• The use of an electronic portal imaging device for exit dosimetry and quality control measurements.

      Kirby, Mike C; Williams, Peter C; North Western Medical Physics Department, Christie Hospital, Manchester, UK. (1995-02-01)
      PURPOSE: To determine ways in which electronic portal imaging devices (EPIDs) could be used to (a) measure exit doses for external beam radiotherapy and (b) perform quality control checks on linear accelerators. METHODS AND MATERIALS: When imaging, our fluoroscopic EPID adjusts the gain, offset, and frame acquisition time of the charge coupled device (CCD) camera automatically, to allow for the range of photon transmissions through the patient, and to optimize the signal-to-noise ratio. However, our EPID can be programmed to act as an integrating dosemeter. EPID dosemeter measurements were made for 20 MV photons, for different field sizes and thicknesses of unit density phantom material placed at varying exit surface to detector distances. These were compared with simultaneous Silicon diode exit dose measurements. Our exit dosimetry technique was verified using an anthropomorphic type phantom, and some initial measurements have been made for patients treated with irregularly shaped 20 MV x-ray fields. In this dosimetry mode, our EPID was also used to measure certain quality control parameters, x-ray field flatness, and the verification of segmented intensity modulated field prescriptions. RESULTS: Configured for dosimetry, our EPID exhibited a highly linear response, capable of resolving individual monitor units. Exit doses could be measured to within about 3% of that measured using Silicon diodes. Field flatness was determined to within 1.5% of Farmer dosemeter measurements. Segmented intensity modulated fields can be easily verified. CONCLUSIONS: Our EPID has the versatility to assess a range of parameters pertinent to the delivery of high quality, high precision radiotherapy. When configured appropriately, it can measure exit doses in vivo, with reasonable accuracy, perform certain quick quality control checks, and analyze segmented intensity modulated treatment fields.
    • Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

      Cuzick, J; Sestak, I; Forbes, JF; Dowsett, M; Cawthorn, S; Mansel, RE; Loibl, S; Bonanni, B; Evans, D Gareth R; Howell, Anthony; et al. (2019)
      BACKGROUND: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period. METHODS: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer. FINDINGS: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0á51, 95% CI 0á39-0á66, p<0á0001). The reduction was larger in the first 5 years (35 vs 89, 0á39, 0á27-0á58, p<0á0001), but still significant after 5 years (50 vs 76 new cases, 0á64, 0á45-0á91, p=0á014), and not significantly different from the first 5 years (p=0á087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0á46, 95% CI 0á33-0á65, p<0á0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0á41, 0á22-0á79, p=0á0081), especially in participants known to be oestrogen receptor-positive (0á22, 0á78-0á65, p<0á0001). No significant difference in deaths was observed overall (69 vs 70, HR 0á96, 95% CI 0á69-1á34, p=0á82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0á72, 95% CI 0á57-0á91, p=0á0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed. INTERPRETATION: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.
    • Use of artificial neural networks to predict biological outcomes for patients receiving radical radiotherapy of the prostate.

      Gulliford, Sarah L; Webb, Steve; Rowbottom, Carl G; Corne, David W; Dearnaley, David P; Joint Department of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey SM2 5PT, UK. (2004-04)
      BACKGROUND AND PURPOSE: This paper discusses the application of artificial neural networks (ANN) in predicting biological outcomes following prostate radiotherapy. A number of model-based methods have been developed to correlate the dose distributions calculated for a patient receiving radiotherapy and the radiobiological effect this will produce. Most widely used are the normal tissue complication probability and tumour control probability models. An alternative method for predicting specific examples of tumour control and normal tissue complications is to use an ANN. One of the advantages of this method is that there is no need for a priori information regarding the relationship between the data being correlated. PATIENTS AND METHODS: A set of retrospective clinical data from patients who received radical prostate radiotherapy was used to train ANNs to predict specific biological outcomes by learning the relationship between the treatment plan prescription, dose distribution and the corresponding biological effect. The dose and volume were included as a differential dose-volume histogram in order to provide a holistic description of the available data. RESULTS: It was shown that the ANNs were able to predict biochemical control and specific bladder and rectum complications with sensitivity and specificity of above 55% when the outcomes were dichotomised. It was also possible to analyse information from the ANNs to investigate the effect of individual treatment parameters on the outcome. CONCLUSION: ANNs have been shown to learn something of the complex relationship between treatment parameters and outcome which, if developed further, may prove to be a useful tool in predicting biological outcomes.
    • The use of carbon fibre material in table tops, cassette fronts and grid covers: magnitude of possible dose reduction.

