The purpose of this study was to evaluate the stability of complex markers implanted into lung tumors throughout a course of stereotactic body radiotherapy (SBRT). Fifteen patients referred for lung SBRT were prospectively included. Radioopaque markers were implanted percutaneously, guided by computed tomography (CT). Deep inspiration breath-hold CT scans (BHCT) were acquired at planning and on three treatment days. The treatment days' BHCTs were registered to the planning BHCT. Intraobserver uncertainty in both tumor and marker registration was determined. Deviations in the difference between tumor and marker-based image registrations of the BHCT scans during treatment quantified the marker stability. Marker position deviation relative to tumor position of less than 2 mm in all three dimensions was considered acceptable for treatment delivery precision. Intra-observer uncertainties for image registration in the left-right (LR), anterior-posterior (AP), craniocaudal (CC) directions and three-dimensional vector (3D) were 0.9 mm, 0.9 mm, 1.0 mm, and 1.1 mm (SD) for tumor registration and 0.3 mm, 0.5 mm, 0.7 mm, and 0.7 mm (SD) for marker registration. Mean 3D differences for tumor registrations on all days were significantly larger than for 3D marker registrations (p = 0.007). Overall median differences between tumor and marker position were 0.0 mm (range -2.9 to 2.6 mm) in LR, 0.0 mm (-1.8 to 1.5 mm) in AP, and -0.2 mm (-2.6 to 2.8 mm) in CC directions. Four patients had deviations exceeding 2 mm in one or more registrations throughout the SBRT course. This is the first study to evaluate stability of complex markers implanted percutaneously into lung tumors for image guidance in SBRT. We conclude that the observed stability of marker position within the tumor indicates that complex markers can be used as surrogates for tumor position during a short course of SBRT as long as the uncertainties related to their position within the tumor are incorporated into the planning target volume.

71 patients whose MPLCs were both stage I, overall survival rates were 68.7% at 3 years and 28.1% at 5 years, with median survival time 59.8 months. Survival seemed better for MMPLC than for SMPLC, but this was not statistically different. In multivariate analysis, poor survival was associated with having CFRT for an index tumor (p Z 0.035) and being oxygen-dependent before treatment (p Z 0.019). Survival rates were not different for patients whose index tumors were treated with SABR versus surgery. The most common toxicity of SABR was chest wall pain (21.8% grade 2 and 3% grade 3), followed by pneumonitis (13.5% grade 2 and 3.1% grade 3/4) and dermatitis (9.4% grade 2 and 1% grade 3). Conclusions: SABR produced excellent local control and survival with tolerable toxicity in MPLC and may be potentially curative in some cases. Author Disclosure: Y. Liu: None. P. Balter: None. R. Komaki: None. Q. Xu: None. S. Swisher: None. J. Chang: None.

Objectives In radiotherapy, delineation uncertainties are important as they contribute to systematic errors and can lead to geographical miss of the target. For margin computation, standard deviations (SDs) of all uncertainties must be included as SDs. The aim of this study was to quantify the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design. Methods 22 consecutive patients with 26 tumours were included. Positron emission tomography/CT scans were acquired for planning of SBRT. Three oncologists and three radiologists independently delineated the gross tumour volume. The interobserver variation was calculated as a mean of multiple SDs of distances to a reference contour, and calculated for the transversal plane (SDtrans) and craniocaudal (CC) direction (SDcc) separately. Concordance indexes and volume deviations were also calculated. Results Median tumour volume was 13.0 cm3, ranging from 0.3 to 60.4 cm3. The mean SDtrans was 0.15 cm (SD 0.08 cm) and the overall mean SDcc was 0.26 cm (SD 0.15 cm). Tumours with pleural contact had a significantly larger SDtrans than tumours surrounded by lung tissue. Conclusions The interobserver delineation variation was very small in this systematic cross-sectional analysis, although significantly larger in the CC direction than in the transversal plane, stressing that anisotropic margins should be applied. This study is the first to make a systematic cross-sectional analysis of delineation variation for peripheral lung tumours referred for SBRT, establishing the evidence that interobserver variation is very small for these tumours.

