Tattoo-Free Setup for Patients With Breast Cancer Receiving Regional Nodal Irradiation.

PURPOSE: Patients undergoing regional nodal irradiation (RNI) with either 3-dimensional conformal radiation therapy (3DCRT) planning or volumetric modulated arc therapy (VMAT) receive permanent tattoos to assist with daily setup alignment and verification. With the advent of surface imaging, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to those without reference to tattoos. METHODS AND MATERIALS: Forty-eight patients receiving RNI at our institution from July 2019 to December 2020 were identified. All patients received tattoos per standard of care. Twenty-four patients underwent setup using tattoos for initial positioning followed by surface and x-ray imaging. A subsequent 24 patients underwent positioning using surface imaging followed by x-ray imaging without reference to tattoos. Patient cohorts were balanced by treatment technique and use of deep inspiration breath hold. Treatment (including setup and delivery) time and x-ray-based shifts after surface imaging were recorded. RESULTS: Among patients in the tattoo group receiving 3DCRT RNI, the average treatment time per fraction was 21.35 versus 19.75 minutes in the 3DCRT RNI no-tattoo cohort (P = .03). Mean 3D vector shifts for patients in the tattoo cohort were 5.6 versus 4.4 mm in the no-tattoo cohort. The average treatment time per fraction for the tattoo VMAT RNI cohort was 23.16 versus 20.82 minutes in the no-tattoo VMAT RNI cohort (P = .08). Mean 3D vector shifts for the patients in the tattoo VMAT cohort were 5.5 versus 7.1 mm in the no-tattoo VMAT cohort. Breath hold technique and body mass index did not affect accuracy in a consistent or clinically relevant way. CONCLUSIONS: Using a combination of surface and x-ray imaging, without reference to tattoos, provides excellent accuracy in alignment and setup verification among patients receiving RNI for breast cancer, regardless of treatment technique and with reduced treatment time. Skin-based tattoos are no longer warranted for patients receiving supine RNI.

Combined clinical and research training in medical physics in a multi-institutional setting: 13-year experience of Harvard Medical Physics Residency Program.

PURPOSE: This manuscript describes the structure, management and outcomes of a multi-institutional clinical and research medical physics residency program (Harvard Medical Physics Residency Program, or HMPRP) to provide potentially useful information to the centers considering a multi-institutional approach for their training programs. METHODS: Data from the program documents and public records was used to describe HMPRP and obtain statistics about participating faculty, enrolled residents, and graduates. Challenges associated with forming and managing a multi-institutional program and developed solutions for effective coordination between several clinical centers are described. RESULTS: HMPRP was formed in 2009 and was accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) in 2011. It is a 3-year therapy program, with a dedicated year of research and the 2 years of clinical training at three academic hospitals. A CAMPEP-accredited Certificate Program is embedded in HMPRP to allow enrolled residents to complete a formal didactic training in medical physics if necessary. The clinical training covers the material required by CAMPEP. In addition, training in protons, CyberKnife, MR-linac, and at network locations is included. The clinical training and academic record of the residents is outstanding. All graduates have found employment within clinical medical physics, mostly at large academic centers and graduates had a 100% pass rate at the oral American Board of Radiology exams. On average, three manuscripts per resident are published during residency, and multiple abstracts are presented at conferences. CONCLUSIONS: A multi-institutional medical physics residency program can be successfully formed and managed. With a collaborative administrative structure, the program creates an environment for high-quality clinical training of the residents and high productivity in research. The main advantage of such program is access to a wide variety of resources. The main challenge is creating a structure for efficient management of multiple resources at different locations. This report may provide valuable information to centers considering starting a multi-institutional residency program.

Tattoo free setup for partial breast irradiation: A feasibility study.

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.

Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana.

There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public-private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability.

Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning.

PURPOSE: To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. METHODS AND MATERIALS: MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. RESULTS: The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively (P < .05). CONCLUSIONS: The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT.

Analysis of setup uncertainties for extremity sarcoma patients using surface imaging.

PURPOSE: Proper positioning of patients with extremity sarcoma tumors can be challenging. A surface imaging technique was utilized to quantify the setup uncertainties for sarcoma patients and to assess whether surface imaging could improve the accuracy of patient positioning. METHODS AND MATERIALS: Pretreatment and posttreatment 3-dimensional (3D) surface images were obtained for 16 patients and 236 treatments. Offline surface registration was performed to quantify interfraction and intrafraction setup errors, and the required planning target volume (PTV) margins were calculated. Setup differences were also assessed using root mean square (RMS) error analysis. RESULTS: For intrafraction variation, the mean 3D vector shift was 2.1 mm, and the systematic and random errors were 1.3 mm or less. When using a reference surface from the first fraction, the mean interfraction setup variation (3D vector shift) was 7.6 mm. Systematic and random errors were 3-4 mm in each direction. When using a computed tomographic based reference surface, the mean 3D vector shift was 9.5 mm. Systematic and random errors ranged from 3.1 to 7.9 mm. The required PTV margins were 1.0 cm, 1.2 cm, and 1.3 cm in the anterior-posterior, superior-inferior, and lateral directions, respectively. The mean (standard deviation) RMS errors for the uncorrected position were 4.7 mm (1.9 mm) and were reduced to 2.2 mm (0.8 mm) and 1.7 mm (0.8 mm), for 4 degree of freedom (DOF) and 6 DOF surface alignment, respectively. CONCLUSIONS: Intrafraction motion is small. Interfraction motion can exceed typical PTV margins and daily imaging should be utilized to reduce setup variations. Surface imaging may reduce setup errors and is a feasible technique for daily image guidance.

Addressing the growing cancer burden in the wake of the AIDS epidemic in Botswana: The BOTSOGO collaborative partnership.

Botswana has experienced a dramatic increase in HIV-related malignancies over the past decade. The BOTSOGO collaboration sought to establish a sustainable partnership with the Botswana oncology community to improve cancer care. This collaboration is anchored by regular tumor boards and on-site visits that have resulted in the introduction of new approaches to treatment and perceived improvements in care, providing a model for partnership between academic oncology centers and high-burden countries with limited resources.

Multicriteria optimization informed VMAT planning.

We developed a patient-specific volumetric-modulated arc therapy (VMAT) optimization procedure using dose-volume histogram (DVH) information from multicriteria optimization (MCO) of intensity-modulated radiotherapy (IMRT) plans. The study included 10 patients with prostate cancer undergoing standard fractionation treatment, 10 patients with prostate cancer undergoing hypofractionation treatment, and 5 patients with head/neck cancer. MCO-IMRT plans using 20 and 7 treatment fields were generated for each patient on the RayStation treatment planning system (clinical version 2.5, RaySearch Laboratories, Stockholm, Sweden). The resulting DVH of the 20-field MCO-IMRT plan for each patient was used as the reference DVH, and the extracted point values of the resulting DVH of the MCO-IMRT plan were used as objectives and constraints for VMAT optimization. Weights of objectives or constraints of VMAT optimization or both were further tuned to generate the best match with the reference DVH of the MCO-IMRT plan. The final optimal VMAT plan quality was evaluated by comparison with MCO-IMRT plans based on homogeneity index, conformity number of planning target volume, and organ at risk sparing. The influence of gantry spacing, arc number, and delivery time on VMAT plan quality for different tumor sites was also evaluated. The resulting VMAT plan quality essentially matched the 20-field MCO-IMRT plan but with a shorter delivery time and less monitor units. VMAT plan quality of head/neck cancer cases improved using dual arcs whereas prostate cases did not. VMAT plan quality was improved by fine gantry spacing of 2 for the head/neck cancer cases and the hypofractionation-treated prostate cancer cases but not for the standard fractionation-treated prostate cancer cases. MCO-informed VMAT optimization is a useful and valuable way to generate patient-specific optimal VMAT plans, though modification of the weights of objectives or constraints extracted from resulting DVH of MCO-IMRT or both is necessary.

Cone-beam computed tomography image guided therapy to evaluate lumpectomy cavity variation before and during breast radiotherapy.

The purpose of this study was to evaluate the rate of change (RoC) in the size of the lumpectomy cavity (LC) before and during breast radiotherapy (RT) using cone-beam computed tomography (CBCT), relative to the initial LC volume at CT simulation (CTVLC) and timing from surgery. A prospective institutional review board-approved study included 26 patients undergoing breast RT: 20 whole breast irradiation (WBI) patients and six partial breast irradiation (PBI) patients, with surgical clips outlining the LC. The patients underwent CT simulation (CTsim) followed by five CBCTs during RT, once daily for PBI and once weekly for WBI. The distance between surgical clips and their centroid (D) acted as a surrogate for LC size. The RoC of the LC size, defined as the percentage change of D between two scans divided by the time interval in days between the scans, was calculated before (CTsim to CBCT1) and during RT (CBCT1 to CBCT5). The mean RoC of D for all patients before starting RT was -0.25%/day (range, -1.3 to 1.4) and for WBI patients during RT was -0.15%/day (range, -0.45 to 0.40). Stratified by median CTVLC, the RoC before RT for large CTVLC group (≥ 25.7 cc) was 15 times higher (-0.47%/day) than for small CTVLC group (< 25.7 cc) (-0.03%/day), p = 0.06. For patients undergoing CTsim < 42 days from surgery, the RoC before RT was -0.43%/day compared to -0.07%/day for patients undergoing CTsim ≥ 42 days from surgery, p = 0.12. For breast cancer RT, the rate of change of the LC is affected by the initial cavity size and the timing from surgery. Resimulation closer to the time of boost treatment should be considered in patients who are initially simulated within six weeks of surgery and/or with large CTVLC.

A voluntary breath-hold treatment technique for the left breast with unfavorable cardiac anatomy using surface imaging.

PURPOSE: Breath-hold (BH) treatments can be used to reduce cardiac dose for patients with left-sided breast cancer and unfavorable cardiac anatomy. A surface imaging technique was developed for accurate patient setup and reproducible real-time BH positioning. METHODS AND MATERIALS: Three-dimensional surface images were obtained for 20 patients. Surface imaging was used to correct the daily setup for each patient. Initial setup data were recorded for 443 fractions and were analyzed to assess random and systematic errors. Real time monitoring was used to verify surface placement during BH. The radiation beam was not turned on if the BH position difference was greater than 5 mm. Real-time surface data were analyzed for 2398 BHs and 363 treatment fractions. The mean and maximum differences were calculated. The percentage of BHs greater than tolerance was calculated. RESULTS: The mean shifts for initial patient setup were 2.0 mm, 1.2 mm, and 0.3 mm in the vertical, longitudinal, and lateral directions, respectively. The mean 3-dimensional vector shift was 7.8 mm. Random and systematic errors were less than 4 mm. Real-time surface monitoring data indicated that 22% of the BHs were outside the 5-mm tolerance (range, 7%-41%), and there was a correlation with breast volume. The mean difference between the treated and reference BH positions was 2 mm in each direction. For out-of-tolerance BHs, the average difference in the BH position was 6.3 mm, and the average maximum difference was 8.8 mm. CONCLUSIONS: Daily real-time surface imaging ensures accurate and reproducible positioning for BH treatment of left-sided breast cancer patients with unfavorable cardiac anatomy.

Evaluation and commissioning of a surface based system for respiratory sensing in 4D CT.

The purpose of this study is to assess the temporal and reconstruction accuracy of a surface imaging system, the GateCT under ideal conditions, and compare the device with a commonly used respiratory surrogate: the Varian RPM. A clinical CT scanner, run in cine mode, was used with two optical devices, GateCT and RPM, to detect respiratory motion. A radiation detector, GM-10, triggers the X-ray on/off to GateCT system, while the RPM is directly synchronized with the CT scanner through an electronic connection. Two phantoms were imaged: the first phantom translated on a rigid plate along the anterior-posterior (AP) direction, and was used to assess the temporal synchronization of each optical system with the CT scanner. The second phantom, consisting of five spheres translating 3 cm peak-to-peak in the superior-inferior direction, was used to assess the quality of rebinned images created by GateCT and RPM. Calibration assessment showed a nearly perfect synchronization with the scanner for both the RPM and GateCT systems, thus demonstrating the good performance of the radiation detector. Results for the volume rebinning test showed discrepancies in volumes for the 3D reconstruction (compared to ground truth) of up to 36% for GateCT and up to 40% for RPM. No statistical difference was proven between the two systems in volume sorting. Errors are mainly due to phase detection inaccuracies and to the large motion of the phantom. This feasibility study assessed the consistency of two optical systems in synchronizing the respiratory signal with the image acquisition. A new patient protocol based on both RPM and GateCT will be soon started.

Accuracy in breast shape alignment with 3D surface fitting algorithms.

Surface imaging is in use in radiotherapy clinical practice for patient setup optimization and monitoring. Breast alignment is accomplished by searching for a tentative spatial correspondence between the reference and daily surface shape models. In this study, the authors quantify whole breast shape alignment by relying on texture features digitized on 3D surface models. Texture feature localization was validated through repeated measurements in a silicone breast phantom, mounted on a high precision mechanical stage. Clinical investigations on breast shape alignment included 133 fractions in 18 patients treated with accelerated partial breast irradiation. The breast shape was detected with a 3D video based surface imaging system so that breathing was compensated. An in-house algorithm for breast alignment, based on surface fitting constrained by nipple matching (constrained surface fitting), was applied. Results were compared with a commercial software where no constraints are utilized (unconstrained surface fitting). Texture feature localization was validated within 2 mm in each anatomical direction. Clinical data show that unconstrained surface fitting achieves adequate accuracy in most cases, though nipple mismatch is considerably higher than residual surface distances (3.9 mm vs 0.6 mm on average). Outliers beyond 1 cm can be experienced as the result of a degenerate surface fit, where unconstrained surface fitting is not sufficient to establish spatial correspondence. In the constrained surface fitting algorithm, average surface mismatch within 1 mm was obtained when nipple position was forced to match in the [1.5; 5] mm range. In conclusion, optimal results can be obtained by trading off the desired overall surface congruence vs matching of selected landmarks (constraint). Constrained surface fitting is put forward to represent an improvement in setup accuracy for those applications where whole breast positional reproducibility is an issue.

Dosimetric impact of motion in free-breathing and gated lung radiotherapy: a 4D Monte Carlo study of intrafraction and interfraction effects.

The purpose of this study was to investigate if interfraction and intrafraction motion in free-breathing and gated lung IMRT can lead to systematic dose differences between 3DCT and 4DCT. Dosimetric effects were studied considering the breathing pattern of three patients monitored during the course of their treatment and an in-house developed 4D Monte Carlo framework. Imaging data were taken in free-breathing and in cine mode for both 3D and 4D acquisition. Treatment planning for IMRT delivery was done based on the free-breathing data with the CORVUS (North American Scientific, Chatsworth, CA) planning system. The dose distributions as a function of phase in the breathing cycle were combined using deformable image registration. The study focused on (a) assessing the accuracy of the CORVUS pencil beam algorithm with Monte Carlo dose calculation in the lung, (b) evaluating the dosimetric effect of motion on the individual breathing phases of the respiratory cycle, and (c) assessing intrafraction and interfraction motion effects during free-breathing or gated radiotherapy. The comparison between (a) the planning system and the Monte Carlo system shows that the pencil beam algorithm underestimates the dose in low-density regions, such as lung tissue, and overestimates the dose in high-density regions, such as bone, by 5% or more of the prescribed dose (corresponding to approximately 3-5 Gy for the cases considered). For the patients studied this could have a significant impact on the dose volume histograms for the target structures depending on the margin added to the clinical target volume (CTV) to produce either the planning target (PTV) or internal target volume (ITV). The dose differences between (b) phases in the breathing cycle and the free-breathing case were shown to be negligible for all phases except for the inhale phase, where an underdosage of the tumor by as much as 9.3 Gy relative to the free-breathing was observed. The large difference was due to breathing-induced motion/deformation affecting the soft/lung tissue density and motion of the bone structures (such as the rib cage) in and out of the beam. Intrafraction and interfraction dosimetric differences between (c) free-breathing and gated delivery were found to be small. However, more significant dosimetric differences, of the order of 3%-5%, were observed between the dose calculations based on static CT (3DCT) and the ones based on time-resolved CT (4DCT). These differences are a consequence of the larger contribution of the inhale phase in the 3DCT data than in the 4DCT.

Comparison of target registration errors for multiple image-guided techniques in accelerated partial breast irradiation.

PURPOSE: External beam accelerated partial breast irradiation requires accurate localization of the target volume for each treatment fraction. Using the concept of target registration error (TRE), the performance of several methods of target localization was compared. METHODS AND MATERIALS: Twelve patients who underwent external beam accelerated partial breast irradiation were included in this study. TRE was quantified for four methods of image guidance: standard laser-based setup, kilovoltage imaging of the chest wall, kilovoltage imaging of surgically implanted clips, and three-dimensional surface imaging of the breast. The use of a reference surface created from a free-breathing computed tomography scan and a reference surface directly captured with three-dimensional video imaging were compared. The effects of respiratory motion were also considered, and gating was used for 8 of 12 patients. RESULTS: The median value of the TRE for the laser, chest wall, and clip alignment was 7.1 mm (n=94), 5.4 mm (n=81), and 2.4 mm (n=93), respectively. The median TRE for gated surface imaging based on the first fraction reference surface was 3.2 mm (n=49), and the TRE for gated surface imaging using the computed tomography-based reference surface was 4.9 mm (n=56). The TRE for nongated surface imaging using the first fraction reference surface was 6.2 mm (n=25). CONCLUSIONS: The TRE of surface imaging using a reference surface directly captured with three-dimensional video and the TRE for clip-based setup were within 1 mm. Gated capture is important for surface imaging to reduce the effects of respiratory motion in accelerated partial breast irradiation.

Assessing residual motion for gated proton-beam radiotherapy.

Gated radiation therapy is a promising method for improving the dose conformality of treatments to moving targets and reducing the total volume of irradiated tissue. Target motion is of particular concern in proton beam radiotherapy, due to the finite range of proton dose deposition in tissue. Gating allows one to reduce the extent of variation, due to respiration, of the radiological depth to target during treatment delivery. However, respiratory surrogates typically used for gating do not always accurately reflect the position of the internal target. For instance, a phase delay often exists between the internal motion and the motion of the surrogate. Another phenomenon, baseline drifting refers to a gradual change in the exhale position over time, which generally affects the external and internal markers differently. This study examines the influence of these two physiological phenomena on gated radiotherapy using an external surrogate.

The correlation between internal and external markers for abdominal tumors: implications for respiratory gating.

PURPOSE: The correlation of the respiratory motion of external patient markers and abdominal tumors was examined. Data of this type are important for image-guided therapy techniques, such as respiratory gating, that monitor the movement of external fiducials. METHODS AND MATERIALS: Fluoroscopy sessions for 4 patients with internal, radiopaque tumor fiducial clips were analyzed by computer vision techniques. The motion of the internal clips and the external markers placed on the patient's abdominal skin surface were quantified and correlated. RESULTS: In general, the motion of the tumor and external markers were well correlated. The maximum amount of peak-to-peak craniocaudal tumor motion was 2.5 cm. The ratio of tumor motion to external-marker motion ranged from 0.85 to 7.1. The variation in tumor position for a given external-marker position ranged from 2 to 9 mm. The period of the breathing cycle ranged from 2.7 to 4.5 seconds, and the frequency patterns for both the tumor and the external markers were similar. CONCLUSIONS: Although tumor motion generally correlated well with external fiducial marker motion, relatively large underlying tumor motion can occur compared with external-marker motion and variations in the tumor position for a given marker position. Treatment margins should be determined on the basis of a detailed understanding of tumor motion, as opposed to relying only on external-marker information.