• c-kit receptors in ovarian tumors and the response of ovarian carcinoma cell lines ro recombinant human stem cell factor

      Wrigley, E; McGown, Alan T; Ward, Timothy H; Ewen, C; Crowther, Derek; Department of Medical Oncology, Christie Hospital; (1996)
    • C-kit receptors in ovarian tumors and the response of ovarian carcinoma cell lines to recombinant human stem cell factor.

      Wrigley, E; McGown, Alan T; Ward, Timothy H; Ewen, C; Crowther, Derek; Christie Hospital, Wilmslow Road, Manchester, M20 4BX (1996)
    • c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial

      Morgan, R. D.; Ferreras, C.; Peset, I.; Avizienyte, E.; Renehan, A. G.; Edmondson, R. J.; Murphy, A. D.; Nicum, S.; Van Brussel, T.; Clamp, A. R.; et al. (2022)
      Introduction Bevacizumab improves survival outcomes in women diagnosed with epithelial ovarian cancer (EOC). Pre-clinical data showed that the c-MET/VEGFR-2 heterocomplex negates VEGF inhibition through activation of c-MET signalling, leading to a more invasive and metastatic phenotype. We evaluated the clinical significance of c-MET and VEGFR-2 co-localisation and its association with VEGF pathway-related single nucleotide polymorphisms (SNPs) in women participating in the phase 3 trial, ICON7 (ClinicalTrials.gov identifier: NCT00262847). Materials and methods Patients had FIGO stage I-IIA grade 3/poorly differentiated or clear cell carcinoma or stage IIB-IV epithelial ovarian, primary peritoneal or fallopian tube cancer. Immunofluorescence staining for co-localised c-MET and VEGFR-2 on tissue microarrays and genotyping of germline DNA from peripheral blood leukocytes for VEGFA and VEGFR-2 SNPs was performed. The significance of these biomarkers was assessed against survival. Results Tissue microarrays from 178 women underwent immunofluorescence staining. Multivariable analysis showed that greater c-MET/VEGFR-2 co-localisation predicted worse OS in patients treated with bevacizumab after adjusting for FIGO stage and debulking surgery outcome (hazard ratio [HR] 1.034, 95% confidence interval [95%CI] 1.010–1.059). Women in the c-MET/VEGFR-2HIGH group treated with bevacizumab demonstrated significantly reduced OS (39.3 versus > 60 months; HR 2.00, 95%CI 1.08–3.72). Germline DNA from 449 women underwent genotyping. In the bevacizumab group, those women with the VEGFR-2 rs2305945 G/G variant had a trend towards shorter PFS compared with G/T or T/T variants (18.3 versus 23.0 months; HR 0.74, 95%CI 0.53–1.03). Conclusions In bevacizumab-treated women diagnosed with EOC, high c-MET/VEGFR-2 co-localisation on tumour tissue and the VEGFR-2 rs2305945 G/G variant, which may be biologically related, were associated with worse survival outcomes.
    • CAcTUS: A parallel arm, biomarker driven, phase II feasibility trial to determine the role of circulating tumor DNA in guiding a switch between targeted therapy and immune therapy in patients with advanced cutaneous melanoma

      Lee, Rebecca J; Rothwell, Dominic G; Chow, Shien; Shaw, H. M.; Turajlic, S.; Smith, N.; Clipson, A.; Clarke, H.; Kelso, N.; Mitchell, J.; et al. (2021)
      Background: Circulating tumor DNA (ctDNA; the tumour derived fraction of circulating free DNA in the blood) has been shown to be a biomarker of tumor burden/progression in many cancers. We recently accurately monitored treatment response and resistance in stage IV melanoma by ctDNA analysis in serial peripheral blood samples. Pre-clinical data has previously revealed that BRAF inhibition provokes a micro-environment with increased T cell infiltration, improved T cell recognition of melanoma associated antigens and reduced production of immunosuppressive cytokines that could enhance immune responses. We aimed to test the hypothesis that ctDNA could be implemented as a personalised, real-time liquid biopsy to identify when tumours are responding to targeted therapy in order optimise a switch to immunotherapy. Methods: We validated the ctDNA assays for BRAF mutation calling as a primary trial endpoint. We designed a phase II multicenter, parallel arm study across 6 UK sites, to assess primary objectives of i). Whether a ctDNA result can be turned around within 7 days and actioned in a clinically relevant timeframe ii). to assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% from baseline on targeted therapy is an appropriate ‘cut off’ to instruct switching to immunotherapy. Secondary endpoints include Overall Response Rate (ORR) to immunotherapy, radiological/clinical and ctDNA determined progression free survival (PFS) on each treatment. Forty patients are planned based on inclusion criteria of stage IV or stage III unresectable cutaneous BRAF mutant melanoma, baseline ctDNA BRAF variant allele frequency (VAF) ≥1.5%, ECOG 0/1/2, no symptomatic brain metastases, no prior adjuvant nivolumab plus ipilimumab (N+I). Prior adjuvant dabrafinib + trametinib (D+T) is allowed as long as recurrence is >6 months from completion. Patients are randomised 1:1 to either standard Arm A; investigator choice of either D+T (150mg BD +2mg OD respectively) or N+I (1 mg/kg N +3 mg/kg I q3 wkly, then N 480mg q4 wkly) first line, then switch on progression to the other treatment. In the experimental Arm B; all patients start on D+T and have BRAF ctDNA monitored q2 wkly for 4 wks then q4 wkly. When ≥80% decrease vs. baseline in ctDNA BRAF VAF occurs, patients switch to N+I. If patients subsequently progress on N+I, they will resume D+T. The study is open with 9 patients enrolled at time of submission.
    • Caecal metastases from cervical cancer--a rare presentation.