Conventional CT (3DCT) during free breathing for lung cancer radiotherapy planning can result in artifacts impacting the imaged tumor volume. These artifacts can be reduced with the use of respiratory correlated imaging i.e. 4D-CT and breathhold CT (BHCT) scans. The aim of this study is to compare the delineated GTV size in 3DCT, 4D-CT and BHCT scans of patients with lung tumors. All patients referred for SBRT of lung tumors from February 2009 to January 2010 were considered for the study. Patients with atelectasis or tumors inseparable from the mediastinum were excluded. A total of 37 patients with 46 tumors were included. All patients had a PET/CT, 4D-CT and BHCT scan, obtained with the patient in a VacFix immobilization device. GTV delineation was done in Eclipse™ (Varian) in a broad window setting (-1000 to 700 HU) by one clinical oncologist. GTV in all CT scans of the individual patients was delineated within one session to minimize systematic delineation uncertainty. GTV size in the BHCT was considered closest to true tumor volume and chosen as reference and compared to GTV size in 3DCT and midventilation- (MidV), inspiration- (Insp) and expiration (Exp) bins from the 4D-CT scan (Wilcoxon paired signed rank test, two tailed level of significance < 0.05). Correlations between GTV displacement in cranio-caudal (CC) direction and the relative numeric deviation between the reference BHCT GTV size and GTV sizes in 3DCT, Insp, Exp and MidV respectively were tested (Spearman rank-order correlation, two tailed level of significance < 0.05). Median (range) GTV displacement in CC direction was 0.4 cm (0 to 2.4 cm). The median BHCT GTV size was 4.9 cm3 (0.1 to 53.3 cm3). Median deviation between 3DCT and BHCT GTV size was 0.3 cm3 (-3.3 to 30.0 cm3), between MidV and BHCT 0.0 cm3 (-5.7 to 19.7 cm3), between Insp and BHCT 0.0 cm3 (-4.7 to 24.8 cm3), and between Exp and BHCT 0.0 cm3 (-4.8 to 25.5 cm3). The 3DCT, MidV, Insp and Exp median GTV sizes were all significantly larger than the BHCT median GTV size. The Exp GTV size was closest to the BHCT GTV size. The relative numeric deviations between BHCT GTV size and 3DCT, Insp, Exp and MidV GTV sizes respectively was significantly correlated to GTV displacement in CC direction. In the present study the choice of CT method significantly influenced the imaged GTV size-on average leading to an increase in GTV size when compared to the reference breathhold CT scan. Attention to this problem is required, especially in case of large tumor motion, as clinical data concerning local control is mainly based on the use of conventional CT, where the GTV size was largest. Thorough follow up of patients is needed to ensure that local control rates are not decreased due to an unintended decrease in the irradiated volume with the use of respiratory correlated imaging.

Purpose/Objective(s)Day-to-day variation in motion and mean position of lung tumors can cause uncertainty in radiation treatment delivery, when patient setup is based on bony anatomy. This study compares setup to implanted fiducial markers and bony anatomy in SBRT of lung tumors.Materials/MethodsEight patients referred for SBRT (45 Gy in 3 fractions) of lung tumors had a fiducial marker implanted in their tumor. All patients were 4D-CT scanned (10 phase bins), and the midventilation bin was used for treatment planning. For daily patient setup the phase gating option in the Real-time Position Management system was used in combination with the On-Board Imager system (both Varian Medical Systems) to acquire orthogonal planar kV images of the tumor in the midventilation phase. A 2D/2D match was done with respect to the fiducial marker with a tolerance of 3 mm, using only translational corrections. A 2D/2D match with respect to bony anatomy was done retrospectively, and the difference between the marker and the bone match was evaluated in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) direction as well as in all three dimensions (3D). The mean and SD for the 3D difference between marker and bone match was calculated for each patient and correlated to tumor motion (Pearson's correlation coefficient, two tailed significance level p < 0.05). Tumor motion was measured as the peak-to-peak displacement of the gross tumor volume throughout the bins of the 4D-CT scans.ResultsRange of tumor motion in LR, AP and CC direction was 1-3 mm, 1-4 mm and 3-24 mm. Mean ± SD difference between marker and bone match in LR, AP and CC direction was 2 ± 1 mm, 1 ± 1 mm, 3 ± 3 mm and 4 ± 2 mm in 3D. A significant linear correlation was found between the SD of 3D difference between marker and bone match for each patient and tumor motion in CC direction (p < 0.0001, r = 0.98). One patient differed