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Purpose: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC)., Methods and Materials: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART., Results: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%., Conclusions: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation., Methods and Materials: We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m 2 ) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40 to 45 Gy 25 fxs with chemotherapy (600-800/75 mg/m 2 ) to 60 to 67.5 Gy/15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m 2 ). The primary endpoint was maximum tolerated dose of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic, or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS)., Results: Thirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m 2 ) and 67.5 Gy/15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% confidence interval [CI], 10.9-28.2 months). The median OS for patients with Eastern Collaborative Oncology Group 0 and carbohydrate antigen 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. Two-year LPFS and DMFS were 85% (95% CI, 63%-94%) and 57% (95% CI, 34%-73%), respectively., Conclusions: Full-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Early clinical results on the application of magnetic resonance imaging (MRI) coupled with a linear accelerator to deliver Magnetic Resonance-guided Radiation Therapy (MRgRT) have demonstrated feasibility for safe delivery of stereotactic body radiation therapy in treatment of oligometastatic disease. Here, we set out to review the clinical evidence and challenges associated with MRgRT in this setting., Methods and Materials: We performed a systematic review of the literature pertaining to clinical experiences and trials on the use of MRgRT primarily for the treatment of oligometastatic cancers. We reviewed the opportunities and challenges associated with the use of MRgRT., Results: Benefits of MRgRT pertaining to superior soft-tissue contrast, real-time imaging and gating, and online adaptive radiation therapy facilitate safe and effective dose escalation to oligometastatic tumors while simultaneously sparing surrounding healthy tissues. Challenges concerning further need for clinical evidence and technical considerations related to planning, delivery, quality assurance of hypofractionated doses, and safety in the MRI environment must be considered., Conclusions: The promising early indications of safety and effectiveness of MRgRT for stereotactic body radiation therapy-based treatment of oligometastatic disease in multiple treatment locations should lead to further clinical evidence to demonstrate the benefit of this technology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included., Methods and Materials: Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival., Results: Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006)., Conclusions: Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution., (Published by Elsevier Inc.)

Purpose: A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial., Methods and Materials: Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity., Results: The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity., Conclusions: SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction with previously reported oncologic outcomes support further evaluation of this regimen in a phase 3 setting., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE)., Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients., Results: The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients., Conclusions: Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811., Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤ 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT., Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations., Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the feasibility of prospectively guiding 4-dimensional (4D) magnetic resonance imaging (MRI) image acquisition using triggers at preselected respiratory amplitudes to achieve T(2) weighting for abdominal motion tracking., Methods and Materials: A respiratory amplitude-based triggering system was developed and integrated into a commercial turbo spin echo MRI sequence. Initial feasibility tests were performed on healthy human study participants. Four respiratory states, the middle and the end of inhalation and exhalation, were used to trigger 4D MRI image acquisition of the liver. To achieve T(2) weighting, the echo time and repetition time were set to 75 milliseconds and 4108 milliseconds, respectively. Single-shot acquisition, together with parallel imaging and partial k-space imaging techniques, was used to improve image acquisition efficiency. 