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Purpose In this study we present a novel method for re‐calculating a treatment plan on different respiratory phases by accurately modeling the panning and tilting beam motion during DTT (the “rotation method”). This method is used to re‐calculate the dose distribution of a plan on multiple breathing phases to accurately assess the dosimetry. Methods sIMRT plans were optimized on a breath hold computed tomography (CT) image taken at exhale (BHexhale) for 10 previous liver stereotactic ablative radiotherapy patients. Our method was used to re‐calculate the plan on the inhale (0%) and exhale (50%) phases of the four‐dimensional CT (4DCT) image set. The dose distributions were deformed to the BHexhale CT and summed together with proper weighting calculated from the patient’s breathing trace. Subsequently, the plan was re‐calculated on all ten phases using our method and the dose distributions were deformed to the BHexhale CT and accumulated together. The maximum dose for certain organs at risk (OARs) was compared between calculating on two phases and all ten phases. Results In total, 26 OARs were examined from 10 patients. When the dose was calculated on the inhale and exhale phases six OARs exceeded their dose limit, and when all 10 phases were used five OARs exceeded their limit. Conclusion Dynamic tumor tracking plans optimized for a single respiratory phase leave an OAR vulnerable to exceeding its dose constraint during other respiratory phases. The rotation method accurately models the beam’s geometry. Using deformable image registration to accumulate dose from all 10 breathing phases provides the most accurate results, however it is a time consuming procedure. Accumulating the dose from two extreme breathing phases (exhale and inhale) and weighting them properly provides accurate results while requiring less time. This approach should be used to confirm the safety of a DTT treatment plan prior to delivery.

The objective of this note is to introduce a clinical tool that generates ideal base plan dose distributions to enable re‐irradiation volumetric modulated arc therapy (VMAT) optimization based on cumulative biological effective dose objectives for specific organs at risk (OARs). The tool is demonstrated with a lung cancer case that required re‐irradiation at our clinic. First, previous treatment dose is deformed onto the retreatment computed tomography (CT) using commercial software. Then, the in‐house Matlab tool alters the deformed previous dose using radiobiological concepts on a voxel‐by‐voxel manner to generate an ideal base plan dose distribution. Ideal base plans that were generated using the in‐house Matlab tool were compatible with the Varian Eclipse™ treatment planning system. The tool enabled optimization of VMAT re‐irradiation plans using cumulative dose limits for OARs and all OAR cumulative dose objectives were met on the first optimization for the recurrent lung cancer case tested.

Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene‐addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)‐positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.

Purpose: The purpose of this work is threefold: (1) to explore biological consequences of the multileaf collimator (MLC) calibration errors in intensity modulated radiotherapy (IMRT) of prostate and head and neck cancers, (2) to determine levels of planning target volume (PTV) and normal tissue under- or overdose flagged with clinically used QA action limits, and (3) to provide biologically based input for MLC QA and IMRT QA action limits. Methods: Ten consecutive prostate IMRT cases and ten consecutive head and neck IMRT cases were used. Systematic MLC offsets (i.e., calibration error) were introduced for each control point of the plan separately for X1 and X2 leaf banks. Offsets were from − 2 to 2 mm with a 0.5 mm increment. The modified files were imported into the planning system for forward dose recalculation. The original plan served as the reference. The generalized equivalent uniform dose (gEUD) was used as the biological index for the targets, rectum, parotid glands, brainstem, and spinal cord. Each plan was recalculated on a CT scan of a 27 cm diameter cylindrical phantom with a contoured 0.6 cc ion chamber. Dose to ion chamber and 3D gamma analysis were compared to the reference plan. QA pass criteria: (1) at least 95% of voxels with a dose cutoff of 50% of maximum dose have to pass at 3 mm/3% and (2) dose to chamber within 2% of the reference dose. Results: For prostate cases, differences in PTV and rectum gEUD greater than 2% were identified. However, a larger proportion of plans leading to greater than 2% difference in prostate PTV gEUD passed the ion chamber QA but not 3D gamma QA. A similar trend was found for the rectum gEUD. For head and neck IMRT, the QA pass criteria flagged plans leading to greater than 4% differences in PTV gEUD and greater than 5% differences in the maximum dose to brainstem. If pass criteria were relaxed to 90% for gamma and 3% for ion chamber QA, plans leading to a 5% difference in PTV gEUD and a 5%–8% difference in brainstem maximum dose would likely pass IMRT QA. A larger proportion of head and neck plans with greater than 2% PTV gEUD difference passed 3D gamma QA compared to ion chamber QA. Conclusions: For low modulation plans, there is a better chance to catch MLC calibration errors with 3D gamma QA rather than ion chamber QA. Conversely, for high modulation plans, there is a better chance to catch MLC calibration errors with ion chamber QA rather than with 3D gamma QA. Ion chamber and 3D gamma analysis IMRT QA can detect greater than 2% change in gEUD for PTVs and critical structures for low modulation treatment plans. For high modulation treatment plans, ion chamber and 3D gamma analysis can detect greater than 2% change in gEUD for PTVs and a 5% change in critical structure gEUD since either QA methods passes the QA criteria. For gEUD changes less than those listed above, either QA method has the same proportion of passing rate.

Purpose: Normal tissue complications following radiotherapy (RT) are commonly estimated from single institutions, limiting generalizability of critical dose-volume thresholds. In this study we use data from five cohorts/institutions to explore dose-volume relations for late rectal bleeding (LRB) after RT for prostate cancer. Methods: The investigated cohorts included 1001 patients treated with various RT techniques for prostate cancer (922 3DCRT, 211 image-guided RT, and 79 intensity-modulated RT patients) to 70–86 Gy@2Gy/fraction in 1991–2007. The rectum extended from the recto-sigmoid flexure to the anal canal, and the median (range) follow-up for LRB was 58 (4–259) months. Rectal cross sectional area, length, and volume were compared between LRB and non- LRB patients (Mann-Whitney-test). The ability of dose metrics to predict moderate-to-severe LRB (prevalence: 14%) was investigated on univariate analysis, UVA, (Spearman’s Rho (Rs) and p-values calculated as medians from 10 0000 Bootstrap-resamples). Dose-volume metrics significantly predicting LRB on UVA (p≤0.05) were considered for multivariate logistic regression, MVA, following removal of correlated metrics (Pearson’s correlation, Pr ≥0.85). Results: Patients with LRB had significantly (p1000 patients) suggest that shorter rectums and intermediate to high doses predict LRB. The wide range of prescribed doses and treatment techniques applied support generalizability of our results to other prostate cancer cohorts.

Purpose: To establish a formalism for biologically‐based optimization of intensity‐modulated radiation therapy(IMRT) for overcoming prostate tumor hypoxia while sparing the urethra. Method and Materials: A formalism based on the concept of equivalent uniform dose (EUD) was used to construct the objective function for biological optimization of IMRT.IMRT planning using VMAT (Volumetric Modulated Arc Therapy) was performed based on hypothetical hypoxic regions manually drawn on CT scans. The developed formalism accounts for impact of chronic and acute hypoxia on cell surviving fraction and re‐oxygenation in chronic hypoxia regions. EUDs for urethra, rectum, bladder and femoral heads were calculated based on power‐law dose‐volume histogram reduction. CTdata sets from 25 prostate cancer patients who recently received external beam radiation therapy were selected. VMAT plans optimized with dose‐volume constraints were used for comparison. Results: Significant dose boost in the target volumes designated as chronic or acute hypoxia regions was achieved. EUD in the PTV exceeded 80 Gy, despite accounting for the effects of hypoxia. This increase was achieved with only minor changes in the dose to normal tissue compared to the dose‐based VMAT plans. Notably, urethra sparing was excellent with a EUD of approximately 64 Gy. The robustness of the proposed approach was validated using various settings of acute and chronic hypoxia consisting of a range of hypoxic volumes, regions and re‐oxygenation patterns. Conclusion: The comparison of IMRT plans obtained with biological and dose‐volume constraint based optimization showed that the biologically‐guided IMRT planning approach is more suitable for critical structure sparing dose painting. In particular, a sterilizing dose may be delivered to hypoxic regions in a variety of scenarios while ensuring rectum, bladder and urethra sparing.

