Validation of Acuros for total body irradiation at extended distance.

PURPOSE: Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. METHODS: Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500 cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508 cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30 cm from the surface of the phantoms as per our clinical set up. RESULTS: The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. CONCLUSIONS: The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500 cm.

A comprehensive review of 30 years of pediatric clinical trial radiotherapy dose constraints.

BACKGROUND: Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which has led to variations in constraints over the years. In this study, we identify these variations in dose constraints within pediatric trials both in the United States and in Europe used in the past 30 years. PROCEDURE: All pediatric trials from the Children's Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs at risk (OAR), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US and European trials RESULTS: One hundred five closed trials were included-93 US trials and 12 European trials. Thirty-eight separate OAR were found with high-dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, the United States constraints were higher for seven OAR, lower for one, and identical for five. No OAR had constraints change systematically over the last 30 years. CONCLUSION: Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OAR. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.

Late effects of radiation therapy in pediatric patients and survivorship.

Advances in multimodality therapy have led to childhood cancer cure rates over 80%. However, surgery, chemotherapy, and radiotherapy may lead to debilitating or even fatal long-term effects among childhood survivors beyond those inflicted by the primary disease process. It is critical to understand, mitigate, and prevent these late effects of cancer therapy to improve the quality of life of childhood cancer survivors. This review summarizes the various late effects of radiotherapy and acknowledges the Pediatric Normal Tissue Effects in the Clinic (PENTEC), an international collaboration that is systematically analyzing the association between radiation treatment dose/volume and consequential organ toxicities, in developing children as a basis to formulate recommendations for clinical practice of pediatric radiation oncology. We also summarize initiatives for survivorship and surveillance of late normal tissue effects related to radiation therapy among long-term survivors of childhood cancer treated in the past.

How low can you go? A CBCT dose reduction study.

PURPOSE: Cone beam computed tomography (CBCT) is often used for patient setup based solely on bony anatomy. The goal of this work was to evaluate whether CBCT dose can be lowered to the level of kV image pair doses when used for bony anatomy-based IGRT without compromising positioning accuracy. METHODS: An anthropomorphic phantom was CT scanned in the head, head and neck, chest, and pelvis regions and setup on the linear accelerator couch with the isocenter near the planned location. Cone beam computed tomographies were performed with the standard "full dose" protocol supplied by the linac vendor. With sequentially lowering the dose, three-dimensional (3D) matching was performed for each without shifting the couch. The standard kV image pair protocol for each site was also used to image the phantoms. For all studies, six degrees of freedom was included in the 2D or 3D matching to the extent they could be employed. Imaging doses were determined in air at isocenter following the TG-61 formalism. RESULTS: Cone beam computed tomography dose was reduced by 81-98% of the standard CBCT protocol to nearly that of the standard kV image pair dose for each site. Relative to the standard CBCT shift values, translational shifts were within 0.3 and 1.6 mm for all sites, for the reduced dose CBCT and kV image pair, respectively. Rotational shifts were within 0.2 degree and 0.7 degrees for all sites, for the reduced dose CBCTs and kV image pair, respectively. CONCLUSION: For bony anatomy-based image guidance, CBCT dose can be reduced to a value similar to that of a kV image pair with similar or better patient positioning accuracy than kV image pair alignment. Where rotations are important to correct, CBCT will be superior to orthogonal kV imaging without significantly increased imaging dose. This is especially important for image guidance for pediatric patient treatments.

AAPM MEDICAL PHYSICS PRACTICE GUIDELINE 2.b.: Commissioning and quality assurance of X-ray-based image-guided radiotherapy systems.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized.

Practice patterns and recommendations for pediatric image-guided radiotherapy: A Children's Oncology Group report.

This report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

The relationship between ventricular volume and whole-brain irradiation dose in central nervous system germ cell tumors.

BACKGROUND: Advanced irradiation techniques, including intensity-modulated radiation therapy (IMRT), aim to limit irradiation to adjoining tissues by conforming beams to a well-defined volume. In intracranial germinomas, whole-ventricular IMRT decreases the volume of irradiation to surrounding parenchyma. This study examined the relationship between ventricular volume and radiation dose to surrounding tissue. PROCEDURE: We retrospectively reviewed age, sex, ventricular and brain volume, ventricular dose, and volume of brain that received 12 Gy (V12) for patients diagnosed with germ cell tumors at our institution treated with whole-ventricular IMRT between 2002 and 2016. Variables were assessed for correlation and statistical significance. RESULTS: Forty-seven patients were analyzed. The median whole-ventricular irradiation dose was 24 Gy with a median boost dose of 30 Gy. The median ventricular volume was 234.3 cm3 , and median brain volume was 1408 cm3 . There was no significant difference between mean ventricular volume of suprasellar versus pineal tumors (P = .95). The median V12 of the brain, including the ventricles, was 58.9%. The strongest correlation was between ventricular volume and V12, with an r2 (coefficient of determination) of .47 (P < .001). Multiple regression analysis indicated that total boost dose and boost planning target volume significantly predicted V12 (P < .001). CONCLUSIONS: Although whole-ventricular IMRT limited irradiation to surrounding tissue in our cohort, a significant percentage of the brain received at least 12 Gy. This study suggests that there is a positive correlation between ventricular volume and the volume of brain parenchyma receiving at least 12 Gy with an important contribution from the boost phase of treatment.

