Lung and Liver Stereotactic Body Radiation Therapy During Mechanically Assisted Deep Inspiration Breath-Holds: A Prospective Feasibility Trial.

Purpose: Radiation therapy for tumors subject to breathing-related motion during breath-holds (BHs) has the potential to substantially reduce the irradiated volume. Mechanically assisted and noninvasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumors. The aim of this work was, therefore, to evaluate the technique's performance under real treatment conditions. Methods and Materials: Patients eligible for lung or liver stereotactic body radiation therapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometric uncertainties extracted from real-time imaging, tolerance to BH, and treatment time. Results: Treatment was successfully delivered in 92.9% (13/14) of patients: 1 patient with a liver tumor was excluded because of a mechanically induced gastric insufflation displacing the liver cranially by more than 1 cm. In the left-right/anteroposterior/craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm/5.1 mm/5.6 mm and 4.7 mm/7.3 mm/5.9 mm for lung and liver lesions, respectively. Compared with the free-breathing internal target volume and midposition approaches, the average reduction in the planning target volume with MANIV reached -47.2% ± 15.3%, P < .001, and -29.4% ± 19.2%, P = .007, for intrathoracic tumors and -23.3% ± 12.4%, P < .001, and -9.3% ± 15.3%, P = .073, for upper abdominal tumors, respectively. For 1 liver lesion, large caudal drifts of occasionally more than 1 cm were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1% ± 10.6%. Conclusions: MANIV enables high treatment feasibility within a nonselected population. Accurate intrafraction tumor repositioning is achieved for lung tumors. Because of occasional intra-BH caudal drifts, pretreatment assessment of BH stability for liver lesions is, however, recommended.

Voluntary versus mechanically-induced deep inspiration breath-hold for left breast cancer: A randomized controlled trial.

BACKGROUND AND PURPOSE: Deep inspiration breath-hold (DIBH) protects critical organs-at-risk (OARs) for adjuvant breast radiotherapy. Guidance systems e.g. surface guided radiation therapy (SGRT) improve the positional breast reproducibility and stability during DIBH. In parallel, OARs sparing with DIBH is enhanced through different techniques e.g. prone position, continuous positive airway pressure (CPAP). By inducing repeated DIBH with the same level of positive pressure, mechanically-assisted and non-invasive ventilation (MANIV) could potentially combine these DIBH optimizations. MATERIALS AND METHODS: We conducted a randomized, open-label, multicenter and single-institution non-inferiority trial. Sixty-six patients eligible for adjuvant left whole-breast radiotherapy in supine position were equally assigned between mechanically-induced DIBH (MANIV-DIBH) and voluntary DIBH guided by SGRT (sDIBH). The co-primary endpoints were positional breast stability and reproducibility with a non-inferiority margin of 1 mm. Secondary endpoints were tolerance assessed daily via validated scales, treatment time, dose to OARs and their inter-fraction positional reproducibility. RESULTS: Differences between both arms for positional breast reproducibility and stability occurred at a sub-millimetric level (p < 0.001 for non-inferiority). The left anterior descending artery near-max dose (14,6 ± 12,0 Gy vs. 7,7 ± 7,1 Gy, p = 0,018) and mean dose (5,0 ± 3,5 Gy vs. 3,0 ± 2,0 Gy, p = 0,009) were improved with MANIV-DIBH. The same applied for the V5Gy of the left ventricle (2,4 ± 4,1 % vs. 0,8 ± 1,6 %, p = 0,001) as well as for the left lung V20Gy (11,4 ± 2,8 % vs. 9,7 ± 2,7 %, p = 0,019) and V30Gy (8,0 ± 2,6 % vs. 6,5 ± 2,3 %, p = 0,0018). Better heart's inter-fraction positional reproducibility was observed with MANIV-DIBH. Tolerance and treatment time were similar. CONCLUSION: Mechanical ventilation provides the same target irradiation accuracy as with SGRT while better protecting and repositioning OARs.

Incorporation of tumor motion directionality in margin recipe: The directional MidP strategy.

PURPOSE: Planning target volume (PTV) definition based on Mid-Position (Mid-P) strategy typically integrates breathing motion from tumor positions variances along the conventional axes of the DICOM coordinate system. Tumor motion directionality is thus neglected even though it is one of its stable characteristics in time. We therefore propose the directional MidP approach (MidP dir), which allows motion directionality to be incorporated into PTV margins. A second objective consists in assessing the ability of the proposed method to better take care of respiratory motion uncertainty. METHODS: 11 lung tumors from 10 patients with supra-centimetric motion were included. PTV were generated according to the MidP and MidP dir strategies starting from planning 4D CT. RESULTS: PTVMidP dir volume didn't differ from the PTVMidP volume: 31351 mm3 IC95% [17242-45459] vs. 31003 mm3 IC95% [ 17347-44659], p = 0.477 respectively. PTVMidP dir morphology was different and appeared more oblong along the main motion axis. The relative difference between 3D and 4D doses was on average 1.09%, p = 0.011 and 0.74%, p = 0.032 improved with directional MidP for D99% and D95%. D2% was not significantly different between both approaches. The improvement in dosimetric coverage fluctuated substantially from one lesion to another and was all the more important as motion showed a large amplitude, some obliquity with respect to conventional axes and small hysteresis. CONCLUSIONS: Directional MidP method allows tumor motion to be taken into account more tightly as a geometrical uncertainty without increasing the irradiation volume.