4D MRI image sets composed of axial or sagittal slices were acquired., Results: Respiratory data measured and logged by the MRI scanner showed that the triggers occurred at the appropriate respiratory levels. Liver motion could be easily observed on both 4D MRI image datasets by sensing either the change of liver in size and shape (axial) or diaphragm motion (sagittal). Both 4D MRI image datasets were T(2)-weighted as expected., Conclusions: This study demonstrated the feasibility of achieving T(2)-weighted 4D MRI images using amplitude-based respiratory triggers. With the aid of the respiratory amplitude-based triggering system, the proposed method is compatible with most MRI sequences and therefore has the potential to improve tumor-tissue contrast in abdominal tumor motion imaging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate whether planning 4-dimensional computed tomography (4DCT) can adequately represent daily motion of abdominal tumors in regularly fractionated and stereotactic body radiation therapy (SBRT) patients., Methods and Materials: Intrafractional tumor motion of 10 patients with abdominal tumors (4 pancreas-fractionated and 6 liver-stereotactic patients) with implanted fiducials was measured based on daily orthogonal fluoroscopic movies over 38 treatment fractions. The needed internal margin for at least 90% of tumor coverage was calculated based on a 95th and fifth percentile of daily 3-dimensional tumor motion. The planning internal margin was generated by fusing 4DCT motion from all phase bins. The disagreement between needed and planning internal margin was analyzed fraction by fraction in 3 motion axes (superior-inferior [SI], anterior-posterior [AP], and left-right [LR]). The 4DCT margin was considered as an overestimation/underestimation of daily motion when disagreement exceeded at least 3 mm in the SI axis and/or 1.2 mm in the AP and LR axes (4DCT image resolution). The underlying reasons for this disagreement were evaluated based on interfractional and intrafractional breathing variation., Results: The 4DCT overestimated daily 3-dimensional motion in 39% of the fractions in 7 of 10 patients and underestimated it in 53% of the fractions in 8 of 10 patients. Median underestimation was 3.9 mm, 3.0 mm, and 1.7 mm in the SI axis, AP axis, and LR axis, respectively. The 4DCT was found to capture irregular deep breaths in 3 of 10 patients, with 4DCT motion larger than mean daily amplitude by 18 to 21 mm. The breathing pattern varied from breath to breath and day to day. The intrafractional variation of amplitude was significantly larger than intrafractional variation (2.7 mm vs 1.3 mm) in the primary motion axis (ie, SI axis). The SBRT patients showed significantly larger intrafractional amplitude variation than fractionated patients (3.0 mm vs 2.1 mm, P<.05)., Conclusions: It may not be appropriate to use 4DCT without monitoring of patient motion on a regular basis for patients with abdominal tumors, especially SBRT patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow., Methods and Materials: Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (Dmin) with the planned Dmin to the CTV. Treatments were considered adequate if the delivered CTV Dmin is at least 95% of the planned CTV Dmin., Results: Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: -0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments., Conclusion: Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate respiratory gating accuracy and intrafractional consistency for abdominal cancer patients treated with respiratory gated treatment on a regular linear accelerator system., Methods and Materials: Twelve abdominal patients implanted with fiducials were treated with amplitude-based respiratory-gated radiation therapy. On the basis of daily orthogonal fluoroscopy, the operator readjusted the couch position and gating window such that the fiducial was within a setup margin (fiducial-planning target volume [f-PTV]) when RPM indicated "beam-ON." Fifty-five pre- and post-treatment fluoroscopic movie pairs with synchronized respiratory gating signal were recorded. Fiducial motion traces were extracted from the fluoroscopic movies using a template matching algorithm and correlated with f-PTV by registering the digitally reconstructed radiographs with the fluoroscopic movies. Treatment was determined to be "accurate" if 50% of the fiducial area stayed within f-PTV while beam-ON. For movie pairs that lost gating accuracy, a MATLAB program was used to assess whether the gating window was optimized, the external-internal correlation (EIC) changed, or the patient moved between movies. A series of safety margins from 0.5 mm to 3 mm was added to f-PTV for reassessing gating accuracy., Results: A decrease in gating accuracy was observed in 44% of movie pairs from daily fluoroscopic movies of 12 abdominal patients. Three main causes for inaccurate gating were identified as change of global EIC over time (∼43%), suboptimal gating setup (∼37%), and imperfect EIC within movie (∼13%)., Conclusions: Inconsistent respiratory gating accuracy may occur within 1 treatment session even with a daily adjusted gating window. To improve or maintain gating accuracy during treatment, we suggest using at least a 2.5-mm safety margin to account for gating and setup uncertainties., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We have