Hypofractionation does not increase radiation pneumonitis risk with modern conformal radiation delivery techniques.
OBJECTIVE
To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models.


METHODS
Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy were selected. For each patient a 3D-conformal plan (3D-CRT) plan was produced in addition to the delivered plan. The standard fractionation schedule was set to 60 Gy in 30 fractions. Iso-efficacy comparisons with hypofractionation were performed by changing the fractionation and the physical prescription dose while keeping the equivalent tumor dose in 2 Gy fractions constant. The risk of developing RP after radiotherapy was estimated using the Mean Equivalent Lung Dose in 2-Gy fractions (MELD(2)) NTCP model with α/β=4 Gy for the residual lung. Overall treatment time was kept constant.


RESULTS
The mean risk of clinical RP after standard fractionation was 7.6% for Tomotherapy (range: 2.8-15.9%) and 9.2% for 3D-CRT (range 3.2-20.2%). Changing to 20 fractions, the Tomotherapy plans became slightly less toxic if the tumor α/β ratio, (α/β)(T), was 7 Gy (mean RP risk 7.5%, range 2.8-16%) while the 3D-CRT plans became marginally more toxic (mean RP risk 9.8%, range 3.2-21%). If (α/β)(T) was 13 Gy, the mean estimated risk of RP is 7.9% for Tomotherapy (range: 2.8-17%) and 10% for 3D-CRT (range 3.2-22%).


CONCLUSIONS
Modern highly conformal dose distributions are radiobiologically more forgiving with respect to hypofractionation, even for a normal tissue endpoint where α/β is lower than for the tumor in question.
Vogelius
Ivan S
IS
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Westerly
David C
DC
Cannon
George M
GM
Bentzen
Søren M
SM
D002138:Calibration; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000209:etiology*; D011836:Radiation Tolerance; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods / Q000592:standards; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods* / Q000592:standards; D012307:Risk Factors; D012922:Social Change; D013810:Therapeutic Equivalency; D036542:Tomography, Spiral Computed / Q000379:methods / Q000592:standards