Adaptive Dose-Staged Stereotactic Ablative Body Radiotherapy for Treatment of Large Central NSCLC Lung Tumors: A Dosimetric Simulation Study

Abstract

Adaptive dose-staged Stereotactic Radiosurgery (SRS) treatment of cranial AVM and personalized ultrafractionated stereotactic ablative radiotherapy (PULSAR) proposed by Timmerman et al. for lung cancer has been shown to be an effective technique with lower toxicities in the management of large lesions. The PULSAR technique requires periodic functional PET imaging or tumor biopsy more than one week apart post stereotactic ablative body radiotherapy (SABR) PULSE to utilize the tumor biological response feedback to delineate the residual active disease for subsequent (SABR) PULSES' adaptive treatment planning. The purpose of this study is to explore dosimetrically the benefit of SABR PULSES for the treatment of large central lungs tumors. A retrospective simulation study of five anonymized patients with large NSCLC was performed. Tumors were located centrally in left (N = 3) and right (N = 2) lungs. The PTVs generated by 5mm symmetric margin to the ITV, the ITV and PTV volumes were 30.0±21.4cc (10.6-64.5cc) and 65.4±35.2cc (30.7-121.0cc), respectively. Depending on the total PTV volume, 4 other adaptive PTVs were simulated by generating a symmetric reduction of the PTV volumes by 2 or 3mm assuming given enough time shrinking the original volume after each PULSE due to biological response during the time between the initial and subsequent SABR PULSES. The organs-at-risk (OARs) were contoured and 3 VMAT arcs plans were generated and optimized for each PTV with the same VMAT objective functions. The original PTV plan with 50 Gy in 5 consecutive fractions was compared with the sum of the 5 PULSES in 10 Gy per PULSE with adaptive volumes. A statistical analysis and a paired t-test of the 50 Gy plan in 5 consecutive fractions were compared with the 5 PULSES summed dose for the ITV, PTV, and the OARs. The t-test showed the 5 PULSES plans significantly lowered the doses to the ipsilateral, and contralateral lungs and heart when compared to 5 consecutive 10 Gy/fraction plans (p-Values, 0.031, 0.01, 0.02, respectively). The 11 Gy ipsilateral lung volume, a precursor for developing normal lung tissue fibrosis about one-year post SABR was significantly lower for the 5 PULSES (136±44cc Vs. 241±83cc) (p-Value, 0.01). The mean and maximum dose to the original PTV was significantly lower in 5 PULSES technique (p-Value, 0.0001, 0.046). The dose to the spinal canal was not statistically different between the two techniques (p-Value, 0.12). The current management of large central lung tumors is conventional fractionation with chemotherapy or delivering lower fractional SABR dose to meet the OAR dose constraints that may hinder the successful radioablation and local control. The PULSAR treatments using SABR dosimetrically provides significant sparing of normal tissue. Dose escalation for larger central lung tumors may be possible using this technique for effective local control and better overall survivorship.