created an automated process using real-time tracking data to evaluate the adequacy of planning target volume (PTV) margins in prostate cancer, allowing a process of adaptive radiotherapy with minimal physician workload. We present an analysis of PTV adequacy and a proposed adaptive process., Methods and Materials: Tracking data were analyzed for 15 patients who underwent step-and-shoot multi-leaf collimation (SMLC) intensity-modulated radiation therapy (IMRT) with uniform 5-mm PTV margins for prostate cancer using the Calypso® Localization System. Additional plans were generated with 0- and 3-mm margins. A custom software application using the planned dose distribution and structure location from computed tomography (CT) simulation was developed to evaluate the dosimetric impact to the target due to motion. The dose delivered to the prostate was calculated for the initial three, five, and 10 fractions, and for the entire treatment. Treatment was accepted as adequate if the minimum delivered prostate dose (D(min)) was at least 98% of the planned D(min)., Results: For 0-, 3-, and 5-mm PTV margins, adequate treatment was obtained in 3 of 15, 12 of 15, and 15 of 15 patients, and the delivered D(min) ranged from 78% to 99%, 96% to 100%, and 99% to 100% of the planned D(min). Changes in D(min) did not correlate with magnitude of prostate motion. Treatment adequacy during the first 10 fractions predicted sufficient dose delivery for the entire treatment for all patients and margins., Conclusions: Our adaptive process successfully used real-time tracking data to predict the need for PTV modifications, without the added burden of physician contouring and image analysis. Our methods are applicable to other uses of real-time tracking, including hypofractionated treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy of three lung stereotactic body radiotherapy (SBRT) regimens in a large institutional cohort., Methods: Between 2004 and 2009, 130 patients underwent definitive lung cancer SBRT to a single lesion at the Mallinckrodt Institute of Radiology. We delivered 18 Gy × 3 fractions for peripheral tumors (n = 111) and either 9 Gy × 5 fractions (n = 8) or 10 Gy × 5 fractions (n = 11) for tumors that were central or near critical structures. Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model., Results: Median follow-up was 11, 16, and 13 months for the 9 Gy × 5, 10 Gy × 5, and 18 Gy × 3 groups, respectively. Local control statistics for Years 1 and 2 were, respectively, 75% and 50% for 9 Gy × 5, 100% and 100% for 10 Gy × 5, and 99% and 91% for 18 Gy × 3. Median overall survival was 14 months, not reached, and 34 months for the 9 Gy × 5, 10 Gy × 5, and 18 Gy × 3 treatments, respectively. No difference in local control or overall survival was found between the 10 Gy × 5 and 18 Gy × 3 groups on log-rank test, but both groups had improved local control and overall survival compared with 9 Gy × 5. Treatment with 9 Gy × 5 was the only independent prognostic factor for reduced local control on multivariate analysis, and increasing age, increasing tumor volume, and poor performance status predicted independently for reduced overall survival., Conclusion: Treatment regimens of 10 Gy × 5 and 18 Gy × 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy × 5., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Continuous tumor position measurement coupled with a tumor tracking system would result in a highly accurate radiation therapy system. Previous internal position monitoring systems have been limited by fluoroscopic radiation dose and low delivery efficiency. We aimed to incorporate a continuous, electromagnetic, three-dimensional position tracking system (Calypso 4D Localization System) with a dynamic multileaf collimator (DMLC)-based dose delivery system., Methods and Materials: A research version of the Calypso System provided real-time position of three Beacon transponders. These real-time three-dimensional positions were sent to research MLC controller with a motion-tracking algorithm that changed the planned leaf sequence. Electromagnetic transponders were embedded in a solid water film phantom that moved with patient lung trajectories while being irradiated with two different plans: a step-and-shoot intensity-modulated radiation therapy (S-IMRT) field and a dynamic IMRT (D-IMRT) field. Dosimetric results were recorded under three conditions: no intervention, DMLC tracking, and a spatial gating system., Results: Dosimetric accuracy was comparable for gating and DMLC tracking. Failure rates for gating/DMLC tracking are as follows: +/-3 cGy 10.9/ 7.5% for S-IMRT, 3.3/7.2% for D-IMRT; gamma (3mm/3%) 0.2/1.2% for S-IMRT, 0.2/0.2% for D-IMRT. DMLC tracking proved to be as efficient as standard delivery, with a two- to fivefold efficiency increase over gating., Conclusions: Real-time target position information was successfully integrated into a DMLC effector system to modify dose delivery. Experimental results show both comparable dosimetric accuracy as well as improved efficiency compared with spatial gating.

Purpose: To evaluate whether pre- and post-treatment imaging (immediately before and after a radiation therapy treatment fraction) and intermittent imaging (at intervals during a treatment fraction) are accurate predictors of prostate motion during the delivery of radiation., Methods and Materials: The Calypso 4D Localization System was used to continuously track the prostate during radiation delivery in 35 prostate cancer patients, for a total of 1,157 fractions (28-45 per patient). Predictions of prostate motion away from isocenter were modeled for a pre- and post-treatment imaging schedule and for multiple intermittent intrafraction imaging schedules and compared with the actual continuous tracking data. The endpoint was drift of the prostate beyond a certain radial displacement for a duration of more than 30 s, 1 min, and 2 min. Results were used to evaluate the sensitivity and specificity of these models as an evaluation of intrafraction prostate motion., Results: The sensitivity of pre- and post-treatment imaging in determining 30 s of intrafraction prostate motion greater than 3, 5, or 7 mm for all fractions was low, with values of 53%, 49%, and 39%, respectively. The specificity of pre- and post-treatment imaging was high for all displacements. The sensitivity of intermittent imaging improved with increasing sampling rate., Conclusions: These results suggest that pre- and post-treatment imaging is not a sensitive method of assessing intrafraction prostate motion, and that intermittent imaging is sufficiently sensitive only at a high sampling rate. These findings support the value of continuous, real-time tracking in prostate cancer radiation therapy.

Purpose: The success of targeted radiation therapy for lung cancer treatment is limited by tumor motion during breathing. A real-time, objective, nonionizing, electromagnetic localization system using implanted electromagnetic transponders has been developed (Beacon electromagnetic transponder, Calypso Medical Technologies, Inc., Seattle, WA). We evaluated the feasibility and fixation of electromagnetic transponders bronchoscopically implanted in small airways of canine lungs and compared to results using gold markers., Methods and Materials: After approval of the Animal Studies Committee, five mongrel dogs were anesthetized, intubated, and ventilated. Three transponders were inserted into the tip of a plastic catheter, passed through the working channel of a flexible bronchoscope, and implanted into small airways of a single lobe using fluoroscopic guidance. This procedure was repeated for three spherical gold markers in the opposite lung. One, 7, 14, 28, and 60 days postimplantation imaging was used to assess implant fixation., Results: Successful bronchoscopic implantation was possible for 15 of 15 transponders and 12 of 15 gold markers; 3 markers were deposited in the pleural space. Fixation at 1 day was 15 of 15 for transponders and 12 of 12 for gold markers. Fixation at 60 days was 6 of 15 for transponders and 7 of 12 for gold markers, p value = 0.45., Conclusions: Bronchoscopic implantation of both transponders and gold markers into the canine lung is feasible, but fixation rates are low. If fixation rates can be improved, implantable electromagnetic transponders may allow improved radiation therapy for lung cancer by providing real-time continuous target tracking. Developmental work is under way to improve the fixation rates and to reduce sensitivity to implantation technique.

Purpose: Respiratory motion is a significant source of anatomic uncertainty in radiotherapy planning and can result in errors of portal size and the subsequent radiation dose. Although four-dimensional computed tomography allows for more accurate analysis of the respiratory cycle, breathing irregularities during data acquisition can cause considerable image distortions. The aim of this study was to examine the effect of respiratory irregularities on four-dimensional computed tomography, and to evaluate a novel image reconstruction algorithm using percentile-based tagging of the respiratory cycle., Methods and Materials: Respiratory-correlated helical computed tomography scans were acquired for 11 consecutive patients. The inspiration and expiration data sets were reconstructed using the default phase-based method, as well as a novel respiration percentile-based method with patient-specific metrics to define the ranges of the reconstruction. The image output was analyzed in a blinded fashion for the phase- and percentile-based reconstructions to determine the prevalence and severity of the image artifacts., Results: The percentile-based algorithm resulted in a significant reduction in artifact severity compared with the phase-based algorithm, although the overall artifact prevalence did not differ between the two algorithms. The magnitude of differences in respiratory tag placement between the phase- and percentile-based algorithms correlated with the presence of image artifacts., Conclusion: The results of our study have indicated that our novel four-dimensional computed tomography reconstruction method could be useful in detecting clinically relevant image distortions that might otherwise go unnoticed and to reduce the image distortion associated with some respiratory irregularities. Additional work is necessary to assess the clinical impact on areas of possible irregular breathing.

