• Optimizing sharing of hospital biobank samples.

      Riegman, P; de Jong, B; Daidone, M; Söderström, T; Thompson, J; Hall, J; Mendy, M; Ten Hoeve, J; Broeks, A; Reed, W; et al. (2015-07-22)
      Implementing technical guidelines and standards as well as ways to boost cooperation should facilitate sharing of hospital biobank samples.
    • Optimizing the indexing of a resolution-enhancing tertiary collimator for radiotherapy.

      Cooper, Phillip A; Mackay, Ranald I; Williams, Peter C; North Western Medical Physics, Christie Hospital NHS Trust, Manchester, UK. phill.cooper@physics.cr.man.ac.uk (2001-12)
      A method for improving the resolution of multileaf collimator (MLC) defined radiotherapy fields using a tertiary, slotted grid collimator has been investigated and developed further. The original concept was for each slot to be aligned with each leaf pair of opposing MLC leaves. The total treated area is composed of a series of sub-fields, a pattern of irradiated strips, with the width of each strip defined by the width of the slot and the length by the relative separation of the MLC leaf pair. To complete the field, the patient must be indexed relative to the collimator, with the number of sub-fields required determined by the width of the slots and the spacing between them. Two methods were considered by which this indexing could be achieved: movement of the patient while holding the tertiary collimator fixed, or rotating the grid with the point of rotation defined as the radiation source. Consideration of the movement resolution and precision required for the patient support system for non-cardinal gantry, collimator and table angles cast doubt on the practicality of the use of such a strategy. To assess the effect of divergence on the abutting sub-fields, measurements were also performed to assess the uniformity of single fields generated by the tertiary collimator in planes above and below the isocentre using both methods of indexing. As expected, rotation of the collimator resulted in a similar degree of non-uniformity for any plane chosen, whereas significant dose heterogeneities were introduced to treatment planes within 5 cm above and below the isocentre if the patient support system was used. Therefore, the rotation strategy will be implemented with all future versions of the device.
    • Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.

      Cunningham, D; Dicato, M; Verweij, J; Crombez, R; De Mulder, P; Du Bois, A; Stewart, Alan L; Smyth, J; Selby, P; Van Straelen, D; et al. (1996-03)
      BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.
    • The optimum dosage in the treatment of cCarcinoma of the uterine cervix by radiation.

      Tod, Margaret C; Christie Hospital and the Holt Radium Institute, Manchester (1941-01)
    • Options for first- and second-line therapy in small cell lung cancer--a workshop discussion.

      Thatcher, Nick; Eckardt, John; Green, Mark; University of Manchester and Christie Hospital, Manchester, UK. (2003-08)
      In a case study-based workshop, physicians were asked to discuss various aspects of patient management in small cell lung cancer (SCLC). For first-line chemotherapy, most investigators recommended treatment with etoposide/cisplatin, with possible dosing variations according to tolerability and convenience. In France (but not elsewhere), medical oncologists tend to use a four-drug regimen (etoposide/cisplatin/cyclophosphamide/epirubicin), based on the results of an extensive-stage SCLC trial. Alternative first-line regimens, such as vincristine/ifosfamide/carboplatin/etoposide (VICE) and topotecan/platinum, are currently being explored. Options for therapy in patients with recurrent disease are more varied, although there was consensus that active treatment at relapse should be considered. Regimens include topotecan (alone or in combination), cyclophosphamide/doxorubicin/vincristine (CAV) and re-induction with the earlier first-line agents. Studies are also investigating the potential benefits of other combinations, including topotecan/vinorelbine and paclitaxel/carboplatin. For patients with relapsed extensive-stage SCLC and brain metastases, whole brain radiation therapy was considered appropriate for both palliative and therapeutic reasons. The potential role of combination therapy with topotecan/temozolomide, both of which cross the blood-brain barrier, is currently being investigated.
    • Opto-electronic sensing of body surface topology changes during radiotherapy for rectal cancer.

