Treatment planning and 4D robust evaluation strategy for proton therapy of lung tumors with large motion amplitude.

PURPOSE: Intensity-modulated proton therapy (IMPT) for lung tumors with a large tumor movement is challenging due to loss of robustness in the target coverage. Often an upper cut-off at 5-mm tumor movement is used for proton patient selection. In this study, we propose (1) a robust and easily implementable treatment planning strategy for lung tumors with a movement larger than 5 mm, and (2) a four-dimensional computed tomography (4DCT) robust evaluation strategy for evaluating the dose distribution on the breathing phases. MATERIALS AND METHODS: We created a treatment planning strategy based on the internal target volume (ITV) concept (aim 1). The ITV was created as a union of the clinical target volumes (CTVs) on the eight 4DCT phases. The ITV expanded by 2 mm was the target during robust optimization on the average CT (avgCT). The clinical plan acceptability was judged based on a robust evaluation, computing the voxel-wise min and max (VWmin/max) doses over 28 error scenarios (range and setup errors) on the avgCT. The plans were created in RayStation (RaySearch Laboratories, Stockholm, Sweden) using a Monte Carlo dose engine, commissioned for our Mevion S250i Hyperscan system (Mevion Medical Systems, Littleton, MA, USA). We developed a new 4D robust evaluation approach (4DRobAvg; aim 2). The 28 scenario doses were computed on each individual 4DCT phase. For each scenario, the dose distributions on the individual phases were deformed to the reference phase and combined to a weighted sum, resulting in 28 weighted sum scenario dose distributions. From these 28 scenario doses, VWmin/max doses were computed. This new 4D robust evaluation was compared to two simpler 4D evaluation strategies: re-computing the nominal plan on each individual 4DCT phase (4DNom) and computing the robust VWmin/max doses on each individual phase (4DRobInd). The treatment planning and dose evaluation strategies were evaluated for 16 lung cancer patients with tumor movement of 4-26 mm. RESULTS: The ratio of the ITV and CTV volumes increased linearly with the tumor amplitude, with an average ratio of 1.4. Despite large ITV volumes, a clinically acceptable plan fulfilling all target and organ at risk (OAR) constraints was feasible for all patients. The 4DNom and 4DRobInd evaluation strategies were found to under- or overestimate the dosimetric effect of the tumor movement, respectively. 4DRobInd showed target underdosage for five patients, not observed in the robust evaluation on the avgCT or in 4DRobAvg. The accuracy of dose deformation used in 4DRobAvg was quantified and found acceptable, with differences for the dose-volume parameters below 1 Gy in most cases. CONCLUSION: The proposed ITV-based planning strategy on the avgCT was found to be a clinically feasible approach with adequate tumor coverage and no OAR overdosage even for large tumor movement. The new proposed 4D robust evaluation, 4DRobAvg, was shown to give an easily interpretable understanding of the effect of respiratory motion dose distribution, and to give an accurate estimate of the dose delivered in the different breathing phases.

Identification of residual metabolic-active areas within NSCLC tumours using a pre-radiotherapy FDG-PET-CT scan: a prospective validation.

It was recently described that high FDG-uptake areas pre-radiotherapy largely correspond with residual metabolic-active areas post-radiotherapy. Here, an independent prospective validation of these results was performed using an overlap-fraction (OF) calculation of various FDG-uptake based thresholds. Data from twelve patients treated at Radboud University Nijmegen Medical Center with lung cancer were analyzed. All patients underwent two FDG-PET-CT scans, one pre-radiotherapy (pre-RT) and one approximately three months after treatment (post-RT). Of the twelve analyzed patients, eight patients showed residual FDG uptake on the post-RT scan and were included for analysis. One of these patients had a residue that was not clearly distinguishable from the surrounding tissue due to FDG avid inflammation. Therefore, seven patients remained for further analysis. The mean volume of the residual metabolic-active areas post-RT was 14.6±10.0% (mean±SD) of the mean volume of the gross tumour volume (GTV) pre-RT. The residual metabolic-active areas largely corresponded with the pre-RT GTV (OF=93.7±7.2%). The pre-RT-scan threshold delineations of 34%, 40% and 50% of the SUV(max) had a large OF with the residual region, 86.9±8.3%, 77.4±8.1% and 67.9±6.8%, respectively. In this independent dataset, we confirmed that the location of residual FDG-uptake areas after radiotherapy corresponds with the high FDG-uptake areas pre-radiotherapy. Therefore, a pre-radiotherapy FDG-PET-CT scan can potentially be used for radiotherapy dose redistribution.

