The use of tumour markers in oesophageal cancer to quantify setup errors and baseline shifts during treatment.

To prospectively evaluate the feasibility of solid gold marker placement in oesophageal cancer patients and to quantify inter-fractional and intra-fractional (baseline shift) marker motion during radiation treatment. Radiotherapy target margins and matching strategies were investigated. Thirty-four markers were implanted by echo-endoscopy in 10 patients. Patients received a planning 4D CT, daily pre-treatment cone-beam CT (CBCT) and a post-treatment CBCT for at least five fractions. For fractions with both pre- and post-treatment CBCT, marker displacement between planning CT and pre-treatment CBCT (inter-fractional) and between pre-treatment and post-treatment CBCT (intra-fractional; only for fractions without rotational treatment couch correction) were calculated in left-right (LR), cranio-caudal (CC) and anterior-posterior (AP) direction after bony-anatomy and soft-tissue matching. Systematic/random setup errors were estimated; treatment margins were calculated. No serious adverse events occurred. Twenty-three (67.6%) markers were visible during radiotherapy (n = 3 middle oesophagus, n = 16 distal oesophagus, n = 4 proximal stomach). Margins for inter-fractional displacement after bony-anatomy match depended on the localisation of the primary tumour and were 11.2 mm (LR), 16.4 mm (CC) and 8.2 mm (AP) for distal markers. Soft-tissue matching reduced the CC margin for these markers (16.4 mm to 10.5 mm). The mean intra-fractional shift of 12 distal markers was 0.4 mm (LR), 2.3 mm (CC) and 0.7 mm (AP). Inclusion of this shift resulted in treatment margins for distal markers of 12.8 mm (LR), 17.3 mm (CC) and 10.4 mm (AP) after bony-anatomy matching and 12.4 mm (LR), 11.4 mm (CC) and 9.7 mm (AP) after soft-tissue matching. This study demonstrated that the implantation of gold markers was safe, albeit less stable compared to other marker types. Inter-fractional motion was largest cranio-caudally for markers in the distal oesophagus, which was reduced after soft-tissue compared to bony-anatomy matching. The impact of intra-fractional baseline shifts on margin calculation was rather small.

Thomas M ，De Roover R ，van der Merwe S ，Lambrecht M ，Defraene G ，Haustermans K ... -  《Clinical and Translational Radiation Oncology》

Setup strategies and uncertainties in esophageal radiotherapy based on detailed intra- and interfractional tumor motion mapping.

Detailed knowledge of target motion is important for improved accuracy and decreased toxicity of esophageal cancer radiotherapy. This study uses the 3D trajectories of implanted markers during setup CBCT scans to investigate the intra- and interfractional tumor motion in esophageal cancer radiotherapy. For 21 esophageal cancer patients with implanted fiducial markers, 60-s 3D marker trajectories were estimated from the 2D marker positions in the projections of daily setup CBCT scans by a probability-based method. The motion was separated into respiratory and cardiac components by frequency analysis and motion magnitude (2nd-98th percentile) was extracted for each marker. The mean motion was calculated over all markers. The daily mean setup interfraction error for bony-anatomy and soft-tissue setup was used to estimate the margin accounting for interfractional motion. A total of 1036 marker trajectories were extracted using 427 CBCT scans and 63 markers. The mean motion magnitude over all markers was 2.9 mm (left-right (LR)), 8.8 mm (cranio-caudal (CC)) and 4.1 mm (anterior-posterior (AP)) for the full motion during CBCT acquisition with mean magnitudes of 2.7 mm (LR), 8.4 mm (CC) and 3.5 mm (AP) for respiratory motion and 1.0 mm (LR), 1.5 mm (CC) and 1.4 mm (AP) for cardiac motion. Substantial daily marker shifts relative to bones resulted in margins of 8.9 mm (LR), 9.5 mm (CC), and 7.3 mm (AP). Soft-tissue based setup in and near the CTV combined with rescanning of patients with anatomical changes reduced the margins to 6.9 mm (LR), 6.8 mm (CC), and 5.6 mm (AP). Esophageal tumor motion was mapped with unprecedented detail throughout the radiotherapy course. Respiratory motion dominated and was largest in the CC direction. Soft-tissue matching and an adaptive strategy reduced interfractional margins by 2-3 mm compared to bony-anatomy matching.