      Hufton, Alan P; Russell, J G; Regional Department of Mediacal Physics and Bioengineering, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, UK (1986-02)
      The X-ray transmission of a number of radiographic components, some of conventional construction and some incorporating carbon fibre material, has been measured under clinically realistic conditions. At 80 kVp the use of carbon fibre materials enables the patient dose to be reduced by 30-50% depending on the existing equipment, type of examination and technique used. Typically the dose can be reduced by 3-15% by changing the table top, 6-12% by changing the front of the film cassette and 20-30% by using a grid with carbon fibre covers and fibre interspace. The higher cost of carbon fibre components can normally be justified by such dose savings. An indication of the absorption of all such components should be provided by manufacturers.
    • Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

      Sutcliffe, P; Hummel, S; Simpson, E; Young, T; Rees, A; Wilkinson, A; Hamdy, F; Clarke, Noel W; Staffurth, J; The University of Sheffield, School of Health and Related Research (ScHARR), UK. (2009-01)
      OBJECTIVES: To provide an evidence-based perspective on the prognostic value of novel markers in localised prostate cancer and to identify the best prognostic model including the three classical markers and investigate whether models incorporating novel markers are better. DATA SOURCES: Eight electronic bibliographic databases were searched during March-April 2007. The reference lists of relevant articles were checked and various health services research-related resources consulted via the internet. The search was restricted to publications from 1970 onwards in the English language. METHODS: Selected studies were assessed, data extracted using a standard template, and quality assessed using an adaptation of published criteria. Because of the heterogeneity regarding populations, outcomes and study type, meta-analyses were not undertaken and the results are presented in tabulated format with a narrative synthesis of the results. RESULTS: In total 30 papers met the inclusion criteria, of which 28 reported on prognostic novel markers and five on prognostic models. A total of 21 novel markers were identified from the 28 novel marker studies. There was considerable variability in the results reported, the quality of the studies was generally poor and there was a shortage of studies in some categories. The marker with the strongest evidence for its prognostic significance was prostate-specific antigen (PSA) velocity (or doubling time). There was a particularly strong association between PSA velocity and prostate cancer death in both clinical and pathological models. In the clinical model the hazard ratio for death from prostate cancer was 9.8 (95% CI 2.8-34.3, p < 0.001) in men with an annual PSA velocity of more than 2 ng/ml versus an annual PSA velocity of 2 ng/ml or less; similarly, the hazard ratio was 12.8 (95% CI 3.7-43.7, p < 0.001) in the pathological model. The quality of the prognostic model studies was adequate and overall better than the quality of the prognostic marker studies. Two issues were poorly dealt with in most or all of the prognostic model studies: inclusion of established markers and consideration of the possible biases from study attrition. Given the heterogeneity of the models, they cannot be considered comparable. Only two models did not include a novel marker, and one of these included several demographic and co-morbidity variables to predict all-cause mortality. Only two models reported a measure of model performance, the C-statistic, and for neither was it calculated in an external data set. It was not possible to assess whether the models that included novel markers performed better than those without. CONCLUSIONS: This review highlighted the poor quality and heterogeneity of studies, which render much of the results inconclusive. It also pinpointed the small proportion of models reported in the literature that are based on patient cohorts with a mean or median follow-up of at least 5 years, thus making long-term predictions unreliable. PSA velocity, however, stood out in terms of the strength of the evidence supporting its prognostic value and the relatively high hazard ratios. There is great interest in PSA velocity as a monitoring tool for active surveillance but there is as yet no consensus on how it should be used and, in particular, what threshold should indicate the need for radical treatment.
    • Use of CMV unselected blood products does not increase the risk of CMV reactivation in patients undergoing hematopoetic stem cell transplant (HSCT).

      Peters, Jayne; Elliott, Jonathon; Bloor, Adrian; Dennis, Michael; Murray, John; Cavet, James; Somervaille, Tim C P; Sommerfeld, Sven A; Mutton, Ken; Mamat, Mohd K; et al. (2015)
    • The use of combined radial forearm cutaneous and radial forearm fascial flaps in head and neck reconstruction: a case series.

      Bondin, Daniela; Smith, Oliver J; Ross, Gary L; Department of Plastic Surgery, The Christie Hospital, NHS Foundation Trust, Manchester, United Kingdom. (2012-10)
      Introduction Reconstruction of complex head and neck cases involving bony and dural defects poses many issues. The primary aims of reconstruction are to provide a tight dural seal with good cranial support while also achieving a satisfactory cosmetic result.Aims This study describes the use of combined radial forearm cutaneous flap and radial forearm fascial flaps for reconstruction of complex skull defects where each component is used for a distinct reconstructive purpose. The benefits of this technique are illustrated in the cases of three patients requiring reconstruction following tumor resection.Methods The fascial component was used as a seal for dural defects. The cutaneous flap was then used to reconstruct the concomitant cutaneous defect.Conclusion The combined use of the fascial and cutaneous components of the radial forearm flap, where each is used for a distinct reconstructive purpose, increased the reconstructive versatility of this commonly used flap. The fascial flap was a thin, pliable, and highly vascularized piece of tissue that was effectively used to provide a watertight seal for the dural defect. The simultaneous use of the cutaneous flap gave support to the bony defect while providing a good cosmetic result.
    • The use of computed radiography for routine linear accelerator and simulator quality control.

      Patel, I; Natarajan, T; Hassan, S S; Kirby, Mike C; North Western Medical Physics, Radiotherapy Department, Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK. imran.patel@lthtr.nhs.uk (2009-10)
      Computed radiography (CR) systems were originally developed for the purpose of clinical imaging, and there has been much work published on its effectiveness as a film replacement for this end. However, there has been little published on its use for routine linear accelerator and simulator quality control, and therefore we have evaluated the use of the Kodak 2000RT system with large Agfa CR plates as a replacement for film for this function. A prerequisite for any such use is a detailed understanding of the system behaviour, hence characteristics such as spatial uniformity of response, reproducibility of spatial accuracy, plate signal decay with time and the dose-response of plates were investigated. Finally, a comparison of results obtained using CR for the measurement of radiation field dimensions was made against those from radiographic film, and found to be in agreement within 0.1 mm (mean difference for high-resolution images, 0.3 mm root mean square difference) for megavoltage images and 0.3 mm (maximum difference) for simulator images. In conclusion, the CR system has been shown to be a good alternative to radiographic film for routine quality control of linear accelerators and simulators.
    • Use of cone beam CT in children and young people in three United Kingdom dental hospitals

      Hidalgo-Rivas, J; Theodorakou, Chrysoula; Carmichael, F; Murray, B; Payne, M; Horner, K (2014)
    • The use of cryopreserved lymphocytes in assessing inter-individual radiosensitivity with the micronucleus assay.

      Burrill, W; Levine, Edward; Hindocha, P; Roberts, Stephen A; Scott, David; CRC Section of Molecular Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK. (2000-03)
      PURPOSE: The feasibility of using cryopreserved lymphocytes to detect inter-individual differences in chromosomal radiosensitivity was investigated. Typically, such studies are conducted with fresh blood samples but, in a clinical setting, when availability of samples is unpredictable, this is not always convenient. The sensitivity of 23 normal healthy donors, 11 breast cancer patients who had shown severe acute skin reactions to radiotherapy and seven ataxia telangiectasia (A-T) heterozygotes was determined. MATERIALS AND METHODS: Thawed lymphocytes were exposed to high (HDR) or low dose rate (LDR) gamma irradiation (3.5 Gy) in Go, stimulated with PHA, treated with cytochalasin-B 24 h later and then harvested at 90 h for the determination of micronucleus (MN) yields in binucleate cells. RESULTS: Each normal donor was tested one to three times. Mean MN yields were 76.1 +/- 9.3/100 cells at HDR and 44.5 +/- 5.3 at LDR, giving an LDR sparing effect of 39.6 +/- 9.3%. A relatively high proportion of tests failed to yield sufficient binucleate cells for analysis. Inter-experimental variability was also high and it was not possible to demonstrate inter-individual differences in sensitivity in spite of the use of an internal control sample from a single normal donor in each experiment. There was a small but significant increase in radiation-induced MN in the breast cancer patients compared with the normals at LDR (but not at HDR), but a complete overlap with the normal range. There was no increase in sensitivity in the A-T heterozygotes at HDR. The LDR samples failed because the LDR protocol reduced proliferation rates, and radiation-induced mitotic inhibition in this group was higher than in normals. CONCLUSIONS: In comparison with previous experience with fresh blood samples, the use of frozen lymphocytes is not as satisfactory because: (1) experimental failures are higher; (2) inter-experiment variability is higher: (3) dose-rate sparing is lower, suggesting poorer repair; and (4) the ability to discriminate between breast cancer cases and normals is probably lower.
    • The use of cultured bone marrow cells for autologous transplantation in patients with acute myeloblastic leukemia.

      Testa, Nydia G; Coutinho, Lucia H; Chang, James; Morgenstern, Godfrey R; Scarffe, J Howard; Dexter, T Michael; Department of Experimental Haematology, Paterson Laboratories, Manchester, England. (1987)
    • Use of cytology to diagnose inherited breast cancer

      Moller, Pal; Evans, D Gareth R; Anderson, Elaine; Maehle, Lovise; Lalloo, Fiona; Heimdal, Ketil; Steel, C Michael; Unit of Medical Genetics, The Norwegian Radium Hospital, Norway (1999)
    • The use of deformable image registration to integrate diagnostic MRI into the radiotherapy planning pathway for head and neck cancer.

      Chuter, Robert; Prestwich, R; Bird, D; Scarsbrook, A; Sykes, J; Wilson, D; Speight, R; Medical Physics and Engineering, Bexley Wing, St. James's University Hospital, Leeds Teaching Hospitals Trust, United Kingdom (2016-08-03)
      To assess the accuracy of gross tumour volume (GTV) delineation for head and neck squamous cell carcinoma (HNSCC) using a diagnostic position MRI (MRI-D) deformably registered to the planning CT (pCT), by comparison with a dedicated planning position MRI (MRI-RT).
    • The use of effervescent agents in the small bowel meal examination.

      Griffiths, P D; Hufton, Alan P; Martin, D F; Department of Radiology, Withington Hospital, University Hospital of South Manchester. (1993-10)
      Some perceived disadvantages of the small bowel meal examination are failure of adequate distension, lack of a double contrast effect and the duration of the procedure. A new use for effervescent granules during the small bowel meal is described which reduces the examination time by 70% and reduces the radiation dose to the patient.
    • Use of electronic portal imaging to assess cardiac irradiation in breast radiotherapy.

      Magee, Brian; Coyle, C A; Kirby, Mike C; Kane, B; Williams, Peter C; Christie Hospital, Manchester, UK. (1997)
      An audit was performed to assess the frequency of cardiac irradiation in patients receiving radiotherapy for left-sided breast cancer. Images from an 'online' electronic portal imaging device were reviewed in patients who were treated with a tangential pair of megavoltage fields. In 169 consecutive patients treated on a Philips SL25 6 MV linear accelerator equipped with an SRI 100 imaging device, the cardiac apex was included in the radiotherapy field in 15 patients (9%). The long term sequelae of such cardiac irradiation is uncertain. The results of this audit suggest that careful treatment technique and quality control with portal imaging can minimize unnecessary cardiac irradiation in the majority of patients.
    • 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.

      Gomes, Fabio; Faivre-Finn, Corinne; Fernandez-Gutierrez, Fabiola; Ryder, W David J; Bezjak, A; Cardenal, F; Fournel, P; Van Meerbeeck, J; Blackhall, Fiona H; Medical Oncology, The Christie NHS Foundation Trust, Manchester (2017-04)
    • Use of G-CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial.

      Sheikh, Hamid Y; Colaco, Rovel J; Lorigan, Paul C; Blackhall, Fiona H; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nick; Faivre-Finn, Corinne; Dept of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2011-10)
      There is paucity of data in the literature regarding the safety of combining granulocyte colony stimulating factor (G-CSF) during chemo-radiotherapy (CTRT) in lung cancer patients. The ASCO 2006 recommendations advise against use of CSFs during concomitant mediastinal CTRT. The only randomised study evaluating CSFs in this context showed significant increase in grade 3/4 thrombocytopenia and an excess of pulmonary toxic deaths. In the context of a phase II trial, 38 patients with limited-stage small cell lung cancer were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy. Radiotherapy (RT) was given concurrently with cisplatin and etoposide. G-CSF was given as primary or secondary prophylaxis or as a therapeutic measure during an episode of febrile neutropenia according to local protocols. Common terminology criteria for adverse events (CTCAE) v3.0 was used to record toxicity. Thirteen (34%) of 38 patients received G-CSF concurrently with RT. With a median follow-up of 16.9 months, there were no treatment related deaths reported. Seven (54%) patients experienced grade 3/4 thrombocytopenia and 5 (38%) experienced grade 3/4 anaemia. Thirty-one percent required platelet transfusions. No episodes of bleeding were observed. There were no cases of grade 3/4 acute pneumonitis. These data suggests that with modern three-dimensional (3D) conformal RT, G-CSF administration concurrently with CTRT does not result in the increase risk of pulmonary toxicity, but does increase the risk of thrombocytopenia. Whether the risks of thrombocytopenia are outweighed by the outcome of timely early concurrent CTRT is being evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563) in which G-CSF is permitted during thoracic irradiation.