Maintaining tumor targeting accuracy in real-time motion compensation systems for respiration-induced tumor motion.

PURPOSE: To determine how best to time respiratory surrogate-based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods. METHODS: Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial-least-squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods: never, respiratory surrogate-based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error-based (when localization error ≥ 3 mm), and always (approximately once per minute). RESULTS: Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. The never-update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively. CONCLUSIONS: The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when the respiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization.

Online monitoring and error detection of real-time tumor displacement prediction accuracy using control limits on respiratory surrogate statistics.

PURPOSE: To evaluate Hotelling's T(2) statistic and the input variable squared prediction error (Q((X))) for detecting large respiratory surrogate-based tumor displacement prediction errors without directly measuring the tumor's position. METHODS: Tumor and external marker positions from a database of 188 Cyberknife Synchrony™ lung, liver, and pancreas treatment fractions were analyzed. The first ten measurements of tumor position in each fraction were used to create fraction-specific models of tumor displacement using external surrogates as input; the models were used to predict tumor position from subsequent external marker measurements. A partial least squares (PLS) model with four scores was developed for each fraction to determine T(2) and Q((X)) confidence limits based on the first ten measurements in a fraction. The T(2) and Q((X)) statistics were then calculated for every set of external marker measurements. Correlations between model error and both T(2) and Q((X)) were determined. Receiver operating characteristic analysis was applied to evaluate sensitivities and specificities of T(2), Q((X)), and T(2)∪Q((X)) for predicting real-time tumor localization errors >3 mm over a range of T(2) and Q((X)) confidence limits. RESULTS: Sensitivity and specificity of detecting errors >3 mm varied with confidence limit selection. At 95% sensitivity, T(2)∪Q((X)) specificity was 15%, 2% higher than either T(2) or Q((X)) alone. The mean time to alarm for T(2)∪Q((X)) at 95% sensitivity was 5.3 min but varied with a standard deviation of 8.2 min. Results did not differ significantly by tumor site. CONCLUSIONS: The results of this study establish the feasibility of respiratory surrogate-based online monitoring of real-time respiration-induced tumor motion model accuracy for lung, liver, and pancreas tumors. The T(2) and Q((X)) statistics were able to indicate whether inferential model errors exceeded 3 mm with high sensitivity. Modest improvements in specificity were achieved by combining T(2) and Q((X)) results.

Mitigating errors in external respiratory surrogate-based models of tumor position.

PURPOSE: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. METHODS AND MATERIALS: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. RESULTS: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. CONCLUSIONS: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

Incidence of changes in respiration-induced tumor motion and its relationship with respiratory surrogates during individual treatment fractions.

PURPOSE: To determine how frequently (1) tumor motion and (2) the spatial relationship between tumor and respiratory surrogate markers change during a treatment fraction in lung and pancreas cancer patients. METHODS AND MATERIALS: A Cyberknife Synchrony system radiographically localized the tumor and simultaneously tracked three respiratory surrogate markers fixed to a form-fitting vest. Data in 55 lung and 29 pancreas fractions were divided into successive 10-min blocks. Mean tumor positions and tumor position distributions were compared across 10-min blocks of data. Treatment margins were calculated from both 10 and 30 min of data. Partial least squares (PLS) regression models of tumor positions as a function of external surrogate marker positions were created from the first 10 min of data in each fraction; the incidence of significant PLS model degradation was used to assess changes in the spatial relationship between tumors and surrogate markers. RESULTS: The absolute change in mean tumor position from first to third 10-min blocks was >5 mm in 13% and 7% of lung and pancreas cases, respectively. Superior-inferior and medial-lateral differences in mean tumor position were significantly associated with the lobe of lung. In 61% and 54% of lung and pancreas fractions, respectively, margins calculated from 30 min of data were larger than margins calculated from 10 min of data. The change in treatment margin magnitude for superior-inferior motion was >1 mm in 42% of lung and 45% of pancreas fractions. Significantly increasing tumor position prediction model error (mean ± standard deviation rates of change of 1.6 ± 2.5 mm per 10 min) over 30 min indicated tumor-surrogate relationship changes in 63% of fractions. CONCLUSIONS: Both tumor motion and the relationship between tumor and respiratory surrogate displacements change in most treatment fractions for patient in-room time of 30 min.

Inferring positions of tumor and nodes in Stage III lung cancer from multiple anatomical surrogates using four-dimensional computed tomography.

