Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

PURPOSE: To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. METHODS: Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior-posterior (AP) and right-left (RL) directions and 8 mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. RESULTS: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and -0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min. CONCLUSION: Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1ß which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.