and recent-onset abdominal pain) and non-specific symptoms (nausea, weight loss, loss of appetite, feeling unwell and tiredness). We obtained information on upper GI cancer diagnosed in a 12-month period after completing the questionnaire from the Danish Cancer Registry. We calculated positive predictive values and positive likelihood ratios for the association between alarm symptom and subsequent upper GI cancer. RESULTS: A total of 33,040 individuals above 45 years completed the questionnaire, yielding a response rate of 54.6%. Respondents were fairly respresentative of the study sample. During the follow-up period, 18 people were diagnosed with upper GI cancer. The number of incident cancers was similar among eligible non-respondents. Two thirds of the respondents with an upper GI malignancy had experienced one or more alarm symptoms. The positive predictive value for being diagnosed with upper GI cancer after reporting a least one alarm symptom was 0.1% (95% CI:0.0-0.1%). The positive likelihood ratio was 4.4 for specific alarm symptoms and 1.1 for non-specific alarm symptoms. CONCLUSIONS: We found that positive predictive values of alarm symptoms of upper GI cancer experienced in the general population are low. It is important knowledge that despite denoted alarm symptoms even patients with specific alarm symptoms of upper GI cancer have a low risk of being diagnosed with upper GI cancer.

Changes in health-related quality of life in oesophagogastric cancer patients participating in palliative and curative therapies.

Background: Various treatments are used to prolong survival and improve quality of life (QOL). The purpose of this study was to assess the change in QOL scores in patients with Oesophagogastric (OG) cancer undergoing curative intent and palliative therapy. Methods: This was a mix-designed cohort study with a consecutive sampling of patients with OG cancer who underwent curative or palliative treatment regimens. The QOL, as a determinant of efficacy and impact of cancer care, was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires. QOL data were collected from the eligible subjects at three points of time. The repeated measurement test was used to compare the significance of change in scores. Results: Overall, 149 patients (54.4% male, 61.1% curative intent, 52.3% esophageal, 37.6 % gastric, 10.1% OG junction cancer; with mean age 62 year) with OG cancer were eligible for inclusion in the study. Compared to the palliative group, the curative group was more likely to have an esophageal tumor site, Squamous Cell Carcinoma, and stage 2 (versus stomach, Adenocarcinoma, and stage 4 in the palliative group). In comparing the patients' functional, global health status, and cancer symptom, considering time, group of treatment, and their mutual effect the result indicated significant difference between the intervention groups. Conclusion: Most patients with Oesophagogastric cancer are diagnosed with an incurable form of the disease. Hence in absence of curative treatment, palliative therapy is the most effective therapy to maintain patient independency and relieve pain and symptom in order to improve their QOL. The present study has shown that palliative similar to curative intervention can improve the QOL in cancer patient especially in short term.

Which interval is most crucial to presentation and survival in gastroesophageal cancer: A systematic review.

AIM: The aim of this study was to identify the most crucial interval to encourage earlier diagnosis in with gastroesophageal cancer and to identify potential factors effecting this interval. BACKGROUND: Gastroesophageal malignancy is the eighth most commonly presenting cancer with one of the worst survival rates. Identifying the most crucial period for intervention to inform earlier diagnosis is an important step towards improving survival. DESIGN: Mixed methods literature review. DATA SOURCES: CINAHL, MEDLINE and Academic search primer online databases were searched using keywords and inclusion/exclusion criteria. Empirical evidence published between 2000-2016 with a focus on gastroesophageal cancer presentation and survival was reviewed to inform this study. REVIEW METHODS: Twelve studies were extracted for further review. Selected studies were appraised and presented through Olensen's "delay interval" framework to inform the most crucial interval to survival in gastroesophageal cancer. RESULTS: The findings identify the patient interval as the most critical period for encouraging earlier presentation and reducing advanced stage presentation in gastroesophageal cancer. The article also highlighted some methodological limitations to cancer research, such as a lack of consensus in definitions which prevent statistical meta-analysis of cancer data, survivor bias in gastroesophageal cancer studies and a significant lack of qualitative evidence to reveal patient experience in presenting with this cancer. CONCLUSION: Further research into the patient interval is required to elicit information on how and why patients present with their cancer symptoms.

Laparoscopic T-tube feeding jejunostomy as an adjunct to staging laparoscopy for upper gastrointestinal malignancies: the technique and review of outcomes.

