title: Increased therapeutic ratio by 18FDG-PET CT planning in patients with clinical CT stage N2-N3M0 non-small-cell lung cancer: a modeling study.
abstract: OBJECTIVE
  With this modeling study, we wanted to estimate the potential gain from incorporating fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning in the radiotherapy treatment planning of CT Stage N2-N3M0 non-small-cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Twenty-one consecutive patients with clinical CT Stage N2-N3M0 NSCLC were studied. For each patient, two three-dimensional conformal treatment plans were made: one with a CT-based planning target volume (PTV) and one with a PET-CT-based PTV, both to deliver 60 Gy in 30 fractions. From the dose-volume histograms and dose distributions on each plan, the dosimetric factors predicting esophageal and lung toxicity were analyzed and compared. For each patient, the maximal tolerable prescribed radiation dose for the CT PTV vs. PET-CT PTV was calculated according to the constraints for the lung, esophagus, and spinal cord. From these results, the tumor control probability (TCP) was estimated, assuming a clinical dose-response curve with a median toxic dose of 84.5 Gy and a gamma(50) of 2.0. Dose-response curves were modeled, taking into account geographic misses according to the accuracy of CT and PET in our institutions.
  
  
  RESULTS
  The gross tumor volume of the nodes decreased from 13.7 +/- 3.8 cm(3) on the CT scan to 9.9 +/- 4.0 cm(3) on the PET-CT scan (p = 0.011). All dose-volume characteristics for the esophagus and lungs decreased in favor of PET-CT. The esophageal V(45) (the volume of the esophagus receiving 45 Gy) decreased from 45.2% +/- 4.9% to 34.0% +/- 5.8% (p = 0.003), esophageal V(55) (the volume of the esophagus receiving 55 Gy) from 30.6% +/- 3.2% to 21.9% +/- 3.8% (p = 0.004), mean esophageal dose from 29.8 +/- 2.5 Gy to 23.7 +/- 3.1 Gy (p = 0.004), lung V(20) (the volume of the lungs minus the PTV receiving 20 Gy) from 24.9% +/- 2.3% to 22.3% +/- 2.2% (p = 0.012), and mean lung dose from 14.7 +/- 1.3 Gy to 13.6 +/- 1.3 Gy (p = 0.004). For the same toxicity levels of the lung, esophagus, and spinal cord, the dose could be increased from 56.0 +/- 5.4 Gy with CT planning to 71.0 +/- 13.7 Gy with PET planning (p = 0.038). The TCP corresponding to these doses was estimated to be 14.2% +/- 5.6% for CT and 22.8% +/- 7.1% for PET-CT planning (p = 0.026). Adjusting for geographic misses by PET-CT vs. CT planning yielded TCP estimates of 12.5% and 18.3% (p = 0.009) for CT and PET-CT planning, respectively.
  
  
  CONCLUSIONS
  In this group of clinical CT Stage N2-N3 NSCLC patients, use of FDG-PET scanning information in radiotherapy planning reduced the radiation exposure of the esophagus and lung, and thus allowed significant radiation dose escalation while respecting all relevant normal tissue constraints. This, together with a reduced risk of geographic misses using PET-CT, led to an estimated increase in TCP from 13% to 18%. The results of this modeling study support clinical trials investigating incorporation of FDG-PET information in CT-based radiotherapy planning.
authors.affiliation: Maastro Clinic, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Antoinet
authors.initials: A
authors.lastname: van Der Wel
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Nijsten
authors.forename: Monique
authors.initials: M
authors.lastname: Hochstenbag
authors.forename: Rob
authors.initials: R
authors.lastname: Lamers
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Boersma
authors.forename: Rinus
authors.initials: R
authors.lastname: Wanders
authors.forename: Ludy
authors.initials: L
authors.lastname: Lutgens
authors.forename: Michael
authors.initials: M
authors.lastname: Zimny
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: Brad
authors.initials: B
authors.lastname: Wouters
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D004947:Esophagus / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011857:Radiographic Image Interpretation, Computer-Assisted; D019275:Radiopharmaceuticals; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18