Occurrence of pituitary hormone deficits in relation to both pituitary and hypothalamic doses after radiotherapy for skull base meningioma.

CONTEXT: Little accurate information is available regarding the risk of hypopituitarism after irradiation of skull base meningiomas. DESIGN: Retrospective study in a single centre. PATIENTS: 48 patients with a skull base meningioma and normal pituitary function at diagnosis, treated with radiotherapy (RXT) between 1998 and 2017 (median follow-up of 90 months). MEASUREMENTS: The GH, TSH, LH/FSH and ACTH hormonal axes were evaluated yearly for the entire follow-up period. Mean doses delivered to the pituitary gland (PitD) and the hypothalamus (HypoD) were calculated, as well as the doses responsible for the development of deficits in 50% of patients after 5 years (TD50). RESULTS: At least one hormone deficit was observed in 38% of irradiated patients and complete hypopituitarism in 13%. The GH (35%), TSH (32%) and LH/FSH axes (28%) were the most frequently affected, while ACTH secretion axis was less altered (13%). The risk of hypopituitarism was independently related to planning target volume (PTV) and to the PitD (threshold dose 45 Gy; TD50 between 50 and 54 Gy). In this series, the risk was less influenced by the HypoD, increasing steadily between doses of 15 and 70 Gy with no clear-cut dose threshold. CONCLUSIONS: Over a median follow-up period of 7.5 years, hypopituitarism occurred in more than one third of patients irradiated for a skull base meningioma, and this prevalence was time- and dose-dependent. In this setting, the risk of developing hypopituitarism was mainly determined by the irradiated target volume and by the dose delivered to the pituitary gland.

Feasibility of a TPS-integrated method to incorporate tumor motion in the margin recipe.

BACKGROUND AND PURPOSE: There are several alternatives to the widespread ITV strategy in order to account for breathing-induced motion in PTV margins. The most sophisticated one includes the generation of a motion-compensated CT scan with the CTV placed in its average position - the mid-position approach (MidP). In such configuration, PTV margins integrate breathing as another random error. Despite overall irradiated volume reduction, such approach is barely used in clinical practice because of its dependence to deformable registration and its unavailability in commercial treatment planning systems. As an alternative, the mid-ventilation approach (MidV) selects the phase in the 4D-CT scan that is the closest to the MidP, with a residual error accounted for in the PTV margin. We propose a treatment planning system-integrated strategy, aiming at better approximating the MidP approach without its drawbacks: Hybrid MidV-MidP approach, i.e., the delineation on the MidV-CT and translation at the mid-position coordinates using treatment planning system built-in capabilities. MATERIAL AND METHODS: Forty-five lung lesions treated with stereotactic radiotherapy were selected. PTV was defined using MidP, MidV, Hybrid MidV-MidP and ITV strategies. Margin definitions were adapted and resulting PTVs were compared. RESULTS: Hybrid MidV-MidP showed similar target volume and location than the MidP and confirmed that margin-incorporated tumor motion strategies lead to significantly smaller PTVs than the ITV with mean reduction of 26 ± 7%. CONCLUSION: We report on the successful implementation of a pseudo-MidP solution without its inherent drawbacks. It answers the need for TPS-embedded tumor motion range identification and related margin's component calculation.

Improvement of kilovoltage intrafraction monitoring accuracy through gantry angles selection.

Kilovoltage intrafraction monitoring (KIM) is a method allowing to precisely infer the tumour trajectory based on cone beam computed tomography (CBCT) 2D-projections. However, its accuracy is deteriorated in the case of highly mobile tumours involving hysteresis. A first adaptation of KIM consisting of a prior amplitude based binning step has been developed in order to minimize the errors of the original model (phase-KIM). In this work, we propose enhanced methods (KIMsub-arc optimand phase-KIMsub-arc optim) to improve the accuracy of KIM and phase-KIM which relies on the selection of the optimal starting CBCT gantry angle. Aiming at demonstrating the interest of our approach, we carried out a simulation study and an experimental study: we compared the accuracy of the conventional versus sub-arc optim methods on simulated realistic tumour motions with amplitudes ranging from 5 to 30 mm in 1 mm increments. The same approach was performed using a lung dynamic phantom generating a 30 mm amplitude sinusoidal motion. The results show that for in-silico simulated motions of 10, 20 and 30 mm amplitude, the three-dimensional root mean square error (3D-RMSE) can be reduced by 0.67 mm, 0.91 mm, 0.94 mm and 0.18 mm, 0.25 mm, 0.28 mm using KIMsub-arc optimand phase-KIMsub-arc optimrespectively. Considering all in-silico simulated trajectories, the percentage of errors larger than 1 mm decreases from 21.9% down to 1.6% for KIM (p < 0.001) and from 6.6% down to 1.2% for phase-KIM (p < 0.001). Experimentally, the 3D-RMSE is lowered by 0.5732 mm for KIM and by 0.1 mm for phase-KIM. The percentage of errors larger than 1 mm falls from 39.7% down to 18.5% for KIM and from 23.2% down to 11.1% for phase-KIM. In conclusion, our method efficiently anticipates CBCT gantry angles associated with a significantly better accuracy by using KIM and phase-KIM.