      Moore, Christopher J; Lilley, Francis; Sauret, Veronique; Lalor, Michael; Burton, David R; North Western Medical Physics, Christie Hospital NHS Trust, Manchester, United Kingdom. chris.moore@physics.cr.man.ac.uk (2003-05-01)
      PURPOSE: The CT body surface underpins millimeter scale dose computation in radical radiotherapy. A lack of technology has prevented measurement of surface topology changes during irradiation. Consequently, body changes are incorporated into plans statistically. We describe the technology for dynamic measurement of continuous surface topology at submillimeter resolution and suggest appropriately modified planning. MATERIALS AND METHODS: An interferometer casts cosinusoidal fringes across the surface of a patient on a treatment couch. Motion-induced changes to the spatial phase of the fringes are used to generate dynamic sequences of body height maps. Volume-conserving CT warping, guided by height change, is used to illustrate potential planning perturbations. RESULTS: We present the results for a prone patient with rectal carcinoma. At most of the simultaneously measured 440 x 440 points in each of the 898 body height maps in a dynamic sequence, the standard deviations were <1-2 mm, with occasional points of 6 mm. Surface motion predominantly occurred along the small of the back. This motion was periodic and could take the spine and bladder across the 95% isodose contour. CONCLUSIONS: Surface changes are most likely to be within 3 mm during irradiation, despite the effects of breathing and the discomfort of lying prone. The dosimetric effects are acceptable.
    • ORACULUM: A retrospective observational epidemiological study using artificial intelligence and natural language processing in electronic health records to characterize the prostate cancer pathway, management and outcomes in Europe, Middle East and Africa (EMEA region)

      Carles, J.; Alcaraz, A.; Clarke, Noel W; Conde, A.; Heidenreich, A.; Juarez, A.; Rey, J. P. M.; Puente, J.; Hernandez-Medrano, I.; Salcedo, I.; et al. (2020)
      Background: In Prostate Cancer, there is a need for real-world clinical practice data given the high prevalence and incidence of the disease and the rapid changes in treatment options and diagnosis over recent years. Prostate cancer is a scenario in which ‘Big Data’ is particularly applicable because patients have a long disease course,included in clinical records from thousands of patients and translate these into hundreds of variables. ORACULUM uses EHR population-based data since January 2014, to more accurately describe the epidemiology, diagnosis, management, outcomes, prognostic and predictive factors of response of Prostate Cancer (PCa) patients, across all disease stages. ORACULUM may also provide potential correlations that could have remained hidden so far in the existing literature. Here we describe the methodology for data collection and privacy. generating an immense amount of data. The outcomes would improve our understanding of the potential implication of different diagnostic /treatment approaches in the different profile of patients suffering from this serious disease in clinical practice. The result of this analysis could also inform the scientific community on new hypothesis for future clinical studies. Trial design: ORACULUM is a multi-country, multi-centre, Artificial Intelligence driven, retrospective, observational study analysing deidentified and aggregated information from original EHRs, in four languages (Spanish, English, French and German). ORACULUM uses SAVANA’s EHRead technology, an innovative data-driven system that applies Artificial Intelligence and Natural Language Program techniques. SAVANA software is able to meaningfully interpret physician notes and numerical values
    • Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial.

      Anderson, Heather; Scarffe, J Howard; Sutton, R N; Hickmott, E; Brigden, D; Burke, C; The Department of Medical Oncology, Christie Hospital and Holt Radium Institute (1984-07)
      Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).
    • Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial.

      Scheithauer, W; McKendrik, J; Begbie, S; Borner, M; Burns, W I; Burris, H A; Cassidy, J; Jodrell, D; Koralewski, P; Levine, Edward; et al. (2003-12)
      BACKGROUND: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. PATIENTS AND METHODS: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m(2) twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m(2) with i.v. leucovorin 20 mg/m(2) on days 1-5, repeated every 28 days (n = 974). RESULTS: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or > or = 65 years old. CONCLUSIONS: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cancer
    • Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast.

      Williams, Gerard; Anderson, Elizabeth; Howell, Anthony; Watson, R; Coyne, J; Roberts, Stephen A; Potten, Christopher S; Department of Clinical Research, Christie Hospital, Manchester, UK. (1991-05-10)
      The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.
    • Oral melphalan as a treatment for platinum-resistant ovarian cancer.

      Hasan, Jurjees; Jayson, Gordon C; Cancer Research UK, Department of Medical Oncology, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK. JurjeesH@aol.com (2003-06-16)
      A large number of drugs have been used to treat recurrent ovarian cancer, yet there are few data that guide the physician's choice. Typically, the decision to re-treat with platinum-based therapy depends on the progression-free interval. However, the optimum agent for the treatment of platinum-resistant or refractory disease is not defined. In this study, we investigated the efficacy of oral melphalan in patients who have platinum refractory or resistant disease. A retrospective analysis was performed on 22 patients with ovarian carcinomas who had relapsed within 6 months of their platinum-based chemotherapy and were treated with oral melphalan. No objective responses were seen and the median overall survival was 3 months from commencement of therapy. Although the treatment was generally well tolerated, only two of the 22 patients managed to complete the planned six cycles of treatment. At the time of analysis, only two patients were alive. Other nonplatinum compounds have demonstrated response rates in the region of 20% in similar patient populations and it is unlikely that any positive responses could have been missed by chance (95% CI 0-15.4). The results of this study serve to eliminate oral melphalan as a treatment option in patients with platinum-resistant or refractory ovarian carcinoma.
    • Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial.

