• The challenges of using MRI during radiotherapy.

      McWilliam, Alan; Rowland, Benjamin; van Herk, Marcel; Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK (2018-11)
      In this article we aim to introduce the main considerations in integrating magnetic resonance imaging (MRI) into the radiotherapy workflow. We will cover the use of MRI for improved delineation, considerations regarding MRI-only workflows, and the potential of functional imaging techniques. The challenges of implementing each of these will be discussed to ensure safe usage in radiotherapy.
    • Delivering functional imaging on the MRI-Linac: current challenges and potential solutions.

      Datta, A; Aznar, Marianne Camille; Dubec, Michael; Parker, G; O'Connor, James P B; Department of Radiology, The Christie Hospital NHS Trust, Manchester, UK (2018-11)
      Magnetic resonance imaging (MRI) is a highly versatile imaging modality that can be used to measure features of the tumour microenvironment including cell death, proliferation, metabolism, angiogenesis, and hypoxia. Mapping and quantifying these pathophysiological features has the potential to alter the use of adaptive radiotherapy planning. Although these methods are available for use on diagnostic machines, several challenges exist for implementing these functional MRI methods on the MRI-linear accelerators (linacs). This review considers these challenges and potential solutions.
    • The potential value of MRI in external-beam radiotherapy for cervical cancer.

      Cree, Anthea; Livsey, Jacqueline E; Barraclough, Lisa H; Dubec, Michael; Hambrock, Thomas; van Herk, Marcel; Choudhury, Ananya; McWilliam, Alan; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M20 4BX, (2018-11)
      The reference standard treatment for cervical cancer is concurrent chemoradiotherapy followed by magnetic resonance imaging (MRI)-guided brachytherapy. Improvements in brachytherapy have increased local control rates, but late toxicity remains high with rates of 11% grade ≥3. The primary clinical target volume (CTV) for external-beam radiotherapy includes the cervix and uterus, which can show significant inter-fraction motion. This means that generous margins are required to cover the primary CTV, increasing the radiation dose to organs at risk and, therefore, toxicity. A number of image-guided radiotherapy techniques (IGRT) have been developed, but motion can be random and difficult to predict prior to treatment. In light of the development of integrated MRI linear accelerators, this review discusses the potential value of MRI in external-beam radiotherapy. Current solutions for managing pelvic organ motion are reviewed, including the potential for online adaptive radiotherapy. The impacts of the use of MRI in tumour delineation and in the delivery of stereotactic ablative body radiotherapy (SABR) are highlighted. The potential role and challenges of using multi parametric MRI to guide radiotherapy are also discussed.
    • Pharmacokinetic effects and safety of olaparib administered with endocrine therapy: A phase I study in patients with advanced solid tumours.

      Plummer, R; Verheul, H; De Vos, F; Leunen, K; Molife, L; Rolfo, C; Grundtvig-Sørensen, P; De Grève, J; Rottey, S; Jerusalem, G; Italiano, A; Spicer, J; Dirix, L; Goessl, C; Birkett, J; Spencer, S; Learoyd, M; Bailey, C; Dean, Emma J; Northern Centre for Cancer Care, Newcastle University, Newcastle upon Tyne, UK. (2018-11)
      The PARP inhibitor olaparib is efficacious as monotherapy and has potential application in combination with endocrine therapy for the treatment of breast cancer. This phase I study assessed the safety and pharmacokinetic (PK) profiles of olaparib combined with tamoxifen, anastrozole or letrozole in patients with advanced solid tumours.
    • Magnetic resonance-guided radiotherapy - can we justify more expensive technology?

      Tree, A; Huddart, R; Choudhury, Ananya; Royal Marsden NHS Foundation Trust, Institute of Cancer Research, London, UK (2018-11)
    • Comparison of intensity modulated radiotherapy plan optimisation methods for a 1.5 T MR-Linac.