BACKGROUND: In recent years, staging laparoscopy has gained acceptance as part of the assessment of resectability of upper gastrointestinal (UGI) malignancies. Not infrequently, we encounter tumours that are either locally advanced; requiring neoadjuvant therapy or occult peritoneal disease that requires palliation. In all these cases, the establishment of enteral feeding during staging laparoscopy is important for patients' nutrition. This review describes our technique of performing laparoscopic feeding jejunostomy and the clinical outcomes. METHODS: The medical records of all patients who underwent laparoscopic feeding jejunostomy following staging laparoscopy for UGI malignancies between January 2010 and July 2015 were retrospectively reviewed. The data included patient demographics, operative technique and clinical outcomes. RESULTS: Fifteen patients (11 males) had feeding jejunostomy done when staging laparoscopy showed unresectable UGI maligancy. Eight (53.3%) had gastric carcinoma, four (26.7%) had oesophageal carcinoma and three (20%) had cardio-oesophageal junction carcinoma. The mean age was 63.3 ± 7.3 years. Mean operative time was 66.0 ± 7.4 min. Mean postoperative stay was 5.6 ± 2.2 days. Laparoscopic feeding jejunostomy was performed without intra-operative complications. There were no major complications requiring reoperation but four patients had excoriation at the T-tube site and three patients had tube dislodgement which required bedside replacement of the feeding tube. The mean duration of feeding tube was 127.3 ± 99.6 days. CONCLUSIONS: Laparoscopic feeding jejunostomy is an important adjunct to staging laparoscopy that can be performed safely with low morbidity. Meticulous attention to surgical techniques is the cornerstone of success.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Ibrutinib in c-MYC and HER2 Amplified Oesophagogastric Carcinoma: Results of the Proof-of-Concept iMYC Study.

Oesophagogastric (OG) cancer is a highly lethal disease requiring novel treatment options. c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib. We evaluated the safety and efficacy of ibrutinib in patients with c-MYC and/or HER2 amplified pre-treated advanced OG cancer. c-MYC and HER2 amplification status were determined by FISH. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DC) at 8 weeks, safety, progression-free survival (PFS) and overall survival (OS). Eleven patients were enrolled. Eight patients had c-MYC amplified tumours, six were HER2 amplified and three were c-MYC and HER2 co-amplified. Grade ≥ 3 adverse events were fever, neutropenia, and vomiting. Grade ≥ 3 gastrointestinal haemorrhage occurred in three patients and was fatal in two cases. Among seven evaluable patients, three patients (43%) achieved a best response of SD at 8 weeks. No PR or CR was observed. Disease control was achieved for 32 weeks in one patient with a dual c-MYC and HER2 highly co-amplified tumour. The median PFS and OS were 1.5 (95% CI: 0.8-5.1) and 5.1 (95% CI: 0.8-14.5) months, respectively. Ibrutinib had limited clinical efficacy in patients with c-MYC and/or HER2 amplified OG cancer. Unexpected gastrointestinal bleeding was observed in 3 out of 8 treated patients which was considered a new safety finding for ibrutinib in this population.

Incidence, Survival and Prognostic Factors of Oesophagogastric Cancer.

INTRODUCTION: Oesophagogastric cancer is one of the leading causes of cancer death worldwide due to its aggressive nature. Despite the high mortality rate, there is limited information regarding this cancer in Brunei. AIM: To estimate the incidence and survival duration of oesophagogastric cancer patients, to identify prognostic factors of oesophagogastric cancer and associated factors for late-stage oesophagogastric cancer detection. METHODS: A retrospective study on all oesophagogastric cancer patients registered in the population-based national cancer registry in Brunei from January 2010 to December 2018. Kaplan-Meier and Cox proportional hazard regression survival analyses and multiple logistic regression were applied. RESULTS: Sixty-eight oesophagogastric cancer patients' data were retrieved from the registry. The incidence was 2.75 cases per 100,000 adults per year. Median survival time was 1.18 years (95% CI: 0.77, 1.80) and the 3-year survival rate was 26.3%. Age (61-70 years) (adjusted HR = 0.38; 95% CI: 0.17, 0.89; p = 0.025) and those who have undergone chemotherapy (adj. HR = 0.40; 95% CI: 0.18, 0.90; p = 0.026) have a significantly lower mortality risk. Obesity (adj. HR = 11.94; 95% CI: 1.94, 73.36; p = 0.007), and stage 4 (advanced stage) cancer (adj. HR=4.11; 95% CI: 1.97, 8.58; p< 0.001) have a significantly higher mortality risk. Females have 3-time odds (adj. OR = 3.05; 95% CI: 1.09, 9.02; p = 0.038) of presenting with stage 4 cancer. Smokers have 13-time odds (Adj. OR=12.99; 95% CI: 1.92, 262.0; p = 0.025) of presenting with stage 4 cancer. CONCLUSION: Prognosis of oesophagogastric cancer remains poor. Addressing late detection and improve endoscopic surveillance and awareness of symptoms may help improve prognosis and mortality.

A feasibility trial of prehabilitation before oesophagogastric cancer surgery using a multi-component home-based exercise programme: the ChemoFit study.

BACKGROUND: Treatment for locally advanced oesophagogastric adenocarcinoma involves neoadjuvant chemotherapy which has a negative impact on patient fitness. Using 'prehabilitation' to increase activity levels and fitness may affect physiology, postoperative outcomes and improve patient wellbeing and quality of life. The aims of the trial were to address the feasibility and acceptability of recruiting participants to a home-based prehabilitation programme and provide data to allow design of future studies. METHODS: We recruited patients to a single-arm feasibility trial of home-based exercise prehabilitation. Eligible patients were aged ≥18years, had operable oesophageal or gastric adenocarcinoma and were receiving neoadjuvant chemotherapy at our tertiary referral hospital. All participants commenced a home-based exercise programme utilising pedometers and step counting to target daily aerobic exercise sessions alongside daily strengthening exercises. A weekly telephone consultation directed the exercise programme and facilitated weekly data collection. The primary (feasibility) outcomes for the trial were (a) recruitment rate, (b) completion rate, (c) engagement with the programme (use of pedometers, recording step counts, telephone consultations) and (d) compliance with exercise sessions, exercise intensity and strengthening exercises. RESULTS: There were 42 patients recruited, and the recruitment rate was 72.4% (42/58). 92.3% (36/39) of patients completed the exercise programme. There was 98.7% (IQR 93.2-100.0%) compliance with wearing a pedometer and recording data, and 100.0% (IQR 93.1-100.0%) compliance with a weekly telephone consultation. Exercise sessions and strengthening exercises were completed 70.2% (IQR 53.1-88.9%) and 69.4% (IQR 52.1-84.3%) of the time, respectively. Appropriate exercise intensity was recorded 96% (IQR 85.4-99.4%) of the time. There were no adverse events. Participants were enrolled in the exercise programme for a median of 91 days (IQR 84 to 105 days). CONCLUSIONS: The results of this trial support the feasibility and acceptability of recruiting participants to an appropriately powered randomised controlled trial of prehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04194463 . Registered on 11th December 2019-retrospectively registered.

Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.

BACKGROUND & AIMS: Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS: This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS: There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION: Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.

Timeliness of cancer care in a regional Victorian health service: A comparison of high-volume (Lung) and low-volume (oesophagogastric) tumour streams.

BACKGROUND: Timeliness of cancer care is vital for improved survival and quality of life of patients. Service and care centralisation at larger-volume centres has been associated with improved outcomes. However, there is a lack of systematic data on the impact of tumour stream volume on timeliness of care. AIMS: To investigate and compare timeliness of care for lung cancer, a high-volume (more commonly diagnosed) tumour stream, and oesophagogastric (OG) cancer, a low-volume (less commonly diagnosed) tumour stream, at a regional health service in Victoria, Australia. METHODS: A retrospective cohort study comprising random samples of 75 people newly diagnosed with lung cancer (International Classification of Diseases and Related Health Problems-10 [ICD-10] diagnosis codes C34 in the Victorian Cancer Registry [VCR]) and 50 people newly diagnosed with OG cancer (ICD-10 diagnosis codes C15 or C16 in VCR) at one regional Victorian health service between 2016 and 2017. Binary logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between patient factors and suboptimal timeliness of care. RESULTS: In comparison to OG cancer patients, lung cancer patients had reduced odds of suboptimal timeliness of care in reference to times outside OCP for referral to diagnosis (OR [95% CI] = 0.34 [0.14 to 0.83]) but increased odds of suboptimal timeliness for diagnosis to treatment (OR [95% CI] = 2.48 [1.01 to 6.09]). CONCLUSION: In the low-volume OG cancer stream, patients had longer wait times from referral to an MDM, where treatment decisions occur, but shorter time to commencement of first treatment. Conversely in the high-volume lung cancer group, there was delayed initiation of first treatment following presentation at MDM. There is need to explore ways to fast-track MDM presentation and commencement of therapy among people diagnosed with low-volume and high-volume cancers, respectively.

Feasibility and Preliminary Effectiveness of a Tele-Prehabilitation Program in Esophagogastric Cancer Patients.