Purpose: To quantify biological consequences of MLCcalibration errors in prostate IMRT and relate those biological consequences to IMRT QA action levels. Methods: Ten consecutive prostate cancer patients treated with a 5‐field IMRT (Varian iX with Millenium 120 leaf MLC) were selected. All cases were treated with a prescription dose of 74 Gy. An in‐house program was used to introduce systematic MLC offsets. Combinations of X1 and X2 offsets in the range from −2 to +2mm were explored. Modified files were imported into the treatment planning system (TPS) to recalculate dose for each modified plan. DVHs were exported from the TPS and generalized equivalent uniform doses (gEUD) were calculated for the rectum (n=0.09) and PTV (a=−10). Each plan was also recalculated on a CT scan of a cylindrical phantom with a contoured ion camber. Dose distributions were exported for 3D gamma analysis with dose and distance to agreement set to 3% and 3 mm, respectively. Pass criteria were: at least 95% of voxels have to pass and dose to chamber has to be within 2% of the reference dose. Results: Plans with offsets of 2 mm, single leaf bank or combined, have not passed gamma QA, however 30% of plans passed chamber dose QA. For 1.5 mm offsets 20% and 70% of plans passed gamma and chamber dose QA, respectively. Change in gEUD for PTV and rectum was of the order of 2% for plans passing both QA methods and larger than 3% for those which failed QA. Conclusions: With currently used methods and criteria for prostate IMRT QA, we can only detect changes in gEUD greater than 3% that are resultant from MLCcalibration errors. This is important because it provides a lower limit on the ability of current IMRT QA to estimate a biological impact for machine errors.

Purpose: To develop a method for improving functional lung sparing utilizing perfusion SPECT information and Monte Carlo(MC)dose calculation in IMRToptimization of lungcancerradiotherapy.Methods and Materials: 99mTc‐macroaggregated albumin (MAA) SPECT scans were acquired before radiotherapy (RT) for five non‐small cell lungcancer patients treated with RT (60Gy / 30 fx). Perfusion SPECTimages were reconstructed with attenuation, scatter correction and rigidly registered with planning CT afterwards. Beamlets generated from MC simulation were incorporated into direct aperture optimization (DAO) of static gantry step and shoot IMRTtreatment planning. For each patient, three RT plans were generated. 1. Clinical plan: 3D‐CRT plan generated in vendor's software which is clinically delivered. 2. DVH driven plan: IMRT plan generated using DAO and MCdose calculation without SPECT guidance. Conventional DVH constraints for targets and OARs were used in the treatment planning, 3. SPECT driven plan: IMRT plan generated using DAO and MCdose calculation with SPECT guidance. SPECT weighted mean dose (SWMD) and Equivalent uniform dose (EUD) constraints were incorporated into the objective function. SWMD constraints were applied to ipsilateral and contralateral lungs respectively as the metric of lung function sparing. EUD was adopted to optimize planning target volume (PTV) dose coverage. Results: 1. Compared to clinical plan, same target dose coverage was achieved in both DVH driven and SPECT driven plans. 95% iso‐dose line covered more than 97% of PTV in both plans. 2. Compared to DVH driven plans, in SPECT driven plans, V5 and V20 were reduced by ∼8% and ∼3% respectively, SWMD were reduced by ∼1Gy. Thus superior sparing of both lung function and volume was achieved. Conclusion: Comparing to conventional DVH driven IMRT plans, superior lung sparing of both anatomical and functional volumes can be achieved in SPECT driven IMRT planning based on EUD and SWMD.