      Chuter, Robert; van Herk, Marcel; Akhiat, H; Voet, P; Mackay, Ranald I; Choudhury, Ananya; McWilliam, Alan; Christie Medical Physics and Engineering (CMPE), The Christie NHS Foundation Trust, Manchester, UK (2018-10-29)
      For the 1.5 T Elekta MR-Linac it is essential that the optimisation of a treatment plan accounts for the electron return effect on the planned dose distribution. The ability of two algorithms for the first stage fluence optimisation, pencil beam (PB) and Monte Carlo (MC), to produce acceptable plan quality was investigated. Optimisation time for each algorithm was also compared.
    • Emergency management of immune-related hypophysitis: Collaboration between specialists is essential to achieve optimal outcomes.

      Cooksley, Timothy J; Higham, Claire E; Lorigan, Paul C; Trainer, Peter J; Departments of Acute Medicine, Endocrinology and Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom (2018-10-23)
    • Quality of life after postmastectomy radiotherapy in patients with intermediate-risk breast cancer (SUPREMO): 2-year follow-up results of a randomised controlled trial.

      Velikova, G; Williams, L; Willis, S; Dixon, J; Loncaster, Juliette A; Hatton, M; Clarke, J; Kunkler, I; Russell, N; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds Cancer Centre, St James's University Hospital, Leeds, UK (2018-10-15)
      Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer.
    • ASO author reflections: Quality of Life after HIPEC for pseudomyxoma peritonei.

      Stearns, Adam T; O'Dwyer, Sarah T; Colorectal and Peritoneal Oncology Centre, The Christie Hospital NHS Foundation Trust, Manchester, UK (2018-10-15)
    • Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.

      Chadi, S; Malcomson, Lee; Ensor, J; Riley, R; Vaccaro, C; Rossi, G; Daniels, I; Smart, N; Osborne, M; Beets, G; Maas, M; Bitterman, D; Du, K; Gollins, S; Sun Myint, A; Smith, F; Saunders, Mark P; Scott, N; O'Dwyer, Sarah T; de Castro Araujo, R; Valadao, M; Lopes, A; Hsiao, C; Lai, C; Smith, R; Paulson, E; Appelt, A; Jakobsen, A; Wexner, S; Habr-Gama, A; Sao Julião, G; Perez, R; Renehan, Andrew G; Division of Surgical Oncology and General Surgery, Princess Margaret Hospital and University Health Network, University of Toronto, Toronto, ON, Canada (2018-10-11)
      In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.
    • Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI.

      O'Connor, James P B; Robinson, S; Waterton, J; Division of Cancer Sciences, University of Manchester , Manchester , UK (2018-10-01)
      Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and targeted therapies. Imaging has potential to identify, spatially map and quantify tumour hypoxia prior to therapy, as well as track changes in hypoxia on treatment. At present no hypoxia imaging methods are available for routine clinical use. Research has largely focused on positron emission tomography (PET)-based techniques, but there is gathering evidence that MRI techniques may provide a practical and more readily translational alternative. In this review we focus on the potential for imaging hypoxia by measuring changes in longitudinal relaxation [R 1; termed oxygen-enhanced MRI or tumour oxygenation level dependent (TOLD) MRI] and effective transverse relaxation (R 2*; termed blood oxygenation level dependent (BOLD) MRI, induced by inhalation of either 100% oxygen or the radiosensitising hyperoxic gas carbogen. We explain the scientific principles behind oxygen-enhanced MRI and BOLD and discuss the significant studies and their limitations. All imaging biomarkers require rigorous validation in order to translate into clinical use and the steps required to further develop oxygen-enhanced MRI and BOLD MRI into decision-making tools are discussed.
    • Irreversible electroporation in pancreatic ductal adenocarcinoma: Is there a role in conjunction with conventional treatment?

