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Purpose/Objective(s) Hypofractionated stereotactic radiotherapy (HSRT) to surgically resected brain metastases is a standard option to reduce local recurrence and spare the toxicity of whole brain radiotherapy. This study examined changes in the clinical target volume (CTV) and associated variations in brain parenchyma dosimetry on a 1.5T MRI linear accelerator. In addition, the suitability of using T2/FLAIR (T2f) as a surrogate to define CTV was explored by assessing contouring variability between different standard MRI sequences during treatment. Materials/Methods Fifteen patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2f axial sequences at the time of planning (FxSim) and at fraction 3 (Fx3) of HSRT to the cavity. Clinical target volumes (CTV) were contoured at both time points on T1c and T2f sequences. All patients were treated with either 27.5Gy or 30Gy in 5 fractions. The total volume of brain minus CTV receiving 30Gy (V30Gy) was obtained at both time points on T1c sequence. Inter-fraction surgical cavity dynamics and CTV delineation variability were quantified using absolute volume, Dice similarity coefficient (DC) and Hausdorff distance (HD) metrics. Results The median time from surgery to HSRT was 22 days. The median CTVs on T1c and T2f sequences at FxSim were 12cm3 (range, 1.2-30.1) and 10.2cm3 (range, 2.9-27.9), respectively. At Fx3, the median CTV decreased slightly in both sequences to 9.7cm3 (range, 3.7-25.9) and 8.7cm3 (range, 2.9-24.9), translating to a median % reduction in CTV compared to FxSim of 11.7% on T1c and 8.9% on T2f, respectively (P Conclusion Clinically meaningful changes in target dynamics were observed during the course of cavity irradiation, supporting the use of MR image guided radiation therapy and treatment adaptation. We also observed variability in CTV delineation between T1c and T2f sequences, highlighting the importance of further work in this field.

Purpose/Objective(s) Bone metastases are a common oncologic development occurring in approximately 60-70% of patients with advanced malignancies. Historically, bone directed radiotherapy at doses of 30 Gy delivered over 10 daily fractions have been commonly employed. However, prospective randomized data suggests equivalent pain relief with shorter course regimens. As such, the ASTRO Choosing Wisely Campaign was created in an effort to encourage clinicians to consider shorter course palliative regimens in patients with uncomplicated bone metastases who have a limited prognosis. We performed a retrospective analysis of our large, integrated health system in an effort to assess utilization patterns of short course and single fraction radiotherapy regimens over the last 5 years. Materials/Methods We queried our internal radiation oncology electronic medical record (MOSAIQ®) from 2016-2020 for patients with bone metastasis who received palliative bone-directed radiotherapy in our network. Patients receiving Medicare approved palliative courses of radiation (30 Gy/10 fractions, 24 Gy/6 fractions, 20 Gy/5 fractions, 8 Gy/1 fraction) were included, as well as, patients receiving > 10 fractions. Treatment site was defined as academic (n = 2) versus community (n = 12). Short course treatment was defined as radiation treatment courses of ≤ 6 fractions, whereas long course included patients receiving ≥ 10 fractions. Patients were subdivided into quartiles based upon age and site of disease (spine, hip/pelvis, extremity, and other). Physicians were grouped according to their year of radiation oncology residency completion (before versus after 2010). Multivariable logistic regression analysis was completed to identify predictors of short course and single fraction treatment. Results We identified 1,004 patients with 1,768 bony metastatic lesions meeting the above criteria. The median patient age was 68 years (Interquartile range: 61-76 years). The spine was the most commonly treated site (46%) followed by pelvis/hip (26%), extremity (15%), and other (13%). Use of short course treatment increased over time from 40% in 2016 to 50% in 2020. Single fraction treatment also increased over time from 7% in 2016 to 11% in 2020. Predictors of short course treatment included: treatment at an academic center, more recent treatment year, patient age > 76 years old, non-spine anatomic site. Predictors of single fraction treatment included: treatment at an academic center, treating physician residency completion after 2010, patient age > 76 years old, and treatment to extremity or other site. Conclusion Rates of short course and single fraction bone-directed radiotherapy utilization increased within our integrated health system over time. Treatment receipt at an academic center was associated with both short course and single fraction regimens. Physicians completing residency after 2010 were more likely to deliver single fraction therapy.

PURPOSE/OBJECTIVE(S) Magnetic resonance image guided brain radiotherapy (MRIgRT) is a promising advance to maximize the therapeutic ratio. An unexplored uncertainty in this approach is the residual setup uncertainty after translation-only MR based patient setup. This work quantified this uncertainty, including intrafraction motion, and determined the impact on planning target volume (PTV) margins. MATERIALS/METHODS Sixty-six patients treated on a 1.5T-based MR-Linac were included. Of these, 49 and 17 patients received conventional (15-30 fractions for glioblastoma) and hypofractionated (5 fractions for post-operative brain metastases) treatments, respectively; 1,329 total patient fractions were analyzed. At each fraction, patients were setup using online MR guidance by translation-only (T) fusion of the T1 volumetric MR to the planning image set to determine the treatment isocenter shift. These fusions were independently validated offline with translational and rotational (T+R) fusion of bony anatomy. The difference between the T and T+R co-registrations was applied to the original clinical target volume (CTV) to yield the CTV at each fraction (CTVtreat). The set of all CTV and CTVtreat volumes was incorporated in a population-based model parameterized by the relative thresholds (CTVmin, Fxmin, Ptmin). This model determined the minimum planning target volume (PTV) margin such that the PTV encompassed CTVmin of the CTVtreat volume in ≥ Fxmin of fractions in ≥ Ptmin of patients. In this work, we determined the PTV margin that for two sets of thresholds: A) (CTVmin, Fxmin, Ptmin) = (98%, 95%, 90%) and B) (CTVmin, Fxmin, Ptmin) = (95%, 95%, 90%). In a subset of 412 fractions, intrafraction motion was determined as the spatial registration difference between a post-treatment acquired MRI and the pre-treatment MRI. RESULTS Residual setup uncertainty (difference between T+R and T registrations) and intrafraction motion results are summarized in Table 1. Across all patient fractions, the vector magnitude of the setup uncertainty and intrafraction motion was 1.3 ± 0.8 mm (mean ± SD) and 0.6 ± 0.5 mm, respectively. To accommodate the setup uncertainty, PTV margins of 2.5 and 1.8 mm were required to meet criteria sets A and B, respectively. CONCLUSION We have quantified residual setup and motion uncertainties for a large series of treated MR-Linac brain tumor patients, generated a model for a population-based PTV, and recommend a minimum PTV of 2-3 mm for this indication. This work is a crucial step towards developing an adaptive brain treatment based on dynamic tumor changes and tumor response.

Purpose Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may allow for ablative biologically equivalent dose to tumors with a lower risk of organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may further improve OAR sparing while maintaining planning target volume (PTV) coverage. We hypothesized that midtreatment adaptive replanning would offer dosimetric advantages during HSRT for central thorax malignancies using magnetic resonance imaging (MRI)–guided radiation therapy. Methods and Materials Twelve patients with central thorax tumors received HSRT using MRI-guided radiation therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in 10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging acquired at each fraction. Daily gross tumor volume (GTV) and OARs were retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions based on fraction 1 MRI. Midtreatment adaptive plans were created based on fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to represent clinically ideal OAR sparing. Plans were then compared for projected OAR sparing and PTV coverage. Results Patients demonstrated significant on-treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At fraction 6, median reduction was 26.7%. All initial plans met OAR constraints. Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All fraction 6 violations persisted at fraction 10. Midpoint adaptive planning reversed 100% of midpoint OAR violations and tended to reduce the magnitude of OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR violation resulted from initial plan application to fraction 6 anatomy, PTV coverage was increased concomitant with violation reversal. Conclusions Midtreatment adaptive planning based on tumor response may be dosimetrically advantageous for sparing of surrounding critical structures in HSRT for central thorax malignancies and could be applied using either an online or offline paradigm.

Purpose We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions. Methods and Materials PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose. Results Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions. Conclusions Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

