Jean M. Moran

Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

PURPOSE Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. METHODS AND MATERIALS A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. RESULTS The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. CONCLUSIONS This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.

Dosimetry tools and techniques for IMRT

Intensity modulated radiation therapy (IMRT) poses a number of challenges for properly measuring commissioning data and quality assurance (QA) radiation dose distributions. This report provides a comprehensive overview of how dosimeters, phantoms, and dose distribution analysis techniques should be used to support the commissioning and quality assurance requirements of an IMRT program. The proper applications of each dosimeter are described along with the limitations of each system. Point detectors, arrays, film, and electronic portal imagers are discussed with respect to their proper use, along with potential applications of 3D dosimetry. Regardless of the IMRT technique utilized, some situations require the use of multiple detectors for the acquisition of accurate commissioning data. The overall goal of this task group report is to provide a document that aids the physicist in the proper selection and use of the dosimetry tools available for IMRT QA and to provide a resource for physicists that describes dosimetry measurement techniques for purposes of IMRT commissioning and measurement-based characterization or verification of IMRT treatment plans. This report is not intended to provide a comprehensive review of commissioning and QA procedures for IMRT. Instead, this report focuses on the aspects of metrology, particularly the practical aspects of measurements that are unique to IMRT. The metrology of IMRT concerns the application of measurement instruments and their suitability, calibration, and quality control of measurements. Each of the dosimetry measurement tools has limitations that need to be considered when incorporating them into a commissioning process or a comprehensive QA program. For example, routine quality assurance procedures require the use of robust field dosimetry systems. These often exhibit limitations with respect to spatial resolution or energy response and need to themselves be commissioned against more established dosimeters. A chain of dosimeters, from secondary standards to field instruments, is established to assure the quantitative nature of the tests. This report is intended to describe the characteristics of the components of these systems; dosimeters, phantoms, and dose evaluation algorithms. This work is the report of AAPM Task Group 120.

VARIABILITY OF TARGET AND NORMAL STRUCTURE DELINEATION FOR BREAST CANCER RADIOTHERAPY : AN RTOG MULTI-INSTITUTIONAL AND MULTIOBSERVER STUDY

PURPOSE To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas. METHODS AND MATERIALS Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. RESULTS Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT. CONCLUSIONS Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT.

Unacceptable Cosmesis in a Protocol Investigating Intensity-Modulated Radiotherapy With Active Breathing Control for Accelerated Partial-Breast Irradiation

PURPOSE To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach. METHODS AND MATERIALS We enrolled breast cancer patients in an institutional review board-approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t-tests. RESULTS Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02). CONCLUSIONS The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting.

Verification of dynamic and segmental IMRT delivery by dynamic log file analysis.

A program has been developed to evaluate the delivered fluence of step‐and‐shoot segmental and sliding window dynamic multileaf collimator (MLC) fields. To automate these checks, a number of tools have been developed using data available from the dynamic log files that can be created each time a dynamic delivery occurs. Experiments were performed with a Varian 2100EX with a 120 leaf MLC equipped with dynamic capabilities. A dynamic leaf sequence is delivered and measured with film or an amorphous silicon imager. After delivery, the dynamic log file is written by the accelerator control system. The file reports the expected and actual position for each leaf and the dose fraction every 0.055 seconds. Leaf trajectories are calculated from this data and expected and actual fluence images are created from the difference of opposing leaf trajectories. These images can be compared with the expected delivery, measurements, and calculations of fluence. Tools have been developed to investigate other aspects of the delivery, such as specific leaf errors, beam hold‐off flags sent by the control system to the MLC, and gap widths. This program is part of a semi‐automated quality assurance (QA) system for pretreatment fluence verification and daily treatment verification of dynamic multileaf collimation (DMLC) delivery. PACS number(s): 87.53.–j, 87.52.–g

Incorporation of realistic delivery limitations into dynamic MLC treatment delivery

The clinical implementation of IMRT involves the use of a number of complex software-based systems, typically including an inverse planning system, a leaf sequencer, and a computer-controlled treatment delivery system. The inverse planning system determines the desired fluence patterns, the leaf sequencer translates those fluence maps into leaf trajectories, and the control system delivers those trajectories. While verification of intensity-modulated treatment fields has focused primarily on the dosimetric aspects of delivery, accurate delivery of the intended fluence distribution is dependent upon both the leaf sequencer and delivery control systems. Leaf sequencing algorithms typically do not incorporate many control system limitations, and this can lead to discrepancies between planned and delivered sequences. In this work, simple and complex fields were sequenced for the dynamic sliding window technique using different leaf speeds and tolerance settings to identify various limitations of the accelerator control system. This work was conducted on a Varian 2100 EX equipped with a Millennium 120 leaf MLC. The identified limitations were then incorporated into the sequencing algorithm using a limiting leaf velocity (less than the maximum leaf velocity), the leaf position tolerance, and the communications delay in the control system. Collision avoidance in leaf pairs was found to depend on a control system-enforced minimum gap between leaves and led to acceleration effects. By incorporating these effects into the leaf sequencing algorithm, dynamic sliding-window leaf sequences were produced which did not require beam interruptions or dose rate modulations for the parameter values used in calculating the sequence (dose rate, tolerance, leaf speed, and total monitor units). Incorporation of control system limitations into the leaf sequencing algorithm results in IMRT fields that are delivered with the prescribed constant dose rate, require less time to deliver, and have well-defined, calculable transmission dose characteristics.

EVALUATION OF FOUR TECHNIQUES USING INTENSITY-MODULATED RADIATION THERAPY FOR COMPREHENSIVE LOCOREGIONAL IRRADIATION OF BREAST CANCER

PURPOSE To establish optimal intensity-modulated radiation therapy (IMRT) techniques for treating the left breast and regional nodes, using moderate deep-inspiration breath hold. METHODS AND MATERIALS We developed four IMRT plans of differing complexity for each of 10 patients following lumpectomy for left breast cancer. A dose of 60 Gy was prescribed to the boost planning target volume (PTV) and 52.2 Gy to the breast and supraclavicular, infraclavicular, and internal mammary nodes. Two plans used inverse-planned beamlet techniques: a 9-field technique, with nine equispaced axial beams, and a tangential beamlet technique, with three to five ipsilateral beams. The third plan (a segmental technique) used a forward-planned multisegment technique, and the fourth plan (a segmental blocked technique) was identical but included a block to limit heart dose. Dose--volume histograms were generated, and metrics chosen for comparison were analyzed using the paired t test. RESULTS Mean heart and left anterior descending coronary artery doses were similar with the tangential beamlet and segmental blocked techniques but higher with the segmental and 9-field techniques (mean paired difference of 15.1 Gy between segmental and tangential beamlet techniques, p < 0.001). Substantial volumes of contralateral tissue received dose with the 9-field technique (mean right breast V2, 58.9%; mean right lung V2, 75.3%). Minimum dose to ≥95% of breast PTV was, on average, 45.9 Gy with tangential beamlet, 45.0 Gy with segmental blocked, 51.4 Gy with segmental, and 50.2 Gy with 9-field techniques. Coverage of the internal mammary region was substantially better with the two beamlet techniques than with the segmental blocked technique. CONCLUSIONS Compared to the 9-field beamlet and segmental techniques, a tangential beamlet IMRT technique reduced exposure to normal tissues and maintained reasonable target coverage.

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

PURPOSE To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. METHODS AND MATERIALS On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. RESULTS The mean difference in pre- and post-RT PD was -0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. CONCLUSIONS Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

Improving IMRT delivery efficiency using intensity limits during inverse planning.

Inverse planned intensity modulated radiotherapy (IMRT) fields can be highly modulated due to the large number of degrees of freedom involved in the inverse planning process. Additional modulation typically results in a more optimal plan, although the clinical rewards may be small or offset by additional delivery complexity and/or increased dose from transmission and leakage. Increasing modulation decreases delivery efficiency, and may lead to plans that are more sensitive to geometrical uncertainties. The purpose of this work is to assess the use of maximum intensity limits in inverse IMRT planning as a simple way to increase delivery efficiency without significantly affecting plan quality. Nine clinical cases (three each for brain, prostate, and head/neck) were used to evaluate advantages and disadvantages of limiting maximum intensity to increase delivery efficiency. IMRT plans were generated using in-house protocol-based constraints and objectives for the brain and head/neck, and RTOG 9406 dose volume objectives in the prostate. Each case was optimized at a series of maximum intensity ratios (the product of the maximum intensity and the number of beams divided by the prescribed dose to the target volume), and evaluated in terms of clinical metrics, dose-volume histograms, monitor units (MU) required per fraction (SMLC and DMLC delivery), and intensity map variation (a measure of the beam modulation). In each site tested, it was possible to reduce total monitor units by constraining the maximum allowed intensity without compromising the clinical acceptability of the plan. Monitor unit reductions up to 38% were observed for SMLC delivery, while reductions up to 29% were achieved for DMLC delivery. In general, complicated geometries saw a smaller reduction in monitor units for both delivery types, although DMLC delivery required significantly more monitor units in all cases. Constraining the maximum intensity in an inverse IMRT plan is a simple way to improve delivery efficiency without compromising plan objectives.

Effect of radiation therapy on permanent pacemaker and implantable cardioverter-defibrillator function

BACKGROUND Radiation therapys (RTs) effects on cardiac implantable electronic devices (CIEDs) such as implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs) are not well established, leading to device removal or relocation in preparation for RT. OBJECTIVE To determine the effect of scattered RT on CIED performance. METHODS We analyzed 69 patients--50 (72%) with PMs and 19 (28%) with ICDs--receiving RT at the University of Michigan. Collected data included device model, anatomic location, and treatment beam energies, treatment type, and estimated dose to the device. Patients were treated with either high-energy (16-MV) and/or low-energy (6 MV) photon beams with or without electron beams (6-16 MeV). The devices were interrogated with pre- and post-RT and/or weekly with either in-treatment or home interrogation, depending on the patients dependence on the device and the estimated or measured delivered dose. Outcomes analyzed were inappropriate ICD therapies, device malfunctions, or device-related clinical events. RESULTS The PMs were exposed to 84.4 ± 99.7 cGy of radiation, and the ICDs were exposed to 92.1 ± 72.6 cGy of radiation. Two patients with ICDs experienced a partial reset of the ICD with the loss of historic diagnostic data after receiving 123 and 4 cGy, respectively. No device malfunction or premature battery depletion was observed at 6-month follow-up from RT completion. CONCLUSIONS CIED malfunction due to indirect RT exposure is uncommon. Regular in-treatment or home interrogation should be done to detect and treat these events and to ensure that diagnostic data are preserved.