title: Inhomogeneous dose escalation increases expected local control for NSCLC patients with lymph node involvement without increased mean lung dose.
abstract: BACKGROUND
  Higher doses to NSCLC tumours are required to increase the low control rates obtained with conventional dose prescriptions. This study presents the concept of inhomogeneous dose distributions as a general way to increase local control probability, not only for isolated lung tumours but also for patients with involved lymph nodes.
  
  
  METHODS
  Highly modulated IMRT plans with homogeneous dose distributions with a prescribed dose of 66Gy/33F were created for 20 NSCLC patients, staged T1b-T4 N0-N3, using standard PTV dose coverage of 95-107%. For each patient, an inhomogeneous dose distribution was created with dose constraints of: PTV-coverage ≥ 95%, same mean lung dose as obtained in the homogeneous dose plan, maximum doses of 45 and 66 Gy to spinal canal and oesophagus, respectively, and V74Gy < 1 cm(3) for each of: aorta, trachea + bronchi, the connective tissue in mediastinum, and the thorax wall. The dose was escalated using a TCP model implemented into the planning system. The difference in TCP values between the homogeneous and inhomogeneous plans were evaluated using two different TCP models.
  
  
  RESULTS
  Dose escalation was possible for all patients. TCP values based on assumed homogeneous distribution of clonogenic cells either in the GTV, CTV or PTV showed absolute TCP increases of approximately 15, 10 and 5 percentage points, respectively. This increase in local control was obtained without increasing the mean lung dose. However, small increases in maximum doses to the mediastinum were observed: 2.5 Gy for aorta, 4.4 Gy for the connective tissue, 1.6 Gy for the heart, and 2.6 Gy for trachea + bronchi.
  
  
  CONCLUSIONS
  Increased target doses and TCP values using inhomogeneous dose distributions could be achieved for all patients, regardless of lymph node involvement, tumour stage, location, and size. These new treatment plans have the potential to increase the local tumour control by 10-15 percentage points without compromising the clinically acceptable lung toxicity level.
authors.affiliation: Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.
authors.forename: Tine B
authors.initials: TB
authors.lastname: Nielsen
authors.forename: Olfred
authors.initials: O
authors.lastname: Hansen
authors.forename: Tine
authors.initials: T
authors.lastname: Schytte
authors.forename: Carsten
authors.initials: C
authors.lastname: Brink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000473:pathology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal; D015996:Survival Rate