Timothy Ritter

CONSIDERATION OF DOSE LIMITS FOR ORGANS AT RISK OF THORACIC RADIOTHERAPY: ATLAS FOR LUNG, PROXIMAL BRONCHIAL TREE, ESOPHAGUS, SPINAL CORD, RIBS, AND BRACHIAL PLEXUS

PURPOSE To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. METHODS AND MATERIALS The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. RESULTS Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. CONCLUSIONS We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.

Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

PURPOSE To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. METHODS AND MATERIALS Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. RESULTS Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ß1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ß1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. CONCLUSIONS Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

Dose to the inferior rectum is strongly associated with patient reported bowel quality of life after radiation therapy for prostate cancer.

PURPOSE To evaluate rectal dose and post-treatment patient-reported bowel quality of life (QOL) following radiation therapy for prostate cancer. METHODS Patient-reported QOL was measured at baseline and 2-years via the expanded prostate cancer index composite (EPIC) for 90 patients. Linear regression modeling was performed using the baseline score for the QUANTEC normal tissue complication probability model and dose volume histogram (DVH) parameters for the whole and segmented rectum (superior, middle, and inferior). RESULTS At 2-years the mean summary score declined from a baseline of 96.0-91.8. The median volume of rectum treated to ≥70 Gy (V70) was 11.7% for the whole rectum and 7.0%, 24.4%, and 1.3% for the inferior, middle, and superior rectum, respectively. Mean dose to the whole and inferior rectum correlated with declines in bowel QOL while dose to the mid and superior rectum did not. Low (V25-V40), intermediate (V50-V60) and high (V70-V80) doses to the inferior rectum influenced bleeding, incontinence, urgency, and overall bowel problems. Only the highest dose (V80) to the mid-rectum correlated with rectal bleeding and overall bowel problems. CONCLUSIONS Segmental DVH analysis of the rectum reveals associations between bowel QOL and inferior rectal dose that could significantly influence radiation planning and prognostic models.

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer: A Phase 2 Clinical Trial

Importance Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. Objective To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). Design, Setting, and Participants A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. Intervention Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. Main Outcomes and Measures The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. Results The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. Conclusions and Relevance Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. Trial Registration clinicaltrials.gov Identifier: NCT01190527

Effect of normal lung definition on lung dosimetry and lung toxicity prediction in radiation therapy treatment planning

PURPOSE This study aimed to compare lung dose-volume histogram (DVH) parameters such as mean lung dose (MLD) and the lung volume receiving ≥20 Gy (V20) of commonly used definitions of normal lung in terms of tumor/target subtraction and to determine to what extent they differ in predicting radiation pneumonitis (RP). METHODS AND MATERIALS One hundred lung cancer patients treated with definitive radiation therapy were assessed. The gross tumor volume (GTV) and clinical planning target volume (PTVc) were defined by the treating physician and dosimetrist. For this study, the clinical target volume (CTV) was defined as GTV with 8-mm uniform expansion, and the PTV was defined as CTV with an 8-mm uniform expansion. Lung DVHs were generated with exclusion of targets: (1) GTV (DVHG); (2) CTV (DVHC); (3) PTV (DVHP); and (4) PTVc (DVHPc). The lung DVHs, V20s, and MLDs from each of the 4 methods were compared, as was their significance in predicting radiation pneumonitis of grade 2 or greater (RP2). RESULTS There are significant differences in dosimetric parameters among the various definition methods (all Ps<.05). The mean and maximum differences in V20 are 4.4% and 12.6% (95% confidence interval 3.6%-5.1%), respectively. The mean and maximum differences in MLD are 3.3 Gy and 7.5 Gy (95% confidence interval, 1.7-4.8 Gy), respectively. MLDs of all methods are highly correlated with each other and significantly correlated with clinical RP2, although V20s are not. For RP2 prediction, on the receiver operating characteristic curve, MLD from DVHG (MLDG) has a greater area under curve of than MLD from DVHC (MLDC) or DVHP (MLDP). Limiting RP2 to 30%, the threshold is 22.4, 20.6, and 18.8 Gy, for MLDG, MLDC, and MLDP, respectively. CONCLUSIONS The differences in MLD and V20 from various lung definitions are significant. MLD from the GTV exclusion method may be more accurate in predicting clinical significant radiation pneumonitis.

Validation of a radiographic model for the assessment of mesh migration

BACKGROUND The natural history of laparoscopically placed mesh remains uncharacterized. Mesh migration is not infrequently discovered at reoperation and implicated as a cause of hernia recurrence, and it has also been associated with more serious complications, such as enteric and bladder erosion and fistula formation. To date, there is no noninvasive method by which to reliably assess the in-vivo behavior of laparoscopically placed mesh. In this study, we devised and validated a safe and noninvasive model, utilizing computed radiography (CR), for measuring postoperative mesh migration that may be applied to the clinical setting. METHODS The anatomical structures of the inguinal region were recreated using a skeletal male pelvic model. A sheet of commercially available surgical mesh, marked with three 5mm surgical clips at its medial and superior corners, was moved along the inguinal ligament wire for various random distances. The mesh displacement was measured from the model, and a CR film was obtained. The corresponding mesh displacement was then measured on the CR using two different calibration methods (calibration disk and clip measurement). RESULTS A total of 60 measurements were made and recorded. There were no statistically significant differences between the true (as measured from the model) and CR-measured distances of mesh migration. In comparing the two methods, only method 1 (calibration disk) showed a tendency towards a significant difference when lateral or superior displacement was measured, but correlation remained excellent (r(2) = 0.99). All other measurements showed no significant difference and excellent correlation (r(2) > 0.96). Pearsons correlation coefficients showed no significant inter-rater variability using either of these methods. CONCLUSION Our CR model reliably provides a noninvasive means to characterize mesh movement in the postoperative clinical setting. This should provide an instrument to facilitate future clinical evaluation of mesh migration in human trials.

