• 196TiP: PREM-LC: Development and pilot testing of a patient reported experience measure in lung cancer.

      Burns, K; Harle, Amelie S; Blackhall, Fiona H; Fenemore, Jackie; Yorke, Janelle; Institute of Cancer Sciences, The University of Manchester, Manchester (2016-04)
    • 1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer.

      Stahel, R; Thatcher, Nick; Früh, M; Le Péchoux, C; Postmus, P E; Sorensen, J B; Felip, E; Faivre-Finn, Corinne; Blackhall, Fiona H; Department of Oncology, University Hospital Zurich, Zurich, Switzerland. (2011-09)
      The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through discussion at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement in SCLC is reported in this article. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.
    • 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337.

      Wells, Paula; Aboagye, E O; Gunn, Roger N; Osman, Saifa; Boddy, Alan V; Taylor, Gordon A; Rafi, Imran; Hughes, Andrew; Calvert, A Hilary; Price, Patricia M; et al. (2003-05-07)
      BACKGROUND: Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans. METHODS: Five patients with advanced gastrointestinal cancer were PET scanned both before and 1 hour after oral administration of the TS inhibitor AG337 (THYMITAQ [nolatrexed]); seven control patients were scanned twice but not treated with AG337. Thymidine salvage kinetics were measured in vivo using 2-[11C]thymidine PET and spectral analysis to obtain the standardized uptake values (SUV), the area under the time-activity curve (AUC), and the fractional retention of thymidine (FRT). Changes in PET parameters between scans in the AG337-treated and control groups were compared using the Mann-Whitney U test. The relationship between AG337 exposure and AG337-induced changes in tumor FRT and in plasma deoxyuridine levels (a conventional pharmacodynamic systemic measure of TS inhibition) was examined using Spearman's regression analysis. Statistical tests were two-sided. RESULTS: The between-scan change in FRT in patients treated with AG337 (38% increase, 95% confidence interval [CI] = 8% to 68%) was higher than that in control patients (3% increase, 95% CI = -11% to 17%) (P =.028). The level of AG337-induced increase in both 2-[11C]thymidine FRT and plasma deoxyuridine levels was statistically significantly correlated with AG337 exposure (r = 1.00, P =.01 for both). CONCLUSIONS: AG337 administration was associated with increased tumor tracer retention that was consistent with tumor cell uptake of exogenous 2-[11C]thymidine as a result of TS inhibition. 2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest.
    • 2-chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III-IV non-Hodgkin's lymphoma.

      Betticher, D; Zucca, E; Von Rohr, A; Egger, T; Radford, John A; Ambrosetti, A; Bürki, K; Rufener, B; Schmitz, S; Cerny, T; et al. (1996-10)
      PURPOSE: This phase II multi-institutional trial was designed to assess response and toxicity of 2-chlorodeoxyadenosine (2-CDA) in patients with previously untreated follicular lymphoma. The clinical significance of detecting cells carrying the t(14;18) translocation (bcl-2/JH rearrangement) in peripheral blood and bone marrow by polymerase chain reaction (PCR) before, during and after treatment was also examined. PATIENTS AND METHODS: Between May 1993 and October 1995, 37 patients were accrued: male/female: 15/22, median age 51 years (range: 20-78), stage III/IV: 9/28. Patients received a total 2-CDA dose of 0.7 mg/kg as continuous s.c. or i.v. infusions over 7 days, every 28 days for a maximum of 5 cycles. A total of 165 cycles were administered. In 25 patients, blood and bone marrow before, during and after treatment were available for PCR analysis of the bcl-2/JH rearrangements. RESULTS: All 37 patients were evaluable for response and toxicity. The overall response rate was 84% (95% confidence interval, 68%-94%) with 14% CR (n = 5) and 70% PR (n = 26) and a median time to treatment failure of 15.7 months. bcl-2/JH rearrangement in peripheral blood and/or bone marrow was found in 10/25 of patients (40%) before treatment and 5 of these became repeatedly negative after 2-CDA therapy. There was no apparent association between bcl-2/ JH result and response. In 11 patients, 2-CDA was stopped because of progressive disease (n = 4), myelotoxicity (grade 2-3, n = 4), and other causes (n = 3, pulmonary embolism, metabolic disorder, and patient's decision). Four patients (11%) suffered from infections (grade 2-3). In 6 patients, persistent thrombocytopenia of 7.5 months (range: 3-21) occurred after completion of the 5 cycles. CONCLUSION: 2-CDA is active in untreated follicular lymphomas, but time to treatment failure suggests no advantage compared with standard treatment and toxicity on haematopoietic stem cells appears to be more pronounced. Molecular remission is induced in a considerable proportion of patients with disappearance of the bcl-2/JH rearrangement, and its possible significance as a predictive factor for quality of response and relapse warrants further study.
    • 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial

      Smith, Ian; Procter, Marion; Gelber, Richard D; Guillaume, Sébastien; Feyereislova, Andrea; Dowsett, Mitch; Goldhirsch, Aron; Untch, Michael; Mariani, Gabriella; Baselga, Jose; et al. (2007-01-06)
      BACKGROUND: Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study. METHODS: HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11. FINDINGS: 97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001). INTERPRETATION: Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
    • A 2018 IPEM audit of MRI in external beam radiotherapy treatment planning in the UK

      Speight, R; Schmidt, M; Liney, G; Johnstone, R; Eccles, Cynthia L; Dubec, Michael; George, B; Henry, A; McCallum, H; Leeds Teaching Hospitals NHS Trust, Leeds Cancer Centre, Leeds (2019)
    • 2020 WHO classification of soft tissue tumours: what's new?

      Shenjere, Patrick; The Christie NHS Foundation Trust (2021)
      Soft tissue tumours are rare and morphologically diverse, making their diagnosis one of the most challenging ?elds in diagnostic surgical pathology. In addition to morphology, classi?cation of mesenchymal tumours is increasingly becoming complex, with incorporation of advances in immunohistochemical and molecular characterisation of the individual entities. The increased understanding of the molecular genetics of tumours, together with the development of a new generation of antibodies has improved diagnostic accuracy and resulted in some new entities and subtypes of existing tumours being recognised. The 2020 WHO classi?cation of bone and soft tissue tumours incorporates these advances and with additional input from clinicians (oncologist, surgeon and radiologist), it re?ects a consensus across the di?erent specialties involved in the management of sarcoma patients. This presentation will highlight some of the recently described entities included in the 2020 WHO classi?cation (CIC-rearranged sarcoma, sarcomas with BCOR genetic alterations, super?cial CD 34 positive ?broblastic tumour, and atypical spindle cell/pleomorphic lipomatous tumour) and also summarise the improved criteria /information for prediction of clinical behaviour of some tumours (solitary ?brous tumours and dedi?erentiated liposarcomas)
    • 24-hour cyclophosphamide infusion therapy for malignant mesothelioma of the pleura.

      Anderson, Heather; Hasleton, Philip S; Michie, A B; Johnson, Richard J; Thatcher, Nick; CRC Department of Medical Oncology, Christie Hospital, Manchester. (1988-01)
      Thirteen patients with malignant mesothelioma of the pleura have been treated with 24-hour cyclophosphamide infusion (2.5 g/m2) therapy. There were no complete responders. Three patients (23%) had a partial response, and a further three patients who did not fulfil the criteria for objective response, had subjective benefit from therapy with increase in performance status. The overall median survival from the onset of therapy was 6 months (range 2-19 months). High dose cyclophosphamide offers no advantage over standard dose therapy.
    • 241PD BEECH: a randomised phase 2 study assessing the efficacy of AKT inhibitor AZD5363 combined with paclitaxel in patients with ER+ve advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population.

      Turner, N; Alarcón, E; Armstrong, Anne C; Philco, M; López Chuken, Y; Sablin, M-P; Tamura, K; Gomez Villanueva, A; Pérez-Fidalgo, J; Foxley, A; et al. (2017-09)
    • 25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial.

      Lipplaa, A; Fernandes, R; Marshall, A; Lorigan, Paul C; Dunn, J; Myers, K; Barker, E; Newton-Bishop, J; Middleton, M; Corrie, P; et al. (2018-07-23)
      Studies evaluating a relationship of vitamin D in patients with primary melanoma have consistently identified an inverse correlation with Breslow thickness, but an inconsistent impact on survival. Vitamin D in later stages of melanoma has been less studied.
    • A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.

      Eustace, Amanda; Mani, Navin; Span, P; Irlam, Joely J; Taylor, Janet; Betts, Guy N J; Denley, H; Miller, Crispin J; Rojas, A; Hoskin, P; et al. (2013-09-01)
      Tumor hypoxia is associated with a poor prognosis, hypoxia modification improves outcome, and hypoxic status predicts benefit from treatment. Yet, there is no universal measure of clinical hypoxia. The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types.
    • 2nd ESMO consensus conference on lung cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up.

      Vansteenkiste, J; Crinò, L; Dooms, C; Douillard, J; Faivre-Finn, Corinne; Lim, E; Rocco, G; Senan, S; Van Schil, P; Veronesi, G; et al. (2014-08)
      To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease.
    • 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.