Purpose: To compare functional lung volume segmentation and Single Photon Emission Computed Tomography(SPECT) weighted mean dose (SWMD) approaches used in SPECT guided treatment planning studies for patients with lungcancer.Methods and Materials: Nine lungcancer patients were consented to have a perfusion SPECT scan with 99mTc‐macroaggregated albumin. Four image sets were reconstructed from each scan: one using a vendor provided ordered subsets expectation maximization (OSEM) algorithm and three quantitative SPECTreconstructions using OSEM methods with different types of attenuation and scatter corrections. SWMDs were calculated for open field with different sizes and gantry angles. Functional lung volumes were segmented in each reconstructed image using 10, 20, …, 90% of maximum SPECT intensity as a threshold. Results:Image reconstruction accuracy and thus functional lung volume segmentation are affected by several factors, such as attenuation and scatter correction, resolution recovery method and number of iterations used in reconstruction. Large differences in functional volumes (more than 50%) were found between images obtained from the four reconstructions. In contrast, the SWMD calculation produced consistent results for all SPECTreconstructions which included attenuation correction, regardless of whether or not scatter correction was used and the number of iterations.Conclusion: Functional volume segmentation is sensitive to the type of attenuation and scatter correction and number of iterations. In contrast, for imagesreconstructed with attenuation correction, the SWMD calculation produces consistent results and appears to be a more robust choice to be used in future studies incorporating SPECT into treatment planning.

Purpose: To quantitatively evaluate the accuracy of several SPECT/CT image registration methods in recent studies and its impact on the functional lung volume segmentation in SPECT guided radiation therapy (RT) treatment planning.Methods and Materials: Five lungcancer patients were consented to have a perfusion SPECT scan with 99mTc‐macroaggregated albumin. During the scan, a low resolution CTimage was acquired using the SPECT/CT scanner. This CT scan was co‐registered to the patient's planning CT scan through four rigid and deformable image registration programs (rigid registration, skin/lung control points based registration and B‐spline deformable registration). After the CT to CT co‐registration, original SPECT reconstructions were warped and co‐registered to the planning CT scan. The functional lung volumes were segmented from each deformed SPECT using 10, 20, …, 90% of maximum pixel value as a threshold. The differences in the size and contours of each functional volume were calculated. Results: Based on the evaluation of registered CTimages, the result from B‐spline registration demonstrated the smallest intensity difference. Using the warped SPECTimages obtained from this registration method as a reference, the smallest difference in the size and contour of functional volumes was found using rigid registration. In the point‐based registrations, a better result was found when the control points were placed on lung volume instead of body contour. Conclusion: Apply B‐spline based image registration method in SPECT‐guided RT studies was shown to be accurate. Point‐based image registration using skin markers with a standalone SPECTscanner was found least accurate.

Purpose: To investigate the impact of different types of image reconstruction and attenuation/scatter (A/S) correction on the calculation of dosimetric indices proposed to be used for Single Photon Emission Computed Tomography(SPECT) guided dose escalation in lungcancer patients. Methods and Materials:SPECTlung perfusion scans were obtained for nine lungcancer patients using 99mTc‐macroaggregated albumin. Four image sets were reconstructed from each scan: one using a vendor provided ordered subsets expectation maximization (OSEM) algorithm, two quantitative SPECTreconstructions using OSEM methods with different types of A/S corrections and the fourth an OSEM reconstruction without any A/S correction. SPECT weighted mean dose (SWMD), dose function histogram, and functional lung volume have been calculated from dose distributions and regional perfusion maps. To investigate the dependence of SWMDs on gantry angle, twelve equally spaced co‐planar open field radiation beams delivering the same MU were centered on the PTV. Three field sizes, 5×5, 7.5×7.5 and 10×10cm2 were considered. SWMDs were calculated for each field and reconstruction. Functional lung volumes were segmented in each reconstruction using 10, 20, …, 90% of maximum SPECT uptake as a threshold. Results: SWMDs calculated from reconstructions without A/S correction showed more than 5% average difference compared to those with corrections. With A/S corrections, more consistent SWMDs were found in all the three OSEM reconstructions (average difference ∼2%). However, a large variation was observed between segmented functional lung volumes and the V20 of these volumes in all four reconstructions. The difference between the volumes reached over 50% regardless of whether A/S correction was applied in the reconstruction.Conclusion: Functional volume segmentation is sensitive to the type of A/S correction. In contrast, SPECT weighted mean dose calculation produces more consistent results and appears to be a more robust choice for clinical outcome analysis and SPECT guided treatment planning.