Hoffmann L ，Poulsen PR ，Ravkilde T ，Bertholet J ，Kruhlikava I ，Helbo BL ，Schmidt ML ，Nordsmark M ... -  《-》

Translational and rotational intra- and inter-fractional errors in patient and target position during a short course of frameless stereotactic body radiotherapy.

Josipovic M ，Persson GF ，Logadottir A ，Smulders B ，Westmann G ，Bangsgaard JP ... -  《-》

Residual setup errors in cranial stereotactic radiosurgery without six degree of freedom robotic couch: Frameless versus rigid immobilization systems.

This IRB-approved study was to compare the residual inter-fractional setup errors and intra-fractional motion of patients treated with cranial stereotactic radiosurgery without a 6 degree of freedom (DoF) couch. We evaluated both frameless non-invasive vacuum-suction immobilization (Aktina PinPoint) and TALON rigid screw immobilization. Twenty consecutive patients treated by Varian TrueBeam STX or Tomotherapy were selected for data collection. The dose and number of fractions received by each patient ranged from 18 Gy in 1 fraction (SRS) to 25 Gy in 5 fractions (SRT). Twelve patients were immobilized using PinPoint, a frameless suction system (Aktina Medical, New York) and eight patients were immobilized using the TALON rigid screw system. Customized head cushions were used for all patients. Six Atkina patients received pre- and post-treatment cone-beam CT (CBCT) to evaluate the intra-fractional motion of the Aktina system. The intra-fractional motion with the TALON rigid screw system has been reported to be negligible and was not repeated in this study. All patients received pre-treatment CBCT or megavoltage CT (MVCT) to assess inter-fractional setup accuracy. Shifts to the final treatment position were determined based on matching bony anatomy in the pre-treatment setup CT and the planning CT. Setup CT and planning CT were registered retrospectively based on bony anatomy using image registration software to quantify rotational and translational errors. For the frameless Aktina system, mean and standard deviation of the intra-fractional motion were -0.5 ± 0.7 mm (lateral), 0.1 ± 0.9 mm (vertical), -0.5 ± 0.6 mm (longitudinal), -0.04 ± 0.18°(pitch), -0.1 ± 0.23°(yaw), and -0.03 ± 0.17°(roll) indicating negligible intra-fractional motion. Inter-fractional rotation errors were -0.10 ± 0.25° (pitch), -0.08 ± 0.16° (yaw), and -0.20 ± 0.41° (roll) for TALON rigid screw immobilization versus 0.20 ± 0.69° (pitch), 0.34 ± 0.56° (yaw), 0.35 ± 0.82° (roll) for frameless vacuum-suction immobilization showing that the rigid immobilization setup is more reproducible than the frameless immobilization. Without rotational correction by a 6 DoF couch, residual registration error exists and increases with distance from the image fusion center. In a 3D vector space, a tumor located 5 cm from the center of image fusion would require a 0.9 mm margin with the TALON system and a 2.1 mm margin with Aktina. With image-guided radiotherapy, translational setup errors can be corrected by image registration between pre-treatment setup CT and planning CT. However, rotational errors cannot be accounted for without a 6 DoF couch. Our study showed that the frameless Aktina immobilization system provided negligible intra-fractional motion. The inter-fractional rotation setup error using Aktina was larger than rigid immobilization with the TALON system. To treat a single lesion far from the center of image registration or for multiple lesions in a single plan, additional margin may be needed to account for the uncorrectable rotational setup errors.

Liu RJ ，Yang SX ，Neylon J ，Hall MD ，Dandapani S ，Vora N ，Wong JYC ，Liu A ... -  《Journal of Applied Clinical Medical Physics》

Quantification of Esophageal Tumor Motion and Investigation of Different Image-Guided Correction Strategies.

To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies. Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations. Fifty-six patients with tumors located in the proximal (n = 1), mid (n = 7), or distal esophagus (n = 25) or at the gastroesophageal junction (n = 23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins. Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy.

Voncken FEM ，Nakhaee S ，Stam B ，Wiersema L ，Vollenbrock SE ，van Dieren JM ，van Leerdam ME ，Sonke JJ ，Aleman BMP ，Remeijer P ... -  《-》