title: Investigating the potential impact of four-dimensional computed tomography (4DCT) on toxicity, outcomes and dose escalation for radical lung cancer radiotherapy.
abstract: OBJECTIVE
  To investigate the potential dosimetric and clinical benefits predicted by using four-dimensional computed tomography (4DCT) compared with 3DCT in the planning of radical radiotherapy for non-small cell lung cancer.
  
  
  METHODS
  Twenty patients were planned using free breathing 4DCT then retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D plans. Plans were compared for differences in planning target volume (PTV) geometrics and normal tissue complication probability (NTCP) for organs at risk using dose volume histograms. Tumour control probability and NTCP were modelled using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive clinical algorithm (Maastro), which is based on patient characteristics, including: age, performance status, smoking history, lung function, tumour staging and concomitant chemotherapy, to predict survival and toxicity outcomes. Potential therapeutic gains were investigated by applying isotoxic dose escalation to both plans using constraints for mean lung dose (18 Gy), oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy).
  
  
  RESULTS
  4DCT based plans had lower PTV volumes, a lower dose to organs at risk and lower predicted NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no difference for predicted 2-year survival and dyspnoea rates between the groups, but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There was no correlation between LKB modelling and the clinical algorithm for lung toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT plans.
  
  
  CONCLUSIONS
  4DCT can theoretically improve therapeutic ratio and dose escalation based on dosimetric parameters and mathematical modelling. However, when individual characteristics are incorporated, this gain may be less evident in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose escalation, which may lead to improved local control and better overall survival.
authors: Northern Ireland Cancer Centre, Belfast, UK; Centre for Cancer Research and Cell Biology, Queens University Belfast, UK. Electronic address: coleaidan@hotmail.com.
authors: A J
authors: AJ
authors: Cole
authors: Northern Ireland Cancer Centre, Belfast, UK.
authors: J M
authors: JM
authors: O'Hare
authors: Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: S J
authors: SJ
authors: McMahon
authors: Northern Ireland Cancer Centre, Belfast, UK.
authors: C K
authors: CK
authors: McGarry
authors: Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: K T
authors: KT
authors: Butterworth
authors: Northern Ireland Cancer Centre, Belfast, UK.
authors: J
authors: J
authors: McAleese
authors: Northern Ireland Cancer Centre, Belfast, UK; Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: S
authors: S
authors: Jain
authors: Northern Ireland Cancer Centre, Belfast, UK.
authors: A R
authors: AR
authors: Hounsell
authors: Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: K M
authors: KM
authors: Prise
authors: Northern Ireland Cancer Centre, Belfast, UK; Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: G G
authors: GG
authors: Hanna
authors: Northern Ireland Cancer Centre, Belfast, UK; Centre for Cancer Research and Cell Biology, Queens University Belfast, UK.
authors: J M
authors: JM
authors: O'Sullivan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D056973:Four-Dimensional Computed Tomography / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*
keywords: 4DCT; TCP/NTCP; dose escalation; non-small cell lung cancer; prediction modelling