Tumor volume changes during stereotactic ablative radiotherapy for adrenal gland metastases under MRI guidance.

PURPOSE: Gross tumor volume (GTV) changes during stereotactic ablative radiotherapy (SABR) for adrenal tumors are not well characterized. We studied treatment-induced GTV changes during, and after, 5-fraction MR-guided SABR on a 0.35 T unit. METHODS AND MATERIALS: Details of patients treated for adrenal metastases using 5-fraction adaptive MR-SABR were accessed. GTV changes between simulation and first fraction (ΔSF1) and all fractions were recorded. Wilcoxon paired tests were used for intrapatient comparisons. Logistic and linear regression models were used for features associated with dichotomous and continuous variables, respectively. RESULTS: Once-daily fractions of 8 Gy or 10 Gy were delivered to 70 adrenal metastases. Median simulation-F1 interval was 13 days; F1-F5 interval was 13 days. Median baseline GTVs at simulation and F1 were 26.6 and 27.2 cc, respectively (p < 0.001). Mean ΔSF1 was + 9.1% (2.9 cc) relative to simulation; 47% of GTVs decreased in volume at F5 versus F1. GTV variations of ≥ 20% occurred in 59% treatments at some point between simulation to end SABR, and these did not correlate with baseline tumor characteristics. At a median follow-up of 20.3 months, a radiological complete response (CR) was seen in 23% of 64 evaluable patients. CR was associated with baseline GTV (p = 0.03) and ΔF1F5 (p = 0.03). Local relapses were seen in 6%. CONCLUSION: Frequent changes in adrenal GTVs during 5-fraction SABR delivery support the use of on-couch adaptive replanning. The likelihood of a radiological CR correlates with the baseline GTV and intra-treatment GTV decline.

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. PURPOSE: We conducted a comparison of accumulated doses for MRgRT, robustly optimized non-adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high-grade toxicities. METHODS: Data of 18 early-stage central lung tumor patients, treated at a 0.35 T MR-linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non-adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose-volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs-at-risk (OARs) within 2 cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed-rank tests between S1 & S2, and S1 & S3. RESULTS: The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: -8%; S3: -23%) and mean heart dose (S2: -79%; S3: -83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1-2 cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantly different for OARs within 1 cm of the PTV. CONCLUSIONS: A significant dose sparing potential of non-adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near-maximum dose to the bronchial tree was not significantly different for MRgRT and non-adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT.

A new approach to quantifying lung damage after stereotactic body radiation therapy.

Radiological pneumonitis and fibrosis are common after stereotactic body radiotherapy (SBRT) but current scoring systems are qualitative and subjective. We evaluated the use of CT density measurements and a deformable registration tool to quantitatively measure lung changes post-SBRT. Material and methods. Four-dimensional CT datasets from 25 patients were imported into an image analysis program. Deformable registration was done using a B-spline algorithm (VelocityAI) and evaluated by landmark matching. The effects of respiration, contrast, and CT scanner on density measurements were evaluated. The relationship between density and clinician-scored radiological pneumonitis was assessed. Results. Deformable registration resulted in more accurate image matching than rigid registration. CT lung density was maximal at end-expiration, and most deformation with breathing occurred in the lower thorax. Use of contrast increased mean lung density by 18 HU (range 16-20 HU; p = 0.004). Diagnostic scans had a lower mean lung density than planning scans (mean difference 57 HU in lung contralateral to tumor; p = 0.048). Post-treatment CT density measurements correlated strongly with clinician-scored radiological pneumonitis (r = 0.75; p < 0.001). Conclusions. Quantitative analysis of changes in lung density correlated strongly with physician-assigned radiologic pneumonitis scores. Deformable registration and CT density measurements permit objective assessment of treatment toxicity.

Renal atrophy following gated delivery of stereotactic ablative radiotherapy to adrenal metastases.

Stereotactic ablative radiotherapy (SABR) planning for adrenal metastases aims to minimize doses to the adjacent kidney. Renal dose constraints for SABR delivery are not well defined. In 20 patients who underwent MR-guided breath-hold SABR in five daily fractions of 8-10 Gy, ipsilateral renal volumes receiving ≥20 Gy best correlated with loss of renal volumes, with median renal volume reduction being 6% (range: 3%-11%, 10th-90th percentiles). Organ function did not deteriorate in 18 patients, who had post treatment renal function tests available. This suggests that the ipsilateral renal volume receiving 20 Gy can be used as partial organ dose constraint for SABR to targets in the upper abdomen.