      De Liguori Carino, N; O'Reilly, D; Siriwardena, A; Valle, Juan W; Radhakrishna, Ganesh; Pihlak, Rille; McNamara, Mairéad G; Regional Hepato-Pancreato-Biliary Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK (2018-10)
      The incidence of pancreatic ductal adenocarcinoma (PDAC) is rapidly increasing. Up to 30% of patients present with locally advanced disease and therefore are not candidates for surgery. Locally advanced pancreatic cancer (LAPC) is an emerging entity lacking in level III evidence-based recommendations for its treatment. Currently, systemic chemotherapy is the main treatment for LAPC. However, due to lack of response or disease progression, downsizing of the tumour, making it resectable is successful in only a small proportion of patients. Radiotherapy is often advocated to improve local disease control if there is stability following chemotherapy. Recently, Irreversible Electroporation (IRE), a novel non-thermal ablation technique, has been proposed for the treatment of LAPC.
    • Targeted lung cancer screening selects individuals at high risk of cardiovascular disease.

      Balata, H; Blandin Knight, S; Barber, P; Colligan, D; Crosbie, Emma J; Duerden, R; Elton, P; Evison, M; Greaves, M; Howells, J; Irion, K; Karunaratne, D; Kirwan, M; Macnab, A; Mellor, S; Miller, C; Newton, T; Novasio, J; Sawyer, R; Sharman, A; Slevin, K; Smith, E; Taylor, B; Taylor, S; Tonge, J; Walsham, A; Waplington, S; Whittaker, J; Booton, R; Crosbie, P; Manchester Thoracic Oncology Centre, North West Lung Centre, Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, UK (2018-10)
      Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention.
    • Understanding the impact of chemotherapy on dignity for older people and their partners.

      Farrell, Carole; Heaven, Catherine; The Christie NHS Trust, Wilmslow Road, Withington, Manchester, M20 4BX, England, UK. (2018-10)
      Chemotherapy poses challenges for older patients, with potential comorbidities, mobility and functional problems that may adversely affect their dignity. Patients may struggle with side-effects but fail to inform health professionals, impacting on clinical management and unresolved needs/concerns. This study aims to explore the impact of dignity during chemotherapy for older people and partners.
    • Management of an anastomotic stricture using a combined laparoscopic and transanal approach - a video vignette.

      Jerome, E; Selvasekar, Chelliah; Paraoan, M; Colorectal Unit, Department of Surgery, Royal Albert Edward Infirmary, Wigan, UK (2018-10)
    • Patient and physician preferences for first-line treatment of classical Hodgkin lymphoma in Germany, France and the United Kingdom.

      Bröckelmann, P; McMullen, S; Wilson, J; Mueller, K; Goring, S; Stamatoullas, A; Zagadailov, E; Gautam, A; Huebner, D; Dalal, M; Illidge, Timothy M; Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany (2018-09-21)
      First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography-driven strategies and ABVD or BEACOPP variants incorporating the antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under investigation in advanced-stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPPescalated and BV-AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross-sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression-free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5-year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians' recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians' treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients.
    • Computer-based intensity measurement assists pathologists in scoring PTEN immunohistochemistry - clinical associations in NSCLC patients of the ETOP Lungscape cohort.

      Rulle, U; Tsourti, Z; Casanova, R; Deml, K; Verbeken, E; Thunnissen, E; Warth, A; Cheney, R; Sejda, A; Speel, E; Madsen, L; Nonaka, Daisuke; Navarro, A; Sansano, I; Marchetti, A; Finn, S; Monkhorst, K; Kerr, K; Haberecker, M; Wu, C; Zygoura, P; Kammler, R; Geiger, T; Gendreau, S; Schulze, K; Vrugt, B; Wild, P; Moch, H; Weder, W; Ciftlik, A; Dafni, U; Peters, S; Bubendorf, L; Stahel, R; Soltermann, A; Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland (2018-09-18)
      PTEN loss is frequently observed in NSCLC and associated with both PI3K activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable read-out, but lacks standardized staining protocol and cut-off value.
    • Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with MCPyV status and prognosis in Merkel cell carcinoma.

      Wardhani, L; Matsushita, M; Iwasaki, T; Kuwamoto, S; Nonaka, Daisuke; Nagata, K; Kato, M; Kitamura, Y; Hayashi, K; Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, 683-8503, Japan (2018-09-18)
      Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer, with approximately 80% of cases related to Merkel cell polyomavirus (MCPyV). Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) are the key rate-limiting enzymes of the tryptophan to kynurenine (KYN) metabolic pathway. With aryl hydrocarbon receptor (AhR), an intracellular transcription factor, they play a role in escaping the immunosurveillance process in several cancers. IDO1/TDO2/AhR expression associated with the MCPyV status and prognosis in MCC was investigated. Samples included 24 MCPyV-positive MCCs, 12 MCPyV-negative MCCs with squamous cell carcinoma, and seven MCPyV-negative pure MCCs. They were stained immunohistochemically with IDO1, TDO2, and AhR antibodies and analyzed. Higher IDO1 expression in MCC tumor cells was found in MCPyV-negative than in MCPyV-positive MCC (P < .001). The tumor microenvironment (TME) in MCPyV-negative MCC expressed higher TDO2 than MCPyV-positive MCC (P < .001). Kaplan-Meier and log-rank tests showed that MCC with lower IDO1 expression in tumor cells and with lower TDO2 and AhR expressions in TME had better overall survival than otherwise (P = .043, .008, and .035, respectively); lower TDO2 expression in TME was also associated with longer disease-specific survival (P = .016). This suggests that IDO1, TDO2, and AhR express differentially in tumor cells or TME and play different roles in tumorigenesis between MCPyV-positive and -negative MCC that may affect the MCC biology. Evaluating IDO1/TDO2/AhR expression is important for selecting the most likely patients with MCC for immunotherapies targeting the IDO1/TDO2-AhR pathway.
    • The role of biomarkers in bladder preservation management of muscle-invasive bladder cancer.

      Mitin, T; Choudhury, Ananya; Department of Radiation Medicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA (2018-09-14)
      Patients with localized muscle-invasive bladder cancer (MIBC) can choose to undergo either neoadjuvant chemotherapy followed by radical cystectomy or radiation therapy-based bladder preservation treatment modality with subsequent close cystoscopic surveillance with salvage cystectomy reserved for patients with evidence of local disease recurrence. At the present time, the decision regarding bladder-directed local therapy for MIBC is based on physicians' and patients' preferences, and does not take into account tumor biology. Predictive biomarkers, once validated, could offer a more patient-centered and biology-driven selection of bladder-directed therapies.
    • Biliary tract cancer: state of the art and potential role of DNA damage repair.

      Lamarca, Angela; Barriuso, Jorge; McNamara, Mairéad G; Valle, Juan W; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK (2018-09-08)
      Biliary tract cancers (BTCs), including cholangiocarcinoma, gallbladder cancer and ampullary cancers, are poor-prognosis malignancies. Most patients are diagnosed with advanced disease, when treatment is limited to palliative chemotherapy. First line chemotherapy is usually administered in the form of cisplatin and gemcitabine. Benefit from second line chemotherapy is still to be confirmed. Even though new systemic treatment targets have been recognised, especially in patients with intrahepatic cholangiocarcinoma (e.g. IDH and FGFR), there is an urgent need for novel treatment strategies. Genomic profiling of BTC is progressively becoming a reality which allows a better understanding of their biology and potential new targets. This review provides an insight into DNA Damage Repair (DDR) mechanisms, prevalence of DDR-deficient tumours in BTC, and the potential role of DDR in cancer development. Some form of DDR deficiency is expected to be present in around 25% of patients with BTC, and this knowledge could be exploited to potentially increase response to currently-available treatment strategies (chemotherapy, radiotherapy or immunotherapy). For patients with DDR-proficient tumours, drug inhibition of DDR could be instituted.