Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial.
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SUBMITTER: Cunningham D
PROVIDER: S-EPMC5337626 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application.MethodsA systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability.Results256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA.ConclusionThis review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.
| S-EPMC4972371 | biostudies-literature
Project description:This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma.A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging.TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P?<?0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P?=?0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P?<?0·001).A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.
| S-EPMC5725679 | biostudies-literature
Project description:BackgroundPatients' demographic and epidemiological characteristics, local variations in clinicians' knowledge and experience and types of surgery can influence peri-operative transfusion practices. Sharing data on transfusion practices and recipients may improve patients' care and implementation of Patient Blood Management (PBM).Materials and methodsThis was a multicentre, prospective, observational, cross-sectional study that included 61 centres. Clinical and transfusion data of patients undergoing major elective surgery were collected; transfusion predictors and patients' outcomes were analysed.ResultsOf 6,121 patients, 1,579 (25.8%) received a peri-operative transfusion. A total of 5,812 blood components were transfused: red blood cells (RBC), fresh-frozen plasma and platelets in 1,425 (23.3%), 762 (12.4%) and 88 (1.4%) cases, respectively). Pre-operative anaemia was identified in 2,019 (33%) patients. Half of the RBC units were used by patients in the age group 45-69 years. Specific procedures with the highest RBC use were coronary artery bypass grafting (16.9% of all units) and hip arthroplasty (14.9%). Low haemoglobin concentration was the most common indication for intra-operative RBC transfusion (57%) and plasma and platelet transfusions were mostly initiated for acute bleeding (61.3% and 61.1%, respectively). The RBC transfusion rate in study centres varied from 2% to 72%. RBC transfusion was inappropriate in 99% (n=150/151) of pre-operative, 23% (n=211/926) of intra-operative and 43% (n=308/716) of post-operative RBC transfusion episodes. Pre-operative haemoglobin, increased blood loss, open surgery and duration of surgery were the main independent predictors of intra-operative RBC transfusion. Low pre-operative haemoglobin concentration was independently associated with post-operative pulmonary complications.ConclusionsThese findings identified areas for improvement in peri-operative transfusion practice and PBM implementation in Turkey.
| S-EPMC7375885 | biostudies-literature
Project description:In resource-constrained settings, where inequalities in access to and quality of surgical care results in excess mortality, peri-operative care registries are uncommon. A south-south collaboration supported the implementation of a context specific, clinician-led, multicentre real-time peri-operative registry in Ethiopia. Peri-operative information, including the Ethiopian Ministry of Health's national 'Saving Lives through Safe Surgery initiative', was linked to real-time dashboards, providing clinicians and administrators with information on service utilisation, surgical access, national surgical key performance indicators and measures of quality of care. We recruited four hospitals representing 285 in-patient beds from the Amhara and Southern Nations Nationalities and Peoples regions and Addis Ababa city, and reported on 1748 consecutive surgical cases from April 2019 to April 2020. Key performance indicators included: compliance with the World Health Organization's Surgical Safety Checklist in 1595 (92.1%) surgical cases; adverse events during anaesthesia in 33 (3.1%) cases; and surgical site infections in 21 (2.0%) patients. This collaboration has successfully implemented a multicentre digital surgical registry that can enable measurement of key performance indicators for surgery and evaluation of peri-operative outcomes. The peri-operative registry is currently being rolled out across the Amhara region and Addis Ababa city administration. It will provide continuous granular healthcare information necessary to empower clinicians to drive context-specific priorities for service improvement and research, in collaboration with national stakeholders and international research consortiums.
| S-EPMC8248420 | biostudies-literature
Project description:The number of patients who develop metastatic brain lesions is increasing as the diagnosis and treatment of systemic cancers continues to improve, resulting in longer patient survival. The role of surgery in the management of brain metastasis (BM), particularly multiple and recurrent metastases, remains controversial and continues to evolve. However, with appropriate patient selection, outcomes after surgery are typically favorable. In addition, surgery is the only means to obtain a tissue diagnosis and is the only effective treatment modality to quickly relieve neurological complications or life-threatening symptoms related to significant mass effect, CSF obstruction, and peritumoral edema. As such, a thorough understanding of the role of surgery in patients with metastatic brain lesions, as well as the factors associated with surgical outcomes, is essential for the effective management of this unique and growing patient population.
| S-EPMC6853809 | biostudies-literature
Project description:Perioperative chemotherapy improves overall survival in patients with oesophagogastric adenocarcinoma (OAC) and locoregional disease. The mainstay of perioperative chemotherapy in these patients is a platinum/fluoropyrimidine combination. The phase III FLOT4 trial has shown that the FLOT triplet regimen (oxaliplatin, infusional 5-FU, and docetaxel) improves the outcome of patients with OAC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and infusional 5-FU). Targeted therapies have currently no role in the perioperative setting for the treatment of patients with OAC. For patients with oligometastatic disease, upfront gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone and thus should be discouraged. Whether surgery should be offered to patients with metastatic OAC achieving a systemic control after upfront chemotherapy is under scrutiny in the phase III FLOT5/Renaissance trial. After neoadjuvant treatment, lymph node status but not pathologic tumor response is an independent factor in the prediction of overall survival. Growing evidence suggests that perioperative chemotherapy may be associated with an increased mortality risk in patients with microsatellite instable (MSI)/mismatch repair-deficient (MMRD) adenocarcinoma, thus validating poor responsiveness to chemotherapy in MSI patients with locoregional disease.
| S-EPMC5530426 | biostudies-other
Project description:IntroductionBrain metastases are the most common brain tumors in adults, whose management remains nuanced. Improved understanding of risk factors for surgical complications and mortality may guide treatment decisions.MethodsA nationwide, multicenter analysis was conducted with a retrospective cohort. Adult patients in the 2012-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) databases who received a craniotomy for resection of brain metastasis were included.Results3500 cases were analyzed, of which 17% were considered frail and 24% were infratentorial. The most common 30-day medical complications were venous thromboembolism (3%, median time-to-event [TTE] 4.5 days), pneumonia (4%, median TTE 6 days), and urinary tract infections (2%, median TTE 5 days). Reoperation and unplanned readmission occurred in 5% and 12% of patients, respectively. Infratentorial approach and frailty were associated with reoperation before discharge (OR 2.0 for both; p=0.01 and p=0.03 respectively), but not after discharge. Infratentorial approaches conferred heightened risk for readmission for hydrocephalus (OR 5.1, p=0.02) and reoperation for cerebrospinal fluid diversion (OR 7.1, p<0.001).Overall 30-day mortality was 4%, with nearly three-quarters occurring after discharge. Pre-frailty and frailty were associated with increased odds for post-discharge mortality (OR 1.7 and 2.7, p<0.05), but not pre-discharge mortality. We developed a model to identify pre-/peri-operative variables associated with death, including frailty, thrombocytopenia, and high American Society of Anesthesiologists score (AUROC 0.75).ConclusionsOptimization of metrics contributing to patient frailty and heightened surveillance in patients with infratentorial metastases may be considered in the peri-operative period.
| S-EPMC8131835 | biostudies-literature
Project description:Oxaliplatin-based chemotherapy is used to treat patients with esophageal adenocarcinoma (EAC), but no biomarkers are currently available for patient selection. We performed a prospective, clinical trial to identify potential biomarkers associated with clinical outcomes. Tumor tissue was obtained from 38 patients with resectable EAC before and after 2 cycles of oxaliplatin-fluorouracil chemotherapy. Pre-treatment mRNA expression of 280 DNA repair (DNAR) genes was tested for association with histopathological regression at surgery, disease-free survival (DFS) and overall survival (OS). High expression of 13 DNA damage repair genes was associated with DFS less than one year (P < 0.05); expression of 11 DNAR genes were associated with worse OS (P < 0.05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers. In cell lines in vitro, we showed the mechanism of action related to repair of oxaliplatin-induced DNA damage by depletion and knockout of protein binding partners of the candidate biomarkers, XPF and MUS81 respectively. In clinical samples from the clinical trial, pre-treatment XPF protein levels were associated with pathological response, and MUS81 protein was associated with 1-year DFS. XPF and MUS81 merit further validation in prospective clinical trials as biomarkers that may predict clinical response of EAC to oxaliplatin-based chemotherapy.
| S-EPMC5940885 | biostudies-literature
Project description:Oesophageal junctional adenocarcinoma is a challenging and increasingly common disease. Optimisation of pre-operative staging and consolidation of surgery in large volume centres have improved outcomes, however the preferred adjunctive treatment approach remains a matter of debate. This review examines the benefits of neoadjuvant, peri-operative, and post-operative chemotherapy and chemoradiotherapy in this setting in an attempt to reach an evidence based conclusion. Recent findings relating to the molecular characterisation of oesophagogastric cancer and their impact on therapeutics are explored, in addition to the potential benefits of fluoro-deoxyglucose positron emission tomography (FDG-PET) directed therapy. Finally, efforts to decrease the incidence of junctional adenocarcinoma using early intervention in Barrett's oesophagus are discussed, including the roles of screening, endoscopic mucosal resection, ablative therapies and chemoprevention.
| S-EPMC4058722 | biostudies-literature
Project description:BackgroundWith improved safety of allogeneic blood supply, the use of preoperative autologous donations (PADs) and perioperative autologous cell salvage (PACS) has evolved. This study evaluated temporal trends in PAD and PACS use in the United States.MethodsThe National Inpatient Sample database, a stratified probability sample of 20% of hospitalizations in the United States, was used to compare temporal trends in hospitalizations reporting use of PADs and PACS from 1995 to 2015. Factors associated with their use were examined between 2012 and 2015 with use of multivariable Poisson regression. Sampling weights were applied to generate nationally representative estimates.ResultsThere was a steady decrease in hospitalizations reporting PAD transfusions from 27.90 per 100 000 in 1995 to 1.48 per 100 000 hospitalizations in 2015 (P-trend <.001). In contrast, PACS increased from a rate of 1.16 per 100 000 in 1995 to peak of 20.51 per 100 000 hospitalizations in 2008 and then steadily declined (P-trend<.001). Higher odds of PACS and PADs were observed in older patients, elective procedures (vs urgent), and urban teaching/nonteaching hospitals (vs rural hospitals) (P < .001). PACS was more common in hospitalizations in patients with higher levels of severity of illness as compared to those with minor severity (adjusted prevalence ratio [adjPR], 2.39; 95% confidence interval [CI], 2.08-2.73; P<.001), while PADs were performed less often in patients with higher underlying severity of illness (All Patient Refined Diagnosis Related Groups, 4 vs 1, adjPR, 0.61; 95% CI, [0.39-0.95]; P = .028).ConclusionsThere was a significant decrease in PAD red blood cell transfusions, while PACS has increased and subsequently decreased; PACS plays an important role in surgical blood conservation. The subsequent decline in PACS likely reflects further optimization of transfusion practice through patient blood management programs and improvement of surgical interventions.
| S-EPMC7902373 | biostudies-literature