PURPOSE: To investigate the feasibility of modeling Stage III lung cancer tumor and node positions from anatomical surrogates. METHODS AND MATERIALS: To localize their centroids, the primary tumor and lymph nodes from 16 Stage III lung cancer patients were contoured in 10 equal-phase planning four-dimensional (4D) computed tomography (CT) image sets. The centroids of anatomical respiratory surrogates (carina, xyphoid, nipples, mid-sternum) in each image set were also localized. The correlations between target and surrogate positions were determined, and ordinary least-squares (OLS) and partial least-squares (PLS) regression models based on a subset of respiratory phases (three to eight randomly selected) were created to predict the target positions in the remaining images. The three-phase image sets that provided the best predictive information were used to create models based on either the carina alone or all surrogates. RESULTS: The surrogate most correlated with target motion varied widely. Depending on the number of phases used to build the models, mean OLS and PLS errors were 1.0 to 1.4 mm and 0.8 to 1.0 mm, respectively. Models trained on the 0%, 40%, and 80% respiration phases had mean (+/- standard deviation) PLS errors of 0.8 +/- 0.5 mm and 1.1 +/- 1.1 mm for models based on all surrogates and carina alone, respectively. For target coordinates with motion >5 mm, the mean three-phase PLS error based on all surrogates was 1.1 mm. CONCLUSIONS: Our results establish the feasibility of inferring primary tumor and nodal motion from anatomical surrogates in 4D CT scans of Stage III lung cancer. Using inferential modeling to decrease the processing time of 4D CT scans may facilitate incorporation of patient-specific treatment margins.

Investigation of motion sickness and inertial stability on a moving couch for intra-fraction motion compensation.

BACKGROUND. Respiration-induced tumor motion compensation using a treatment couch requires moving the patient at non-trivial speeds. The purpose of this work was to investigate motion sickness and stability of the patient's external surface due to a moving couch with respiration-comparable velocities and accelerations. MATERIAL AND METHODS. A couch was designed to move with a peak-peak displacement of 5 cm and 1 cm in the S-I and A-P directions, respectively, and a period of 3.6 s. Fifty patients completed a 16-question motion sickness assessment questionnaire (MSAQ) prior to, during, and after the study. Seven optical reflectors affixed to the abdomen of each patient were monitored by infrared cameras. The relationship between reflector positions under stationary and moving conditions was evaluated to assess the stability of the patient's external surface. RESULTS AND DISCUSSION. Among the 4800 responses, 95% were 1 (no discomfort) of 9, and there were no scores of 6 or higher. Mild discomfort (scores of 4-5) was similar during couch motion and before couch motion (p = 0.39). Mild discomfort was less common after couch motion (p = 0.039) than before or during couch movement. There was a near 1:1 correspondence between marker-pair regression coefficients and phase offset values during couch-stationary and couch-moving conditions. Our results show that patients do not suffer motion sickness or external surface instability on a moving couch.

Evaluation of linear accelerator gating with real-time electromagnetic tracking.

PURPOSE: Intrafraction organ motion can produce dosimetric errors in radiotherapy. Commonly, the linear accelerator is gated using real-time breathing phase obtained by way of external sensors. However, the external anatomy does not always correlate well with the internal position. We examined a beam gating technique using signals from implanted wireless transponders that provided real-time feedback on the tumor location without an imaging dose to the patient. METHODS AND MATERIALS: An interface was developed between Calypso Medical's four-dimensional electromagnetic tracking system and a Varian Trilogy linear accelerator. A film phantom was mounted on a motion platform programmed with lung motion trajectories. Deliveries were performed when the beam was gated according to the signal from the wireless transponders. The dosimetric advantages of beam gating and the system latencies were quantified. RESULTS: Beam gating using on internal position monitoring provided up to a twofold increase in the dose gradients. The percentage of points failing to be within +/-10 cGy of the planned dose (maximal dose, approximately 200 cGy) was 3.4% for gating and 32.1% for no intervention in the presence of motion. The mean latencies between the transponder position and linear accelerator modulation were 75.0 +/-12.7 ms for beam on and 65.1 +/- 12.9 ms for beam off. CONCLUSION: We have presented the results from a novel method for gating the linear accelerator using trackable wireless internal fiducial markers without the use of ionizing radiation for imaging. The latencies observed were suitable for gating using electromagnetic fiducial markers, which results in dosimetric improvements for irradiation in the presence of motion.

Feasibility of small animal cranial irradiation with the microRT system.

