Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy.

Purpose: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and Methods: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. Conclusion: Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.

Using Failure Mode and Effects Analysis to Evaluate Risk in the Clinical Adoption of Automated Contouring and Treatment Planning Tools.

PURPOSE: In this study, we applied the failure mode and effects analysis (FMEA) approach to an automated radiation therapy contouring and treatment planning tool to assess, and subsequently limit, the risk of deploying automated tools. METHODS AND MATERIALS: Using an FMEA, we quantified the risks associated with the Radiation Planning Assistant (RPA), an automated contouring and treatment planning tool currently under development. A multidisciplinary team identified and scored each failure mode, using a combination of RPA plan data and experience for guidance. A 1-to-10 scale for severity, occurrence, and detectability of potential errors was used, following American Association of Physicists in Medicine Task Group 100 recommendations. High-risk failure modes were further explored to determine how the workflow could be improved to reduce the associated risk. RESULTS: Of 290 possible failure modes, we identified 126 errors that were unique to the RPA workflow, with a mean risk priority number (RPN) of 56.3 and a maximum RPN of 486. The top 10 failure modes were caused by automation bias, operator error, and software error. Twenty-one failure modes were above the action threshold of RPN = 125, leading to corrective actions. The workflow was modified to simplify the user interface and better training resources were developed, which highlight the importance of thorough review of the output of automated systems. After the changes, we rescored the high-risk errors, resulting in a final mean and maximum RPN of 33.7 and 288, respectively. CONCLUSIONS: We identified 126 errors specific to the automated workflow, most of which were caused by automation bias or operator error, which emphasized the need to simplify the user interface and ensure adequate user training. As a result of changes made to the software and the enhancement of training resources, the RPNs subsequently decreased, showing that FMEA is an effective way to assess and reduce risk associated with the deployment of automated planning tools.

The radiotherapy quality assurance gap among phase III cancer clinical trials.

PURPOSE: Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT). METHODS AND MATERIALS: We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson's Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials. RESULTS: Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p = 0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p < 0.001). CONCLUSIONS: There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

BACKGROUND: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. MATERIALS AND METHODS: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. RESULTS: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). CONCLUSIONS: Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Our Experience Leading a Large Medical Physics Practice During the COVID-19 Pandemic.

PURPOSE: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. METHODS AND MATERIALS: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. RESULTS: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. CONCLUSIONS: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.

Mitigating the impact of COVID-19 on oncology: Clinical and operational lessons from a prospective radiation oncology cohort tested for COVID-19.

BACKGROUND AND PURPOSE: The COVID-19 pandemic warrants operational initiatives to minimize transmission, particularly among cancer patients who are thought to be at high-risk. Within our department, a multidisciplinary tracer team prospectively monitored all patients under investigation, tracking their test status, treatment delays, clinical outcomes, employee exposures, and quarantines. MATERIALS AND METHODS: Prospective cohort tested for SARS-COV-2 infection over 35 consecutive days of the early pandemic (03/19/2020-04/22/2020). RESULTS: A total of 121 Radiation Oncology patients underwent RT-PCR testing during this timeframe. Of the 7 (6%) confirmed-positive cases, 6 patients were admitted (4 warranting intensive care), and 2 died from acute respiratory distress syndrome. Radiotherapy was deferred or interrupted for 40 patients awaiting testing. As the median turnaround time for RT-PCR testing decreased from 1.5 (IQR: 1-4) to ≤1-day (P < 0.001), the median treatment delay also decreased from 3.5 (IQR: 1.75-5) to 1 business day (IQR: 1-2) [P < 0.001]. Each patient was an exposure risk to a median of 5 employees (IQR: 3-6.5) through prolonged close contact. During this timeframe, 39 care-team members were quarantined for a median of 3 days (IQR: 2-11), with a peak of 17 employees simultaneously quarantined. Following implementation of a "dual PPE policy," newly quarantined employees decreased from 2.9 to 0.5 per day. CONCLUSION: The severe adverse events noted among these confirmed-positive cases support the notion that cancer patients are vulnerable to COVID-19. Active tracking, rapid diagnosis, and aggressive source control can mitigate the adverse effects on treatment delays, workforce incapacitation, and ideally outcomes.

A snapshot of medical physics practice patterns.

A large number of surveys have been sent to the medical physics community addressing many clinical topics for which the medical physicist is, or may be, responsible. Each survey provides an insight into clinical practice relevant to the medical physics community. The goal of this study was to create a summary of these surveys giving a snapshot of clinical practice patterns. Surveys used in this study were created using SurveyMonkey and distributed between February 6, 2013 and January 2, 2018 via the MEDPHYS and MEDDOS listserv groups. The format of the surveys included questions that were multiple choice and free response. Surveys were included in this analysis if they met the following criteria: more than 20 responses, relevant to radiation therapy physics practice, not single-vendor specific, and formatted as multiple-choice questions (i.e., not exclusively free-text responses). Although the results of free response questions were not explicitly reported, they were carefully reviewed, and the responses were considered in the discussion of each topic. Two-hundred and fifty-two surveys were available, of which 139 passed the inclusion criteria. The mean number of questions per survey was 4. The mean number of respondents per survey was 63. Summaries were made for the following topics: simulation, treatment planning, electron treatments, linac commissioning and quality assurance, setup and treatment verification, IMRT and VMAT treatments, SRS/SBRT, breast treatments, prostate treatments, brachytherapy, TBI, facial lesion treatments, clinical workflow, and after-hours/emergent treatments. We have provided a coherent overview of medical physics practice according to surveys conducted over the last 5 yr, which will be instructive for medical physicists.

Independent validation of machine performance check for the Halcyon and TrueBeam linacs for daily quality assurance.

PURPOSE: To evaluate the ability of the machine performance check (MPC) on the Halcyon to detect errors, with comparison with the TrueBeam. METHODS: MPC is an automated set of quality assurance (QA) tests that use a phantom placed on the couch and the linac's imaging system(s) to verify the beam constancy and mechanical performance of the Halcyon and TrueBeam linacs. In order to evaluate the beam constancy tests, we inserted solid water slabs between the beam source and the megavoltage imager to simulate changes in beam output, flatness, and symmetry. The MPC results were compared with measurements, using two-dimensional array under the same conditions. We then studied the accuracy of MPC geometric tests. The accuracies of the relative gantry offset and couch shift tests were evaluated by intentionally inserting phantom shifts, using a rotating or linear motion stage. The MLC offset and absolute gantry offset tests were assessed by miscalibrating these motions on a Halcyon linac. RESULTS: For the Halcyon system, the average difference in the measured beam output between the IC Profiler and MPC, after intentional changes, was 1.3 ± 0.5% (for changes ≤5%). For Halcyon, the MPC test failed (i.e., prevented treatment) when the beam symmetry change was over 1.9%. The accuracy of the MLC offset test was within 0.05 mm. The absolute gantry offset test was able to detect an offset as small as 0.02°. The accuracy of the absolute couch shift test was 0.03 mm. The accuracy of relative couch shift test of Halcyon was measured as 0.16 mm. CONCLUSION: We intentionally inserted errors to evaluate the ability of the MPC to identify errors in dosimetric and geometric parameters. These results showed that the MPC is sufficiently accurate to be effectively used for daily QA of the Halcyon and TrueBeam treatment devices.

Interplay effect on a 6-MV flattening-filter-free linear accelerator with high dose rate and fast multi-leaf collimator motion treating breast and lung phantoms.

PURPOSE: Using a new linear accelerator with high dose rate (800 MU/min), fast MLC motions (5.0 cm/s), fast gantry rotation (15 s/rotation), and 1 cm wide MLCs, we aimed to quantify the effects of complexity, arc number, and fractionation on interplay for breast and lung treatments under target motion. METHODS: To study lung interplay, eight VMAT plans (1-6 arcs) and four-nine-field sliding-window IMRT plans varying in complexity were created. For the breast plans, four-four-field sliding-window IMRT plans were created. Using the Halcyon 1.0 linear accelerator, each plan was delivered five times each under sinusoidal breathing motion to a phantom with 20 implanted MOSFET detectors; MOSFET dose (cGy), delivery time, and MU/cGy values were recorded. Maximum and mean dose deviations were calculated from MOSFET data. The number of MOSFETs with at least 19 of 20 detectors agreeing with their expected dose within 5% per fraction was calculated across 106 iterations to model dose deviation as function of fraction number for all plan variants. To put interplay plans into clinical context, additional IMRT and VMAT plans were created and delivered for the sites of head and neck, prostate, whole brain, breast, pelvis, and lung. Average modulation and interplay effect were compared to those from conventional linear accelerators, as reported from previous studies. RESULTS: The mean beam modulation for plans created for the Halcyon 1.0 linear accelerator was 2.9 MU/cGy (two- to four-field IMRT breast plans), 6.2 MU/cGy (at least five-field IMRT), and 3.6 MU/cGy (four-arc VMAT). To achieve treatment plan objectives, Halcyon 1.0 VMAT plans require more arcs and modulation than VMAT on conventional linear accelerators. Maximum and mean dose deviations increased with increasing plan complexity under tumor motion for breast and lung treatments. Concerning VMAT plans under motion, maximum, and mean dose deviations were higher for one arc than for two arcs regardless of plan complexity. For plan variants with maximum dose deviations greater than 3.7%, dose deviation as a function of fraction number was protracted. CONCLUSION: For treatments on the Halcyon 1.0 linear accelerator, the convergence of dose deviation with fraction number happened more slowly than reported for conventional linear accelerators. However, if plan complexity is reduced for IMRT and if tumor motion is less than ~10-mm, interplay is greatly reduced. To minimize dose deviations across multiple fractions for dynamic targets, we recommend limiting treatment plan complexity and avoiding one-arc VMAT on the Halcyon 1.0 linear accelerator when interplay is a concern.

Normal tissue doses from MV image-guided radiation therapy (IGRT) using orthogonal MV and MV-CBCT.

PURPOSE: The aim of this study was to measure and compare the mega-voltage imaging dose from the Halcyon medical linear accelerator (Varian Medical Systems) with measured imaging doses with the dose calculated by Eclipse treatment planning system. METHODS: An anthropomorphic thorax phantom was imaged using all imaging techniques available with the Halcyon linac - MV cone-beam computed tomography (MV-CBCT) and orthogonal anterior-posterior/lateral pairs (MV-MV), both with high-quality and low-dose modes. In total, 54 imaging technique, isocenter position, and field size combinations were evaluated. The imaging doses delivered to 11 points in the phantom (in-target and extra-target) were measured using an ion chamber, and compared with the imaging doses calculated using Eclipse. RESULTS: For high-quality MV-MV mode, the mean extra-target doses delivered to the heart, left lung, right lung and spine were 1.18, 1.64, 0.80, and 1.11 cGy per fraction, respectively. The corresponding mean in-target doses were 3.36, 3.72, 2.61, and 2.69 cGy per fraction, respectively. For MV-MV technique, the extra-target imaging dose had greater variation and dependency on imaging field size than did the in-target dose. Compared to MV-MV technique, the imaging dose from MV-CBCT was less sensitive to the location of the organ relative to the treatment field. For high-quality MV-CBCT mode, the mean imaging doses to the heart, left lung, right lung, and spine were 8.45, 7.16, 7.19, and 6.51 cGy per fraction, respectively. For both MV-MV and MV-CBCT techniques, the low-dose mode resulted in an imaging dose about half of that in high-quality mode. CONCLUSION: The in-target doses due to MV imaging using the Halcyon ranged from 0.59 to 9.75 cGy, depending on the choice of imaging technique. Extra-target doses from MV-MV technique ranged from 0 to 2.54 cGy. The MV imaging dose was accurately calculated by Eclipse, with maximum differences less than 0.5% of a typical treatment dose (assuming a 60 Gy prescription). Therefore, the cumulative imaging and treatment plan dose distribution can be expected to accurately reflect the actual dose.

Out-of-field doses and neutron dose equivalents for electron beams from modern Varian and Elekta linear accelerators.

Out-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases.

Long-term outcome of accelerated partial breast irradiation using a multilumen balloon applicator in a patient with existing breast implants.

PURPOSE: Accelerated partial breast irradiation is now an accepted component of breast-conserving therapy. However, data regarding long-term outcomes of patients treated with multilumen catheter systems who have existing breast implants are limited. METHODS AND MATERIALS: We report the treatment and outcome of our patient who had existing bilateral silicone subpectoral implants at the time of presentation. Ultrasound-guided core needle biopsy of the right breast showed infiltrating mucinous carcinoma. Right breast lumpectomy revealed an 8 mm area of infiltrating ductal carcinoma with mucinous features and nuclear grade 1. A 4-5 cm Contura (Bard Biopsy Systems, Tempe, AZ) device was placed, and she was treated over the course of 5 days twice daily to a dose of 34 Gy using a high-dose-rate iridium-192 source. RESULTS: The planning target volume for evaluation was 73.9 cc. The percentage of the planning target volume for evaluation receiving 90%, 95%, and 100% of the prescribed dose was 99.9%, 99.3%, and 97.8%, respectively. The total implant volume was 234.5 cc and received a mean dose of 15.4 Gy and a maximum dose of 72.8 Gy. The percentage of implant volume receiving 50%, 75%, 100%, and 200% of the prescribed dose was 31.1%, 16.5%, 8.6%, 2.0%, and 0%, respectively. Maximum skin dose was 97% of the prescribed dose. With a followup of nearly 5 years, she continues to be cancer free with minimal late toxicities and good to excellent cosmetic outcome. CONCLUSIONS: Accelerated partial breast irradiation using a multilumen balloon applicator in patients with existing breast implants can safely be performed with excellent long-term cosmetic outcome. Further studies are needed to establish the absolute dosimetric tolerance of breast implants.

Estimating dynamic lung images from high-dimension chest surface motion using 4D statistical model.

Computed Tomography (CT) has been widely used in image-guided procedures such as intervention and radiotherapy of lung cancer. However, due to poor reproducibility of breath holding or respiratory cycles, discrepancies between static images and patient's current lung shape and tumor location could potentially reduce the accuracy for image guidance. Current methods are either using multiple intra-procedural scans or monitoring respiratory motion with tracking sensors. Although intra-procedural scanning provides more accurate information, it increases the radiation dose and still only provides snapshots of patient's chest. Tracking-based breath monitoring techniques can effectively detect respiratory phases but have not yet provided accurate tumor shape and location due to low dimensional signals. Therefore, estimating the lung motion and generating dynamic CT images from real-time captured high-dimensional sensor signals acts as a key component for image-guided procedures. This paper applies a principal component analysis (PCA)-based statistical model to establish the relationship between lung motion and chest surface motion from training samples, on a template space, and then uses this model to estimate dynamic images for a new patient from the chest surface motion. Qualitative and quantitative results showed that the proposed high-dimensional estimation algorithm yielded more accurate 4D-CT compared to fiducial marker-based estimation.

Helical mode lung 4D-CT reconstruction using Bayesian model.

4D computed tomography (CT) has been widely used for treatment planning of thoracic and abdominal cancer radiotherapy. Current 4D-CT lung image reconstruction methods rely on respiratory gating to rearrange the large number of axial images into different phases, which may be subject to external surrogate errors due to poor reproducibility of breathing cycles. New image-matching-based reconstruction works better for the cine mode of 4D-CT acquisition than the helical mode because the table position of each axial image is different in helical mode and image matching might suffer from bigger errors. In helical mode, not only the phases but also the un-uniform table positions of images need to be considered. We propose a Bayesian method for automated 4D-CT lung image reconstruction in helical mode 4D scans. Each axial image is assigned to a respiratory phase based on the Bayesian framework that ensures spatial and temporal smoothness of surfaces of anatomical structures. Iterative optimization is used to reconstruct a series of 3D-CT images for subjects undergoing 4D scans. In experiments, we compared visually and quantitatively the results of the proposed Bayesian 4D-CT reconstruction algorithm with the respiratory surrogate and the image matching-based method. The results showed that the proposed algorithm yielded better 4D-CT for helical scans.

Angular dose dependence of Matrixx TM and its calibration.

One of the applications of MatriXX (IBA Dosimetry) is experimental verification of dose for IMRT, VMAT, and tomotherapy. For cumulative plan verification, dose is delivered for all the treatment gantry angles to a stationary detector. Experimental calibration of MatriXX detector recommended by the manufacturer involves only AP calibration fields and does not address angular dependency of MatriXX. Angular dependency may introduce dose bias in cumulative plan verification if not corrected. For this reason, we characterized angular dependency of MatriXX and developed a method for its calibration. We found relatively large discrepancies in responses to posterior vs. anterior fields for four MatriXX (Evolution series) detectors (up to 11%), and relatively large variability of responses as a function of gantry angle in the gantry angle ranges of 91 degrees-110 degrees and 269 degrees-260 degrees. With our calibration method, the bias due to angular dependency is effectively removed in experimental verification of IMRT and VMAT plans.