by having a small tumor motion but a large mean 3D difference between marker and bone match. For this patient, the marker implantation had caused a pneumothorax, which had fully recovered at the time of treatment but not at planning, creating a systematic error in marker position of about 5 mm. If this patient was excluded, a significant linear correlation was found between the mean 3D difference between marker and bone match for each patient and tumor motion in CC direction (p = 0.0233, r = 0.82).ConclusionsSetup to implanted fiducial markers and bony anatomy would have resulted in different treatment positions for all patients in the present study; the mean difference was 4 mm in 3D. The random as well as systematic difference between marker and bone match increased with increasing tumor motion. Therefore, setup to bony anatomy could be expected to introduce a larger uncertainty in radiation treatment delivery for patients with large tumor motion. Purpose/Objective(s)Day-to-day variation in motion and mean position of lung tumors can cause uncertainty in radiation treatment delivery, when patient setup is based on bony anatomy. This study compares setup to implanted fiducial markers and bony anatomy in SBRT of lung tumors. Day-to-day variation in motion and mean position of lung tumors can cause uncertainty in radiation treatment delivery, when patient setup is based on bony anatomy. This study compares setup to implanted fiducial markers and bony anatomy in SBRT of lung tumors. Materials/MethodsEight patients referred for SBRT (45 Gy in 3 fractions) of lung tumors had a fiducial marker implanted in their tumor. All patients were 4D-CT scanned (10 phase bins), and the midventilation bin was used for treatment planning. For daily patient setup the phase gating option in the Real-time Position Management system was used in combination with the On-Board Imager system (both Varian Medical Systems) to acquire orthogonal planar kV images of the tumor in the midventilation phase. A 2D/2D match was done with respect to the fiducial marker with a tolerance of 3 mm, using only translational corrections. A 2D/2D match with respect to bony anatomy was done retrospectively, and the difference between the marker and the bone match was evaluated in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) direction as well as in all three dimensions (3D). The mean and SD for the 3D difference between marker and bone match was calculated for each patient and correlated to tumor motion (Pearson's correlation coefficient, two tailed significance level p < 0.05). Tumor motion was measured as the peak-to-peak displacement of the gross tumor volume throughout the bins of the 4D-CT scans. Eight patients referred for SBRT (45 Gy in 3 fractions) of lung tumors had a fiducial marker implanted in their tumor. All patients were 4D-CT scanned (10 phase bins), and the midventilation bin was used for treatment planning. For daily patient setup the phase gating option in the Real-time Position Management system was used in combination with the On-Board Imager system (both Varian Medical Systems) to acquire orthogonal planar kV images of the tumor in the midventilation phase. A 2D/2D match was done with respect to the fiducial marker with a tolerance of 3 mm, using only translational corrections. A 2D/2D match with respect to bony anatomy was done retrospectively, and the difference between the marker and the bone match was evaluated in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) direction as well as in all three dimensions (3D). The mean and SD for the 3D difference between marker and bone match was calculated for each patient and correlated to tumor motion (Pearson's correlation coefficient, two tailed significance level p < 0.05). Tumor motion was measured as the peak-to-peak displacement of the gross tumor volume throughout the bins of the 4D-CT scans. ResultsRange of tumor motion in LR, AP and CC direction was 1-3 mm, 1-4 mm and 3-24 mm. Mean ± SD difference between marker and bone match in LR, AP and CC direction was 2 ± 1 mm, 1 ± 1 mm, 3 ± 3 mm and 4 ± 2 mm in 3D. A significant linear correlation was found between the SD of 3D difference between marker and bone match for each patient and tumor motion in CC direction (p < 0.0001, r = 0.98). One patient differed by having a small tumor motion but a large mean 3D difference between marker and bone match. For this patient, the marker implantation had caused a pneumothorax, which had fully recovered at the time of treatment but not at planning, creating a systematic error in marker position of about 5 mm. If this patient was excluded, a significant linear correlation was found between the mean 3D difference between marker and bone