Tele-rehabilitation provides better access to healthcare services and optimizes exercise adherence. However, its feasibility and effectiveness are unknown in the preoperative period in esophagogastric cancer patients. We aimed to assess the feasibility and the preliminary effects of a "tele-prehabilitation" program in esophagogastric cancer patients requiring surgery. Enrolled participants performed an internet-based tele-prehabilitation including aerobic, resistance and inspiratory muscle training over 2-4 weeks. The primary outcome was feasibility, measured in terms of recruitment, retention and attendance rates, adverse events and patient satisfaction. Secondary outcomes (functional exercise capacity, fatigue, quality of life, anxiety and depression) were assessed at baseline, presurgery, and 4 and 12 weeks postsurgery. Among the 24 eligible subjects, 23 were enrolled, 22 performed the intervention and 15 completed the study. Recruitment and retention rates were both 96%. Attendances to aerobic and resistance sessions and inspiratory muscle training were 77% and 68%, respectively. No adverse events occurred, and the satisfaction was excellent. After prehabilitation, participants significantly improved fatigue (p = 0.039), quality of life (p = 0.009), physical well-being (p = 0.034), emotional well-being (p = 0.005) and anxiety (p = 0.044). This study demonstrated the feasibility of a tele-prehabilitation in esophagogastric cancer patients undergoing surgery, with a high recruitment rate, retention rate and satisfaction, a good attendance to exercise sessions and no exercise-related adverse events.

Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC): A phase I dose escalating safety study and randomised dose expansion of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophagogastric adenocarcinoma.

BACKGROUND: AZD8931 has equipotent activity against epidermal growth factor receptor, erbB2, and erbB3. Primary objectives were to determine the recommended phase II dose (RP2D) of AZD8931 + chemotherapy, and subsequently assess safety/preliminary clinical activity in patients with operable oesophagogastric cancer (OGC). METHODS: AZD8931 (20 mg, 40 mg or 60 mg bd) was given with Xelox (oxaliplatin + capecitabine) for eight 21-day cycles, continuously or with intermittent schedule (4 days on/3 off every week; 14 days on/7 off, per cycle) in a rolling-six design. Subsequently, patients with OGC were randomised 2:1 to AZD8931 + Xelox at RP2D or Xelox only for two cycles, followed by radical oesophagogastric surgery. Secondary outcomes were safety, complete resection (R0) rate, six-month progression-free survival (PFS) and overall survival. RESULTS: During escalation, four dose-limiting toxicities were observed among 24 patients: skin rash (1) and failure to deliver 100% of Xelox because of treatment-associated grade III-IV adverse events (AEs) (3: diarrhoea and vomiting; vomiting; fatigue). Serious adverse events (SAE) occurred in 15 of 24 (63%) patients. RP2D was 20-mg bd with the 4/3 schedule. In the expansion phase, 2 of 20 (10%) patients in the Xelox + AZD8931 group and 5/10 (50%) patients in the Xelox group had grade III-IV AEs. Six-month PFS was 85% (90% CI: 66%-94%) in Xelox + AZD8931 and 100% in Xelox alone. Seven deaths (35%) occurred with Xelox + AZD8931 and one (10%) with Xelox. R0 rate was 45% (9/20) with Xelox + AZD8931 and 90% (9/10) with Xelox-alone (P = 0.024). CONCLUSION: Xelox + AZD8931 (20 mg bd 4/3 days) has an acceptable safety profile administered as neoadjuvant therapy in operable patients with OGC. (Trial registration: EudraCT 2011-003169-13, ISRCTN-68093791).

Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.

INTRODUCTION: The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced pretreated MYC- and/or HER2-amplified oesophagogastric cancer, representing the first attempt to prospectively identify MYC amplifications in this tumour type for the purposes of therapeutic targeting. METHODS: Screening utilising a fluorescent in situ hybridisation (FISH) assay for assessment of tumour MYC amplification has been instituted. An experimental digital droplet polymerase chain reaction (ddPCR) assay to assess MYC amplification in both tumour and circulating-tumour (ct)DNA has been developed and investigated. RESULTS: One hundred thirty-five archival tumour specimens have undergone successful FISH analysis with 23% displaying evidence of MYC amplification. Intertumour heterogeneity was observed, with the percentage of cancer cells harbouring MYC amplification ranging widely between samples (median 51%, range 11-94%). Intratumoural clonal diversity of MYC amplification was also observed, with a significant degree of variance in amplification ratios (Bartlett's test for equal variance p < 0.001), and an association between greater variance in MYC amplification and improved outcome with prior first-line chemotherapy. ddPCR was most accurate in quantifying MYC amplification in tumour-derived DNA from cases with a high proportion (>70%) of amplified cells within the tumour specimen but was not reliable in samples containing a low proportion of amplified cells or in ctDNA. CONCLUSIONS: Our results illustrate the utility of FISH to assess MYC amplification prospectively for a biomarker-selected trial by providing reliable and reproducible results in real time, with a high degree of heterogeneity of MYC amplification observed. We show that ddPCR can potentially detect high-level MYC amplifications in tumour tissue.