title: Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation.
abstract: OBJECTIVE
  We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation.
  
  
  METHODS
  We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; α/β = 2 for spinal cord; α/β = 3 for other critical structures).
  
  
  RESULTS
  We identified 82 courses (44 for retreatment) in 38 patients reirradiated at a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24-month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving ≥75 Gy EQD2 included spinal cord (1 cm(3); n=1), esophagus (1 cm(3); n=10), trachea (1 cm(3); n=11), heart (1 cm(3); n=9), aorta (1 cm(3); n=16), superior vena cava (1 cm(3); n=12), brachial plexus (0.2 cm(3); n=2), vagus nerve (0.2 cm(3); n=7), sympathetic trunk (0.2 cm(3); n=4), chest wall (30 cm(3); n=12), and proximal bronchial tree (1 cm(3); n=17). Cumulative dose-volume (D cm(3)) toxicity following reirradiation data included esophagitis grade ≥2 (n=3, D1 cm(3) range: 41.0-100.6 Gy), chest wall grade ≥2 (n=4; D30 cm(3) range: 35.0-117.2 Gy), lung grade 2 (n=7; V20combined-lung range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm(3) range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm(3) = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm(3) = 130.8 Gy). No grade ≥4 toxicity was observed.
  
  
  CONCLUSIONS
  Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures.
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Binkley
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hiniker
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Aadel
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Maxim
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. Electronic address: BWLoo@Stanford.edu.
authors.forename: Billy W
authors.initials: BW
authors.lastname: Loo
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address: David.Shultz@rmp.uhn.on.ca.
authors.forename: David Benjamin
authors.initials: DB
authors.lastname: Shultz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000528:radiation effects; D001980:Bronchi / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D004941:Esophagitis / Q000209:etiology; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D058958:Organs at Risk / Q000528:radiation effects*; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D000069475:Re-Irradiation / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D013116:Spinal Cord / Q000528:radiation effects; D015996:Survival Rate; D013909:Thorax / Q000528:radiation effects; D013997:Time Factors; D014132:Trachea / Q000528:radiation effects