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Pancreatic Neoplasms: HELP
Articles by Somnath Mukherjee
Based on 16 articles published since 2010
(Why 16 articles?)
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Between 2010 and 2020, Somnath Mukherjee wrote the following 16 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence. 2018

O'Reilly, Derek / Fou, Linyun / Hasler, Elise / Hawkins, James / O'Connell, Susan / Pelone, Ferruccio / Callaway, Mark / Campbell, Fiona / Capel, Margred / Charnley, Richard / Corrie, Pippa / Elliot, Dawn / Goodburn, Lesley / Jewell, Anna / Joharchi, Suzanne / McGeeney, Laura / Mukherjee, Somnath / Oppong, Kofi / Whelan, Phil / Primrose, John / Neoptolemos, John. ·Manchester Royal Infirmary, Central Manchester NHS Foundation Trust and University of Manchester, United Kingdom. Electronic address: doreilly@doctors.org.uk. · National Institute for Health and Care Excellence, United Kingdom. · Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, United Kingdom. · University of Liverpool, The Royal Liverpool & Broadgreen University Hospital NHS Trust, United Kingdom. · George Thomas Hospice, United Kingdom. · Freeman Hospital, Newcastle upon Tyne, United Kingdom. · Cambridge University Hospitals NHS Foundation Trust and University of Cambridge, United Kingdom. · Northumbria Healthcare Foundation Trust, United Kingdom. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford & Churchill Hospital, United Kingdom. · University of Southampton, Southampton General Hospital, United Kingdom. · University of Heidelberg, Germany. ·Pancreatology · Pubmed #30292643.

ABSTRACT: To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

2 Review Translational molecular imaging in exocrine pancreatic cancer. 2018

Cornelissen, Bart / Knight, James C / Mukherjee, Somnath / Evangelista, Laura / Xavier, Catarina / Caobelli, Federico / Del Vecchio, Silvana / Rbah-Vidal, Latifa / Barbet, Jacques / de Jong, Marion / van Leeuwen, Fijs W B. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. bart.cornelissen@oncology.ox.ac.uk. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. · Istituto Oncologico Veneto I.R.C.C.S., Padova, Italy. · Vrije Universiteit Brussel, Brussels, Belgium. · Department of Radiology, Universitätsspital Basel, Basel, Switzerland. · Universita' degli Studi di Napoli "Federico II", Naples, Italy. · CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France. · Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. · Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. ·Eur J Nucl Med Mol Imaging · Pubmed #30225616.

ABSTRACT: Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management.

3 Review Pancreatic ductal adenocarcinoma: From genetics to biology to radiobiology to oncoimmunology and all the way back to the clinic. 2015

Fokas, Emmanouil / O'Neill, Eric / Gordon-Weeks, Alex / Mukherjee, Somnath / McKenna, W Gillies / Muschel, Ruth J. ·Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK. Electronic address: emmanouil.fokas@oncology.ox.ac.uk. · Department of Oncology, Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK. · Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. ·Biochim Biophys Acta · Pubmed #25489989.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells. Next, we will explore the characteristics and merits of the different mouse models of PDAC. The inflammatory milieu and the immunosuppressive microenvironment mediate tumour initiation and treatment failure. Hence, we will also review the inflammatory and immune escaping mechanisms and the new immunotherapies tested in PDAC. A better understanding of the different mechanisms of tumour formation and progression will help us to identify the best targets for testing in future clinical studies of PDAC.

4 Clinical Trial Study protocol: a multi-centre randomised study of induction chemotherapy followed by capecitabine ± nelfinavir with high- or standard-dose radiotherapy for locally advanced pancreatic cancer (SCALOP-2). 2019

Strauss, Victoria Y / Shaw, Rachel / Virdee, Pradeep S / Hurt, Christopher N / Ward, Elizabeth / Tranter, Bethan / Patel, Neel / Bridgewater, John / Parsons, Philip / Radhakrishna, Ganesh / O'Neill, Eric / Sebag-Montefiore, David / Hawkins, Maria / Corrie, Pippa G / Maughan, Timothy / Mukherjee, Somnath. ·Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · Oncology Clinical Trials Office, University of Oxford, Oxford, UK. · Centre for Trials Research, Cardiff University, Cardiff, UK. · Clinical Trials and Evaluation Unit, Bristol Royal Infirmary, Bristol, UK. · Pharmacy Department, Velindre Cancer Centre, Velindre NHS University Trust, Cardiff, UK. · Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, UK. · Department of Oncology, University College London Hospitals, London, UK. · Cardiff NCRI RTTQA group, Department of Medical Physics, Velindre Cancer Centre, Cardiff, UK. · Oncology Department, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, UK. · Department of Oncology, University of Oxford, CRUK MRC Oxford Institute for Radiation Oncology, Oxford, UK. · University of Leeds, Leeds Cancer Centre, St James's University Hospital, Leeds, UK. · Cambridge Cancer Centre, Addenbrooke's Hospital, Cambridge, UK. · Department of Oncology, University of Oxford, CRUK MRC Oxford Institute for Radiation Oncology, Oxford, UK. somnath.mukherjee@oncology.ox.ac.uk. ·BMC Cancer · Pubmed #30717707.

ABSTRACT: BACKGROUND: Induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2). METHODS: Patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19-9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme. DISCUSSION: SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen. TRIAL REGISTRATION: Eudract No: 2013-004968-56; ClinicalTrials.gov : NCT02024009.

5 Clinical Trial A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol. 2016

Holyoake, Daniel L P / Ward, Elizabeth / Grose, Derek / McIntosh, David / Sebag-Montefiore, David / Radhakrishna, Ganesh / Patel, Neel / Silva, Michael / Mukherjee, Somnath / Strauss, Victoria Y / Odondi, Lang'o / Fokas, Emmanouil / Melcher, Alan / Hawkins, Maria A. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. · Oncology Clinical Trials Office, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. · The Beatson West of Scotland Cancer Centre, 1053 Great Western Rd, Glasgow, G12 0YN, UK. · The University of Leeds, Cancer Research UK Leeds Centre,14 Leeds Institute of Cancer and Pathology, Cancer Genetics Building, St James's University Hospital, 15 Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK. · Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Bexley Wing, Beckett Street, Leeds, LS9 7TF, UK. · Oxford University Hospitals NHS Foundation Trust, Old Road, Headington, Oxford, OX3 7LE, UK. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK. · The Institute of Cancer Research, Chester Beatty Laboratories, 237, Fulham Rd, London, SW3 6JB, UK. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. maria.hawkins@oncology.ox.ac.uk. ·BMC Cancer · Pubmed #27619800.

ABSTRACT: BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options. TRIAL REGISTRATION: ISRCTN14138956 . Funded by CRUK.

6 Clinical Trial Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial. 2016

Fokas, Emmanouil / Spezi, Emiliano / Patel, Neel / Hurt, Chris / Nixon, Lisette / Chu, Kwun-Ye / Staffurth, John / Abrams, Ross / Mukherjee, Somnath. ·Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. · School of Engineering, Cardiff University, UK. · Oxford University Hospital NHS Foundation Trust, UK. · Wales Cancer Trials Unit, Centre for Trials Research, Cardiff University, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. · Institute of Cancer and Genetics, Cardiff University, UK; Cardiff NCRI RTTQA Centre, Velindre NHS Trust, UK. · Department of Radiation Oncology, Rush University Medical Center, Chicago, USA. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Oxford University Hospital NHS Foundation Trust, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk. ·Radiother Oncol · Pubmed #27497804.

ABSTRACT: BACKGROUND AND PURPOSE: We performed a retrospective central review of tumour outlines in patients undergoing radiotherapy in the SCALOP trial. MATERIALS AND METHODS: The planning CT scans were reviewed retrospectively by a central review team, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was compared to the trials team-defined gold standard (gsGTV and gsPTV) using the Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI). The prognostic value of JCI and GMI was also assessed. The RT plans were also reviewed against protocol-defined constraints. RESULTS: 60 patients with diagnostic-quality planning scans were included. The median whole volume JCI for GTV was 0.64 (IQR: 0.43-0.82), and the median GMI was 0.11 (IQR: 0.05-0.22). For PTVs, the median JCI and GMI were 0.80 (IQR: 0.71-0.88) and 0.04 (IQR: 0.02-0.12) respectively. Tumour was completely missed in 1 patient, and⩾50% of the tumour was missed in 3. Patients with JCI for GTV⩾0.7 had 7.12 (95% CIs: 1.83-27.67, p=0.005) higher odds of progressing by 9months in multivariate analysis. Major deviations in RT planning were noted in 4.5% of cases. CONCLUSIONS: Radiotherapy workshops and real-time central review of contours are required in RT trials of pancreatic cancer.

7 Clinical Trial ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer. 2016

Wilson, James M / Fokas, Emmanouil / Dutton, Susan J / Patel, Neel / Hawkins, Maria A / Eccles, Cynthia / Chu, Kwun-Ye / Durrant, Lisa / Abraham, Aswin G / Partridge, Mike / Woodward, Martha / O'Neill, Eric / Maughan, Tim / McKenna, W Gillies / Mukherjee, Somnath / Brunner, Thomas B. ·Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. · Department of Radiology, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK; Department of Radiotherapy, Oxford University Hospitals NHS Foundation Trust, UK. · Early Phase Research Hub, Department of Oncology, Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk. · Department of Radiation Oncology, University of Freiburg, Germany; German Cancer Consortium (DKTK), Heidelberg, Partner Site Freiburg, Germany. ·Radiother Oncol · Pubmed #27117177.

ABSTRACT: BACKGROUND AND PURPOSE: Nelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. We conducted a phase II trial combining nelfinavir with chemoradiotherapy (CRT) for locally advanced inoperable pancreatic cancer (LAPC). MATERIALS AND METHODS: Radiotherapy (50.4Gy/28 fractions; boost to 59.4Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3-10days before and was continued during CRT. The primary end-point was 1-year overall survival (OS). Secondary end-points included histological downstaging, radiological response, 1-year progression free survival (PFS), overall survival (OS) and treatment toxicity. An imaging sub-study (n=6) evaluated hypoxia ((18)F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir. RESULTS: The study closed after recruiting 23 patients, due to non-availability of Nelfinavir in Europe. The 1-year OS was 73.4% (90% CI: 54.5-85.5%) and median OS was 17.4months (90% CI: 12.8-18.8). The 1-year PFS was 21.8% (90% CI: 8.9-38.3%) and median PFS was 5.5months (90% CI: 4.1-8.3). All patients experienced Grade 3/4 toxicity, but many were asymptomatic laboratory abnormalities. Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion post-nelfinavir. CONCLUSIONS: CRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.

8 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.

9 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.

10 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.

11 Article None 2017

Knight, James C / Mosley, Michael J / Bravo, Luisa Contreras / Kersemans, Veerle / Allen, P Danny / Mukherjee, Somnath / O'Neill, Eric / Cornelissen, Bart. ·CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom. · CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom. bart.cornelissen@oncology.ox.ac.uk. ·Clin Cancer Res · Pubmed #28774899.

ABSTRACT:

12 Article Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data. 2017

Holyoake, Daniel L P / Aznar, Marianne / Mukherjee, Somnath / Partridge, Mike / Hawkins, Maria A. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, United Kingdom. · Nuffield Department of Population Health, University of Oxford, United Kingdom. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, United Kingdom; Oxford University Hospitals NHS Foundation Trust, United Kingdom. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, United Kingdom. Electronic address: maria.hawkins@oncology.ox.ac.uk. ·Radiother Oncol · Pubmed #28600084.

ABSTRACT: BACKGROUND AND PURPOSE: Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. MATERIAL AND METHODS: A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials. RESULTS: Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n=0.070, m=0.46, TD CONCLUSIONS: LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose.

13 Article Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer. 2016

Holyoake, Daniel L P / Robinson, Maxwell / Grose, Derek / McIntosh, David / Sebag-Montefiore, David / Radhakrishna, Ganesh / Patel, Neel / Partridge, Mike / Mukherjee, Somnath / Hawkins, Maria A. ·CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK; The Churchill Hospital, Oxford, UK. · The Beatson West of Scotland Cancer Centre, Glasgow, UK. · University of Leeds, CRUK Leeds Centre, UK; Leeds Cancer Centre, St James's University Hospital, Leeds, UK. · Leeds Cancer Centre, St James's University Hospital, Leeds, UK. · The Churchill Hospital, Oxford, UK. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK. · CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK; The Churchill Hospital, Oxford, UK. Electronic address: maria.hawkins@oncology.ox.ac.uk. ·Radiother Oncol · Pubmed #27519585.

ABSTRACT: BACKGROUND AND PURPOSE: Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study. MATERIAL AND METHODS: Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled. RESULTS: For GTV, reference volume was 2.1cm CONCLUSIONS: Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated.

14 Article Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Balaban, Edward P / Mangu, Pamela B / Khorana, Alok A / Shah, Manish A / Mukherjee, Somnath / Crane, Christopher H / Javle, Milind M / Eads, Jennifer R / Allen, Peter / Ko, Andrew H / Engebretson, Anitra / Herman, Joseph M / Strickler, John H / Benson, Al B / Urba, Susan / Yee, Nelson S. ·Edward P. Balaban, Cancer Care Partnership, State College · Edward P. Balaban and Nelson S. Yee, Penn State Hershey Cancer Institute, Hershey, PA · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Alok A. Khorana, Cleveland Clinic · Jennifer R. Eads, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH · Manish A. Shah, The Weill Cornell Medical Center · Peter Allen, Memorial Sloan Kettering Cancer Center, New York, NY · Somnath Mukherjee, University of Oxford, Oxford, United Kingdom · Christopher H. Crane and Milind M. Javle, The University of Texas MD Anderson Cancer Center, Houston, TX · Andrew H. Ko, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA · Anitra Engebretson, Patient Representative, Portland, OR · Joseph M. Herman, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD · John H. Strickler, Duke University Medical Center, Durham, NC · Al B. Benson III, Lurie Comprehensive Cancer Center of Northwestern, Chicago, IL · and Susan Urba, University of Michigan Cancer Center, Ann Arbor, MI. ·J Clin Oncol · Pubmed #27247216.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-six randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

15 Article The prognostic role of desmoplastic stroma in pancreatic ductal adenocarcinoma. 2016

Wang, Lai Mun / Silva, Michael A / D'Costa, Zenobia / Bockelmann, Robin / Soonawalla, Zahir / Liu, Stanley / O'Neill, Eric / Mukherjee, Somnath / McKenna, W Gillies / Muschel, Ruth / Fokas, Emmanouil. ·Department of Pathology, Oxford University Hospital NHS Trust, University of Oxford, Oxford, UK. · Department of Surgery, Oxford University Hospital NHS Trust, Oxford, UK. · Department of Oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK. · Department of Radiation Oncology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. ·Oncotarget · Pubmed #26716653.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. We examined the prognostic value of stroma density and activity in patients with resectable PDAC treated with surgery and adjuvant gemcitabine-based chemotherapy. FFPE-tissue from the pancreatectomy of 145 patients was immunohistochemically stained for haematoxylin-eosin and Masson's trichrome to assess stroma density, and alpha-smooth muscle actin (αSMA) expression for activated pancreatic stellate cells. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS). After a mean follow-up of 20 months (range, 2-69 months), the median OS was 21 months and the 3-year OS was 35.7%. In multivariate analysis, highly-dense stroma was an independent prognostic parameter for OS (p = 0.001), PFS (p = 0.007), LPFS (p = 0.001) and DMFS (p = 0.002), while αSMA expression lacked significance. Interestingly, highly-dense stroma retained significance for the four clinical endpoints only in early (pT1-2) but not late (pT3-4) stage tumors. Additionally, late pT-stage (pT3-4), the presence of lymph node metastases (pN+ vs pN0), perineural/neural invasion and administration of adjuvant chemotherapy also correlated with prognosis in multivariate analysis. Altogether, stroma density constitutes an independent prognostic marker in PDAC patients treated with adjuvant chemotherapy. Our findings highlight the dynamic complexity of desmoplasia and indicate that highly-dense stroma is correlated with better outcome. Further validation of the prognostic value of stroma as a biomarker and its role in PDAC patients after adjuvant chemotherapy is warranted and will be performed in a prospective study.

16 Article Challenges in using ¹⁸F-fluorodeoxyglucose-PET-CT to define a biological radiotherapy boost volume in locally advanced pancreatic cancer. 2014

Wilson, James M / Mukherjee, Somnath / Chu, Kwun-Ye / Brunner, Thomas B / Partridge, Mike / Hawkins, Maria. ·CRUK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX3 7DQ, UK. james.wilson@oncology.ox.ac.uk. ·Radiat Oncol · Pubmed #24962658.

ABSTRACT: BACKGROUND: The best method of identifying regions within pancreatic tumours that might benefit from an increased radiotherapy dose is not known. We investigated the utility of pre-treatment FDG-PET in predicting the spatial distribution of residual metabolic activity following chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: 17 patients had FDG-PET/CT scans at baseline and six weeks post-CRT. Tumour segmentation was performed at 40% and 50% of SUVmax at baseline and 60%, 70%, 80% and 90% post-CRT. FDG-PET scans were non-rigidly registered to the radiotherapy planning CT using the CT component of the FDG-PET/CT. Percentage overlap of the post-CRT volumes with the pre-CRT volumes with one another and the gross tumour volume (GTV) was calculated. RESULTS: SUVmax decreased during CRT (median pre- 8.0 and post- 3.6, p < 0.0001). For spatial correlation analysis, 9 pairs of scans were included (Four were excluded following complete metabolic response, one patient had a non-FDG avid tumour, one had no post-CRT imaging, one had diffuse FDG uptake that could not be separated from normal tissues and one had an elevated blood glucose). The Pre40% and 50% of SUVmax volumes covered a mean of 50.8% and 30.3% of the GTV respectively. The mean% overlap of the 90%, 80%, 70%, 60% of SUVmax post-CRT with the Pre40% and Pre50% volumes were 83.3%, 84.0%, 83.7%, 77.9% and 77.8%, 69.9%, 74.5%, 64.8% respectively. CONCLUSIONS: Regions of residual metabolic activity following CRT can be predicted from the baseline FDG-PET and could aid definition of a biological target volume for non-uniform dose prescriptions.