Investigation of inter‐fraction target motion variations in the context of pencil beam scanned proton therapy in non‐small cell lung cancer patients

Abstract

For locally advanced-stage non-small cell lung cancer (NSCLC), inter-fraction target motion variations during the whole time span of a fractionated treatment course are assessed in a large and representative patient cohort. The primary objective is to develop a suitable motion monitoring strategy for pencil beam scanning proton therapy (PBS-PT) treatments of NSCLC patients during free breathing. Methods: Weekly 4D computed tomography (4DCT; 41 patients) and daily 4D cone beam computed tomography (4DCBCT; 10 of 41 patients) scans were analyzed for a fully fractionated treatment course. Gross tumor volumes (GTVs) were contoured and the 3D displacement vectors of the centroid positions were compared for all scans. Furthermore, motion amplitude variations in different lung segments were statistically analyzed. The dosimetric impact of target motion variations and target motion assessment was investigated in exemplary patient cases. Results: The median observed centroid motion was 3.4 mm (range: 0.2-12.4 mm) with an average variation of 2.2 mm (range: 0.1-8.8 mm). Ten of 32 patients (31.3%) with an initial motion <5 mm increased beyond a 5-mm motion amplitude during the treatment course. Motion observed in the 4DCBCT scans deviated on average 1.5 mm (range: 0.0-6.0 mm) from the motion observed in the 4DCTs. Larger motion variations for one example patient compromised treatment plan robustness while no dosimetric influence was seen due to motion assessment biases in another example case. Conclusions: Target motion variations were investigated during the course of radiotherapy for NSCLC patients. Patients with initial GTV motion amplitudes of < 2 mm can be assumed to be stable in motion during the treatment course. For treatments of NSCLC patients who exhibit motion amplitudes of > 2 mm, 4DCBCT should be considered for motion monitoring due to substantial motion variations observed.

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information

“…The largest variations were observed in IMPT_3D plans for D 1 (spine) for lung cancer patient 1 (42.67 2.38 ± Gy RBE ), and MHD for oesophageal cancer patient 11 (14. 43 1.51 Gy RBE ). ±…”

“…For the oesophageal cancer patients, these did not exceed 9.1 ± 1.5 mm. By chance, this population of lung and oesophageal cancer patients, did not include 'big movers', which are not the most representative thoracic patients of the admissions in our radiotherapy clinic [43]. The target motion amplitudes reported in this study were quantified by the mean of all deformation vector lengths from DIR within the whole CTV (CTV of primary tumour and CTV of [multiple] pathological lymph nodes).…”

“…The 2.0 mm remaining setup uncertainty in the 4DREM (calculated internally) has been established due to the use of the available repeated imaging, which led to the disregard of the patient inter-fractional setup error in the magnitude of the simulated shifts (see Suppl. 7) [25,28,29,[41][42][43]. A fraction dose was calculated by applying the same setup and range errors to all sub-plan doses of that fraction specific 4DCT.…”

Dosimetric influence of deformable image registration uncertainties on propagated structures for online daily adaptive proton therapy of lung cancer patients

“…Besides intra-fractional motion, the dose calculation in low-density lung tissue has large uncertainties and large inter-fractional changes are expected to occur [24,[51][52][53]. Each of these challenges are discussed separately in the following paragraphs.…”

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

“…Otter et al found that tumor amplitude changes were largest for lung patients with large tumor amplitudes, and they found changes in the amplitude up to 8.8 mm. 30 Applying a VW evaluation is a bit conservative since this evaluation is not based on a realistic error scenario, but instead the lowest (VWmin) or highest (VWmax) dose value in each voxel. The VWmin/ VWmax dose distributions can, therefore, result in a physically unrealizable dose distribution.…”