Christie NHS Foundation Trust

Manchester, United Kingdom

Christie NHS Foundation Trust

Manchester, United Kingdom
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Geneva, Switzerland, May 5, 2017 - A late breaking subanalysis of the phase III CONVERT trial presented at the European Lung Cancer Conference (ELCC) shows that white blood cell boosting drugs are safe during concurrent chemo-radiotherapy of small cell lung cancer (SCLC).1 "The optimal treatment for limited-stage SCLC is concurrent chemo-radiotherapy," said lead author Dr Fabio Gomes, a medical oncologist at the Christie NHS Foundation Trust, Manchester, UK. "The efficacy of this intensive treatment is balanced by more toxicity, mainly haematological but also oesophageal and pulmonary. Meaning this is not a treatment to be considered for every patient and many more will struggle to stay on track with the planned treatment". Granulocyte colony-stimulating factors (G-CSFs) are commonly used as a supportive measure to boost the survival, proliferation and differentiation of neutrophils. The expected neutropenia is less severe and patients recover more quickly, reducing their risk for infectious complications. However, its use during concurrent chemo-radiotherapy in SCLC is controversial and the American Society of Clinical Oncology (ASCO) recommends against its routine use.2 This is due to a randomised trial with 215 eligible patients performed between 1989 and 1991, which showed a significant increase in severe thrombocytopenia, severe anaemia, pulmonary complications and toxic deaths when granulocyte-macrophage CSFs (GM-CSFs) were used during concurrent chemo-radiotherapy.3 Gomes said: "There have been two major changes since this trial was published in 1995 which may affect the safety of CSF in this context. First, the trial tested GM-CSFs which act on more than one blood cell lineage and are not commonly used nowadays. Instead we use G-CSFs, which are more specific and aim for the neutrophil lineage only. Second, modern radiotherapy techniques have evolved significantly since then and are more precise, which reduces the risks of toxicity." The phase III CONVERT trial enrolled 547 patients with limited-stage SCLC for concurrent chemo-radiotherapy who were randomised to once-daily or twice-daily radiotherapy. There was no difference in overall survival between the two groups.4 The trial protocol allowed the use of G-CSF, and around 40% of patients received it at some point during the treatment. For the analysis presented today, the researchers compared the toxicities and outcomes between patients who received G-CSF during concurrent chemo-radiotherapy and those who did not. They confirmed that the chance of severe thrombocytopenia or anaemia during treatment almost doubled in patients given G-CSF to around 30% and 20%, respectively, however these were lower than previously reported. That was followed by a significantly higher use of further supportive measures such as platelets and blood transfusions. However, there was no difference in the incidence of pulmonary complications or in survival. Gomes said: "G-CSF had no significant negative impact on the outcomes of these patients, which is a very comforting result. The higher haematological toxicity was balanced by an appropriate supportive care throughout treatment." He continued: "We can conclude from this analysis that the use of G-CSF during thoracic radiotherapy is safe and should support patients to receive the full planned course of concurrent chemo-radiotherapy and achieve the best possible benefit. These findings should give clinicians the confidence to use G-CSF when needed in this context. We aim to publish a complete analysis later this year which may hopefully help change the current guidelines." Commenting on the findings, Dr Stefan Zimmermann, Senior Consultant, Medical Oncology Department, HFR - Hôpital Cantonal, Fribourg, Switzerland, said: "Oncologists do need G-CSF to mitigate neutropenia and increase chemotherapy delivery and compliance, but want the beneficial effect of timely concurrent therapy to outweigh the toxic risks." "In this analysis, the use of G-CSF did not result in an increased risk of pneumonitis, but the incidence of severe thrombocytopenia is a concern," he continued. "The use of G-CSF was not detrimental to progression-free survival or overall survival. We can conclude that primary or secondary prophylaxis of febrile neutropenia with G-CSF is justified, but patients at higher risk for thrombocytopenia should be treated with caution." 1 Abstract LBA2_PR - 'Use of G-CSF and prophylactic antibiotics with concurrent chemo-radiotherapy in limited-stage small cell lung cancer: results from the phase III CONVERT trial,' will be presented by Dr Fabio Gomes during the Proffered Paper session 'SCLC and early stage NSCLC' on Sunday, 7 May, 09:00 (CEST). 2 Smith TJ, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28): 3199-3212. 3 Bunn PA Jr, et al. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995;13(7):1632-1641. This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO or IASLC who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct. The European Lung Cancer Conference (ELCC) is the reference event in Europe for professionals treating lung cancers. It is organised by the European Society for Medical Oncology and the International Association for the Study of Lung Cancer in partnership with ESTRO and ETOP. ELCC provides a comprehensive multidisciplinary overview of the latest as well as of the state-of-the-art knowledge in thoracic malignancies, covering different aspects such as prevention, screening, diagnosis, treatment modalities and the results of basic, clinical and translational research, presented by top international academic experts. Around 2,000 attendees are expected from throughout Europe and the rest of the world. About the European Society for Medical Oncology (ESMO) ESMO is the leading professional organisation for medical oncology. With more than 15,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment. http://www. About the International Association for the Study of Lung Cancer (IASLC) The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association's membership includes more than 5,000 lung cancer specialists in over 100 countries. Visit http://www. for more information.

Califano R.,Christie NHS Foundation Trust | Landi L.,Instituto Toscano Tumori | Cappuzzo F.,Instituto Toscano Tumori
Drugs | Year: 2012

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, caused by the presence of different clinically relevant molecular subtypes. Genetic mutations are emerging as potential biomarkers of response and treatment selection in patients with NSCLC. Over the past few years, activating mutations of epidermal growth factor receptor (EGFR) have been recognized as the most important predictor of response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib and also as a favourable prognostic factor. The RAS genes, including H-RAS, K-RAS and N-RAS, encode a family of proteins regulating cell growth, differentiation and apoptosis. Mutations in the K-RAS gene, mainly in codons 12 and 13, have been found in 20-30% of NSCLC tumor samples and occur most commonly, but not exclusively, in adenocarcinoma histology and in heavy smokers. In NSCLC, the presence of K-RAS mutations has generally been considered to be associated with worse prognosis and resistance to systemic therapy in the adjuvant as well as the metastatic setting. In early stage NSCLC, the prognostic role of K-RAS mutations has been evaluated in several studies without definitive conclusion. On the other hand, in advanced NSCLC, the presence of K-RAS mutations identifies a subgroup of patients who do not respond to EGFR-TKI therapy but, at the same time, a positive survival effect from EGFR-TKIs cannot be excluded in these patients. Similarly, K-RAS mutational status does not predict benefit from the anti-EGFR monoclonal antibody cetuximab, high-lighting the biological difference between lung cancer and colorectal cancer. As a result of the lack of conclusive data, K-RAS mutations do not represent a validated biomarker for the negative selection of patients who are candidates for anti-EGFR therapy. The aim of this article is to review and discuss the data on the prognostic and predictive value of K-RAS mutations in NSCLC. Adis © 2012 Springer International Publishing AG. All rights reserved.

News Article | December 15, 2016

Manchester is set to receive a major cash injection from Cancer Research UK. The charity plans to invest around £39 million over the next five years into the Cancer Research UK Manchester Centre, a partnership between Cancer Research UK, The University of Manchester and the Christie NHS Foundation Trust. The grant will fund ground-breaking work as part of the development of a unique chain of cutting-edge research hubs around the UK focusing on translational research. A further £2.75 million investment is planned for the Manchester Experimental Cancer Medicine Centre, from Cancer Research UK and the National Institute for Health Research. Funding will also support training of the next generation of cancer researchers - including 45 PhD students - to ensure the brightest scientists are attracted and supported in their career in cancer research. Professor Nic Jones, Director of the Cancer Research UK Manchester Centre, based at The University of Manchester, said: "This funding award is fantastic news for the city and for our Centre and we are especially honoured to be selected as a Major Centre. The award represents a critical investment in the research infrastructure that will equip us with the tools needed to advance the understanding and treatment of cancer. "This investment will boost efforts to transform treatments through the development of new approaches in personalised medicine. "Our aim is to transform cancer treatment by optimising the delivery of radiotherapy, and by developing new approaches to treatment where decisions are guided by the specific characteristics of a patient's tumour. This includes studying and characterising blood samples taken from patients at diagnosis and throughout their journey. We do this to look for markers released from the tumour that can provide key information to help doctors pick the right drug for the right patient. "We also aim to detect early warning signs of cancer to provide earlier diagnosis, or to give a clear indication if a patient's cancer has come back after treatment." Manchester has been chosen, by an international panel of experts, as one of just 13 locations to secure funding in the latest review of the Cancer Research UK Centres network of excellence and one of two to receive major centre status - the highest award. These research centres draw together world class research and medical expertise to provide the best possible results for cancer patients - getting cutting edge discoveries from the laboratory to patients and learning as much as possible from them to initiate new research ideas and programmes. Additionally, the panel chose Manchester as one of 18 Experimental Cancer Medicine Centres (ECMCs). The ECMCs aim to bring better treatments faster to cancer patients in the UK through both the adult and children's network of Centres. They are hubs where promising cancer treatments - including small molecule drugs, surgery, immunotherapy, and vaccines - are safely tested through clinical trials. These Centres help give people with cancer access to cutting-edge treatments by testing new ways of detecting and monitoring the disease and how it responds to treatment. Every year, 41,700 of people are diagnosed with cancer in the North West. Sir Harpal Kumar, chief executive at Cancer Research UK, said: "This is an exciting time for cancer research. "Cancer Research UK's projections are that we will reach more than 500,000 new diagnoses of cancer a year in the UK by 2035. By that time, our goal is that three in four people will survive their cancer. Funding these Centres, like the ones in Manchester, is one of the charity's most important strategic priorities and one which will help us reach this ambition. This huge investment is only made possible through generous donations from the public and the tireless fundraising of our supporters." Professor Dame Nancy Rothwell, President and Vice-Chancellor of The University of Manchester said: "Manchester is now one of the world's leading research centres for cancer and this funding represents an important step forward in finding new treatments, carrying out more trials and training the brightest minds to continue this work. Working with our partners at The Christie and Cancer Research UK gives us great strength, bringing together researchers and doctors to make new discoveries that benefit of people here and around the world." Roger Spencer, Chief Executive at The Christie said: "This investment in research and development of new cancer medicines will be vital to the Manchester partnership achieving its ambition to become one of the largest centres for experimental cancer medicine trials worldwide. "Patients are at the heart of everything we do at The Christie and this funding will enable us to deliver personalised treatments to even more patients. This in turn will translate into better outcomes for our patients." Professor Andrew Hughes, Joint Lead at Manchester's Experimental Cancer Medicine Centre and Strategic Director of the Experimental Cancer Medicine Team at The Christie, said: "This funding boost will enable us to deliver more novel clinical trials right here in Manchester - this will mean cancer patients from the North West will have access to new pioneering drugs as quickly as possible across all major cancer types. "Specifically, the funding will be used to treat an additional 200 patients per year with the goal that by 2020 over 500 patients each year will have access to pioneering new drugs in experimental cancer medicine clinical trials." Nicola Blackwood, Minister for Public Health and Innovation, said: "We want to lead the world in fighting cancer. The work of Experimental Cancer Medicine Centres is crucial in this fight. This next phase of funding from the National Institute for Health Research will help our world-leading researchers to continue to make new discoveries. "The collaboration between universities, NHS Trusts and the research community is a key reason these centres are successful, and illustrates why the UK is the best place in the world to be a researcher. "I hope this funding will ultimately lead to more life-saving treatments for patients."

Monaghan P.J.,Christie NHS Foundation Trust | Keevil B.G.,University of Manchester | Trainer P.J.,Christie NHS Foundation Trust
Reviews in Endocrine and Metabolic Disorders | Year: 2013

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is becoming a standard analytical tool in the clinical laboratory for the measurement of small molecules, including steroid hormones. Endocrinologists are coming to acknowledge the superior quality of measurement that is achievable by LC-MS/MS through the enhanced analytical specificity and high sensitivity that this technique offers over conventional immunoassay (IA) methodologies. Additionally, LC-MS/MS overcomes many of the problems encountered in immunoassays, such as anti-reagent antibody interferences and cross-reactivity with structurally related compounds. The potential benefits of applying LC-MS/MS for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis are beginning to be realised. This review critically evaluates recent developments in the application of LC-MS/MS for measurement of glucocorticoids and mineralocorticoids towards the diagnosis and management of HPA axis disorders and aims to address the current unmet need in this expanding field of endocrinology for which future studies into the potential applications of LC-MS/MS should be directed. © 2013 Springer Science+Business Media New York.

Hill S.,Christie NHS Foundation Trust
British Journal of Nursing | Year: 2015

Implanted ports (IPs) are an essential device for many patients who require long-term vascular access. IPs offer some advantages over other central venous access devices, such as lifestyle, body image benefits and lower infection rates. A typical implantation site for a port is the anterior chest wall. For some patients with breast cancer who have metastatic chest wall disease this site may lead to problems with the function of the device if disease spreads to the port site. One option for this patient group is to place the implanted port over the trapezius muscle. This article discusses six patients, all of whom had metastatic breast cancer with some degree of subcutaneous disease on the anterior chest wall. Three patients had received trapezius port placements and three had anterior chest wall placements. A retrospective review of the patients' medical records was undertaken from the time of insertion until removal or until the patient died. The anterior chest wall group of patients had their devices in for an average of 368 days vs 214 in the trapezius group. The total complications were higher in the anterior chest wall group (7 vs 2 in the trapezius group). Disease spread to two of the devices in the anterior chest wall group meaning the devices could no longer be used. The trapezius approach appears to be a safe and a reliable form of vascular access and may offer fewer complications than the traditional method of anterior chest wall placement when standard anterior chest wall approach is not suitable.

Bhaskar A.K.,Christie NHS Foundation Trust
Current Opinion in Supportive and Palliative Care | Year: 2012

Purpose of review Interventional techniques were the mainstay for cancer pain management before the WHO ladder and opioids were freely available. The three-step WHO ladder has its limitations, and cancer pain is often under treated. Advances in treatment options mean that cancer patients are living longer and pain interventions may have a role to play even early in the cancer diagnosis for better quality of analgesia. The role of high doses of opioids in pain management is also currently under scrutiny. Recent findings Recent advances in intrathecal analgesia, radiofrequency techniques, both in tumour ablation and neurotomies, are being widely used for palliation. Vertebroplasty techniques have been used not only for pain relief, but also for stabilization. Improved imaging and thoracoscopic techniques have made coeliac plexus and splanchnic blockade safer and more efficacious. There has been recent interest in percutaneous cordotomy with newer techniques using computed tomography/MRI and endoscopy guidance. Percutaneous electrical nerve stimulation and 8% capsaicin patches have been successfully used for managing neuropathic pain in cancer. Summary Interventions form an integral part in providing pain relief in complex cancer pains. Oncologists and palliative care physicians are to be educated on the usefulness and timing of interventions in the management of complex cancer pain. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Nonaka D.,Christie NHS Foundation Trust
American Journal of Surgical Pathology | Year: 2011

Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has not been reported yet. In this study, a total of 58 cases of parathyroid lesions including 40 adenomas, 2 atypical adenomas, 2 carcinomas, 9 hyperplastic lesions, 4 parathyroid cysts, and 1 case of recurrent hyperplasia of an autograft gland were stained with anti-Gcm2 antibody. Anti-Gcm2 was also applied to a variety of endocrine tumors, including thyroid tumors and nonendocrine tumors, and normal tissues from a variety of organs, including the parathyroid and thyroid glands. Gcm2 nuclear expression was seen in all the normal parathyroid glands, and cystic, hyperplastic, and neoplastic parathyroid lesions in a diffuse manner, whereas no Gcm2 expression was seen in any other normal tissues and tumors, including those of the thymus and thyroid gland. Anti-Gcm2 antibody is a highly sensitive and specific marker for parathyroid lesions. Although the immunohistochemistry stain for parathyroid hormone is a useful marker, its reaction tends to be variable in extent and intensity in parathyroid neoplasia, and it is often negative in parathyroid cysts, and Gcm2 would serve as a useful adjunct marker. © 2010 by Lippincott Williams & Wilkins.

Craciunas L.,Worthing Hospital | Sajid M.S.,Worthing Hospital | Ahmed A.S.,Christie NHS Foundation Trust
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2014

Background The incidence of postoperative ileus (POI) after gynaecological surgery is 10-15% Chewing gum following general surgery improves outcomes, including early flatus, early bowel sounds, and shortening of hospitalisation periods. There is currently no guideline that supports the use of chewing gum after caesarean sections. Objectives To systematically analyse the published randomised controlled trials regarding the effectiveness of chewing gum in preventing POI in women undergoing caesarean sections. Search strategy Systematic search of medical databases up to March 2013. Selection criteria Randomised controlled trials that reported the role of chewing gum in preventing POI in women undergoing caesarean sections. Data collection and analysis Two authors independently identified the relevant studies for inclusion, extracted outcome-related data, and analysed it systematically using revman ®. The combined outcome was expressed as an odds ratio and standardised mean difference. Main results Seven randomised controlled trials involving 1462 women (728 in the chewing gum group, 734 controls) were systematically analysed. There was significant heterogeneity (χ2 = 29.02, df = 7; P < 0.0001; I2 = 76%) among the included trials. Among women undergoing caesarean sections, chewing gum reduced the risk of POI (odds ratio 0.36; 95% confidence interval 0.19-0.69; z = 3.08; P < 0.002) but did not affect duration of hospitalisation (P = 0.32). Conclusions Chewing gum for 30-60 minutes at least three times a day appears to be effective in reducing the incidence and consequences of POI following caesarean sections. © 2014 Royal College of Obstetricians and Gynaecologists.

Dean E.,Christie NHS Foundation Trust | Lorigan P.,Christie NHS Foundation Trust
Expert Review of Anticancer Therapy | Year: 2012

Metastatic melanoma is an aggressive, immunogenic and molecularly heterogeneous disease for which most patients require systemic treatment. Recently, significant clinical breakthroughs have revolutionized the treatment of advanced melanoma, leading to the licensing of ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4, and vemurafenib, a BRAF inhibitor used in patients whose tumors contain a V600 mutation in the BRAF gene. This recent success has led to optimism and momentum has gathered with updated trial results from these therapies, next-generation compounds that target validated molecular pathways and novel agents that are mechanistically distinct. This review summarizes the recent advances and updated results since the licensing of vemurafenib and ipilimumab, the benefits and limitations of these agents, future strategies to improve upon existing treatments and overcome acquired resistance, in-progress and future clinical trials, as well as novel therapeutic targets, pathways and therapies that hold promise in advancing clinical benefit. © 2012 2012 Expert Reviews Ltd.

Recurrent tumour after radical pancreaticoduodenectomy may cause obstruction of the small bowel loop draining the liver. Roux-loop obstruction presents a particular therapeutic challenge, since the postsurgical anatomy usually prevents endoscopic access. Careful multidisciplinary discussion and multimodality preprocedure imaging are essential to accurately demonstrate the cause and anatomical location of the obstruction. Transhepatic or direct percutaneous stent placement should be possible in most cases, thereby avoiding long-term external biliary drainage. Gastropexy T-fasteners will secure the percutaneous access and reduce the risk of bile leakage. The static bile is invariably contaminated by gut bacteria, and systemic sepsis is to be expected. Enteral stents are preferable to biliary stents, and compound covered stents in a sandwich construction are likely to give the best long-term results. Transhepatic and direct percutaneous enteral stent insertion after jejunopexy is illustrated and the literature reviewed.

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