Impact of daily plan adaptation on organ-at-risk normal tissue complication probability for adrenal lesions undergoing stereotactic ablative radiation therapy.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) can achieve good local control for metastatic adrenal lesions. Magnetic resonance (MR)-guidance with daily on-table plan adaptation can augment the delivery of SABR with greater dose certainty. The goal of this study was to quantify the potential clinical benefit MR-guided daily-adaptive adrenal SABR using the normal tissue complication probability (NTCP) framework. METHODS: Patients treated with adrenal MR-guided SABR at a single institution were retrospectively reviewed. Lyman-Kutcher-Burman NTCP models were used to calculate the NTCP of upper abdominal organs-at-risk (OARs) at simulation and both before and after daily on-table plan adaptation. Differences in OAR NTCPs were assessed using signed-rank tests. Potential predictors of the benefits of adaptation were assessed by linear regression. RESULTS: Fifty-two adrenal MR-guided SABR courses were analyzed. The baseline simulation plan underestimated the absolute stomach NTCP by 10.0% on average (95% confidence interval: 4.7-15.2%, p < 0.001). Daily on-table adaptation lowered absolute NTCP by 8.7% (4.2-13.2%, p < 0.001). The most significant predictor of the benefits of adaptation was lesion laterality (p = 0.018), with left-sided lesions benefitting more (13.3% [6.3-20.4%], p < 0.001) than right-sided lesions (2.1% [-1.6-5.7%], p = 0.25). Sensitivity analyses did not change the statistical significance of the findings. CONCLUSION: NTCP analysis revealed that patients with left adrenal tumors were more likely to benefit from MR-guided daily on-table adaptive SABR using current dose/fractionation regimens due to reductions in predicted gastric toxicity. Right-sided adrenal lesions may be considered for dose escalation due to low predicted NTCP.

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy.

BACKGROUND AND PURPOSE: Single-fraction stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage lung cancer, but concerns remain about the accurate delivery of SABR in a single session. We evaluated the delivery of single-fraction lung SABR using magnetic resonance (MR)-guidance. MATERIALS AND METHODS: An MR-simulation was performed in 17 patients, seven of whom were found to be unsuitable, largely due to unreliable tracking of small tumors. Ten patients underwent single-fraction SABR to 34 Gy on a 0.35 T MR-linac system, with online plan adaptation. Gated breath-hold SABR was delivered using a planning target volume (PTV) margin of 5 mm, and a 3 mm gating window. Continuous MR-tracking of the gross tumor volume (GTVt) was performed in sagittal plane, with visual patient feedback provided using an in-room monitor. The real-time MR images were analyzed to determine precision and efficiency of gated delivery. RESULTS: All but one patient completed treatment in a single session. The median total in-room procedure was 120 min, with a median SABR delivery session of 39 min. Review of 7.4 h of cine-MR imaging revealed a mean GTVt coverage by the PTV during beam-on of 99.6%. Breath-hold patterns were variable, resulting in a mean duty cycle efficiency of 51%, but GTVt coverage was not influenced due to real-time MR-guidance. On-table adaptation improved PTV coverage, but had limited impact on GTV doses. CONCLUSIONS: Single-fraction gated SABR of lung tumors can be performed with high precision using MR-guidance. However, improvements are needed to ensure MR-tracking of small tumors, and to reduce treatment times.

Changes in gastric anatomy after delivery of breath-hold MR-guided SABR for adrenal metastases.

Delivery of breath-hold MR-guided SABR is time-consuming, and the use of real-time tumor-tracking in a sagittal plane may fail to detect out-of-plane displacements of organs-at-risk. Analysis of daily MR-scans performed pre- and post-SABR revealed frequent decreases in stomach volumes, and in the planned stomach doses.

Impact of audio-coaching on the position of lung tumors.