match for each patient and tumor motion in CC direction (p = 0.0233, r = 0.82). Range of tumor motion in LR, AP and CC direction was 1-3 mm, 1-4 mm and 3-24 mm. Mean ± SD difference between marker and bone match in LR, AP and CC direction was 2 ± 1 mm, 1 ± 1 mm, 3 ± 3 mm and 4 ± 2 mm in 3D. A significant linear correlation was found between the SD of 3D difference between marker and bone match for each patient and tumor motion in CC direction (p < 0.0001, r = 0.98). One patient differed by having a small tumor motion but a large mean 3D difference between marker and bone match. For this patient, the marker implantation had caused a pneumothorax, which had fully recovered at the time of treatment but not at planning, creating a systematic error in marker position of about 5 mm. If this patient was excluded, a significant linear correlation was found between the mean 3D difference between marker and bone match for each patient and tumor motion in CC direction (p = 0.0233, r = 0.82). ConclusionsSetup to implanted fiducial markers and bony anatomy would have resulted in different treatment positions for all patients in the present study; the mean difference was 4 mm in 3D. The random as well as systematic difference between marker and bone match increased with increasing tumor motion. Therefore, setup to bony anatomy could be expected to introduce a larger uncertainty in radiation treatment delivery for patients with large tumor motion. Setup to implanted fiducial markers and bony anatomy would have resulted in different treatment positions for all patients in the present study; the mean difference was 4 mm in 3D. The random as well as systematic difference between marker and bone match increased with increasing tumor motion. Therefore, setup to bony anatomy could be expected to introduce a larger uncertainty in radiation treatment delivery for patients with large tumor motion.

In radiotherapy of targets moving with respiration, beam gating is offered for reduction of target motion. The purpose of this study is to evaluate the magnitudes of possible margin reduction for respiratory gated beam delivery when all sources of positional uncertainties are considered. The study is based on respiratory correlated images for 16 lung cancer patients participating in three separate protocols at three institutes in Europe and the United States. Nine patients were imaged with 4D-CT scans, and 7 patients were imaged using fluoroscopy (gold seeds in tumors). The magnitude of respiratory motion was quantified by peak-to-peak displacement (5–95 percentile range in fluoroscopies). The required treatment field margins were calculated using a statistical recipe (van Herk et al., 2000), including delineation uncertainty, respiratory motion, other internal motion, and setup uncertainty. Magnitudes of all uncertainties, except respiratory motion, were the same for all patients, and were taken from literature (Steenbakkers et al., 2006; Wolthaus et al., 2008). The required margins for respiratory management were calculated using the same recipe with the total respiratory motion substituted with the residual respiratory motion for each patient. The margin reduction from respiration management was calculated in three steps; (1) Imaging for treatment planning (4D-CT, residual motion was motion in one phase bin approximately 20% of total motion); (2) Daily image guidance (residual motion was motion in an imaging frame approximately 10% of total motion); and (3) Gated beam delivery (residual motion was the motion in a 35% duty cycle end-expiration gating window). The median peak-to-peak displacement of the tumors was 6.5 mm for the 16 patients (range, 2–29.3 mm). This required treatment field margins of 17.6–38.5 mm (median 18.9 mm). By using 4D-CT, the required margin was reduced by 0.9 mm (median). By applying daily image guidance with respiratory correlation, the required margin was further reduced by 2.9 mm. The total required margin for treatment based on 4D-CT with daily image guidance was 14.6–23.2 mm, median 15.1 mm. By applying gated beam delivery, the required margin was further reduced by 0.2 mm (median), to a total of 14.6–16.6 mm. The effect of gated beam delivery on required treatment field margins for lung cancer radiotherapy is negligible compared to the effects of 4D-CT and respiratory correlated image guidance for most patients. The reason is that only the random part of the respiratory motion contribution to the required margin is affected. A respiratory management strategy for lung cancer radiotherapy including planning on 4D-CT scans and daily image guidance (focused on the tumor mean position), provides potential of up to approximately 17–40% reduction in-field margins.