      Besse, B; Adjei, A; Baas, P; Meldgaard, P; Nicolson, M; Paz-Ares, L; Reck, M; Smit, E F; Syrigos, K; Stahel, R; et al. (2014-08)
      To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.
    • 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

      Iveson, T; Kerr, R; Saunders, Mark P; Cassidy, J; Hollander, N; Tabernero, J; Haydon, A; Glimelius, B; Harkin, A; Allan, K; et al. (2018-04)
      6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.
    • 3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT

      Iveson, T; Boyd, KA; Kerr, RS; Robles-Zurita, J; Saunders, Mark P; Briggs, AH; Cassidy, J; Hollander, NH; Tabernero, J; Haydon, A; et al. (2019)
      BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ³?18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n?=?3035; 6-month analysis, n?=?3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority?=?0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ³?3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ³?5 years (p?<?0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894). PLAIN-LANGUAGE-SUMMARY: Patients diagnosed with bowel cancer are likely to have surgery to remove the tumour. Patients diagnosed with a more advanced stage of the disease are then likely to be offered what is known as adjuvant chemotherapy Ð chemotherapy to kill any cancer cells that have already spread but cannot be seen. Adjuvant chemotherapy is usually given over 6 months using two medicines known as oxaliplatin and fluoropyrimidine. This chemotherapy has side effects of diarrhoea, nausea and vomiting, and it reduces the numbers of cells in the blood. It can also damage nerves, which causes discomfort, numbness and tingling; in some cases, this can go on for years. These side effects are more likely to develop with longer treatment. This study looked at whether or not shortening the time over which patients were given oxaliplatin and fluoropyrimidine chemotherapy reduced its effectiveness. In this large study of over 6000 patients, half of the patients were allocated by chance to be treated for 3 months and the other half to be treated for 6 months. Reducing the time that patients had chemotherapy from 6 months to 3 months did not make the treatment less effective. When patients treated with chemotherapy over 3 months were compared with those treated over 6 months, 77% of patients in both groups were well with no detectable disease 3 years after surgery. Patients were less likely to get side effects with 3-month chemotherapy. In particular, the chance of persistent long-term nerve damage was lower, resulting in patients with 3-month chemotherapy having better health-related quality of life. Overall, the study showed that 3-month adjuvant chemotherapy for patients with bowel cancer is as effective as 6-month adjuvant chemotherapy and causes fewer side effects.
    • 30-day mortality associated with systemic anti-cancer therapy (SACT) in gastrointestinal malignancies: The Christie experience.

      Marti-Marti, Francisca; McGurk, Antony; Alam, Nooreen; Bhatt, Lubna; Braun, Michael S; Hubner, Richard A; Mansoor, Was; McBain, C; McNamara, Mairéad G; Mullamitha, Saifee A; et al. (2018-06)
    • 32: Screening for brain metastases in non small cell lung cancer (NSCLC).

      Harris, Maggie A; Mehdi, M; Faivre-Finn, Corinne; Blackhall, Fiona H; Sheikh, Hamid Y; Coote, Joanna H; Bayman, Neil A; Summers, Yvonne J; Califano, Raffaele; Taylor, Paul; et al. (2017-01)
    • 331 cases of clinically node-negative supraglottic carcinoma of the larynx: a study of a modest size fixed field radiotherapy approach.

      Sykes, Andrew J; Slevin, Nicholas J; Gupta, Nirmal K; Brewster, Alison E; Christie Hospital NHS Trust, Manchester, UK. (2000-03-15)
      PURPOSE: For node-negative supraglottic carcinoma of the larynx, radiotherapy with surgery in reserve commonly provides very good results in terms of both local control and survival, while preserving function. However uncertainty exists over the treatment of the node-negative neck. Elective whole neck radiotherapy, while effective, may be associated with significant morbidity. The purpose of this study was to examine our practice of treating a modest size, fixed field to a high biologically effective dose and compare it with the patterns of recurrence from other centers that use different dose/volume approaches. METHODS AND MATERIALS: Over a 10-year period 331 patients with node-negative supraglottic carcinoma of the larynx were treated with radiotherapy at the Christie Hospital Manchester. Patients were treated with doses of 50-55 Gy in 16 fractions over 3 weeks. Data were collected retrospectively for local and regional control, survival, and morbidity. RESULTS: Overall local control, after surgical salvage in 17 cases, was 79% (T1-92%, T2-81%, T3-67%, T4-73%). Overall regional lymph node control, after surgical salvage in 13 cases, was 84% (T1-91%, T2-88%, T3-81%, T4-72%). Five-year crude survival was 50%, but after correcting for intercurrent deaths was 70% (T1-83%, T2-78%, T3-53%, T4-61%). Serious morbidity requiring surgery was seen in 7 cases (2.1%) and was related to prescribed dose (50 Gy-0%, 52.5 Gy-1. 3%, 55 Gy-3.4%). DISCUSSION: Our results confirm that treating a modest size, fixed field to a high biologically effective dose is highly effective. It enables preservation of the larynx in most cases, with acceptable regional control and no loss of survival compared to whole neck radiotherapy regimes.