Purpose: To quantify the amount of free-breathing motion measured using Four-dimensional (4D) CT scans of mediastinal and hilar lymph nodes and to compare this motion to the primary lung tumor motion., Methods and Materials: Twenty patients with primary lung cancer, radiographically positive lymph nodes, and prior 4D CT scans were retrospectively analyzed. The 4D CT data sets were divided into four respiratory phases, and the primary tumor and radiographically positive nodes were contoured. Geometric and volumetric analysis was performed to analyze the motion of the primary tumors and the lymph nodes., Results: The mean lymph node motion was 2.6 mm in the mediolateral direction, 2.5 mm in the anterior-posterior direction, and 5.2 mm in the cranial-caudal direction with a maximum of 14.4 mm. All lymph nodes were found to move inferiorly during inspiration, with 12.5% of nodes moving more than 1 cm. Lymph nodes located below the carina showed significantly more motion than those above the carina (p = 0.01). In comparing the primary tumor motion to the lymph node motion, no correlation was identified., Conclusions: Four-dimensional CT scans can be used to measure the motion of the primary lung tumor and pathologic lymph nodes encountered during the respiratory cycle. Both the primary lung tumor and the lymph node must to be examined to assess their individual degree of motion. This study demonstrates the need for individualized plans to assess the heterogeneous motion encountered in both primary lung tumors and among lymph node stations.

Purpose: An accurate model of breathing motion under quiet respiration is desirable to obtain the most accurate and conformal dose distributions for mobile lung cancer lesions. On the basis of recent lung motion measurements and the physiologic functioning of the lungs, we have determined that the motion of lung and lung tumor tissues can be modeled as a function of five degrees of freedom, the position of the tissues at a user-specified reference breathing phase, tidal volume and its temporal derivative airflow (tidal volume phase space). Time is an implicit variable in this model., Methods and Materials: To test this hypothesis, a mathematical model of motion was developed that described the motion of objects p in the lungs as linear functions of tidal volume and airflow. The position of an object was described relative to its position -->P0 at the reference tidal volume and zero airflow, and the motion of the object was referenced to this position. Hysteresis behavior was hypothesized to be caused by pressure imbalances in the lung during breathing and was, in this model, a function of airflow. The motion was modeled as independent tidal volume and airflow displacement vectors, with the position of the object at time t equal to the vector sum -->rP(t) = -->rv(t) + -->rf(t) where -->rv(t) and -->rf(t) were displacement vectors with magnitudes approximated by linear functions of the tidal volume and airflow. To test this model, we analyzed five-dimensional CT scans (CT scans acquired with simultaneous real-time monitoring of the tidal volume) of 4 patients. The scans were acquired throughout the lungs, but the trajectories were analyzed in the couch positions near the diaphragm. A template-matching algorithm was implemented to identify the positions of the points throughout the 15 scans. In total, 76 points throughout the 4 patients were tracked. The lateral motion of these points was minimal; thus, the model was described in two spatial dimensions, with a total of six parameters necessary to describe the 30 degrees of freedom inherent in the 15 positions., Results: For the 76 evaluated points, the average discrepancy (the distance between the measured and prediction positions) of the 15 locations for each tracked point was 0.75 +/- 0.25 mm, with an average maximal discrepancy of 1.55 +/- 0.54 mm. The average discrepancy was also tabulated as a fraction of the breathing motion. Discrepancies of <10% and 15% of the overall motion occurred in 73% and 95% of the tracked points, respectively., Conclusion: The motion tracking algorithms are being improved and automated to provide more motion data to test the models. This may allow a measurement of the motion-fitting parameters throughout the lungs. If the parameters vary smoothly, interpolation may be possible, yielding a continuous mathematical model of the breathing motion throughout the lungs. The utility of the model will depend on its stability as a function of time. If the model is only robust during the measurement session, it may be useful for determining lung function. If it is robust for weeks, it may be useful for treatment planning and gating of lung treatments. The use of tidal volume phase space for characterizing breathing motion appears to have provided, for the first time, the potential for a patient-specific mathematical model of breathing motion.