      Ansari, H A K; Manoharan, Prakash; Department of Diagnostic Radiology, Christie Hospital, Manchester, UK. doctorkhan75@yahoo.co.uk (2008-08)
    • Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer.

      Ranson, Malcolm R; Cheeseman, Sue; White, Shane C; Margison, Jennifer M; Department of Medical Oncology, Cancer Research Campaign, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M204BX, UK. malcolm.ransom@man.ac.uk (2001-02)
      Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.
    • Calcitonin in the treatment of intractable pain from advanced malignancy.

      Allan, Ernest; Christie Hospital, Manchester (1983)
      Clinical details are given of 8 patients who complained of severe pain from metastatic bone disease or from multiple myeloma. Four of the patients were included in a double-blind pilot trial designed to compare the effectiveness of salmon calcitonin (200 i.u. intramuscularly) and placebo given twice daily for 4 days. Two of these patients experienced pain relief and were found to have been given salmon calcitonin; the other 2 had no pain relief and had been given placebo. The other 4 of the 8 patients were treated with salmon calcitonin and also had relief of their pain. It would appear, therefore, that salmon calcitonin may be dramatically effective in the treatment of intractable pain from advanced malignancy and its use warrants further study.
    • The calculation of dosage and an additional distribution rule for cylindrical “volume” implantations with radium

      Meredith, W Jack; Stephenson, S K; Christie Hospital and Holt Radium Institute, Manchester (1945-02)
    • Calibration of pre-cut iridium-192 wires for low dose rate interstitial brachytherapy using a Farmer-type ionization chamber.

      Vollans, S E; Wilkinson, James M; North Western Medical Physics, Christie Hospital, Manchester, UK. (2000-02)
      A technique, originally developed for calibrating small low activity caesium sources, which uses a Farmer-type ionization chamber, has been further developed for use with iridium wires. Correction factors have been generated to account for the finite source and detector sizes, and attenuation in the source carriers. The air kerma calibration factor for heavily filtered 280 kV X-rays was used for reference back to the National Standard. The results of this calibration method have been compared with the calibration figures given by the manufacturers over a 5 year period for the emissions from 50 batches of wires of varying strengths. Agreement to within +/- 3.2% was achieved in all cases, establishing that the method is satisfactory for acceptance testing purposes. The mean agreement was good to within 0.2%, but the possibility of a systematic error of between 1% and 3% existing both in this method and in the method used by the manufacturer is discussed.
    • A call for standardized reporting of adverse events

      Fankhauser, Christian D; Wettstein, M. S.; Pedregal, M.; Clarke, Noel W; Sweeney, C. J.; Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; (2020)
    • A call to action on chemotherapy services.

      Davis, Carole; The Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, U.K. (2009)
    • CAM and cancer care: champions for integration.

      Mackereth, Peter A; Stringer, Jacqui; Clinical Leads, Complementary Therapy Service, Rehabilitation Unit, Christie Hospital, Manchester, UK. peter.a.mackereth@virgin.net (2005-02)
      The paper reviews challenges and developments in the integration of complementary therapies in cancer care. These issues are examined by reflecting on papers published in CTNM in the last 10 years by champions of CAM in cancer care. Given the aim of the journal to encourage an inclusive readership, multidisciplinary and user perspectives are included. The paper argues for better information, improved service provision and CAM choices in public healthcare, leadership support, funded research and audit, and user and non-users views.
    • The CamGFR model for renal function in patients with cancer: validation and extension for use with data from isotope mass dilution spectrometry creatinine assays

      Williams, E; Whitley, C; Weaver, Jamie M; Connell, C; Geisler, S; Giglio, D; Tavare, S; Jodrell, D; Janowitz, T; Liver Unit, Barcelona Clinic Liver Cancer group, Hospital Clinic Barcelona (2018)
    • CamGFR v2: a new model for estimating the glomerular filtration rate from standardized or non-standardized creatinine in patients with cancer