Acute toxicity of craniospinal irradiation with volumetric-modulated arc therapy in children with solid tumors.

BACKGROUND: Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off-target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease. PROCEDURE: Pediatric patients with brain tumors were identified at Children's Hospital Los Angeles from 2013 to 2015. Clinical characteristics, acute toxicity, and radiotherapy data were abstracted from their medical records. We identified 19 patients who received VMAT CSI. Quality assurance was performed with a cylindrical detector array and ion chamber measurements at the arc junctions. RESULTS: Patients had medulloblastoma or supratentorial primitive neuro-ectodermal tumor (n = 14, 11 high risk), germ cell tumors (two), relapsed neuroblastoma (two), and atypical teratoid/rhabdoid tumor (one). The most common acute toxicity was hematologic, including leukopenia (11% grade [Gr] 2, 26% Gr 3, and 63% Gr 4), anemia (89% Gr 2), and thrombocytopenia (16% Gr 1-2, 26% Gr 3, and 37% Gr 4). Despite leukopenia, we encountered only two Gr 3 infections (urinary tract and lung). The majority required blood products (89% red blood cells and 68% platelets). Weight loss was also common (47% Gr 1 and 26% Gr 2). CONCLUSIONS: VMAT CSI, along with chemotherapy and anesthesia, is feasible with supportive care. Daily image-guided RT improves accuracy and reduces the risk of spinal cord overdose without increasing treatment time. Further research is needed to determine whether reducing doses to organs, such as thyroid, heart, or hippocampus, offsets the risk of increased volume of low-dose irradiation.

Sensitivity study of an automated system for daily patient QA using EPID exit dose images.

The dosimetric consequences of errors in patient setup or beam delivery and anatomical changes are not readily known. A new product, PerFRACTION (Sun Nuclear Corporation), is designed to identify these errors by comparing the exit dose image measured on an electronic portal imaging device (EPID) from each field of each fraction to those from baseline fraction images. This work investigates the sensitivity of PerFRACTION to detect the deviation caused by these errors in a variety of realistic scenarios. Integrated EPID images were acquired in clinical mode and saved in ARIA. PerFRACTION automatically pulled the images into its database and performed the user-defined comparison. We induced errors of 1 mm and greater in jaw, multileaf collimator (MLC), and couch position, 1° and greater in collimation rotation (patient yaw), 0.5-1.5% in machine output, rail position, and setup errors of 1-2 mm shifts and 0.5-1° roll rotation. The planning techniques included static, intensity modulated radiation therapy (IMRT) and VMAT fields. Rectangular solid water phantom or anthropomorphic head phantom were used in the beam path in the delivery of some fields. PerFRACTION detected position errors of the jaws, MLC, and couch with an accuracy of better than 0.4 mm, and 0.5° for collimator rotation error and detected the machine output error within 0.2%. The rail position error resulted in PerFRACTION detected dose deviations up to 8% and 3% in open field and VMAT field delivery, respectively. PerFRACTION detected induced errors in IMRT fields within 2.2% of the gamma passing rate using an independent conventional analysis. Using an anthropomorphic phantom, setup errors as small as 1 mm and 0.5° were detected. Our work demonstrates that PerFRACTION, using integrated EPID image, is sensitive enough to identify positional, angular, and dosimetric errors.

Executive summary of AAPM Report Task Group 113: Guidance for the physics aspects of clinical trials.

The charge of AAPM Task Group 113 is to provide guidance for the physics aspects of clinical trials to minimize variability in planning and dose delivery for external beam trials involving photons and electrons. Several studies have demonstrated the importance of protocol compliance on patient outcome. Minimizing variability for treatments at different centers improves the quality and efficiency of clinical trials. Attention is focused on areas where variability can be minimized through standardization of protocols and processes through all aspects of clinical trials. Recommendations are presented for clinical trial designers, physicists supporting clinical trials at their individual clinics, quality assurance centers, and manufacturers.

Radiotherapy after high-dose chemotherapy with autologous hematopoietic cell rescue: Quality assessment of Head Start III.