Transition from a simple to a more advanced dose calculation algorithm for radiotherapy of non-small cell lung cancer (NSCLC): implications for clinical implementation in an individualized dose-escalation protocol.

BACKGROUND AND PURPOSE: To investigate the clinical consequences of the transition from a simple convolution algorithm (CA) to a more advanced superposition dose calculation algorithm (SA) in an individualized isotoxic dose-escalation protocol for NSCLC patients. MATERIAL AND METHODS: First, treatment plans designed according to ICRU50-criteria using the CA were recalculated using the SA, for 16 patients. Next, two additional plans were designed for each patient using only the SA: one with 95%-isodose coverage (ICRU50-criteria), the other allowing PTV coverage with 90%-isodose at the lung side. PTV dose was escalated to a maximum dose of 79.2Gy or lower when limited by either a mean lung dose (MLD) of 19Gy or a maximum spinal cord dose of 54Gy. Equivalent uniform doses (EUD) in the PTV were compared. RESULTS: Recalculation of the CA plans using the SA, showed PTV underdosage in the CA plans: the median PTV EUD was 61.3Gy (range 44.9-80.4Gy) and 55.5Gy (43.9-76.8Gy), for CA and SA, respectively (p<0.001). Redesigning plans using the SA resulted in an almost identical PTV EUD of 55.1Gy (43.7-79.2Gy). For the subgroup (N=9) with MLD as dose-limiting factor a gain in PTV EUD of 2.7+/-1.8Gy (p=0.008) was achieved using the 90%-isodose coverage plan. CONCLUSIONS: Plans calculated using the CA caused large PTV underdosage. Plans designed using the SA often lead to lower maximum achievable tumour doses due to higher MLD values. Allowing somewhat relaxed PTV coverage criteria increased the PTV dose again for MLD restricted cases. Consequently, in clinics where isotoxic individual dose-escalation is applied, implementation of an SA should be accompanied by accepting limited PTV underdosage in patients with MLD as the dose-limiting factor.

An "in silico" clinical trial comparing free breathing, slow and respiration correlated computed tomography in lung cancer patients.

BACKGROUND AND PURPOSE: To determine which method of internal target volume (ITV) definition based on a respiration correlated CT (RCCT) allows optimal tumor coverage. MATERIAL AND METHODS: A free breathing CT (CT(fb)) and an RCCT scan were acquired in 41 lung cancer patients. For 12 patients with a motion >7 mm in any direction, a detailed analysis was made. The RCCT scan was used to measure tumor motion and to reconstruct a CT at 10 phases (CT(10ph)), amongst which the half ventilation CT (CT(hv)). By averaging the CT(10ph), a slow CT (CT(slow)) was reconstructed. Based on those scans ITVs were delineated and treatments were planned, where for the ITV(hv) an internal margin of (motion amplitude)/4 was used. The treatment plans for the ITVs were projected on the 10 respiration phases. Doses were calculated and averaged over the 10 phases to estimate the actual CTV coverage. RESULTS: The 3D motion was on average 8.1+/-1.0 mm (1 SD) for all patients; no statistical difference was found between lower and upper lobe tumors. The ITV(slow) was the smallest volume on average (142+/-38 cm(3)), followed by the ITV(hv) (160+/-40 cm(3)), the ITV(10ph) (161+/-41 cm(3)) and the ITV(fb) (250+/-63 cm(3)). Mean CTV doses were between 95% and 107% of the prescribed dose for nearly all patients and treatment plans. Analysis of the CTV coverage suggested that underdosage may occur when the CT(slow) is used and a geographic miss occurred using the CT(fb), due to uncorrect localization of the average tumor position. CONCLUSIONS: The CT(hv) seems to be the optimal dataset for delineation, using an adequate anisotropic internal margin of (motion amplitude)/4.