Purpose: To quantify the accuracy of dose distributions produced according to the stereotactic body radiation therapy(SBRT) protocol BR25 using Monte Carlo (MC).Method and Materials: Eleven NSCLC patients previously treated with conventional radiotherapy, were selected as suitable for SBRT. For each patient three plans were produced in Eclipse TPS. Plan 1 was based on the BR25 protocol, i.e., a conformal plan with no inhomogeneity corrections. Plan 2 had inhomogeneity corrections enabled, but was otherwise identical to plan 1 (as QA requirement for the RTOG 0618 protocol). Plan 3 designed to meet planning objectives with inhomogeneity corrections enabled. Dose distribution from MC simulations for plans 2 and 3 were compared with those generated in Eclipse for target volumes and normal lung. Equivalent uniform dose (EUD) was calculated for PTV, and normal lung minus GTV. V20 was calculated for normal lung minus GTV. Results: Underdosing of PTV was observed in the MC simulations of Eclipse plans. While planning without inhomogeneity corrections gave the desired 100% PTV coverage with 95% of the prescription dose,MC simulation showed that typically less than 90% of the PTV was actually covered with this dose. For a representative patient, the PTV EUD was 60Gy as planned, 61.4Gy if the same plan was calculated with inhomogeneity enabled, and 58.8Gy if MC calculation was used. This underdosing was more pronounced for plans generated with inhomogeneity correction enabled: planned EUD=60.8Gy, and MC EUD=58.6Gy. Conclusion: Current SBRT protocols require that no inhomogeneity corrections are to be applied, which is a better choice than allowing inhomogeneity corrections. However, producing plans with inhomogeneity corrections for QA purposes, as required in these protocols, leads to misrepresentative dose distributions because of improper accounting for lack of backscatter and lateral electronic equilibrium. MC‐based dose calculation should be recommended as a QA tool for lungSBRT.

Purpose: To estimate the lung and other critical organ doses of the patients in total body irradiation before bone marrow transplant which is a general protocol for curing leukemia. Method and Materials: Total body irradiation was performed using the photo beam produced by the linear accelerator in the conditions of 415 cm source‐to‐surface distance (SSD), 40×40 cm2field size and 15 MV beam energy in parallel opposed irradiation in this work. A Rando phantom, a diode detector and thermoluminescent dosimeter(TLD) chips were selected to perform the dose investigation. The diode detector has small volume, and can provide real‐time reading and high accuracy. TLD chips were placed inside the Rando phantom to get the dose distributions along the longitude of the phantom and the critical organs suggested by the ICRP‐60 report. In the meantime, a diode detector and TLD chips were also placed at the entrance surface point to evaluate the dose conversion factors for the critical organs to the entrance surface dose (ESD).Results: The doses of upper mediastinum lung in the Rando phantom are about 20 % higher than the prescribed doses at the center in field. The doses of thyroids, gonad glands and eyes are lower than prescribed doses. The organ‐dose conversion factors for the critical organs to the entrance surface dose were evaluated. Conclusion: The increased doses of lung should be considered in clinical practice. The organ‐dose conversion factors established in this work can be used to estimate the critical organ doses, by means of measuring only the entrance surface dose of the patient in clinical irradiation. The diode detector is accurate and convenient to be used in the evaluation of real‐time ESD of the patient in the clinical total body irradiation.

Purpose: To explore means of incorporating prostate motion and setup uncertainties into biologically‐based adaptive IMRT optimization for Volumetric Modulated Arc Therapy (VMAT). Method and Materials:IMRT planning objectives were set to produce a dose distribution, which, after accounting for setup uncertainties and prostate motion, meets the following requirements. 1) The CTV is covered with the desired dose; 2) Hypoxia volumes arbitrarily drawn inside CTV are boosted; 3) Desired urethra sparing is achieved. The objective function was based on equivalent uniform dose (EUD). Repositioning data from five prostate patients with implanted fiducial markers were used. Systematic and random uncertainties for each patient were incorporated into an in‐house treatment planning platform for VMAT. During the optimization, the dose matrix was shifted based on the systematic error, then convolved with a pre‐calculated Gaussian kernel to account for random errors. For each of these patients seven plans were generated using uncertainty data accumulated in 5 fraction increments. Results: The urethra EUD increased by >5Gy when the dose distribution from the static plan was propagated to account for geometrical uncertainties. In contrast, if uncertainties were accounted for in planning, urethra EUD was reduced without compromising CTV coverage (EUD decreased

Purpose: With IGRT, the geometric uncertainty in treatment can be reduced, which makes it feasible to implement IMRT dose painting with a reasonable resolution. In this cancer center, an on‐line realignment protocol is utilized for prostate cancer patients. This IGRT protocol is based on use of implanted gold fiducial markers and EPI. In this study, dose escalations with urethra sparing have been tested by using IMRT dose painting. Method and Materials:CT scans of three patients were chosen from the IGRT group. The original 3D‐CRT plan (74Gy/37fr, 10mm PTV margin) was used as a reference. In test IMRT plans two PTVs were generated. PTV1 was defined as 5mm extension of prostate. PTV2 was generated from PTV1 with 5mm margin subtracted for bladder, rectum, and urethra. Two raw plans were generated. Plan 1 was 74Gy/37fr to PTV1, and Plan 2 was 74Gy/37fr to PTV2. Then, the urethra sparing IMRT boost plan was generated as a weighted sum of the two raw plans, e.g. Real Plan = w 1 × Plan 1+ w 2 × Plan 2 . Different combinations of weighting factors were tested: w1∈[0.6, 1], w2∈. [0.1, 0.5]. The dose to each organ was calculated with organ motion simulated based on actually recorded EPI image mismatches. The tumor control probability (TCP) and effective dose were used to evaluate the plans. Results: To achieve the same urethra D50 (minimum dose to 50% volume) as the reference plan, the highest weighting combination was w1=0.7, w2=0.5 ( Prescription Dose = (0.7+0.5) ×74 Gy =88.8 Gy ) . This yields significant dose reduction in bladder and rectum. For the considered patient the TCP increases from ∼74% to ∼95%. Conclusion: With IGRT, the urethra sparing IMRT dose painting is superior to the 3D‐CRT plan. The total prescription dose can be as high as 88Gy, with TCP of ∼95% and lower GI complication. Since urethra has been spared, the GU complication will be less.

Purpose: We simulated effects of full (no repositioning) and reduced (using fiducial markers and on‐line repositioning following EPI) uncertainties on dose distributions in PTV, prostate, and organs at risk — bladder and rectum; and evaluated limits for dose escalation if on‐line repositioning is implemented and tight PTV margins are applied. Method and Materials: Three patients' anatomies, with large (68cc), medium (55cc) and small (40cc) prostate volumes were used. PTV margins of 2, 4, 6, 9 and 12mm were tested for a conventional 70Gy/35fr, and dose escalated schedules of 74Gy/37fr and 78Gy/39fr. Setup and organ motion uncertainties were modeled in a stochastic manner to generate a dose population histogram. The outcome of each treatment was then scored based on dose distributions in organs. These have been summarized as equivalent uniform doses (EUD) calculated on survival basis for prostate and effective doses from reduced dose‐volume histograms for bladder and rectum. We deemed dose escalation acceptable as long as the currently observed complication rate was not exceeded. To verify validity of obtained margin prescription, 20 patients were studied with the above simulation methods with acceptable margins only. Results: With reduced positioning uncertainties using fiducials, the dose can be escalated to 78 Gy with a reduced PTV margin of 4mm without compromising tumor control probability. Even if large PTV margins (12mm) were applied and dose was escalated to 78Gy, bladder doses did not exceed tolerance levels. The rectal complication probability is comparable to the currently observed rates or even less if rectal bleeding is proven to show strong volume dependence (parallel model) even treating to 78Gy with 4mm margin. The additional 20 patients studied provided similar results. Conclusion: educed positioning uncertainties using fiducial markers allow us to reduce PTV margin to 4mm and escalate dose to 78Gy with similar or lower rectal toxicity rates.