Automating linear accelerator quality assurance.

PURPOSE The purpose of this study was 2-fold. One purpose was to develop an automated, streamlined quality assurance (QA) program for use by multiple centers. The second purpose was to evaluate machine performance over time for multiple centers using linear accelerator (Linac) log files and electronic portal images. The authors sought to evaluate variations in Linac performance to establish as a reference for other centers. METHODS The authors developed analytical software tools for a QA program using both log files and electronic portal imaging device (EPID) measurements. The first tool is a general analysis tool which can read and visually represent data in the log file. This tool, which can be used to automatically analyze patient treatment or QA log files, examines the files for Linac deviations which exceed thresholds. The second set of tools consists of a test suite of QA fields, a standard phantom, and software to collect information from the log files on deviations from the expected values. The test suite was designed to focus on the mechanical tests of the Linac to include jaw, MLC, and collimator positions during static, IMRT, and volumetric modulated arc therapy delivery. A consortium of eight institutions delivered the test suite at monthly or weekly intervals on each Linac using a standard phantom. The behavior of various components was analyzed for eight TrueBeam Linacs. RESULTS For the EPID and trajectory log file analysis, all observed deviations which exceeded established thresholds for Linac behavior resulted in a beam hold off. In the absence of an interlock-triggering event, the maximum observed log file deviations between the expected and actual component positions (such as MLC leaves) varied from less than 1% to 26% of published tolerance thresholds. The maximum and standard deviations of the variations due to gantry sag, collimator angle, jaw position, and MLC positions are presented. Gantry sag among Linacs was 0.336 ± 0.072 mm. The standard deviation in MLC position, as determined by EPID measurements, across the consortium was 0.33 mm for IMRT fields. With respect to the log files, the deviations between expected and actual positions for parameters were small (<0.12 mm) for all Linacs. Considering both log files and EPID measurements, all parameters were well within published tolerance values. Variations in collimator angle, MLC position, and gantry sag were also evaluated for all Linacs. CONCLUSIONS The performance of the TrueBeam Linac model was shown to be consistent based on automated analysis of trajectory log files and EPID images acquired during delivery of a standardized test suite. The results can be compared directly to tolerance thresholds. In addition, sharing of results from standard tests across institutions can facilitate the identification of QA process and Linac changes. These reference values are presented along with the standard deviation for common tests so that the test suite can be used by other centers to evaluate their Linac performance against those in this consortium.

Technical Report: Evaluation of peripheral dose for flattening filter free photon beams

PURPOSE To develop a comprehensive peripheral dose (PD) dataset for the two unflattened beams of nominal energy 6 and 10 MV for use in clinical care. METHODS Measurements were made in a 40 × 120 × 20 cm(3) (width × length × depth) stack of solid water using an ionization chamber at varying depths (dmax, 5, and 10 cm), field sizes (3 × 3 to 30 × 30 cm(2)), and distances from the field edge (5-40 cm). The effects of the multileaf collimator (MLC) and collimator rotation were also evaluated for a 10 × 10 cm(2) field. Using the same phantom geometry, the accuracy of the analytic anisotropic algorithm (AAA) and Acuros dose calculation algorithm was assessed and compared to the measured values. RESULTS The PDs for both the 6 flattening filter free (FFF) and 10 FFF photon beams were found to decrease with increasing distance from the radiation field edge and the decreasing field size. The measured PD was observed to be higher for the 6 FFF than for the 10 FFF for all field sizes and depths. The impact of collimator rotation was not found to be clinically significant when used in conjunction with MLCs. AAA and Acuros algorithms both underestimated the PD with average errors of -13.6% and -7.8%, respectively, for all field sizes and depths at distances of 5 and 10 cm from the field edge, but the average error was found to increase to nearly -69% at greater distances. CONCLUSIONS Given the known inaccuracies of peripheral dose calculations, this comprehensive dataset can be used to estimate the out-of-field dose to regions of interest such as organs at risk, electronic implantable devices, and a fetus. While the impact of collimator rotation was not found to significantly decrease PD when used in conjunction with MLCs, results are expected to be machine model and beam energy dependent. It is not recommended to use a treatment planning system to estimate PD due to the underestimation of the out-of-field dose and the inability to calculate dose at extended distances due to the limits of the dose calculation matrix.

Audit tool for external beam radiation therapy departments

PURPOSE Development of a self-contained audit tool for external beam radiation therapy to assess compliance with the major recommendations from professional organizations and generally accepted standards of practice. Intensity modulated radiation therapy, stereotactic body radiation therapy, stereotactic radiosurgery, and volumetric modulated arc therapy were included in this review. METHODS AND MATERIALS A physics quality working group developed a department vision, distinguished and summarized key references, and condensed important elements of good documentation practices. The results were then compiled in a checklist format and used to perform audits at 3 sites. RESULTS The final audit tool contains 65 items spanning a wide range of external beam radiation therapy practices. Several of the audit items address issues not commonly identified by other authoritative sources. A total of 48 process improvements were identified at the 3 sites audited. CONCLUSIONS The enclosed self-inspection list may be useful to a site as an annual review tool, as an aid in preparation for the American College of Radiology-American Society for Therapeutic Radiology and Oncology practice accreditation, or as a catalyst for general quality improvement. Sites can quickly identify opportunities for improvement by concentrating on high importance items and commonly identified areas of noncompliance.

American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology

A substantial barrier to the single- and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, dose–volume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children’s Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials.