title: Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.
abstract: BACKGROUND
  The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.
  
  
  METHODS
  Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.
  
  
  BACKGROUND
  The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.
  
  
  BACKGROUND
  NCT01836692; Pre-results.
authors.affiliation: Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Haslett
authors.affiliation: Leeds Cancer Centre, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Franks
authors.affiliation: Department of Clinical Oncology, Centre for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK.
authors.forename: Gerard G
authors.identifier: http://orcid.org/0000-0003-1003-5138
authors.initials: GG
authors.lastname: Hanna
authors.affiliation: Department of Clinical Oncology, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Harden
authors.affiliation: Department of Clinical Oncology, Weston Park Hospital, Sheffield, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hatton
authors.affiliation: Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Stephen
authors.identifier: http://orcid.org/0000-0002-2062-5417
authors.initials: S
authors.lastname: Harrow
authors.affiliation: Department of Radiotherapy, The Royal Marsden, NHS Foundation Trust, London, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: McDonald
authors.affiliation: Manchester Academic Health Science Centre Trials Co-ordination Unit (MAHSC-CTU), The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Ashcroft
authors.affiliation: Manchester Academic Health Science Centre Trials Co-ordination Unit (MAHSC-CTU), The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Falk
authors.affiliation: Radiotherapy Trials Quality Assurance Team, Mount Vernon Hospital, Northwood, UK.
authors.forename: Nicki
authors.initials: N
authors.lastname: Groom
authors.affiliation: Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Harris
authors.affiliation: Department of Clinical Oncology, Northern Ireland Cancer Centre, Belfast, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: McCloskey
authors.affiliation: Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Whitehurst
authors.affiliation: Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Bayman
authors.affiliation: Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, UK The University of Manchester, Manchester Academic Health Science Centre, Institute of Cancer Sciences, Manchester Cancer Research Centre (MCRC), Manchester, UK.
authors.forename: Corinne
authors.identifier: http://orcid.org/0000-0001-5617-9781
authors.initials: C
authors.lastname: Faivre-Finn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002985:Clinical Protocols; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D006113:United Kingdom; D055815:Young Adult