BACKGROUND: The use of high-dose chemotherapy with autologous hematopoietic cell rescue (AuHCR) in Head Start III is a potentially curative approach for the management of young children with central nervous system neoplasms. We report the potential influence of quality and timing of radiation therapy on the survival of patients treated on the study. PROCEDURE: Between 2003 and 2009, 220 children with newly diagnosed central nervous system neoplasms were enrolled on the study. Radiation therapy was indicated following AuHCR for children between 6 and 10 years old or those younger than 6 years with residual tumor preconsolidation. Records were received for 42 patients and reviewed to determine adherence to protocol treatment volume and dose guidelines. Of these patients, seven were irradiated prior to consolidation, and additional four patients who initially avoided radiation therapy after AuHCR were subsequently treated at relapse. RESULTS: Of the 31 patients who were fully evaluable, 2 refused radiation therapy until recurrence and 4 progressed between recovery from AuHCR and radiation therapy. Of the remaining 25 patients, 8 had violations in their indication, dose, or treatment volume. All violations occurred in patients under 6 years of age. Two patients could have avoided radiation therapy. There were 6 violations in the 23 patients who received radiation therapy for guideline indications. CONCLUSION: All protocol violations occurred in patients under 6 years of age and were associated with decreased overall survival as was the time to start radiotherapy of greater than 11 weeks. When indicated, starting radiation therapy soon after neutrophil and platelet recovery may improve the outcome for these high-risk children.

Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation.

BACKGROUND: Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols. PROCEDURES: Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained. RESULTS: The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes. CONCLUSION: In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

A retrospective analysis of recurrent intracranial ependymoma.

BACKGROUND: Recurrence occurs in almost 50% of patients with intracranial ependymoma, and their outcome following recurrence is poor. METHODS: We retrospectively reviewed the medical records of 22 patients with intracranial ependymoma and subsequent relapse(s) (59 recurrences) treated at Children's Hospital Los Angeles or New York University between January 1997 and December 2012. RESULTS: Median duration of follow-up was 52 months (7-171 months). Median age at initial diagnosis was 4 years (0.3-19 years) with 8 patients younger than 3 years at presentation. Eleven patients had anaplastic and 11 cellular pathologies. Eighteen patients had infratentorial tumors at diagnosis and 3 (all infratentorial) had metastatic spinal cord involvement at presentation. Cerebrospinal fluid involvement was not identified at diagnosis or relapse. Median time to first recurrence was 16 months (1.3 to 115 months). The number of recurrences in each patient ranged from 1 to 9 (median = 2). Thirty-seven recurrences (63%) were detected asymptomatically by surveillance imaging. Fifteen recurrences (26%) arose outside the initial tumor site. Recurrences were treated by surgical resection (45), with irradiation (30), and with various oral chemotherapies (23) with (7) or without (16) conventional chemotherapy. The 5 and 10 year overall survival rates from first recurrence were 0.37 ± 0.14 and 0.25 ± 0.14. CONCLUSION: Prolonged (5-10 year) survival from first relapse was noted in over one-quarter of our patients. It remains unclear whether early radiographic diagnosis, differing treatment modalities beyond radical surgical resection or possibly unrecognized biological differences contributed towards this prolonged survival.

Predictive Factors Associated With Radiation Myelopathy in Pediatric Patients With Cancer: A PENTEC Comprehensive Review.

PURPOSE: Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex. METHODS AND MATERIALS: We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity. RESULTS: Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events. CONCLUSIONS: This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.

Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC.

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

PURPOSE: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. METHODS AND MATERIALS: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. RESULTS: Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/ß value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46). CONCLUSIONS: Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

PURPOSE: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement. METHODS AND MATERIALS: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores. RESULTS: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points. CONCLUSIONS: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes.

Physics Considerations for Evaluation of Dose for Dose-Response Models of Pediatric Late Effects From Radiation Therapy.

PURPOSE: We describe the methods used to estimate the accuracy of dosimetric data found in literature sources used to construct the Pediatric Normal Tissue Effects in the Clinic (PENTEC) dose-response models, summarize these findings of each organ-specific task force, describe some of the dosimetric challenges and the extent to which these efforts affected the final modeling results, and provide guidance on the interpretation of the dose-response results given the various dosimetric uncertainties. METHODS AND MATERIALS: Each of the PENTEC task force medical physicists reviewed all the journal articles used for dose-response modeling to identify, categorize, and quantify dosimetric uncertainties. These uncertainties fell into 6 broad categories. A uniform nomenclature was developed for describing the "dosimetric quality" of the articles used in the PENTEC reviews. Among the multidisciplinary experts in the PENTEC effort, the medical physicists were charged with the dosimetric evaluation, as they are most expert in this subject. RESULTS: The percentage dosimetric uncertainty was estimated for each late effect endpoint for all PENTEC organ reports. Twelve specific sources of dose uncertainty were identified related to the 6 broad categories. The most common reason for organ dose uncertainty was that prescribed dose rather than organ dose was reported. Percentage dose uncertainties ranged from 5% to 200%. Systematic uncertainties were used to correct the dose component of the models. Random uncertainties were also described in each report and in some cases used to modify dose axis error bars. In addition, the potential effects of dose binning were described. CONCLUSIONS: PENTEC reports are designed to provide guidance to radiation oncologists and treatment planners for organ dose constraints. It is critical that these dose constraint recommendations are as accurate as possible, acknowledging the large error bars for many. Achieving this accuracy is important as it enables clinicians to better balance target dose coverage with risk of late effects. Evidence-based dose constraints for pediatric patients have been lacking and, in this regard, PENTEC fills an important unmet need. One must be aware of the limitations of our recommendations, and that for some organ systems, large uncertainties exist in the dose-response model because of clinical endpoint uncertainty, dosimetric uncertainty, or both.