PURPOSE: To develop and validate methods for small-animal CNS radiotherapy using the microRT system. MATERIALS AND METHODS: A custom head immobilizer was designed and built to integrate with a pre-existing microRT animal couch. The Delrin couch-immobilizer assembly, compatible with multiple imaging modalities (CT, microCT, microMR, microPET, microSPECT, optical), was first imaged via CT in order to verify the safety and reproducibility of the immobilization method. Once verified, the subject animals were CT-scanned while positioned within the couch-immobilizer assembly for treatment planning purposes. The resultant images were then imported into CERR, an in-house-developed research treatment planning system, and registered to the microRTP treatment planning space using rigid registration. The targeted brain was then contoured and conformal radiotherapy plans were constructed for two separate studies: (1) a whole-brain irradiation comprised of two lateral beams at the 90 degree and 270 degree microRT treatment positions and (2) a hemispheric (left-brain) irradiation comprised of a single A-P vertex beam at the 0 degree microRT treatment position. During treatment, subject animals (n=48) were positioned to the CERR-generated treatment coordinates using the three-axis microRT motor positioning system and were irradiated using a clinical Ir-192 high-dose-rate remote after-loading system. The radiation treatment course consisted of 5 Gy fractions, 3 days per week. 90% of the subjects received a total dose of 30 Gy and 10% received a dose of 60 Gy. RESULTS: Image analysis verified the safety and reproducibility of the immobilizer. CT scans generated from repeated reloading and repositioning of the same subject animal in the couch-immobilizer assembly were fused to a baseline CT. The resultant analysis revealed a 0.09 mm average, center-of-mass translocation and negligible volumetric error in the contoured, murine brain. The experimental use of the head immobilizer added 0.1 mm to microRT spatial uncertainty along each axis. Overall, the total spatial uncertainty for the prescribed treatments was +/-0.3 mm in all three axes, a 0.2 mm functional improvement over the original version of microRT. Subject tolerance was good, with minimal observed side effects and a low procedure-induced mortality rate. Throughput was high, with average treatment times of 7.72 and 3.13 min/animal for the whole-brain and hemispheric plans, respectively (dependent on source strength). CONCLUSIONS: The method described exhibits conformality more in line with the size differential between human and animal patients than provided by previous prevalent approaches. Using pretreatment imaging and microRT-specific treatment planning, our method can deliver an accurate, conformal dose distribution to the targeted murine brain (or a subregion of the brain) while minimizing excess dose to the surrounding tissue. Thus, preclinical animal studies assessing the radiotherapeutic response of both normal and malignant CNS tissue to complex dose distributions, which closer resemble human-type radiotherapy, are better enabled. The procedural and mechanistic framework for this method logically provides for future adaptation into other murine target organs or regions.

Efficient use of continuous, real-time prostate localization.

Recent technological advances make it possible to monitor prostate movement during radiation delivery. Using previously published data from 35 patients who underwent continuous localization during prostate cancer treatment, we simulated various interventions to identify the radiation-gating and patient-repositioning strategies that least prolonged the time to complete the daily treatment. Acceptable response protocols were those that resulted in at least 95% of patients' prostates remaining within the planning margins at least 95% of the time. Gating and repositioning were not necessary for margins of 7 or 10 mm because of the rarity of excursions at these margins. However, intervention was routinely necessary for margins of 3 and 5 mm. In simulated interventions for which the therapist could reposition the treatment couch without entering the room, the most time-efficient response protocol was to reposition the couch immediately after the prostate position was outside the treatment margins. In simulations in which the therapist had to enter the room to reposition the couch, overall treatment time could be reduced and accuracy could be increased by manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively, before interrupting treatment to reposition the treatment couch.

Fiducial-based translational localization accuracy of electromagnetic tracking system and on-board kilovoltage imaging system.

PURPOSE: The Calypso medical four-dimensional localization system uses AC electromagnetics, which do not require ionizing radiation, for accurate, real-time tumor tracking. This investigation compared the static and dynamic tracking accuracy of this system to that of an on-board imaging kilovoltage X-ray system for concurrent use of the two systems. METHODS AND MATERIALS: The localization accuracies of a kilovoltage imaging system and a continuous electromagnetic tracking system were compared. Using an in-house developed four-dimensional stage, quality-assurance fixture containing three radiofrequency transponders was positioned at a series of static locations and then moved through the ellipsoidal and nonuniform continuous paths. The transponder positions were tracked concurrently by the Calypso system. For static localization, the transponders were localized using portal images and digitally reconstructed radiographs by commercial matching software. For dynamic localization, the transponders were fluoroscopically imaged, and their positions were determined retrospectively using custom-written image processing programs. The localization data sets were synchronized with and compared to the known quality assurance fixture positions. The experiment was repeated to retrospectively track three transponders implanted in a canine lung. RESULTS: The root mean square error of the on-board imaging and Calypso systems was 0.1 cm and 0.0 cm, respectively, for static localization, 0.22 mm and 0.33 mm for dynamic phantom positioning, and 0.42 mm for the canine study. CONCLUSION: The results showed that both localization systems provide submillimeter accuracy. The Calypso and on-board imaging tracking systems offer distinct sets of advantages and, given their compatibility, patients could benefit from the complementary nature of the two systems when used concurrently.