• Dacarbazine and interferon-alpha 2a in advanced malignant melanoma: high response rate and prolongation of response duration occur in different patient subpopulations.

      Betticher, Daniel C; Lee, Siow Ming; Morris, C; Clemons, Mark; Thatcher, Nick; CRC Department of Medical Oncology, Christie Hospital, Manchester, UK. (1995-08)
      Fifty-three evaluable patients with metastatic malignant melanoma were enrolled in a phase II prospective study designed to assess the response rate, time to progression and survival after dacarbazine (DTIC) and interferon-alpha 2a (IFN-alpha 2a) treatment in patients with local metastatic disease compared with patients with distant metastases. Patients received intravenous DTIC from day 1 at a dosage of 400-500 mg/m2, repeated every 21 days (in the case of good tolerance--25 patients--the dose was increased to 600-800 mg/m2) combined with subcutaneous IFN-alpha 2a (9 x 10(6) U three times/week, increased in the case of good tolerance to 15 x 10(6) U three times/week). Forty-two patients with distant metastases were compared with 11 patients who had local metastatic disease. Three complete (6%) and six partial (11%) responses were seen, with an overall response rate of 17% (95% confidence interval 8-29). Patients with local metastases had a higher response rate (50%) compared with patients with distant metastases (visceral involvement, mediastinal and para-aortic lymph node metastases) (10%; p = 0.01). The median overall survival was 4.5 months. The progression-free interval for responders with distant metastases was significantly longer (11 months), than for responders with local metastases (4.5 months) (p = 0.004). These results may suggest that the combination treatment DTIC/IFN-alpha has a greater benefit in terms of longer progression-free interval in responders with distant metastases.
    • Daily D-T neutron irradiation of mouse intestine.

      Hendry, Jolyon H; Major, D; Greene, D; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (1975-07)
    • Daily monitoring of linear accelerator beam parameters using an amorphous silicon EPID.

      Budgell, Geoff J; Zhang, R; Mackay, Ranald I; North Western Medical Physics, Christie Hospital NHS Trust, Withington, Manchester, M20 4BX, UK. (2007-03-21)
      An amorphous silicon EPID has been investigated to test its suitability as a daily check device for linac output and to provide daily monitoring of beam profile parameters such as flatness, symmetry, field size and wedge factor. Open and wedged 6 and 8 MV photon beams were collected on a daily basis for a period of just over a year and analysed in software to determine daily values of these parameters. Daily output results gave agreement between EPID measured dose and ion chamber measurements with a standard deviation of 0.65%. Step changes in flatness, symmetry and field size were readily detected by the EPID and could be correlated with adjustments made on service days and QC sessions. The results could also be used to assess the long term beam stability. Recalibration of the EPID required new baseline values of the parameters to be set. Wedge factors measured at one collimator angle proved stable but sensitive to changes in beam steering. The EPID proved to be a useful daily check device for linac output which can simultaneously be used for daily monitoring of beam profiles and field sizes.
    • The dark side of T1 non-appendiceal small bowel neuroendocrine tumours.

      Salih, Zena; Lamarca, Angela; Nonaka, Daisuke; Hubner, Richard A; de Liguori-Carino, N; McNamara, Mairéad G; Fulford, Paul E; Minicozzi, Annamaria; O'Dwyer, Sarah T; Chakrabarty, Bipasha; et al. (2017-05-09)
    • Data mining identifies the base of the heart as a dose-sensitive region affecting survival in lung cancer patients.

      McWilliam, Alan; Faivre-Finn, Corinne; Kennedy, Jason; Kershaw, Lucy E; van Herk, Marcel; The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester (2016-10)
    • Data mining in oncology: The UKCAT project and the practicalities of working with routine patient data.

      Price, Gareth J; van Herk, Marcel; Faivre-Finn, Corinne; The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK (2017-08-03)
    • A data science approach for early-stage prediction of Patient's susceptibility to acute side effects of advanced radiotherapy

      Aldraimli, M.; Soria, D.; Grishchuck, D.; Ingram, Samuel; Lyon, R.; Mistry, A.; Oliveira, J.; Samuel, R.; Shelley, L. E. A.; Osman, S.; et al. (2021)
      The prediction by classification of side effects incidence in a given medical treatment is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of such algorithms is to use several features to predict dichotomous responses (e.g., disease positive/negative). Similar to statistical inference modelling, ML modelling is subject to the class imbalance problem and is affected by the majority class, increasing the false-negative rate. In this study, seventy-nine ML models were built and evaluated to classify approximately 2000 participants from 26 hospitals in eight different countries into two groups of radiotherapy (RT) side effects incidence based on recorded observations from the international study of RT related toxicity "REQUITE". We also examined the effect of sampling techniques and cost-sensitive learning methods on the models when dealing with class imbalance. The combinations of such techniques used had a significant impact on the classification. They resulted in an improvement in incidence status prediction by shifting classifiers' attention to the minority group. The best classification model for RT acute toxicity prediction was identified based on domain experts' success criteria. The Area Under Receiver Operator Characteristic curve of the models tested with an isolated dataset ranged from 0.50 to 0.77. The scale of improved results is promising and will guide further development of models to predict RT acute toxicities. One model was optimised and found to be beneficial to identify patients who are at risk of developing acute RT early-stage toxicities as a result of undergoing breast RT ensuring relevant treatment interventions can be appropriately targeted. The design of the approach presented in this paper resulted in producing a preclinical-valid prediction model. The study was developed by a multi-disciplinary collaboration of data scientists, medical physicists, oncologists and surgeons in the UK Radiotherapy Machine Learning Network.
    • Data set for the reporting of carcinoma of the renal pelvis and ureter-nephroureterectomy and ureterectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR)

      Samaratunga, H; Judge, M; Delahunt, B; Srigley, J; Brimo, F; Comperat, E; Koch, M; Lopez-Beltran, A; Reuter, V; Shanks, Jonathan H; et al. (2019)
      Cancer reporting guidelines have been developed and utilized in many countries throughout the world. The International Collaboration on Cancer Reporting (ICCR), through an alliance of colleges and other pathology organizations in Australasia, United Kingdom, Ireland, Europe, USA, and Canada, has developed comprehensive standardized data sets to provide for global usage and promote uniformity in cancer reporting. Structured reporting facilitates provision of all necessary information, which ensures accurate and comprehensive data collection, with the ultimate aim of improving cancer diagnostics and treatment. The data set for primary carcinoma of the renal pelvis and ureter treated with nephroureterectomy or ureterectomy had input from an expert panel of international uropathologists. This data set was based on current evidence-based practice and incorporated information from the 2016 fourth edition of the World Health Organization (WHO) Bluebook on tumors of the urinary and male genital systems and the 2017 American Joint Committee on Cancer (AJCC) TNM staging eighth edition. This protocol applies to both noninvasive and invasive carcinomas in these locations. Reporting elements are considered to be essential (required) or nonessential (recommended). Required elements include operative procedure, specimens submitted, tumor location, focality and size, histologic tumor type, subtype/variant of urothelial carcinoma, WHO grade, extent of invasion, presence or absence of vascular invasion, status of the resection margins and lymph nodes and pathologic stage. The data set provides a detailed template for the collection of data and it is anticipated that this will facilitate appropriate patient management with the potential to foster collaborative research internationally.
    • Data-driven mapping of hypoxia-related tumor heterogeneity using DCE-MRI and OE-MRI.

      Featherstone, Adam K; O'Connor, James P B; Little, R; Watson, Y; Cheung, S; Babur, M; Williams, Kaye J; Matthews, Julian C; Parker, Geoff J M; Division of Informatics, Imaging & Data Sciences, The University of Manchester, Manchester, UK (2017-08-30)
      Previous work has shown that combining dynamic contrast-enhanced (DCE)-MRI and oxygen-enhanced (OE)-MRI binary enhancement maps can identify tumor hypoxia. The current work proposes a novel, data-driven method for mapping tissue oxygenation and perfusion heterogeneity, based on clustering DCE/OE-MRI data.
    • A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases.

      Pathak, Ryan; Ragheb, Hossein; Thacker, Neil A; Morris, D; Amiri, H; Kuijer, J; deSouza, N; Heerschap, A; Jackson, Alan; University of Manchester, Wolfson Molecular Imaging Centre, Manchester (2017-10-26)
      Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observed ADC is then standardised against this estimation of uncertainty for any given measurement. 20 patients were recruited prospectively and equitably across 4 sites, and scanned twice (test-retest) within 7 days. Repeatability measurements of defined regions (ROIs) of tumour and normal tissue were quantified as percentage change in mean ADC (test vs. re-test) and then standardised against an estimation of uncertainty. Multi-site reproducibility, (quantified as width of the 95% confidence bound between the lower confidence interval and higher confidence interval for all repeatability measurements), was compared before and after standardisation to the model. The 95% confidence interval width used to determine a statistically significant change reduced from 21.1 to 2.7% after standardisation. Small tumour volumes and respiratory motion were found to be important contributors to poor reproducibility. A look up chart has been provided for investigators who would like to estimate uncertainty from statistical error on individual ADC measurements.
    • Dataset for reporting of carcinoma of the urethra (in urethrectomy specimens): recommendations from the International Collaboration on Cancer Reporting (ICCR)

      Shanks, Jonathan H; Srigley, J; Brimo, F; Comperat, E; Delahunt, B; Koch, M; Lopez-Beltran, A; Reuter, V; Samaratunga, H; Tsuzuki, T; et al. (2019)
      AIMS: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organisation sponsored by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists in association with the Canadian Partnership Against Cancer, the European Society of Pathology, the American Society of Clinical Pathology and the Faculty of Pathology, Royal College of Physicians of Ireland. Its goal is to produce standardized, internationally agreed upon, evidence-based datasets for cancer pathology reporting throughout the world. METHODS AND RESULTS: This paper describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of carcinoma of the urethra in urethrectomy specimens. The dataset is composed of 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are based on a review of the most recent evidence and supported by explanatory commentary. Fourteen required elements and eight recommended elements were agreed by the international dataset authoring committee to represent the essential/required (core) and recommended (non-core) information for the reporting of carcinoma of the urethra in urethrectomy specimens. CONCLUSIONS: Use of an internationally agreed, structured pathology dataset for reporting carcinoma of the urethra (in urethrectomy specimens) will provide the necessary information for optimal patient management, will facilitate consistent data collection, and will provide valuable data for research and international benchmarking. The dataset will be valuable for those countries and institutions that are not in a position to develop their own datasets. This article is protected by copyright. All rights reserved.
    • Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR)

