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Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):849-55. doi: 10.1016/j.ijrobp.2010.12.001. Epub 2011 May 11.

Isotoxic dose escalation in the treatment of lung cancer by means of heterogeneous dose distributions in the presence of respiratory motion.

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Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark.



To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered.


Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin.


A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively.


The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.

[Indexed for MEDLINE]

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