      Williams, E. H.; Flint, T. R.; Connell, C. M.; Giglio, D.; Lee, H.; Ha, T.; Gablenz, E.; Bird, N. J.; Weaver, Jamie M; Potts, H.; et al. (2020)
      Purpose: Management of patients with cancer, specifically carboplatin dosing, requires accurate knowledge of glomerular filtration rate (GFR). Direct measurement of GFR is resource-limited. Available models for estimated GFR (eGFR) are optimized for patients without cancer and either isotope dilution mass spectrometry (IDMS)- or non-IDMS-standardized creatinine measurements. We present an eGFR model for patients with cancer compatible with both creatinine measurement methods. Methods: GFR measurements, biometrics, and IDMS- or non-IDMS-standardized creatinine values were collected for adult patients from three cancer centers. Using statistical modelling, an IDMS- and non-IDMS creatinine compatible eGFR model (CamGFR v2) was developed. Its performance was compared to that of the existing models CKD-EPI, MDRD, FAS, Lund-Malmo Revised and CamGFR v1 using statistics for bias, precision, accuracy, and clinical robustness. Results: 3,083 IDMS- and 4,612 non-IDMS-standardized creatinine measurements were obtained from 7,240 patients. IDMS-standardized creatinine values were lower than non-IDMS-standardized values in within-centercomparisons (13.8% lower in Cambridge, p<0.0001; 19.3% lower in Manchester, p <0.0001), and more consistent between centers. CamGFR v2 was the most accurate (root-mean-squared error for IDMS = 14.97ml/min[95% CI 13.84,16.13]; non-IDMS = 15.74ml/min[14.86,16.63]), most clinically robust (proportion with >20% error of calculated carboplatin dose for IDMS = 0.12[0.09, 0.14]; non-IDMS = 0.17[0.15, 0.2]) and least biased (median residual for IDMS = 0.73ml/min[-0.68,2.2]; non-IDMS = -0.43ml/min[-1.48,0.91]) eGFR model, particularly when eGFR was larger than 60ml/min. Conclusions: CamGFR v2 can utilize IDMS- and non-IDMS-standardized creatinine measurements and outperforms previous models. CamGFR v2 should be examined prospectively as a practice-changing standard of care for eGFR-based carboplatin dosing.
    • Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study

      Hamadani, M.; Collins, G. P.; Caimi, P. F.; Samaniego, F.; Spira, A.; Davies, A.; Radford, John A; Menne, T.; Karnad, A.; Zain, J. M.; et al. (2021)
      Background: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population. Methods: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 μg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235. Findings: Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 μg/kg and 45 μg/kg for patients with classical Hodgkin lymphoma and 80 μg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81). Interpretation: These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma
    • CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma.

      Lundin, J; Osterborg, Anders; Brittinger, G; Crowther, Derek; Dombret, Herve; Engert, Andreas; Epenetos, A; Gisselbrecht, Christian; Huhn, D; Jaeger, U; et al. (1998-10)
      PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS: Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION: CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.
    • Campto effective and flexible chemotherapy for advanced colorectal cancer.

      Ferns, Helen; Christie Hospital NHS Trust, Manchester M20 4BX, UK. (2003-07)
      The use of chemotherapy with patients with advanced colorectal cancer is increasing. There is a growing appreciation of the potential of traditional and newer treatments to improve quality of life, and of their value in the palliation of symptoms, in addition to providing modest gains in overall survival. Possible benefits have to be weighed up against the risk of side effects and patients need to be supported in making difficult decisions. This article provides a brief overview of chemotherapy agents for advanced colorectal cancer and focuses on one new agent, Campto. The evidence supporting its use, common side effects and management recommendations are discussed. The role of the oncology team and the implications for nurses are outlined.
    • Can a brief psychological intervention prevent anxiety or depressive disorders in cancer patients? A randomised controlled trial.

      Pitceathly, Carolyn; Maguire, Peter; Fletcher, I; Parle, Michael; Tomenson, B; Creed, Francis; CRUK Psychological Medicine Group, Stanley House, Christie Hospital, Manchester. (2009-01-06)
      BACKGROUND: We tested whether a brief psychological intervention could prevent anxiety or depressive disorders among newly diagnosed cancer patients. PATIENTS AND METHODS: Patients free of anxiety or depressive disorder were randomised to receive immediate intervention (start of cancer treatment), delayed intervention (8 weeks after starting treatment) or usual care. They were stratified according to risk of developing anxiety or depressive disorders. Primary outcome was measured using a standardised psychiatric interview to detect any anxiety or depressive disorder at 6 and 12 months following the cancer diagnosis. Analyses used conditional odds logistic regression models adjusting for age, gender, concerns and past history to compare outcome of all intervention patients with usual care. RESULTS: A total of 465 patients were recruited. In all, 313 (79%) of the 397 well enough to be interviewed completed the study. At 12 months, there was no difference between the groups receiving the intervention and usual care [odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.41-1.17, P = 0.17]. In high-risk patients, those who received the intervention were less likely to develop an anxiety or depressive disorder compared with those who received usual care (OR = 0.54, 95% CI 0.29-1.00, P = 0.050). In low-risk patients, there was no difference (OR = 1.50, 95% CI 0.51-4.43, P = 0.47). CONCLUSION: A brief intervention, delivered by nonspecialists, promoted adjustment among newly diagnosed cancer patients at high risk of developing anxiety or depressive disorders.