      Tutt, Andrew; Robson, Mark; Garber, Judy E; Domchek, Susan M; Audeh, M William; Weitzel, Jeffrey N; Friedlander, Michael; Arun, Banu; Loman, Niklas; Schmutzler, Rita K; et al. (2010-07-24)
      BACKGROUND: Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer. METHODS: Women (aged >or=18 years) with confirmed BRCA1 or BRCA2 mutations and recurrent, advanced breast cancer were assigned to two sequential cohorts in a phase 2 study undertaken in 16 centres in Australia, Germany, Spain, Sweden, the UK, and the USA. The first cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lower dose (100 mg twice daily). The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494234. FINDINGS: Patients had been given a median of three previous chemotherapy regimens (range 1-5 in cohort 1, and 2-4 in cohort 2). ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort assigned to 100 mg twice daily. Toxicities were mainly at low grades. The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, 11 [41%]; none grade 3 or 4) and fatigue (grade 1 or 2, seven [26%]; grade 3 or 4, one [4%]). INTERPRETATION: The results of this study provide positive proof of concept for PARP inhibition in BRCA-deficient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1-associated or BRCA2-associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations. FUNDING: AstraZeneca.
    • Oral vinorelbine: a narrative review

      Farrell, Carole; Harmer, Victoria; The Christie NHS Foundation Trust, Manchester (2018)
    • Orchestrating timely check cystoscopy after radical radiotherapy to the bladder

      Walshaw, Richard; Taylor, J; Warburton, H; Oates, J; Hussain, J; Keegan; Burke, D; German, A; Elliott, Tony; Clinical Oncology, The Christie NHS Foundation Trust, Manchester (2016)
    • Organ preservation in bladder cancer: an opportunity for truly personalized treatment

      Song, Yee Pei; McWilliam, Alan; Hoskin, Peter J; Choudhury, Ananya; Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK (2019)
      Radical treatment of many solid tumours has moved from surgery to multimodal organ preservation strategies combining systemic and local treatments. Trimodality bladder-preserving treatment (TMT) comprises maximal transurethral resection of the bladder tumour followed by radiotherapy and concurrent radiosensitizing treatment, thereby sparing the urinary bladder. From the patient's perspective, the choice of maintaining quality of life without a negative effect on the chances of cure and long-term survival is attractive. In muscle-invasive bladder cancer (MIBC), the evidence shows comparable clinical outcomes between patients undergoing radical cystectomy and TMT. Despite this evidence, many patients continue to be offered radical surgery as the standard-of-care treatment. Improvements in radiotherapy techniques with adaptive radiotherapy and advances in imaging translate to increases in the accuracy of treatment delivery and reductions in long-term toxicities. With the advent of novel biomarkers promising improved prediction of treatment response, stratification of patients for different treatments on the basis of tumour biology could soon be a reality. The future of oncological treatment lies in personalized medicine with the combination of technological and biological advances leading to truly bespoke management for patients with MIBC.
    • Organ-specific SPECT activity calibration using 3D printed phantoms for molecular radiotherapy dosimetry.

      Robinson, A; Tipping, Jill; Cullen, D; Hamilton, David; Brown, R; Flynn, A; Oldfield, C; Page, Emma; Price, E; Smith, A; et al. (2016-12)
      Patient-specific absorbed dose calculations for molecular radiotherapy require accurate activity quantification. This is commonly derived from Single-Photon Emission Computed Tomography (SPECT) imaging using a calibration factor relating detected counts to known activity in a phantom insert.
    • Organisation of prostate cancer services in the English National Health Service.

      Aggarwal, A; Nossiter, J; Cathcart, P; van der Meulen, J; Rashbass, J; Clarke, N; Payne, H; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK (2016-03)
    • The origin of the bone scan as a tumour marker in prostate cancer.

      Clarke, Noel W; Hope and Christie Hospitals, Manchester, UK (2006-11)
    • Origins of breast cancer subtypes and therapeutic implications.

      Sims, Andrew H; Howell, Anthony; Howell, Sacha J; Clarke, Robert B; Breast Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK. (2007-09)
      This Review summarizes and evaluates the current evidence for the cellular origins of breast cancer subtypes identified by different approaches such as histology, molecular pathology, genetic and gene-expression analysis. Emerging knowledge of the normal breast cell types has led to the hypothesis that the subtypes of breast cancer might arise from mutations or genetic rearrangements occurring in different populations of stem cells and progenitor cells. We describe the common distinguishing features of these breast cancer subtypes and explain how these features relate both to prognosis and to selection of the most appropriate therapy. Recent data indicate that breast tumors may originate from cancer stem cells. Consequently, inhibition of stem-cell self-renewal pathways should be explored because of the likelihood that residual stem cells might be resistant to current therapies.