Comparison of Risks of Late Effects From Radiation Therapy in Children Versus Adults: Insights From the QUANTEC, HyTEC, and PENTEC Efforts.

Pediatric Normal Tissue Effects in the Clinic (PENTEC) seeks to refine quantitative radiation dose-volume relationships for normal-tissue complication probabilities (NTCPs) in survivors of pediatric cancer. This article summarizes the evolution of PENTEC and compares it with similar adult-focused efforts (eg, Quantitative Analysis of Normal Tissue Effects in the Clinic [QUANTEC] and Hypofractionated Treatment Effects in the Clinic [HyTEC]) with respect to content, oversight, support, scope, and methodology of literature review. It then summarizes key organ-specific findings from PENTEC in an attempt to compare NTCP estimates in children versus adults. In brief, select normal-tissue risks within developing organs and tissues (eg, maldevelopment of musculoskeletal tissue, teeth, breasts, and reproductive organs) are primarily relevant only in children. For some organs and tissues, children appear to have similar (eg, brain for necrosis, optic apparatus, parotid gland, liver), greater (eg, brain for neurocognition, cerebrovascular, breast for lactation), less (ovary), or perhaps slightly less (eg, lung) risks of toxicity versus adults. Similarly, even within the broad pediatric age range (including adolescence), for some endpoints, younger children have greater (eg, hearing and brain for neurocognition) or lesser (eg, ovary, thyroid) risks of radiation-associated toxicities. NTCP comparisons in adults versus children are often confounded by marked differences in treatment paradigms that expose normal tissues to radiation (ie, cancer types, prescribed radiation therapy dose and fields, and chemotherapy agents used). To add to the complexity, it is unclear if age is best analyzed as a continuous variable versus with age groupings (eg, infants, young children, adolescents, young adults, middle-aged adults, older adults). Further work is needed to better understand the complex manner in which age and developmental status affect risk.

AAPM Task Group Report 307: Use of EPIDs for Patient-Specific IMRT and VMAT QA.

PURPOSE: Electronic portal imaging devices (EPIDs) have been widely utilized for patient-specific quality assurance (PSQA) and their use for transit dosimetry applications is emerging. Yet there are no specific guidelines on the potential uses, limitations, and correct utilization of EPIDs for these purposes. The American Association of Physicists in Medicine (AAPM) Task Group 307 (TG-307) provides a comprehensive review of the physics, modeling, algorithms and clinical experience with EPID-based pre-treatment and transit dosimetry techniques. This review also includes the limitations and challenges in the clinical implementation of EPIDs, including recommendations for commissioning, calibration and validation, routine QA, tolerance levels for gamma analysis and risk-based analysis. METHODS: Characteristics of the currently available EPID systems and EPID-based PSQA techniques are reviewed. The details of the physics, modeling, and algorithms for both pre-treatment and transit dosimetry methods are discussed, including clinical experience with different EPID dosimetry systems. Commissioning, calibration, and validation, tolerance levels and recommended tests, are reviewed, and analyzed. Risk-based analysis for EPID dosimetry is also addressed. RESULTS: Clinical experience, commissioning methods and tolerances for EPID-based PSQA system are described for pre-treatment and transit dosimetry applications. The sensitivity, specificity, and clinical results for EPID dosimetry techniques are presented as well as examples of patient-related and machine-related error detection by these dosimetry solutions. Limitations and challenges in clinical implementation of EPIDs for dosimetric purposes are discussed and acceptance and rejection criteria are outlined. Potential causes of and evaluations of pre-treatment and transit dosimetry failures are discussed. Guidelines and recommendations developed in this report are based on the extensive published data on EPID QA along with the clinical experience of the TG-307 members. CONCLUSION: TG-307 focused on the commercially available EPID-based dosimetric tools and provides guidance for medical physicists in the clinical implementation of EPID-based patient-specific pre-treatment and transit dosimetry QA solutions including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatments.