• Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay.

      Hoefig, C S; Köhrle, J; Brabant, Georg E; Dixit, Kashinath C S; Yap, Beng K; Strasburger, C J; Wu, Z; Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. (2011-06)
      Thyronamines are thyronergic metabolites of thyroid hormones. Lack of reliable and sensitive detection methods for endogenous 3-iodothyronamine (3-T(1)AM) has so far hampered progress in understanding their physiological action and role in endocrine homeostasis or pathophysiology of diseases.
    • Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01).

      Le Péchoux, C; Laplanche, A; Faivre-Finn, Corinne; Ciuleanu, T; Wanders, R; Lerouge, D; Keus, R; Hatton, M; Videtic, G M; Senan, S; et al. (2011-05)
      We recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a major issue surrounding PCI, we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life (QoL).
    • Preoperative chemoradiotherapy using concurrent capecitabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes.

      Gollins, S; Sun Myint, A; Haylock, Brian; Wise, M; Saunders, Mark P; Neupane, R; Essapen, S; Samuel, L; Dougal, Mark; Lloyd, A; et al. (2011-03-10)
      To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)-defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine.
    • Collagen vascular diseases and enhanced radiotherapy-induced normal tissue effects--a case report and a review of published studies.

      Lee, C E; Prabhu, V; Slevin, Nicholas J; Department of Clinical Oncology, Christie Hospital, Manchester, UK. carolinelee@christie.nhs.co.uk (2011-03)
      Collagen vascular diseases (CVD) are a group of chronic, autoimmune conditions that can affect multiple organ systems. The mainstay of treatment involves the use of immunosuppressants. CVDs and immunosuppression increase the risk of these patients developing malignancy. The mechanisms through which these patients develop CVDs show similarities to those for radiotherapy late effects, especially fibrosis (via transforming growth factor β). Radiotherapy may in fact cause an active state to develop from a quiescent state of CVD, or exacerbate a pre-existing CVD. CVDs are said to be associated with increased normal tissue toxicity after radiotherapy. Here we present a case report of a patient with a long history of systemic lupus erythematosus and oropharyngeal carcinoma, treated with synchronous chemoradiotherapy. We also review published studies and formulate some guidance on the radiotherapy management of these patients.
    • Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

      Jegannathen, Apurna; Mais, Kathleen L; Sykes, Andrew J; Lee, Lip W; Yap, Beng K; Birzgalis, Andrew R; Homer, Jarrod J; Ryder, W David J; Slevin, Nicholas J; Department of Clinical Oncology, Christie NHS Foundation Trust, Manchester, UK. (2011-03)
      To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN).
    • Evaluation of educational methods in dermatology and confidence levels: a national survey of UK medical students.

      Chiang, Yi Zhen; Tan, Kian Tjon; Chiang, Yi Ning; Burge, Susan M; Griffiths, Christopher E M; Verbov, Julian L; Department of Medicine, Salford Royal National Health Service Foundation Trust, Manchester, UK. chiangyizhen@gmail.com (2011-02)
      The high prevalence of skin conditions makes dermatology education an essential part of the undergraduate medical curriculum. The aim of this study was to assess the impact of different educational methods on confidence levels in dermatology among UK medical students.
    • Management of hyponatraemia.

      Mittal, Rahul; Sheftel, H; Demssie, Y; Christie Hospital NHS Foundation Trust, Manchester, UK. (2011-02)
      Hyponatraemia (serum sodium level < 135 mmol/litre) is the most common electrolyte abnormality among hospitalized patients. A prevalence rate as high as 15-30% has been reported among patients admitted to acute and intensive care units (Hoorn et al, 2004; Jaber et al, 2006). Evidence suggests an increase in mortality associated with even a mild degree of hyponatraemia (Waikar et al, 2009). Besides its significance as a potential cause of morbidity and mortality, hyponatraemia could also serve as a useful indicator for undiagnosed underlying pathology such as endocrine disorders or malignancy. A systematic approach towards the clinical assessment and interpretation of biochemical abnormalities is vital to facilitate the diagnosis and management of hyponatraemia. The optimal treatment of hyponatraemia should take into account its severity, duration and mode of clinical presentation. Overzealous correction could result in irreversible neurological complications.
    • Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

      Nutting, C; Morden, J; Harrington, K; Urbano, Teresa G; Bhide, S A; Clark, C; Miles, E A; Miah, A B; Newbold, K; Tanay, M A; et al. (2011-02)
      Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.
    • What Three Wise Men have to say about diagnosis.

      Mani, Navin; Slevin, Nicholas J; Hudson, Andrew M; Department of Head and Neck Surgical Oncology, Christie Hospital, Manchester M20 4BX, UK. (2011)
    • Metastatic bladder cancer: a review of current management.

      Fletcher, Andrew; Choudhury, Ananya; Alam, Nooreen; Department of Palliative and Supportive Care, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. (2011)
      Bladder cancer continues to result in substantial morbidity and mortality for affected individuals. Advances in the management of metastatic bladder cancer have been limited. Chemotherapy with platinum-based regimes remains the mainstay of first-line treatment. Studies investigating alternative regimes have offered no survival advantage. Targeted therapies may offer benefit either as single agent or in combination with chemotherapy. Symptoms due to metastatic bladder cancer impact patients' quality of life, and therefore holistic management is vital. Such management includes radiotherapy, bisphosphonates, and the involvement of specialist palliative care services. This review will discuss the current management for metastatic bladder cancer, future potential treatment modalities, and the evidence to support the management strategies.
    • Symptom experience in patients with primary brain tumours: a longitudinal exploratory study.

      Molassiotis, Alexander; Wilson, Barbara; Brunton, Lisa; Chaudhary, Haseeb; Gattamaneni, Rao; McBain, Catherine A; University of Manchester, School of Nursing, University Place, Manchester M13 9PL, UK. alex.molassiotis@manchester.ac.uk (2010-12)
      This study was undertaken to further understand the symptom experience and the impact of symptoms in daily life in people treated for brain tumours.
    • Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.

      Ranson, Malcolm R; Wilson, R H; O'Sullivan, J M; Maruoka, M; Yamaguchi, A; Cowan, Richard A; Logue, John P; Tomkinson, H; Tominaga, N; Swaisland, H; et al. (2010-11)
      Objective: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. Methods: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. Results: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. Conclusions: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.
    • Guidelines on the radical management of patients with lung cancer.

      Lim, E; Baldwin, D; Beckles, M; Duffy, J; Entwisle, J; Faivre-Finn, Corinne; Kerr, K; Macfie, A; McGuigan, J; Padley, S; et al. (2010-10)
      A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.
    • Rechallenging with anthracyclines and taxanes in metastatic breast cancer.

      Palmieri, C; Krell, J; James, C R; Harper-Wynne, C; Misra, Vivek; Cleator, S; Miles, D; Cancer Research UK Laboratories, Department of Oncology, MRC Cyclotron Building, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK. c.palmieri@imperial.ac.uk (2010-10)
      Adjuvant use of anthracycline-taxane combination therapy is an accepted strategy in the management of high-risk early-stage breast cancer. However, the introduction of this regimen raises the question of how best to manage those patients who relapse following adjuvant therapy, and whether there is a role for rechallenging in the metastatic setting with the same agent, or class of agent, that has been utilized in the adjuvant setting. This Review examines the evidence for rechallenging with both anthracyclines and taxanes, and highlights the issues that need to be examined in the context of future clinical trials.
    • MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer.

      Choudhury, Ananya; Nelson, L D; Teo, M T W; Chilka, S; Bhattarai, S; Johnston, C F; Elliott, F; Lowery, J; Taylor, C F; Churchman, M; et al. (2010-09-15)
      Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer, but the choice of which treatment would be most beneficial cannot currently be predicted for individual patients. The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor samples taken before irradiation could be used as a predictive marker of radiotherapy response, or rather was prognostic. Protein expression of MRE11, RAD50, NBS1, ATM, and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients (validation cohort prospectively acquired) treated with radical radiotherapy and one cohort of cystectomy patients. In the radiotherapy test cohort (n = 86), low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [43.1% versus 68.7% 3-year cause-specific survival (CSS), P = 0.012] by Kaplan-Meier analysis. This was confirmed in the radiotherapy validation cohort (n = 93; 43.0% versus 71.2%, P = 0.020). However, in the cystectomy cohort (n = 88), MRE11 expression was not associated with cancer-specific survival, commensurate with MRE11 being a predictive marker. High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort (69.9% versus 53.8% 3-year CSS, P = 0.021). In this validated immunohistochemistry study, MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy, justifying its inclusion in subsequent trial designs. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy, thus improving overall cure rates.
    • A retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies.

      Omed, A; Lawrance, Jeremy A L; Murphy, G; Laasch, Hans-Ulrich; Wilson, G; Illidge, Timothy M; Tipping, Jill; Zivanovic, M; Jeans, S; Manchester Medical School, University of Manchester, Stopford Building, Manchester, UK. aliomed0101@doctors.org.uk (2010-09)
      AIM: To evaluate the efficacy and safety of selective internal radiation therapy (SIRT). MATERIALS AND METHODS: A retrospective analysis was undertaken of all patients who underwent SIRT at a single institution. Diagnostic and therapeutic angiograms, computed tomography (CT) images, positron-emission tomography (PET) images, and planar isotope images were analysed. The response to SIRT was analysed using radiological data and tumour markers. Overall survival, complications, and side effects of SIRT were also analysed. RESULTS: The initial 12 patients were included on an intention-to-treat basis, between 21/09/2005 and 07/05/2008. All patients had advanced disease and multiple prior courses of chemotherapy. One patient did not receive yttrium-90 due to complex vascular anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following work-up angiography. A response was seen using PET in 80% of patients. Using CT, the response of the tumour to therapy in the treated hepatic segments demonstrated a 20% partial response, stable disease in 50%, and progressive disease in 30%. Estimated median survival was 229 days, with 64% of patients still alive at the time of writing. No major complications were observed, although 82% of patients experienced side-effects following SIRT, mainly nausea, vomiting, and abdominal pain. CONCLUSIONS: There have been no complications in the 12 SIRT patients. Tumour response was seen in four out of five patients who underwent PET. Objective CT response rates were mixed and are perhaps partially explained by advanced disease and limitations of using measurements to assess response. This complex and potentially hazardous service has been successfully and safely established.
    • Addressing the health technology assessment of biosimilar pharmaceuticals.

      Stewart, Alan L; Aubrey, Philip; Belsey, Jonathan (2010-09)
      Abstract The growing number of biosimilars presents challenges to regulatory and health technology assessment (HTA) systems. This paper illustrates these challenges by focusing on biosimilars used in the oncological setting. In particular, discordances between data required by regulatory and HTA authorities potentially deprive patients of effective treatments and hinder optimal resource allocation. Regulatory and HTA authorities need to harmonize requirements to foster the development and widespread use of biosimilars, which potentially release considerable resources. The authors believe that often-inappropriate methodology creates a very real chance that HTA authorities will reject some biosimilars. This would effectively extend patent protection and, in the absence of competitor pressure from biosimilars, result in prices remaining unnecessarily high. The authors propose that HTA organizations should accept pharmacokinetic and pharmacodynamic equivalence between the brand and the biosimilar as a proxy of biological comparability. HTA organizations should then adopt, in the absence of compelling reasons otherwise, cost-minimization analysis (CMA) as the basis of the cost-effectiveness deliberations. In the absence of adequate studies demonstrating equivalent efficacy, a prerequisite of CMA, HTA organizations should require threshold analysis. Once approved, biosimilar manufacturers and regulators should maintain rigorous pharmacovigilance to exclude immunoreactivity or other rare adverse events. Furthermore, cancer centres and trusts should regularly audit and publish the impact of biosimilars on clinical outcomes and resource use. When appropriate, regulatory and HTA authorities should demand revised cost-effectiveness analyses from biosimilar manufacturers. This approach would hone the accuracy of the cost-effectiveness analyses, protect patients and allow health services rapid access to low cost treatments.
    • Improving survival with thoracic radiotherapy in patients with small cell lung cancer. The CONVERT and the REST Trials.

      Faivre-Finn, Corinne; Blackhall, Fiona H; Snee, Michael; Harden, S; Hulse, Paul; Lorigan, Paul C (2010-09)
    • Treatment for advanced cervical cancer: Impact on quality of life.

      Davidson, Susan E; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. (2010-08-30)
      Cisplatin-based combinations can potentially improve response rates in patients with cervical cancer, but unacceptable toxicity must be avoided. Quality of life (QoL) measures are increasingly used to assess the benefits versus limitations of chemotherapy regimens. A MEDLINE search of English language publications from January 2000 to December 2008 was conducted using the search terms: 'quality of life' OR 'QoL' OR 'HRQoL' AND 'cervical cancer'. Abstracts from the Association of Clinical Oncology meeting, 2008, were also searched. Article inclusion was based on abstract content. Several cervical cancer therapies have shown response rate improvements in combination with cisplatin, including topotecan and paclitaxel. However, only topotecan/cisplatin demonstrates a significant overall survival advantage over cisplatin monotherapy, while both topotecan/cisplatin and paclitaxel/cisplatin demonstrate comparable impact on QoL to cisplatin alone. Few trials of combination chemotherapy for cervical cancer have directly assessed QoL. The combination of topotecan/cisplatin significantly increases overall survival rates without reducing patient QoL.
    • Point: why choose pulsed-dose-rate brachytherapy for treating gynecologic cancers?

      Davidson, Susan E; Hendry, Jolyon H; West, Catharine M L; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. Susan.Davidson@christie.nhs.uk (2010-08-09)