Purpose/Objective(s) Biology-guided radiotherapy (BgRT) is a new radiation modality that utilizes real-time limited time sampled FDG PET images of a tumor to deliver a dynamically tracked dose distribution. Since the delivered radiotherapy dose is dependent on the FDG distribution at each fraction, the ability to deliver the planned dose despite variations in daily FDG signal must be established. This study evaluates the predicted dose distribution for BgRT based on serial FDG scans obtained over a course of stereotactic ablative radiotherapy (SABR). Materials/Methods Six patients with 1 (n = 5) or 2 (n = 1) lung tumors at least 2 cm in diameter with SUVmax ≥ 6 treated with SABR (50 Gy in 5 fractions) were selected for this investigation. These patients received 3 PET/CT scans as part of an IRB approved prospective clinical trial: within 2 weeks of treatment start (PET1), between fractions 1 and 2 (PET2), and between fractions 4 and 5 (PET3). A simulation tool was developed to convert PET1 into a simulated BgRT planning PET image accounting for differences in system sensitivity, acquisition time, reconstruction method and geometry between the diagnostic PET/CT system and the BgRT machine. This same tool was used to convert PET2 and PET3 into simulated pre-scan PET images, short PET acquisitions made just prior to a BgRT delivery fraction to ensure the current FDG distribution is safe for treatment. BgRT plans designed to deliver 50 Gy in 5 fractions following RTOG 0813 dose constraints were developed for each of the 7 targets using the simulated planning PET images as input. Expected variations in the dynamically calculated dose delivery are presented as bounds on the dose-volume histogram (DVH). For each plan, the predicted DVH for fractions 2 and 5 was calculated from the simulated pre-scan PET images and compared to the bounded DVH of the BgRT plan. The pass %, defined as the percentage of points on the predicted DVH curves falling within the planned DVH bounds, was automatically calculated; the pass % must be ≥ 95% to proceed with BgRT delivery. Results All 7 BgRT plans met target coverage objectives and normal tissue constraints. The mean pass % for the 14 pre-scans was 98.6%, with 13 exceeding the 95% threshold required for BgRT. There was no statistically significant difference between pass % at fraction 2 versus fraction 5 (two-tailed paired t-test, P = 0.44). The pass % was 92.2% for 1 pre-scan. In this case, the target SUVmax had decreased by 55.5% of the baseline value. Conclusion This investigation provides initial evidence that FDG scans remain stable enough over a course of ablative radiotherapy to enable dynamically tracked dose delivery with BgRT. Significant changes in FDG biodistribution that would prevent dose from being delivered within the pre-approved bounds of the BgRT plan can be identified through analysis of a pre-scan PET image. A prospective clinical trial to confirm these results is in preparation. Clinical trial number NCT03493789.

Purpose/Objective(s) Stereotactic Body Radiation Therapy (SBRT) is considered standard of care for inoperable early stage non-small cell lung cancer (NSCLC) and is commonly delivered in 1-5 fractions. Single fraction SBRT is supported by randomized data demonstrating equivalent safety compared to fractionated approaches. The purpose of this study is to measure trends in the utilization of SBRT fractionation in NSCLC patients in the National Cancer Database (NCDB) from 2004-2016. Materials/Methods The NCDB was queried for patients with cT1-T3N0M0 NSCLC who were treated with a known SBRT dosing schema during the study period (including 30-34 Gy/1 fraction, 54-60 Gy/3 fractions, 48-50 Gy/4 fractions, and 50-60 Gy/5 fractions). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received SBRT using 1, 3, 4, and 5 fractions. Average annual percentage changes (AAPC) were computed and compared to determine if a significant change (defined a priori as P Results The analytic cohort consisted of 39,536 patients. Use of 3 fraction SBRT decreased from 72.6% in 2004 to 20.3% in 2016 (AAPC -10.6% per year, 95% CI: [-12.1%, -9.1%], P 2 (Odds Ratio 1.447, 95% CI: 1.038-2.017) were significantly associated with receipt of single fraction SBRT. Age, insurance, distance to treatment facility, and treatment year were not significantly associated with single fraction SBRT. Conclusion Single fraction SBRT use remained scarce in the United States during 2004-2016, with no clear indication of increased utilization after 2014 when RTOG0915 was first reported. With prospective evidence that long-term toxicity, local control, and survival are similar to 3-4 fraction regimens, the application of single fraction SBRT in the clinic may warrant further interest in light of the recent COVID-19 pandemic and the implementation of the alternative payment model.

Purpose/objective(s) Supplementing intracavitary (IC) applicators with interstitial needles enables more customized dose distributions and allows treatment of more complex cervical cancer cases. However, there are currently no tools to assist physicians in deciding when needles are needed. The purpose of this study is to test the feasibility of using knowledge-based dose predictions to guide needle supplementation. Materials/methods Knowledge-based models for tandem-and-ring/ovoids (TR if all aims were met it was classified as IC. We generated a receiver operating characteristic (ROC) curve and used the Youden index to determine the optimal classification threshold. To explore how clinical implementation could proceed, we used fraction 1 predictions to guide needle choice for fraction 2, fraction 2 to guide fraction 3, etc., with choice for fraction 1 based on physician. We applied this workflow to our dataset and compared model results to physicians' applicator choice, with replan OAR results determining the true classification. Results The area under ROC curve for TO this is consistent with trends observed in ROC. There likely is a band of uncertainty around the dose aims (e.g., ± 5% of aims) where physicians would accept either choice depending on preference or other factors. E.g., a physician may prefer to avoid needles if doses are very close to aims for patient comfort. In 25% of cases, replan D2cc fell within this band, making accurate binary classification more challenging and perhaps less crucial in these cases. Model thresholds could be tuned to better reflect physician preferences. Conclusion The suggested workflow using model-predicted dose to guide needle choice proved feasible, with accuracy comparable to experienced physicians. Predictions for same-day needle usage were more accurate than for subsequent fractions due to anatomical and contouring variability. Dose predictions could standardize optimal applicator selection in gynecologic brachytherapy, which is traditionally based on physician experience.

Purpose/Objective(s) Stereotactic radiosurgery (SRS) requires very sharp dose gradients, high conformality and typically uses minimal expansion margins. Immobilization with an open face mask is more comfortable and less invasive than frame-based immobilization but concerns about intra-fraction motion must be addressed. Surface guided radiation therapy (SGRT) is an attractive option for intra-fraction patient monitoring because it is continuous, has sub-millimeter accuracy and uses no ionizing radiation. The purpose of this study was to investigate the dosimetric consequences of uncorrected intra-fraction patient motion detected during frameless Linac-based SRS. Materials/Methods All SRS patients (pts) were immobilized in an SRS-specific open face thermoplastic mask with bite plate and were monitored during treatment using SGRT with tolerances of 1 mm translations and 1° rotations; the treatment beam automatically turned off if these tolerances were exceeded. SRS pts received 18 or 21 Gy in 1 fraction or 27 Gy in 3 fractions based on tumor size and location. GTV to PTV margins ranged from 0 to 3 mm. Twelve pts were treated with circular cones and 13 were treated with MLC-based plans with the technique chosen based on PTV size. If the SGRT system detected motion greater than tolerance during treatment, conebeam CT(CBCT) was repeated and the necessary shifts were made prior to continuing treatment. For the 25 pts with intra-fraction 3D vector shifts of at least 1 mm, we offset the isocenter in the treatment planning system using the translational shifts from the repeat CBCT and re-calculated the plans with the planned MU to determine the dosimetric effect the shift would have caused had it not been detected. The GTV and PTV coverage and normal brain V12 for the shifted plans were compared to the planned values. Wilcoxon signed rank tests were used to compare planned and shifted dosimetric indices and median 2 sample tests were used to investigate these differences between cone and MLC plans. Results From the recalculated plans, the resulting median V12 increased by 0.24 cc (P = 0.006) and the median GTV and PTV coverage decreased 9% (P Conclusion SGRT detected clinically meaningful intra-fraction motion during frameless SRS, which could potentially lead to large underdoses and increased normal brain dose if not corrected. Dosimetric differences between planned and shifted plans were statistically significant. Author Disclosure R.D. Foster: None. B.J. Moeller: Independent Contractor; Novant Health. Partner; SERO. Stock; Moderna. M. Robinson: None. M. Bright: SEAAPM.J.L. Ruiz: Stock; Obseva USA, Inc. C.J. Hampton: None. J.H. Heinzerling: Research Grant; Vision RT, Inc, AstraZeneca. Honoraria; Vision RT, Inc, AstraZeneca. Consultant; Vision RT, Inc.

Purpose/Objective(s) Uncertainty of deformable image registration (DIR) based dose accumulation is a concern due to the uncertainty with the DIR, in particular for a large deformation. In this work, we introduce a practical workflow of using a DVH overlay technique to check consistency in DIR-based dose accumulation during off-line adaptive replanning for large deformations observed during radiation therapy for abdominal tumors. Materials/Methods Required inputs to the DVH overlay workflow are deformably registered primary (original plan) and secondary (re-plan) images, primary regions-of-interest (ROIs), and a secondary dose distribution. Primary ROIs are forward warped to the secondary image, secondary dose is inversely warped to the primary image, and the ROI DVHs for each image are overlaid. Differences between the DVHs at a given dose point (e.g., V45Gy) quantify the dose uncertainty due to inverse consistency error (ICE) inherent in the DIR. We applied the workflow to a pancreas case treated using modulated arc therapy (mARC) on a Linac equipped with integrated kVCT-on-rails IGRT. For the original plan, 65.25-Gy and 50.75-Gy PTVs were concurrently treated over 29 fractions. After fraction 21, the patient was observed to have lost sufficient weight to justify an adaptive mARC plan based on an updated kVCT image. A composite dose distribution was compiled on the original plan CT by summing 21 fractions of the original planned dose and 8 fractions of a dose distribution warped from the re-plan CT to the original plan CT. Warping was performed using a hybrid DIR algorithm combining contour-based and image-based registration. For each organ-at-risk (OAR) DVH dose point, the workflow-derived ICE (scaled to 8 fractions) was additively applied as an uncertainty to the summation DVH. Results For the re-planned pancreas case, ICE based on the DVH overlay workflow was greatest for the small bowel V45Gy (approximately 5%) and for the stomach V45Gy and V56Gy (approximately 2% for both). ICE was also approximately 4% at V15Gy for the duodenum and colon. For all other ROIs, ICE was 1% or less from the DVH overlay, indicating a favorable DIR for those regions. When applying the DVH overlay-based ICE the resulting accumulated dose remained compliant with the original plan objectives for all OARs except for the stomach V56Gy, which equaled 7.9 cm3 with ICE included (plan objective Conclusion A DVH overlay technique was used to estimate ICE attributable to the uncertainty in DIR-based dose accumulation. The method was applied to a pancreas case for which dose accumulation was performed due to off-line adaptive re-planning for a large anatomic change during the treatment course. In instances where the ICE is over a pre-defined threshold or the summation dose exceeds plan objectives if ICE is included, it is prudent to review the DIR dose transfer and accumulation before using it to make clinical decisions.

Purpose/Objective(s) Biological effective dose (BED) distribution calculation is desirable for combining multiple treatments based on image sets at different times and/or with different fractionations, e.g., re-irradiation. In addition, the composite BED plan needs to be converted back to a physical dose plan in a common fractionation for plan evaluation and/or comparison. The purpose of this work is to develop a practical workflow to composite 3D BED plan and to convert it back to a physical dose plan. Materials/Methods The workflow was developed using contouring software. The organ-specific radiobiological parameters (e.g., α/β, γ/α and dt) for different organs at risk (OAR) were obtained by fitting available clinical dose volume constraint data using a linear-quadratic-linear (LQ-L) model and were stored in the software. The BEDs in each voxel for two separate treatments were calculated using the LQ-L model for each OAR. By contour-based deformable image registration (DIR) algorithm in the software, the two images were registered to obtain a 3D composite BED. Using the rearranged LQ-L model in the software extension, the physical dose was calculated for a given fractionation scheme voxel by voxel from the 3D composite BED. Results The contouring software workflow along with the organ-specific BED parameters was implemented and successfully tested with two head and neck cancer re-irradiation cases. Case I was initially treated with 36 Gy in 6 fractions in 2017 and was re-irradiated with 35 Gy in 5 fractions in 2020. The case II had the first treatment of 70 Gy in 35 fractions in 2008 and the second treatment with 40 Gy in 5 fractions in 2020. The composite BED distributions calculated by the contouring software workflow were converted back to physical dose distributions with 2 Gy per fraction. The total physical doses received by the OARs after second treatments were all within acceptable clinical dose limits, consistent with the fact that no radiation related toxicity was reported for both patients. The obtained organ-specific parameters and the calculation results for these two cases are tabulated below. Conclusion A practical workflow along with organ-specific radiobiological parameters was developed to generate BED composite plan and to convert it back into physical dose distribution. This study provides an additional tool to evaluate overall dose for each OAR in re-irradiation or iso-toxic adaptive radiation therapy.

Purpose To develop a framework with which to evaluate locations of radiation therapy (RT) centers in a region based on geographic access. Methods and Materials Patient records were obtained for all external beam radiation therapy started in 2011 for the province of British Columbia, Canada. Two metrics of geographic access were defined. The primary analysis was percentage of patients (coverage) within a 90-minute drive from an RT center (C90), and the secondary analysis was the average drive time (ADT) to an RT center. An integer programming model was developed to determine optimal center locations, catchment areas, and capacity required under different scenarios. Results Records consisted of 11,096 courses of radiation corresponding to 161,616 fractions. Baseline geographic access was estimated at 102.5 minutes ADT (each way, per fraction) and 75.9% C90. Adding 2 and 3 new centers increased C90 to 88% and 92%, respectively, and decreased ADT by between 43% and 61%, respectively. A scenario in which RT was provided in every potential location that could support at least 1 fully utilized linear accelerator resulted in 35.3 minutes' ADT and 93.6% C90. Conclusions The proposed framework and model provide a data-driven means to quantitatively evaluate alternative configurations of a regional RT system. Results suggest that the choice of location for future centers can significantly improve geographic access to RT.

Purpose To examine the impact of stereotactic body radiation therapy (SBRT) dose on outcomes in early-stage non-small cell lung cancer in a large single-institution series. Methods and Materials We reviewed 600 patients treated from 2003 to 2012 for early-stage non-small cell lung cancer. The SBRT dose was at physician discretion on the basis of tumor size and location. Peripheral tumors were treated to 60 Gy in 3 fractions (homogeneous planning), 48-50 Gy in 4-5 fractions, or 30-34 Gy in 1 fraction. Central tumors were treated to 50 Gy in 5 fractions, 60 Gy in 8 fractions, or 50 Gy in 10 fractions. Patient, tumor, and treatment factors were assessed for their impact on patterns of failure, toxicity, and survival. Results An SBRT dose of 54-60 Gy in 3 fractions was associated with a statistically significant lower rate of local failure (LF) (4.3% at 2 years) compared with 30-34 Gy in 1 fraction (21%), 48-50 Gy in 4-5 fractions (15.5%), and 50-60 Gy in 8-10 fractions (13.3%). Lower pre-SBRT hemoglobin and higher positron emission tomography standardized uptake value were also associated with LF. Nodal failure, distant failure, and overall survival were similar between fractionation groups. Pulmonary toxicity (crude rate, any grade) was slightly higher for 3 fractions (5.0%) compared with 1 (3.2%) or 4-5 fractions (3.8%). Chest wall toxicity was also higher for 3 (23.7%) compared with 1 (8.6%) or 4-5 (7.7%) fraction regimens. Conclusions Although higher biologically equivalent dose SBRT (150-180 Gy10) may be associated with slightly lower LF, it was also associated with mildly increased toxicity and no difference in other patterns of failure or overall survival.

Summary This study evaluated if the information gained from the initial fractions are able to predict which patients are likely to consistently receive a higher than planned dose during image-guided prostate radiotherapy. Each patient’s treatment MVCT of first three to five fractions were analyzed. We report a methodology of accurately predicting consistent overdosing using re-planning data from the first three treated fractions. This has the potential to be extrapolated to other sites as well. Purpose: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning doseevolume constraints during the course of radiotherapy for prostate cancer. Methods and Materials: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving � 100% and � 70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction for which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (Dmax) was � 1% for the rectum and bladder, the fraction was considered a dose failure. Each patient’s first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., � 20% of fractions) during the course of their radiotherapy. Results: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received � 100% and � 70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV100 ,R V70 ,B V100 ,B V70 ,R Dmax, and BDmax, respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV70 ,B V100, and RV100), 90% (BV70), and 100% (RDmax and BDmax) of the times. Conclusions: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their treatment, using information from the first 3 to 5 fractions. 2012 Elsevier Inc.

Purpose To examine patterns of bladder wall motion during high-dose hypofractionated bladder radiotherapy and to validate a novel adaptive planning method, A-POLO, to prevent subsequent geographic miss. Methods and Materials Patterns of individual bladder filling were obtained with repeat computed tomography planning scans at 0, 15, and 30 minutes after voiding. A series of patient-specific plans corresponding to these time-displacement points was created. Pretreatment cone-beam computed tomography was performed before each fraction and assessed retrospectively for adaptive intervention. In fractions that would have required intervention, the most appropriate plan was chosen from the patient's “library,” and the resulting target coverage was reassessed with repeat cone-beam computed tomography. Results A large variation in patterns of bladder filling and interfraction displacement was seen. During radiotherapy, predominant translations occurred cranially (maximum 2.5 cm) and anteriorly (maximum 1.75 cm). No apparent explanation was found for this variation using pretreatment patient factors. A need for adaptive planning was demonstrated by 51% of fractions, and 73% of fractions would have been delivered correctly using A-POLO. The adaptive strategy improved target coverage and was able to account for intrafraction motion also. Conclusions Bladder volume variation will result in geographic miss in a high proportion of delivered bladder radiotherapy treatments. The A-POLO strategy can be used to correct for this and can be implemented from the first fraction of radiotherapy; thus, it is particularly suited to hypofractionated bladder radiotherapy regimens.

Purpose: To explore the biologic relevance of deviations from the intended uniform fractionation scheme. Methods and Materials: We study the effect of the variance of the dose per fraction on the normalized total dose (NTD), which incorporates the linear-quadratic model of radiation effects. In regions of steep dose gradients, we determine the shift between NTD isodose lines and physical isodose lines. We also look at ways to compensate for dose-variation effects through dose adjustments, without changing the number of fractions. Results: Simple equations quantify effects of dose variation on the NTD. If the standard deviation of the dose is 10% of the daily dose fraction, the effects on the NTD for a given point in the irradiated area are always less than 1%, independent of the biologic parameters. In adaptive dose-correction schemes, the dose correction should be applied uniformly over the remaining fractions, to minimize the variance. Incomplete repair leads to a coupling of doses delivered on different days, which complicates the issue. Repopulation appears to be insignificant in the context of this study (constant overall treatment time). Conclusions: A variation of the dose between fractions always leads to a larger biologic effect than does the same total dose delivered with standard uniform fractionation. The increase in NTD is negligible if the standard deviation of the dose is less than 10% of the dose per fraction.

Purpose Dosimetric errors in delivering the prescribed dose per fraction made early in a treatment can be corrected by modifying the dose per fraction and total dose given subsequently to discovery of the error, using the linear-quadratic model to calculate the correcting doses which should be completed within the same overall time as originally prescribed. This study shows how these calculations can be carried out independently of any α/β ratios to bring the treatment back exactly to planned tolerance simultaneously for all tissues and tumor involved. Methods Planned treatment is defined as p Gy per fraction to a total dose P Gy; the initial error is e Gy per fraction given to a total of E Gy. The linear-quadratic formula is assumed to describe all isoeffect relationships between total dose and dose per fraction. Results and conclusion An exact solution is found that describes a compensating dose of d Gy per fraction to a total of D Gy. The formulae are: D=P−Ed=Pp−EeP−E Thus the total dose for the complete treatment (error plus compensation) remains as originally prescribed, with hyperfractionation being used to correct an initial hypofractionation error and hypofractionation being used to correct an initial hyperfractionation error. Incomplete repair is shown to perturb this exact solution. Thus compensating treatments calculated with these formulae should not be scheduled in such a manner that would introduce incomplete repair.

Purpose To determine the dose per fraction that could be used when gamma knife or linear accelerator–based stereotactic treatments are delivered in 2 or more fractions. Methods and materials The linear-quadratic (LQ) model was used to calculate the dose per fraction for a multiple-fraction regimen which is biologically equivalent to a given single-fraction treatment. The results are summarized in lookup tables. Results and conclusions The tables can be used by practicing clinicians as a guide in planning fractionated treatment. For the large doses used in typical stereotactic treatments and for small fraction numbers, the model is not very sensitive to the value of the α/β ratio in the LQ model. A simple rule of thumb is found that for two-fraction and three-fraction treatments the dose per fraction is roughly two-thirds and one-half of the single-fraction treatment dose, respectively.

Purpose Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The purpose of this work is to explore the potential impact of such prolonged fraction delivery times on treatment outcome. Methods and materials The generalized linear-quadratic (LQ) model, which accounts for sublethal damage repair and clonogen proliferation, was used to calculate the cell-killing efficiency of various simulated and clinical IMRT plans. LQ parameters derived from compiled clinical data for prostate cancer ( α = 0.15 Gy −1 , α / β = 3.1 Gy, and a 16-min repair half-time) were used to compute changes in the equivalent uniform dose (EUD) and tumor control probability (TCP) due to prolonged delivery time of IMRT as compared with conventional EBRT. EUD and TCP calculations were also evaluated for a wide range of radiosensitivity parameters. The effects of fraction delivery times ranging from 0 to 45 min on cell killing were studied. Results Our calculations indicate that fraction delivery times in the range of 15–45 min may significantly decrease cell killing. For a prescription dose of 81 Gy in 1.8 Gy fractions, the EUD for prostate cancer decreases from 78 Gy for a conventional EBRT to 69 Gy for an IMRT with a fraction delivery time of 30 min. The values of EUD are sensitive to the α / β ratio, the repair half-time, and the fraction delivery time. The instantaneous dose-rate, beam-on time, number of leaf shapes (segments), and leaf-sequencing patterns given the same overall fraction delivery time were found to have negligible effect on cell killing. Conclusions The total time to deliver a single fraction may have a significant impact on IMRT treatment outcome for tumors with a low α / β ratio and a short repair half-time, such as prostate cancer. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments.

Purpose: The purpose of this study was to evaluate the performance of different radiotherapy workload models using a prospectively collected dataset of patient and treatment information from a single center. Methods and Materials: Information about all individual radiotherapy treatments was collected for 2 weeks from the three linear accelerators (linacs) in our department. This information included diagnosis code, treatment site, treatment unit, treatment time, fields per fraction, technique, beam type, blocks, wedges, junctions, port films, and Eastern Cooperative Oncology Group (ECOG) performance status. We evaluated the accuracy and precision of the original and revised basic treatment equivalent (BTE) model, the simple and complex Addenbrooke models, the equivalent simple treatment visit (ESTV) model, fields per hour, and two local standards of workload measurement. Results: Data were collected for 2 weeks in June 2001. During this time, 151 patients were treated with 857 fractions. The revised BTE model performed better than the other models with a mean observed ‐predicted of 2.62 (2.44 ‐2.80). It estimated 88.0% of treatment times within 5 min, which is similar to the previously reported accuracy of the model. Conclusion: The revised BTE model had similar accuracy and precision for data collected in our center as it did for the original dataset and performed the best of the models assessed. This model would have uses for patient scheduling, and describing workloads and case complexity. © 2003 Elsevier Science Inc.

Purpose : Here we study the magnitude of prostate motion during the delivery of a radiotherapy fraction. These motions have clinical consequences for on-line position verification and the choice of margins around the target volume. Methods and Materials : We studied the motion of the prostate for 10 patients during 251 radiotherapy treatment fractions by assessing the position of implanted gold markers. Gold markers of 1 mm diameter and 5 mm length were implanted in the prostate before the start of the radiotherapy. We obtained movies during each fraction using an a-Si flat-panel imager. The markers could be detected in separate frames using a marker extraction kernel. Results : Marker displacements as large as 9.5 mm were detected in one fraction. The motion of the prostate is greatest in the caudal-cranial and the anterior-posterior directions. Within a time window of 2 to 3 min, deviations from the initial marker position, averaged over all patients, are 0.3 ± 0.5 mm and −0.4 ± 0.7 mm in the anterior-posterior and caudal-cranial directions, respectively. Conclusions : It appeared that on average, the intrafraction prostate motions did not result in margins larger than 1 mm, provided that the position verification is performed at time intervals of 2 to 3 min. Only for some patients performing more frequent position verification or adding extra margins of 2 to 3 mm is required to account for intrafraction prostate motions.

Because of the large amount of data generated by 3D treatment planning, new tools are being developed for the evaluation and optimization of the plans. Estimates of the probability of local control of the tumor and for the probability of specific normal tissue complications are among the new tools. The normal tissue complication probability (NTCP) is based on clinical estimates of the tolerance doses for specific tissues/organs. These tolerance doses are assumed to apply for uniform partial and full volume irradiations delivered at 2 Gy per fraction and 5 fractions per week. A different tolerance dose may apply when the dose is delivered at a different dose per fraction and over a different period of time. This study evaluates the maximum change expected in the NTCP when the normal structure receives the dose at a different dose per fraction than the target volume due to different choices in the delivery of the daily fraction.

To quantify the target and normal structures on dose distributing variations during intensity-modulated radiotherapy (IMRT) and to assess the value of replanning for nasopharyngeal carcinoma (NPC) patients.Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was acquired for all patients. According to the dose constraint criterion in the Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was generated on the new simulation CT. With the Quality Assessment Center of a CORVUS 6.3 treatment planning system, a phantom plan was generated for each patient by applying the beam configurations of the initial plan to the anatomy of the new simulation CT. The dose-volume histograms of the phantom plan were compared with the replanning.The percentage of prescription dose delivered to the clinical target volume (CTV1) was significantly increased by 4.91% +/- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the left parotid, and V30 to the right parotid were significantly decreased by 5.00 +/- 9.23Gy, 4.23 +/- 10.03Gy, and 11.47% +/- 18.89% respectively in the replanning, compared with the phantom plan (p0.05). Based on the dose constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were out of limit for the dose to the normal critical structures, whereas no plan was out of limit in replanning (p0.001).Replanning for patients with NPC before the 25th fraction during IMRT helps to ensure adequate dose to the target volumes and safe doses to critical normal structures.

Purpose Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image–guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye–view. Methods and materials The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye–view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose–volume histograms and dose–volume and dose–response indices are also computed. These data are compared with the corresponding data derived ( a ) from the original treatment plan applied to the original image, ( b ) from the original treatment plan applied to today's image, and ( c ) from a new full-fledged IMRT plan designed based on today's image. Results Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye–view are a good approximation of full-fledged replanning compared with other alternatives. Conclusions Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

discrepancies was observed in the low density insert (0.2 g/cm3), where the transit dosimetry algorithm overestimated the TPS dose by average of 2.70% (SD Z 1.03%). The evaluated software for transit dosimetry achieves the goal of an efficient and independent in vivo dosimetry validation method of the helical delivery pattern, although the overestimation of the reconstructed dose in low density area has to be taken into account. It is also important to note that every fraction can be evaluated without additional measurement. Author Disclosure: L. Matulewicz: C. Partner; Math Resolutions, LLC.K. Slosarek: None.