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Pancreatic Neoplasms: HELP
Articles by George Joseph
Based on 4 articles published since 2010
(Why 4 articles?)

Between 2010 and 2020, G. Joseph wrote the following 4 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Clinical Trial Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer. 2017

Hurt, C N / Falk, S / Crosby, T / McDonald, A / Ray, R / Joseph, G / Staffurth, J / Abrams, R A / Griffiths, G / Maughan, T / Mukherjee, S. ·Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK. · Bristol Haematology and Oncology Centre, Bristol BS2 8ED, UK. · Velindre Cancer Centre, Velindre Hospital, Velindre Road, Cardiff CF14 2TL, UK. · Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. · Department of Radiation Oncology, Rush University Medical Center, 500 S. Paulina, 013 Atrium Building, Chicago, IL 60612, USA. · Southampton Clinical Trials Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. · CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford OX3 7DQ, UK. ·Br J Cancer · Pubmed #28376080.

ABSTRACT: BACKGROUND: SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes. METHODS: Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m RESULTS: One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9-18.7). Updated median OS was 17.6 months (95% CI: 14.6-22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1-16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38-1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0-15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8-12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32-1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l CONCLUSIONS: CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml

2 Clinical Trial Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer. 2015

Hurt, Christopher N / Mukherjee, Somnath / Bridgewater, John / Falk, Stephen / Crosby, Tom / McDonald, Alec / Joseph, George / Staffurth, John / Abrams, Ross A / Blazeby, Jane M / Bridges, Sarah / Dutton, Peter / Griffiths, Gareth / Maughan, Tim / Johnson, Colin. ·Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Electronic address: hurtcn@cardiff.ac.uk. · Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford, United Kingdom. · UCL Cancer Institute, London, United Kingdom. · Bristol Haematology and Oncology Centre, Bristol, United Kingdom. · Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales, United Kingdom. · Beatson West of Scotland Cancer Centre, Glasgow, Scotland, United Kingdom. · Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales, United Kingdom. · Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois. · Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, United Kingdom. · Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom. · Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton, United Kingdom. · University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton, United Kingdom. ·Int J Radiat Oncol Biol Phys · Pubmed #26530749.

ABSTRACT: PURPOSE: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. METHODS AND MATERIALS: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). RESULTS: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. CONCLUSIONS: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

3 Clinical Trial Comparison of investigator-delineated gross tumor volumes and quality assurance in pancreatic cancer: Analysis of the pretrial benchmark case for the SCALOP trial. 2015

Fokas, Emmanouil / Clifford, Charlotte / Spezi, Emiliano / Joseph, George / Branagan, Jennifer / Hurt, Chris / Nixon, Lisette / Abrams, Ross / Staffurth, John / Mukherjee, Somnath. ·Radiotherapy Physics Department, University Hospitals Birmingham NHS Foundation Trust, UK. Electronic address: emmanouil.fokas@oncology.ox.ac.uk. · Department of Oncology, University of Oxford, UK. · Department of Medical Physics, Velindre Hospital, Cardiff, UK. · Velindre Cancer Centre, Velindre Hospital, Cardiff, UK. · Oncology Department, Northampton General Hospital, UK. · Wales Cancer Trials Unit, Cardiff University, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. · Institute of Cancer and Genetics, Cardiff University, UK; Cardiff NCRI RTTQA Centre, Velindre NHS Trust, UK. · Radiotherapy Physics Department, University Hospitals Birmingham NHS Foundation Trust, UK. ·Radiother Oncol · Pubmed #26328939.

ABSTRACT: BACKGROUND AND PURPOSE: To evaluate the variation in investigator-delineated volumes and assess plans from the radiotherapy trial quality assurance (RTTQA) program of SCALOP, a phase II trial in locally advanced pancreatic cancer. MATERIALS AND METHODS: Participating investigators (n=25) outlined a pre-trial benchmark case as per RT protocol, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was evaluated, against the trials team-defined gold standard GTV (gsGTV) and PTV (gsPTV), using both qualitative and geometric analyses. The median Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI) were calculated. Participating RT centers also submitted a radiotherapy plan for this benchmark case, which was centrally reviewed against protocol-defined constraints. RESULTS: Twenty-five investigator-defined contours were evaluated. The median JCI and GMI of iGTVs were 0.57 (IQR: 0.51-0.65) and 0.26 (IQR: 0.15-0.40). For iPTVs, these were 0.75 (IQR: 0.71-0.79) and 0.14 (IQR: 0.11-0.22) respectively. Qualitative analysis showed largest variation at the tumor edges and failure to recognize a peri-pancreatic lymph node. There were no major protocol deviations in RT planning, but three minor PTV coverage deviations were identified. . CONCLUSIONS: SCALOP demonstrated considerable variation in iGTV delineation. RTTQA workshops and real-time central review of delineations are needed in future trials.

4 Clinical Trial Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. 2013

Mukherjee, Somnath / Hurt, Christopher N / Bridgewater, John / Falk, Stephen / Cummins, Sebastian / Wasan, Harpreet / Crosby, Tom / Jephcott, Catherine / Roy, Rajarshi / Radhakrishna, Ganesh / McDonald, Alec / Ray, Ruby / Joseph, George / Staffurth, John / Abrams, Ross A / Griffiths, Gareth / Maughan, Tim. ·Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk ·Lancet Oncol · Pubmed #23474363.

ABSTRACT: BACKGROUND: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. METHODS: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m(2) on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m(2) twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m(2) once per week) or capecitabine (830 mg/m(2) twice daily, Monday to Friday only), both in combination with radiation (50·4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. FINDINGS: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62·9%, 80% CI 50·6-73·9) in the capecitabine group and 18 of 35 assessable patients (51·4%, 39·4-63·4) in the gemcitabine group had not progressed. Median overall survival was 15·2 months (95% CI 13·9-19·2) in the capecitabine group and 13·4 months (95% CI 11·0-15·7) in the gemcitabine group (adjusted hazard ratio [HR] 0·39, 95% CI 0·18-0·81; p=0·012). 12-month overall survival was 79·2% (95% CI 61·1-89·5) in the capecitabine group and 64·2 (95% CI 46·4-77·5) in the gemcitabine group. Median progression-free survival was 12·0 months (95% CI 10·2-14·6) in the capecitabine group and 10·4 months (95% CI 8·9-12·5) in the gemcitabine group (adjusted HR 0·60, 95% CI 0·32-1·12; p=0·11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3-4 haematological toxic effects (seven [18%] vs none, p=0·008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0·12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. INTERPRETATION: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. FUNDING: Cancer Research UK.