      Comperat, E; Srigley, JR; Brimo, F; Delahunt, B; Koch, M; Lopez-Beltran, A; Reuter, V; Samaratunga, H; Shanks, Jonathan H; Tsuzuki, T; et al. (2020)
      The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.
    • Dataset for the reporting of urinary tract carcinoma-biopsy and transurethral resection specimen: recommendations from the International Collaboration on Cancer Reporting (ICCR)

      Varma, M; Srigley, JR; Brimo, F; Comperat, E; Delahunt, B; Koch, M; Lopez-Beltran, A; Reuter, V; Samaratunga, H; Shanks, Jonathan H; et al. (2019)
      The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.
    • The dawn of another new era

      Choudhury, Ananya; Division of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK. (2021)
    • Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study.

      Gilham, C; Peto, J; Simpson, J; Roman, E; Eden, Tim O B; Greaves, M; Alexander, F E; Cancer Research UK Epidemiology and Genetics Unit, Institute of Cancer Research, Sutton SM2 5NG. (2005-06-04)
      OBJECTIVE: To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK. PARTICIPANTS: 6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL). MAIN OUTCOME MEASURE: Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy. RESULTS: Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years. CONCLUSION: These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.
    • Dealing with loss: food and eating in women with ovarian cancer on parenteral nutrition

      Sowerbutts, AM; Lal, S; Sremanakova, J; Clamp, Andrew R; Jayson, Gordon C; Hardy, L; Sutton, E; Raftery, Anne-Marie; Teubner, A; Burden,S; et al. (2020)
      BACKGROUND: Malignant bowel obstruction is a common complication of ovarian cancer, resulting in limited oral intake. Home parenteral nutrition (HPN) may be offered to patients in this condition to meet nutritional requirements. However, it is not known how they experience being unable to eat. The present study reports how patients related to food when receiving HPN. METHODS: The investigation was a qualitative study underpinned by phenomenology with women with advanced ovarian cancer in bowel obstruction receiving parenteral nutrition. Interview transcripts were analysed thematically guided by the techniques of Van Manen. RESULTS: We recruited 20 women to the study. Participants were interviewed a maximum of four times and a total of 39 in-depth longitudinal interviews were conducted. Participants could tolerate minimal amounts of food, if they had a venting gastrostomy. Not being able to eat engendered a sense of sadness and loss, and most women found it challenging to be in the presence of others eating. They adopted strategies to cope, which included fantasising about food and watching cookery programmes. These approaches were not a long-term solution; either participants came to terms with their loss or the strategies became less effective in providing relief. CONCLUSIONS: Home parenteral nutrition meets the nutritional requirements of patients with malignant bowel obstruction but cannot replace the non-nutritive functions of food. Healthcare professionals can offer a patient-centred approach by acknowledging the difficulties that patients may face and, wherever possible, encourage them to focus on the positive benefits of interacting with people rather than the loss of eating on social occasions.
    • Deciphering driver mechanisms for tumorigenesis in BRAF/NRAS double wild-type melanoma through integration of heterogeneous genome-wide datasets

      Mandal, Amit Kumar; Girotti, Maria Romina; Viros, Amaya; Gremel, Gabriela; Galvani, Elena; Lee, Rebecca J; Lim, Kok Haw Jonathan; Furney, Simon J; Lorigan, Paul C; Marais, Richard; et al. (2015)
    • A decision tool for whole-body CT in major trauma that safely reduces unnecessary scanning and associated radiation risks: An initial exploratory analysis.

      Davies, R; Scrimshire, A; Sweetman, Lorna; Anderton, M; Holt, E; Department of Orthopaedics, University Hospital of South Manchester, Southmoor Road, Wythenshawe M239LT, United Kingdom (2015-09-01)
      Whole-body CT (WBCT) has become routine practice in the assessment of major trauma patients. Whilst this may be associated with increased survival, several studies report high rates of negative scans. As no national guideline exists, selection criteria for WBCT vary widely. This study aims to (1) produce a scoring system that improves patient selection for WBCT (2) quantify patient radiation doses and their concomitant risk of malignancy.
    • Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer.

      Grunnet, M; Christensen, I; Lassen, U; Jensen, L; Lydolph, M; Knox, J; McNamara, Mairéad G; Jitlal, M; Wasan, H; Bridgewater, J; et al. (2015-07)
      Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer.
    • Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis

      Gillessen, S.; Choudhury, Ananya; Rodriguez-Vida, A.; Nole, F.; Diaz, E. G.; Roumeguere, T. A.; Daugaard, G.; Loriot, Y.; Saad, F.; McDermott, R. S.; et al. (2021)
      Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas.