title: Adaptive Dose Escalation using Serial Four-dimensional Positron Emission Tomography/Computed Tomography Scans during Radiotherapy for Locally Advanced Non-small Cell Lung Cancer.
abstract: Computed tomography (CT)-based radiotherapy dose escalation for locally advanced non-small cell lung cancer (LA-NSCLC) has had limited success. In this planning study, we investigated the potential for adaptive dose escalation using respiratory-gated 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans (4DPET/4DCT) acquired before and during a course of chemoradiotherapy (CRT).
  
  
  
  We prospectively enrolled patients with LA-NSCLC receiving curative intent CRT. Radiotherapy was delivered using intensity-modulated radiotherapy (IMRT) using the week 0 4DCT scan. Three alternative, dose-escalated IMRT plans were developed offline based on the week 0, 2 and 4 4DPET/4DCT scans. The FDG-avid primary (PET-T) and nodal disease (PET-N) volumes defined by the 50% of maximum standard uptake value threshold were dose escalated to as high as possible while respecting organ at risk constraints.
  
  
  
  Thirty-two patients were recruited, 27 completing all scans. Twenty-five patients (93%) were boosted successfully above the clinical plan doses at week 0, 23 (85%) at week 2 and 20 (74%) at week 4. The median dose received by 95% of the planning target volume (D95) at week 0, 2 and 4 to PET-T were 74.4 Gy, 75.3 Gy and 74.1 Gy and to PET-N were 74.3 Gy, 71.0 Gy and 69.5 Gy.
  
  
  
  Using 18F-FDG-4DPET/4DCT, it is feasible to dose escalate both primary and nodal disease in most patients. Choosing week 0 images to plan a course with an integrated boost to PET-avid disease allows for more patients to be successfully dose escalated with the highest boost dose.
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M L
authors.initials: ML
authors.lastname: Yap
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address: alex.sun@rmp.uhn.on.ca.
authors.forename: A
authors.initials: A
authors.lastname: Sun
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Higgins
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Becker
authors.affiliation: Division of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: L W
authors.initials: LW
authors.lastname: Le
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D C
authors.initials: DC
authors.lastname: Vines
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bezjak
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J-P
authors.initials: JP
authors.lastname: Bissonnette
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D019788:Fluorodeoxyglucose F18; D056973:Four-Dimensional Computed Tomography / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy*; D064847:Multimodal Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Adaptive radiotherapy; dose escalation; four-dimensional PET/CT; intensity-modulated radiotherapy; lung cancer; radiotherapy