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.

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

BACKGROUND: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. RESULTS: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

Long-Term Update of NRG/RTOG 0522: A Randomized Phase 3 Trial of Concurrent Radiation and Cisplatin With or Without Cetuximab in Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS). METHODS AND MATERIALS: Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). RESULTS: Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P = .74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P = .94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P = .10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P = .36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P = .26). CONCLUSIONS: With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status.

Safety considerations for IMRT: executive summary.

This report on intensity-modulated radiation therapy (IMRT) is part of a series of white papers addressing patient safety commissioned by the American Society for Radiation Oncology's (ASTRO) Target Safely Campaign. The document has been approved by the ASTRO Board of Directors, endorsed by the American Association of Physicists in Medicine (AAPM) and American Association of Medical Dosimetrists (AAMD), and reviewed and accepted by the American College of Radiology's Commission on Radiation Oncology. This report is related to other reports of the ASTRO white paper series on patient safety which are still in preparation, and when appropriate it defers to guidance that will be published by those groups in future white papers. This document takes advantage of the large body of work on quality assurance and quality control principles within radiation oncology whenever possible. IMRT provides increased capability to conform isodose distributions to the shape of the target(s), thereby reducing dose to some adjacent critical structures. This promise of IMRT is one of the reasons for its widespread use. However, the promise of IMRT is counterbalanced by the complexity of the IMRT planning and delivery processes, and the associated risks, some of which have been demonstrated by the New York Times reports on serious accidents involving both IMRT and other radiation treatment modalities. This report provides an opportunity to broadly address safe delivery of IMRT, with a primary focus on recommendations for human error prevention and methods to reduce the occurrence of errors or machine malfunctions that can lead to catastrophic failures or errors.

Stereotactic body radiation therapy: the report of AAPM Task Group 101.

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Quality assurance procedures for stereotactic body radiation therapy.

Cranial stereotactic radiosurgery (SRS) and radiotherapy (SRT) are established treatment modalities. Initial implementations of these techniques rigidly attached frames to the patient's head for single-fraction treatments. The head frame accommodates an external fiducial marker system that is a reliable reference for targets within the cranium and accurately links the imaging equipment used for treatment planning to the treatment device. Fractionated SRT treatments use noninvasive "relocatable"-type head immobilization that fixes to the patient's head and face features. Clearly defined quality assurance (QA) procedures exist for both cranial SRS and SRT but are not as well developed for extracranial SRT. Procedures for demonstrating the geometric relationship between the planning imaging and treatment have to some degree copied the techniques used for intracranial stereotactic irradiation. However, there are some unique QA issues that are specific to extracranial irradiation. One major consideration is the large number of methodologies available for stereotactic body radiation therapy. In addition to the variety of integrated image-guided frameless systems, there are immobilization devices (called body frame systems) that use a fiducial reference system similar to the cranial devices. This article describes generic QA approaches that can be adapted to the various stereotactic body radiation therapy methodologies.

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy.

PURPOSE: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. METHODS AND MATERIALS: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. RESULTS: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. CONCLUSIONS: Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.

On Linear Infeasibility Arising in Intensity-Modulated Radiation Therapy Inverse Planning.

Intensity-modulated radiation therapy (IMRT) gives rise to systems of linear inequalities, representing the effects of radiation on the irradiated body. These systems are often infeasible, in which case one settles for an approximate solution, such as an {α, ß}-relaxation, meaning that no more than α percent of the inequalities are violated by no more than ß percent. For real-world IMRT problems, there is a feasible {α, ß}-relaxation for sufficiently large α, ß > 0, however large values of these parameters may be unacceptable medically.The {α, ß}-relaxation problem is combinatorial, and for given values of the parameters can be solved exactly by Mixed Integer Programming (MIP), but this may be impractical because of problem size, and the need for repeated solutions as the treatment progresses.As a practical alternative to the MIP approach we present a heuristic non-combinatorial method for finding an approximate relaxation. The method solves a Linear Program (LP) for each pair of values of the parameters {α, ß} and progresses through successively increasing values until an acceptable solution is found, or is determined non-existent. The method is fast and reliable, since it consists of solving a sequence of LP's.

NRG Oncology medical physicists' manpower survey quantifying support demands for multi-institutional clinical trials.

PURPOSE: A survey was created by NRG to assess a medical physicists' percent full time equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 American Society for Radiation Oncology report, "Safety Is No Accident," quantified medical physics staffing contributions in FTE factors for clinical departments. No quantification of FTE effort associated with clinical trials was included. METHODS: To address this lack of information, the NRG Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of 16 questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiation therapy institutions included on the membership rosters of the 5 National Clinical Trials Network clinical trial groups. RESULTS: Of the 451 institutions who responded, 50% (226) reported currently participating in radiation therapy trials. On average, the designated physicist at each institution spent 2.4 hours (standard deviation [SD], 5.5) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD, 3.1), 1.8 hours (SD, 3.9), and 0.6 hours (SD, 1.1) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a Digital Imaging and Communications in Medicine server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD, 57.2) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD, 3.4) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD, 1.9) per month. CONCLUSION: On average, physicist spent a nontrivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiation therapy clinical trials and should be taken into account when staffing radiation therapy institutions.

Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases.

PURPOSE: The NRG-BR001 trial is the first National Cancer Institute-sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates. METHODS AND MATERIALS: The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) against OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests. RESULTS: Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs. CONCLUSIONS: Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements.

Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

Alternative methods for intensity-modulated radiation therapy inverse planning and dose delivery.

A large number of IMRT systems are currently being marketed. Many of these systems appear to be unique, and manufacturers often emphasize design differences as they argue the merits of their particular approach. This paper focuses on highlighting the underlying feature that is intrinsically part of all IMRT systems. On the other hand, major differences often appear at the implementation stage for dose delivery. Such variations are evident because each manufacturer has a unique approach to balancing the issues of treatment time, leakage radiation reaching the patient's total body, aperture approximation of the ideal intensity maps, increasing the angles of approach for the treatment fields, integration of on-line imaging, selection of treatment distance, availability of different photon energies, and overall system complexity (i.e., cost). How these different issues are handled in the process of system design affects the relative advantages and disadvantages that appear in the final product. This paper takes the approach of dividing the various IMRT methods into categories that are divided roughly along the lines of the technique used during dose delivery to approximate the intensity patterns. Other features of each system are included under these sub-sections.

Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases.

INTRODUCTION: In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection. METHODS AND MATERIALS: Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed. RESULTS: Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity. DISCUSSION: NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases.

Real-time pretreatment review limits unacceptable deviations on a cooperative group radiation therapy technique trial: quality assurance results of RTOG 0933.

PURPOSE: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. METHODS AND MATERIALS: Before enrolling patients, all treating physicians and sites were required to successfully complete a "dry-run" credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging-computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. RESULTS: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. CONCLUSIONS: Although >95% of the cases passed the pre-enrollment credentialing, the pretreatment centralized review disqualified 5.7% of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases, and limited the final unacceptable deviation rate to 5%. Thus, pretreatment review is deemed necessary in future hippocampal avoidance trials and is potentially useful in other similarly challenging radiation therapy technique trials.

Contouring variations and the role of atlas in non-small cell lung cancer radiation therapy: Analysis of a multi-institutional preclinical trial planning study.

PURPOSE: To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation. METHODS AND MATERIALS: Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases. RESULTS: Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions' plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire. CONCLUSIONS: The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial.

Output variation from an intensity modulating dynamic collimator.

Intensity modulated radiation therapy (IMRT) offers a method of delivering radiation dose conforming to the shape of targets while minimizing the dose to the surrounding tissue and nearby critical organs. One popular device is the NOMOS MIMiC Collimator coupled to the CORVUS treatment planning system. The MIMiC collimator, mounted on a linac head, opens and closes one or more of its 40 small leaves as determined by the planner while the linac delivers radiation and the gantry rotates. This dynamic IMRT allows the intensity to be modulated yielding a highly conformal dose distribution. However, the dose output becomes a function of the detailed manner in which the leaves open and close, since the opening and closing are not instantaneous. We investigate the effect of switch rates and delay in the open/close events on the output profiles. The output is enhanced as the switch rate increases. The enhancement factor at any point of measurement is dependent on its distance from the central plane. We interpret these variations in terms of a simple model, which includes the effect of leaf travel time during the process of opening and closing. We also include the time delay in establishing the specified pressure in the pneumonic device, which controls the opening and closing of the leaves. The information presented here offers a means for incorporating these output changes into the planning system. This may avoid the current situation where many patient plans need to be renormalized based on the actual measurement taken during the delivery of the specified intensity pattern to a phantom.

Comparison of characteristics of photon and electron beams generated by Philips/Elekta and Varian linear accelerators.

Commissioning data of the common energy of 6 MV photon beams are analyzed for seven Philips/ Elekta linacs of five different models: SL 75/5, SL 15, SL 25, SLi Precise, and SLi. The observed beam quality %dd(10)x of 67.7% +/- 0.3 agrees with the manufacturer's specification of 67.5% +/- 2% but with a much smaller variation, suggesting the possibility of a more accurate beam quality guideline for acceptance commissioning of these linac models. Field size factors are less uniform, especially for the biggest field size of 40 x 40 cm2, but all agree within 1.1% between the five models. These 6 MV photon beams are also shown to be 0.4 MV harder than the Varian 2100C model. For commissioning electron beams generated by the Philips/Elekta models SL 15, SLi Precise and SLi, guidelines can be found from this work for the following parameters: actual field size at 100 SSD (up to +/- 0.6%) (different from manufacturer specified values at 95 SSD), and virtual source distance (up to +/- 0.7%). Significant differences are seen for R50 (up to 3.7 mm), sigma-theta-x, effective source distance, and cone size factor. However, except for R50 where Varian 2100C datasets are not available for comparison, the differences between the different Philips/Elekta models are comparable to those between the same Varian 2100C model linacs measured by us and Watts.

A graph-searching method for MLC leaf sequencing under constraints.

A new leaf-sequencing algorithm for step-and-shoot IMRT that is based on a graph-searching technique is described. An iterative process guided by a quantitative measure for the complexity of the initial or residual intensity pattern is used to identify the field segments shaped by a multileaf collimator (MLC). Given a user selected number of intensity levels, the algorithm searches deliverable segment candidates considering all intensity levels and two collimator positions separated by 90 degrees. The candidates for each intensity level are obtained as the least number of segments to cover the areas with equal or higher intensity. The shape of a deliverable segment is adjusted by leaving out certain beam elements for later delivery if this results in a simpler residual intensity pattern and the segment is still deliverable. For a MLC design that does not allow leaf interdigitation, it is initially assumed that a single segment cannot cover two disjoined areas. Among all candidates the segment with the greatest reduction of the complexity of the residual intensity distribution is chosen for the current step of iteration. The iterative process generates a set of deliverable segments of simply connected areas. These segments are combined later under specific MLC constraints. Different orders of segment combination are considered for minimizing the beam-on time. The final segments are sequenced to minimize the leaf travel. This algorithm has been tested using randomly generated intensity distributions and clinical cases for the Varian, Siemens, and Elekta MLC systems. The results show that as the number of intensity levels is increased, the numbers of segments and MUs increase only modestly. Using two collimator angles results in decreases in the required number of segments and the number of monitor units that can be as much as 20%.

Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.

We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.

An optimization algorithm for intensity modulated radiotherapy--the simulated dynamics with dose-volume constraints.

We have developed a new method for optimization in intensity modulated radiation therapy (IMRT) that makes use of simulated dynamics in a classical system of interacting particles. An analogy is drawn between intensity profile optimization in IMRT and relaxation to the equilibrium configuration in a dynamic system. The intensities of beamlets are equivalent to the positions of the virtual particles. The potential energy of the system is defined by the objective function, which determines the equations of motion for the virtual particles. In this paper, we present the implementation of dose constraints and dose-volume constraints. Our strategy is to optimize the dose to the planned target volume (PTV) while keeping all constraints to the organs at risk (OARs) satisfied rigorously. A simple quadratic objective function is used that only includes terms for PTV voxels. By this approach, no additional parameters other than that for prescribing desired dose and constraints, such as importance factors, are needed. The hard constraints that require non-negative beamlet intensities and that the dose at any voxel in an OAR cannot exceed a maximum tolerance, are implemented as semi-transmittable potential barriers of infinite height. Dose-volume constraints are handled by placing hard constraints on partial volumes. Handling of the clinically applied constraints was tested using phantoms and clinical cases. Our results show that the dose-volume histogram (DVH) type of plan prescription can be fulfilled with satisfactory PTV coverage. In addition to the convenience of implementation, our method can achieve a high computational efficiency with the understanding of the dynamic behavior of the system.