PURPOSE: Respiration-induced organ motion is a major source of positional, or geometric, uncertainty in thoracic radiotherapy. Interventions to mitigate the impact of motion include audio-coached respiration-gated radiotherapy (RGRT). To assess the impact of coaching on average tumor position during gating, we analyzed four-dimensional computed tomography (4DCT) scans performed both with and without audio-coaching. METHODS AND MATERIALS: Our RGRT protocol requires that an audio-coached 4DCT scan is performed when the initial free-breathing 4DCT indicates a potential benefit with gating. We retrospectively analyzed 22 such paired scans in patients with well-circumscribed tumors. Changes in lung volume and position of internal target volumes (ITV) generated in three consecutive respiratory phases at both end-inspiration and end-expiration were analyzed. RESULTS: Audio-coaching increased end-inspiration lung volumes by a mean of 10.2% (range, -13% to +43%) when compared with free breathing (p = 0.001). The mean three-dimensional displacement of the center of ITV was 3.6 mm (SD, 2.5; range, 0.3-9.6mm), mainly caused by displacement in the craniocaudal direction. Displacement of ITV caused by coaching was more than 5 mm in 5 patients, all of whom were in the subgroup of 9 patients showing total tumor motion of 10 mm or more during both coached and uncoached breathing. Comparable ITV displacements were observed at end-expiration phases of the 4DCT. CONCLUSIONS: Differences in ITV position exceeding 5 mm between coached and uncoached 4DCT scans were detected in up to 56% of mobile tumors. Both end-inspiration and end-expiration RGRT were susceptible to displacements. This indicates that the method of audio-coaching should remain unchanged throughout the course of treatment.

Analysis of carina position as surrogate marker for delivering phase-gated radiotherapy.

PURPOSE: Respiratory gating can mitigate the effect of tumor mobility in radiotherapy (RT) for lung cancer. Because the tumor is generally not visualized, external surrogates of tumor position are used to trigger respiration-gated RT. We evaluated the suitability of the carina position as a surrogate in respiration-gated RT. METHODS AND MATERIALS: A total of 30 four-dimensional (4D) computed tomography (CT) scans from 14 patients with lung cancer were retrospectively analyzed. Both uncoached (free breathing) and audio-coached 4D-CT scans were acquired from 9 patients, and 12 uncoached 4D-CT scans were acquired from 5 other patients during a 2-4-week period of stereotactic RT. The repeat scans were co-registered. The carina position was identified on the coronal cut planes in all 4D-CT phases. The correlation between the carina position and the total lung volume for each phase was determined, and the reproducibility of the carina position was studied in the 5 patients with repeat uncoached 4D-CT scans. RESULTS: The mean extent of carina motion in 21 uncoached scans was 5.3 +/- 1.6 mm in the craniocaudal (CC), 2.3 +/- 1.4 mm in the anteroposterior, and 1.5 +/- 0.7 mm in the mediolateral direction. Audio coaching resulted in a twofold increase in carina mobility in all directions. The CC carina position correlated with changes in the total lung volume (R = 0.89 +/- 0.14), but the correlation was better for the audio-coached than for the uncoached 4D-CT scans (R = 0.93 +/- 0.08 vs. R = 0.85 +/- 0.17; paired t test, p = 0.034). Preliminary data from the 5 patients indicated that the CC carina motion correlated better with tumor motion than did the motion of the diaphragm. CONCLUSIONS: The CC position of the carina correlated well with the total lung volume, indicating that the carina is a good surrogate for verifying the total lung volume during respiration-gated RT.

Analysis of reproducibility of respiration-triggered gated radiotherapy for lung tumors.

PURPOSE: Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo-radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a predictable relationship between tumor position and external surrogate, which must be verified during treatment. Time-integrated electronic portal imaging (TI-EPI) identifies mean intra-fractional positions of moving structures, and was used to study reproducibility of anatomy during RGRT for lung tumors. MATERIALS AND METHODS: TI-EPIs were acquired using an amorphous silicon-based electronic portal imaging system (EPID, aS500) in continuous image acquisition mode in 11 patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All TI-EPI portals were co-registered to corresponding digitally reconstructed radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in tumor position or that of an adjacent bronchus during RGRT was measured relative to the reference structure on the DRR. RESULTS: Vertebra-matched portals revealed systematic (Sigma) and random (sigma) errors of 1.8 and 1.3mm in medial-lateral direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a reproducible tumor/bronchus position during the RPM-triggered gates. CONCLUSIONS: RGRT delivery at end-inspiration can achieve reproducible internal anatomy in 'gated' fields delivered with audio-coaching.

MR-guided Gated Stereotactic Radiation Therapy Delivery for Lung, Adrenal, and Pancreatic Tumors: A Geometric Analysis.

PURPOSE: We implemented magnetic resonance-guided breath-hold stereotactic body radiation therapy in combination with visual feedback using the MRIdian system. Both accuracy of gated delivery and reproducibility of tumor positions were studied. METHODS AND MATERIALS: Tumor tracking is realized through repeated magnetic resonance imaging in a single sagittal plane at 4 frames per second with deformable image registration. An in-room monitor allowed visualization of the tracked gross tumor volume (GTV) contour and the planning target volume (PTV) (GTV + 3 mm), which was the gating boundary. For each delivery, a predefined threshold-region of interest percentage (ROI%) allows a percentage of GTV area to be outside the gating boundary before a beam-hold is triggered. Accuracy of gated delivery and tumor position reproducibility during breath-holds was analyzed for 15 patients (87 fractions) with lung, adrenal, and pancreas tumors. For each fraction, we analyzed (1) reproducibility of system-tracked GTV centroid position within the PTV; (2) geometric coverage of GTV area within the PTV; (3) treatment duty cycle efficiency; (4) effects of threshold ROI% settings on treatment duty cycle efficiency and GTV area coverage; and (5) beam-off latency effect on mean GTV coverage. RESULTS: For lung, adrenal, and pancreatic tumors, grouped 5th to 95th percentile distributions of GTV centroid positions in the dorsoventral direction, relative to PTV-center of mass (COM), were, respectively, -3.3 mm to 2.8 mm, -2.5 mm to 3.7 mm, and -4.4 mm to 2.9 mm. Corresponding distributions in the craniocaudal direction were -2.6 mm to 4.6 mm, -4.1 mm to 4.4 mm, and -4.4 mm to 4.5 mm, respectively. Mean GTV areas encompassed during beam-on for all fractions were 94.6%, 94.3%, and 95.3% for lung, adrenal, and pancreas tumors, respectively. Mean treatment duty cycle efficiency ranged from 67% to 87% for these tumors. Use of higher threshold-ROI% resulted in increased duty cycle efficiency, at the cost of a small decrease in GTV area coverage. The beam-off latency had a marginal impact on the GTV coverage. CONCLUSIONS: Gated stereotactic body radiation therapy delivery during breath-hold, real-time magnetic resonance guidance resulted in at least 95% geometric GTV coverage in lung, adrenal, and pancreatic tumors.

A four-dimensional CT-based evaluation of techniques for gastric irradiation.

PURPOSE: To evaluate three-dimensional conformal (3D-CRT), intensity-modulated (IMRT) and respiration-gated radiotherapy (RGRT) techniques for gastric irradiation for target coverage and minimization of renal doses. All techniques were four-dimensional (4D)-CT based, incorporating the intrafractional mobility of the target volume and organs at risk (OAR). METHODS AND MATERIALS: The stomach, duodenal C-loop, and OAR (kidneys, liver, and heart) were contoured in all 10 phases of planning 4D-CT scans for five patients who underwent abdominal radiotherapy. Planning target volumes (PTVs) encompassing all positions of the stomach (PTV(all phases)) were generated. Three respiratory phases for RGRT in inspiration and expiration were identified, and corresponding PTV(inspiration) and PTV(expiration) and OAR volumes were created. Landmark-based fields recommended for the Radiation Therapy Oncology Group (RTOG) 99-04 study protocol were simulated to assess PTV coverage. IMRT and 3D-CRT planning with and without additional RGRT planning were performed for all PTVs, and corresponding dose volume histograms were analyzed. RESULTS: Use of landmark-based fields did not result in full geometric coverage of the PTV(all phases) in any patient. IMRT significantly reduced mean renal doses compared with 3D-CRT (15.0 Gy +/- 0.9 Gy vs. 20.1 Gy +/- 9.3 Gy and 16.6 Gy +/- 1.5 Gy vs. 32.6 Gy +/- 7.1 Gy for the left and right kidneys, respectively; p = 0.04). No significant increase in renal sparing was seen when adding RGRT to either 3D-CRT or IMRT. Tolerance doses to the other OAR were not exceeded. CONCLUSIONS: Individualized field margins are essential for gastric irradiation. IMRT plans significantly reduce renal doses, but the benefits of RGRT in gastric irradiation appear to be limited.

Four-dimensional computed tomographic analysis of esophageal mobility during normal respiration.

BACKGROUND: Chemo-radiotherapy for thoracic tumors can result in high-grade radiation esophagitis. Treatment planning to reduce esophageal irradiation requires organ motion to be accounted for. In this study, esophageal mobility was assessed using four-dimensional computed tomography (4DCT). METHODS AND MATERIALS: Thoracic 4DCT scans were acquired on a 16-slice CT scanner in 29 patients. The outer esophageal wall was contoured in two extreme phases of respiration in 9 patients with nonesophageal malignancies. The displacement of the center of contour was measured at 2-cm intervals. In 20 additional patients with Stage I lung cancer, the esophagus was contoured in all 10 phases of each 4DCT at five defined anatomic levels. Both approaches were then applied to 4DCT scans of 4 patients who each had two repeat scans performed. A linear mixed effects model was constructed with fixed effects: measurement direction, measurement type, and measurement location along the cranio-caudal axis. RESULTS: Measurement location and direction were significant descriptive parameters (Wald F-tests, p < 0.001), and the interaction term between the two was significant (p = 0.02). Medio-lateral mobility exceeded dorso-ventral mobility in the lower half of the esophagus but was of a similar magnitude in the upper half. Margins that would have incorporated all movement in medio-lateral and dorso-ventral directions were 5 mm proximally, 7 mm and 6 mm respectively in the mid-esophagus, and 9 mm and 8 mm respectively in the distal esophagus. CONCLUSIONS: The distal esophagus shows more mobility. Margins for mobility that can encompass all movement were derived for use in treatment planning, particularly for stereotactic radiotherapy.

Can mediastinal nodal mobility explain the low yield rates for transbronchial needle aspiration without real-time imaging?

BACKGROUND: The diagnostic yields with transbronchial needle aspiration (TBNA) for mediastinal nodes are highly variable. Nodal positions, as assessed on a breath-hold conventional CT scan, do not account for nodal motion. We studied nodal motion on four-dimensional (4D) CT scans. METHODS: A total of 47 mediastinal nodes were identified on 4D CT scans performed for radiotherapy planning in 25 patients with lung cancer. Nodes were mainly located at stations 4R, 4L, 7, and 2R, and each identified node was contoured in all 10 phases of the 4D CT scan. Nodal motion was correlated with changes in carina position. RESULTS: The mean (+/- SD) nodal diameter was 10.2 +/- 4.0 mm; and the mean nodal volume was 1.8 +/- 2.3 mL. Movement was maximal in the craniocaudal axis (mean length, 4.7 +/- 2.3 mm), and the corresponding mean mediolateral and ventrodorsal movements were 2.8 +/- 1.9 mm and 2.4 +/- 1.8 mm, respectively. The mean three-dimensional displacement of the nodal center was 6.2 +/- 2.9 mm, and it exceeded 10 mm in five nodes. The nodal mass was constantly present in only 25 +/- 14% of the region encompassing all nodal positions. The mean variation in craniocaudal distance between all nodes and the carina position during respiration was 5.3 +/- 2.1 mm (range, 2.2 to 10.5 mm). CONCLUSIONS: Both nodal motion and the varying distance between the carina and nodal position may explain the lower diagnostic yields for TBNA procedures performed without real-time guidance.

Renal mobility during uncoached quiet respiration: an analysis of 4DCT scans.

PURPOSE: Data on organ mobility is required for optimizing radiotherapy. Renal mobility was studied in four-dimensional computed tomography (4DCT) scans acquired during uncoached respiration. METHODS AND MATERIALS: The 4DCT scans of 54 patients, in whom at least the upper pole of both kidneys were visualized in all 10 respiratory phases, were analyzed. Scans were performed on a 16-slice CT scanner (slice index and reconstruction, 2.5 mm) during quiet, uncoached respiration. Mobility of the renal apex was evaluated in all patients by use of the z-position on CT slices. Reproducibility of mobility was studied in 8 patients who underwent 1 or 2 repeat 4DCT scans. RESULTS: Mobility was predominantly craniocaudal, with a mean of 9.8 mm for the left kidney and 9.0 mm for the right kidney. Large interpatient variations were observed that ranged from 2.5 to 30 mm (left) and 2.5 to 20 mm (right), and mobility of 1 kidney did not predict for mobility of the contralateral organ. Reproducibility of renal mobility and position at end-expiration was poor, with positional variations in repeat scans appearing to correlate with changes in the amplitude of respiratory waveform and total lung volume. CONCLUSIONS: Large interpatient variations in renal movement occur during uncoached respiration, which indicates that respiratory coaching is useful for 4DCT imaging and treatment delivery.

Evaluating mobility for radiotherapy planning of lung tumors: a comparison of virtual fluoroscopy and 4DCT.

PURPOSE: Fluoroscopy is widely used for evaluating tumor mobility in radiotherapy planning. Lung tumor mobility was scored using virtual fluoroscopy, and this was compared to mobility derived from contoured tumors in all phases of a respiration-correlated (or 4D) CT scan. METHODS AND MATERIALS: 4DCT datasets were reviewed and 29 patients were identified in whom tumors were visible on anterior-posterior fluoroscopy views. Mobility in all directions was estimated on fluoroscopy movie loops by four clinicians. These results were compared to mobility measured from contoured tumor volumes in all phases of the same 4DCT. Internal target volumes (ITV) were generated for both approaches. RESULTS: In eight patients, fluoroscopy did not allow for tumor mobility to be assessed in at least one direction. No significant inter-clinician variation was observed with respect to fluoroscopic assessment of mobility. Clinicians systematically overestimated mobility in all three directions (p<0.05). The mean ITVs derived using fluoroscopy were 52.2% larger than those derived using 4DCT contours, but the individual ITVs were smaller in three patients. CONCLUSION: Use of virtual fluoroscopy generally overestimates the mobility of visible lung tumors, and results in irradiation of unnecessarily large target volumes. In contrast, use of 4DCT minimizes the risk of normal tissue toxicity.

Use of CD-ROM-based tool for analyzing contouring variations in involved-field radiotherapy for Stage III NSCLC.

BACKGROUND: Interclinician variability in defining target volumes is a problem in conformal radiotherapy. A CD-ROM-based contouring tool was used to conduct a dummy run in an international trial of involved-field chemoradiotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: The CT scan of an eligible patient was installed on an "auto-run" CD-ROM incorporating a contouring program based on ImageJ for Windows, which runs on any personal computer equipped with a CD-ROM drive. This tool was initially piloted at four academic centers and was subsequently mailed, together with all relevant clinical, radiologic, and positron emission tomography findings, to all participating centers in the international trial. Clinicians were instructed to contour separate gross tumor volumes (GTVs) for the tumor and two enlarged nodes and a clinical target volume for the hilus. A reference "consensus" target volume for each target was jointly generated by three other clinicians. RESULTS: The data received from the four academic centers and 16 study participants were suitable for analysis. Data from one center was unsuitable for detailed analysis because the target volumes were contoured at 1.2-cm intervals. GTVs were available for a total of 21 tumors and 19 nodes, and 15 hilar clinical target volumes were available. The mean GTV of the primary tumor was 13.6 cm(3) (SD, 5.2; median, 12.3; range, 8.3-26.9). The variation in the center of the mass relative to the mean center of the mass in the left-right, ventrodorsal, and craniocaudal axes was 1.5, 0.4, and 1.0 mm, respectively. The largest volume variation was observed for the right hilar clinical target volume (mean, 33.7 cm(3); SD, 31.2; median, 20.3; range, 4.8-109.9). Smaller variations were observed for the subcarinal node (mean, GTV, 1.9 cm(3); SD, 1.2; median, 1.7; range, 0.5-5.3), except caudally where the node was difficult to distinguish from the pericardium. The "consensus" volumes for all targets were generally close to the median of the contoured values. CONCLUSION: Most clinicians were able to use this CD-ROM tool to contour target volumes in compliance with the study protocol. The rapid completion of the dummy run indicated the suitability of this approach for quality assurance in multicenter clinical trials. Routine use of similar tools will reduce the risk that new techniques (or study objectives) are misunderstood and/or misapplied in clinical trials.

Parenchymal lung changes on computed tomography after stereotactic radiotherapy using high dose rate flattening filter free beams.

Flattening filter free (FFF) beams allow fast delivery of stereotactic radiotherapy. To evaluate biological effects of FFF in lung, we compared parenchymal changes after FFF and non-FFF stereotactic volumetric modulated arc therapy. Standardized multi-observer consensus evaluation of follow-up CT scans revealed no major differences between FFF and non-FFF.

Markerless tracking of small lung tumors for stereotactic radiotherapy.

PURPOSE: (1) To validate retrospective markerless tracking software for small lung tumors by comparing tracked motion in 4-dimensional planning computed tomography (4DCT) derived kV projection images and known tumor motion in the same 4DCT. (2) To evaluate variability of tumor motion using kV projection images from cone-beam computed tomography (CBCT) scans acquired on different days. METHODS: Nonclinical tumor tracking software (TTS) used a normalized cross correlation algorithm to track the tumor on enhanced kV projection images (e.g., from a CBCT scan). The reference dataset consisted of digitally reconstructed radiographs (DRRs) from one phase of a planning 4DCT. TTS matches two in-plane coordinates and obtains the out-of-plane coordinate by triangulating with match results from other projections. (1) To validate TTS, tracking results were compared with known 4DCT tumor motion for two patients (A and B). Projection images (1 image/1°) were digitally reconstructed for each 4DCT phase. From these, kV projection series were composed simulating full breathing cycles every 20° of gantry rotation [breathing period = 20°/(6°/s) = 3.33 s]. Reference templates were 360 "tumor enhanced" DRRs from the 4DCT expiration phase. TTS-derived tumor motion was compared to known tumor motion on 4DCT. (2) For five patients, TTS-assessed motion during clinical CBCT acquisition was compared with motion on the planning 4DCT, and the motion component in the Y (cranio-caudal)-direction was compared with the motion of an external marker box (RPM, real-time position management). RESULTS: (1) Validation results: TTS for case A (tumor 6.2 cm(3), 32 mm axial diameter) over 360° showed mean motion X (medial-lateral) = 3.4, Y = 11.5, and Z (ventral-dorsal) = 4.9 mm (1 SD < 1.0 mm). Corresponding 4DCT motion was X = 3.1, Y = 11.3, and Z = 5.1 mm. Correlation coefficients between TTS tumor motion and displacement of the tumor's center of mass (CoM) on 4DCT were 0.64, 0.96, and 0.82 (X, Y, and Z, respectively). For case B (4.1 cm(3), 20 mm diameter), due to temporarily decreased tumor visibility preventing TTS from resolving the tumor, robust tracking data were only available between angles 300°-40° and 120°-220°. Mean motion according to TTS was X = 2.0, Y = 7.7, and Z = 8.2 mm (1 SD < 0.9 mm). Tumor motion on 4DCT was X = 1.8, Y = 7.6, and Z = 9.5 mm and correlation coefficients between TTS motion and CoM displacement were 0.59, 0.95, and 0.93 (X, Y, and Z, respectively). (2) CLINICAL RESULTS: TTS revealed a mean intrafraction variation in tumor motion in Y-direction of >2.0 mm (1 SD) in four of five patients. In addition, clinical tumor motion amplitude differed from that seen on planning 4DCT. Internal and external structures that create abrupt density change (e.g., table-top edge, interface between lung/mediastinum and lung/heart) were observed to prevent 360° tracking of the tumor. Correlation coefficients between TTS motion in the Y-direction and the RPM signal (22 observations) ranged from 0.78 to 0.96. In 2D, 241 TTS matches at end-inspiration and end-expiration were visually validated: mean difference was 0.8 mm (SD = 0.7) for both. CONCLUSIONS: TTS can track small lung tumors if these are visible in kV projections. A 4DCT dataset can be used to validate kV tracking of moving targets. TTS and 4DCT displacement agreed to within 2 mm. TTS and RPM motion were closely associated but tumor motion during CBCT can vary from the planning 4DCT.