title: DART-bid for loco-regionally advanced NSCLC : Summary of acute and late toxicity with long-term follow-up; experiences with pulmonary dose constraints.
abstract: BACKGROUND
  To report acute and late toxicity with long-term follow-up, and to describe our experiences with pulmonary dose constraints.
  
  
  METHODS
  Between 2002 and 2009, 150 patients with 155 histologically/cytologically proven non-small cell lung cancer (NSCLC; tumor stages II, IIIA, IIIB in 6, 55 and 39%, respectively) received the following median doses: primary tumors 79.2 Gy (range 72.0-90.0 Gy), lymph node metastases 59.4 Gy (54.0-73.8 Gy), nodes electively 45 Gy; with fractional doses of 1.8 Gy twice daily (bid). In all, 86% of patients received 2 cycles of chemotherapy previously.
  
  
  RESULTS
  Five treatment-related deaths occurred: pneumonitis, n = 1; progressive pulmonary fibrosis in patients with pre-existing pulmonary fibrosis, n = 2; haemorrhage, n = 2. In all, 8% of patients experienced grade 3 and 1.3% grade 4 pneumonitis; 11% showed late fibrotic alterations grade 2 in lung parenchyma. Clinically relevant acute esophagitis (grade 2 and 3) was seen in 33.3% of patients, 2 patients developed late esophageal stenosis (G3). Patients with upper lobe, middle lobe and central lower lobe tumours (n = 130) were treated with V20 (total lung) up to 50% and patients with peripheral lower lobe tumours (n = 14, basal lateral tumours excluded) up to 42%, without observing acute or late pulmonary toxicity >grade 3. Only patients with basal lateral lower lobe tumours (n = 5) experienced grade 4/5 pulmonary toxicity; V20 for this latter group ranged between 30 and 53%. The mean lung dose was below the QUANTEC recommendation of 20-23 Gy in all patients. The median follow-up time of all patients is 26.3 months (range 2.9-149.4) and of patients alive 80.2 months (range 63.9-149.4.). The median overall survival time of all patients is 26.3 months; the 2-, 5- and 8‑year survival rates of 54, 21 and 15%, respectively. The local tumour control rate at 2 and 5 years is 70 and 64%, the regional control rate 90 and 88%, respectively.
  
  
  CONCLUSIONS
  Grade 4 or 5 toxicity occurred in 7/150 patients (4.7%), which can be partially avoided in the future (e.g. by excluding patients with pre-existing pulmonary fibrosis). Tolerance and oncologic outcome compare favourably to concomitant chemoradiation also in long-term follow-up.
authors.affiliation: Institute for research and development on Advanced Radiation Technologies (radART), Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria. k.wurstbauer@salk.at.
authors.forename: Karl
authors.identifier: http://orcid.org/0000-0003-3628-7907
authors.initials: K
authors.lastname: Wurstbauer
authors.affiliation: Institute for research and development on Advanced Radiation Technologies (radART), Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria.|Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Zehentmayr
authors.affiliation: Institute for research and development on Advanced Radiation Technologies (radART), Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria.|Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Deutschmann
authors.affiliation: Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Dagn
authors.affiliation: Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Exeli
authors.affiliation: Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Kopp
authors.affiliation: Departement of Pneumology, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Porsch
authors.affiliation: Departement of Pneumology, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Maurer
authors.affiliation: Departement of Pneumology, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Studnicka
authors.affiliation: Institute for research and development on Advanced Radiation Technologies (radART), Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria.|Department of Radiotherapy and Radiation Oncology , Landeskrankenhaus, Paracelsus Medical University Clinics, Salzburg, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Sedlmayer
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments / Q000401:mortality; D015995:Prevalence; D011379:Prognosis; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000401:mortality* / Q000517:prevention & control; D011835:Radiation Protection / Q000379:methods; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Chemotherapy; Dose-Differentiated Accelerated Radiation Therapy; Non-small-cell lung cancer; Pneumonitis; Pulmonary fibrosis