title: Radiobiological determination of dose escalation and normal tissue toxicity in definitive chemoradiation therapy for esophageal cancer.
abstract: OBJECTIVE
  This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity.
  
  
  METHODS
  Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm(3). A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared.
  
  
  RESULTS
  Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001.
  
  
  CONCLUSIONS
  Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.
authors.affiliation: Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom. Electronic address: Samantha.warren@oncology.ox.ac.uk.
authors.forename: Samantha
authors.initials: S
authors.lastname: Warren
authors.affiliation: Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Partridge
authors.affiliation: Velindre Cancer Centre, Velindre Hospital, Cardiff, United Kingdom.
authors.forename: Rhys
authors.initials: R
authors.lastname: Carrington
authors.affiliation: Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Hurt
authors.affiliation: Velindre Cancer Centre, Velindre Hospital, Cardiff, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crosby
authors.affiliation: Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hawkins
mesh_terms: D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D019583:Dose Fractionation, Radiation; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D005240:Feasibility Studies; D006321:Heart / Q000528:radiation effects*; D006801:Humans; D008168:Lung / Q000528:radiation effects*; D008954:Models, Biological; D058958:Organs at Risk / Q000528:radiation effects*; D011336:Probability; D047368:Tumor Burden