Report of Task Group 201 of the American Association of Physicists in Medicine: Quality management of external beam therapy data transfer.

With the advancement of data-intensive technologies, such as image-guided radiation therapy (IGRT) and intensity-modulated radiation therapy (IMRT), the amount and complexity of data to be transferred between clinical subsystems have increased beyond the reach of manual checking. As a result, unintended treatment deviations (e.g., dose errors) may occur if the treatment system is not closely monitored by a comprehensive data transfer quality management program (QM). This report summarizes the findings and recommendations from the task group (TG) on quality assurance (QA) of external beam treatment data transfer (TG-201), with the aim to assist medical physicists in designing their own data transfer QM. As a background, a section of this report describes various models of data flow (distributed data repositories and single data base systems) and general data test characteristics (data integrity, interpretation, and consistency). Recommended tests are suggested based on the collective experience of TG-201 members. These tests are for the acceptance of, commissioning of, and upgrades to subsystems that store and/or modify clinical treatment data. As treatment complexity continues to evolve, we will need to do and know more about ensuring the quality of data transfers. The report concludes with the recommendation to move toward data transfer open standards compatibility and to develop tools that automate data transfer QA.

Required transition from research to clinical application: Report on the 4D treatment planning workshops 2014 and 2015.

Since 2009, a 4D treatment planning workshop has taken place annually, gathering researchers working on the treatment of moving targets, mainly with scanned ion beams. Topics discussed during the workshops range from problems of time resolved imaging, the challenges of motion modelling, the implementation of 4D capabilities for treatment planning, up to different aspects related to 4D dosimetry and treatment verification. This report gives an overview on topics discussed at the 4D workshops in 2014 and 2015. It summarizes recent findings, developments and challenges in the field and discusses the relevant literature of the recent years. The report is structured in three parts pointing out developments in the context of understanding moving geometries, of treating moving targets and of 4D quality assurance (QA) and 4D dosimetry. The community represented at the 4D workshops agrees that research in the context of treating moving targets with scanned ion beams faces a crucial phase of clinical translation. In the coming years it will be important to define standards for motion monitoring, to establish 4D treatment planning guidelines and to develop 4D QA tools. These basic requirements for the clinical application of scanned ion beams to moving targets could e.g. be determined by a dedicated ESTRO task group. Besides reviewing recent research results and pointing out urgent needs when treating moving targets with scanned ion beams, the report also gives an outlook on the upcoming 4D workshop organized at the University Medical Center Groningen (UMCG) in the Netherlands at the end of 2016.

Simultaneous optimization of dose distributions and fractionation schemes in particle radiotherapy.

PURPOSE: The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities. METHODS: This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED-based treatment planning problem. RESULTS: For this model, it is shown that a small α∕ß ratio in the tumor gives rise to a hypofractionated treatment, whereas a large α∕ß ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate α∕ß ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam. CONCLUSIONS: The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized simultaneously. Although the projected benefits are likely to be small, the approach may give rise to an improved therapeutic ratio for tumors treated with stereotactic techniques to high doses per fraction.

Physics controversies in proton therapy.

The physical characteristics of proton beams are appealing for cancer therapy. The rapid increase in operational and planned proton therapy facilities may suggest that this technology is a "plug-and-play" valuable addition to the arsenal of the radiation oncologist and medical physicist. In reality, the technology is still evolving, so planning and delivery of proton therapy in patients face many practical challenges. This review article discusses the current status of proton therapy treatment planning and delivery techniques, indicates current limitations in dealing with range uncertainties, and proposes possible developments for proton therapy and supplementary technology to try to realize the actual potential of proton therapy.

Proton SBRT for medically inoperable stage I NSCLC.

INTRODUCTION: The physical properties of proton beam radiation may offer advantages for treating patients with non-small-cell lung cancer (NSCLC). However, its utility for the treatment of medically inoperable stage I NSCLC patients with stereotactic body radiation therapy (SBRT) is unknown. METHODS: Outcomes for patients with medically inoperable stage I NSCLC treated with proton SBRT were retrospectively analyzed. Proton SBRT was selected as the treatment modality based on pulmonary comorbidities (n = 5), prior chest radiation or/and multiple primary tumors (n = 7), or other reasons (n = 3). Treatments were administered using 2 to 3 proton beams. Treatment toxicity was scored according to common toxicity criteria for adverse events version 4 criteria. RESULTS: Fifteen consecutive patients and 20 tumors were treated with proton SBRT to 42 to 50 Gy(relative biological effectiveness) in 3 to 5 fractions between July 2008 and September 2010. Treatments were well tolerated with only one case of grade 2 fatigue, one case of grade 2 dermatitis, three cases of rib fracture (maximum grade 2), and one case of grade 3 pneumonitis in a patient with severe chronic obstructive pulmonary disease. With a median follow-up of 24.1 months, 2-year overall survival and local control rates were 64% (95% confidence limits, 34%-83%) and 100% (83%-100%), respectively. CONCLUSIONS: We conclude that proton SBRT is effective and well tolerated in this unfavorable group of patients. Prospective clinical trials testing the utility of proton SBRT in stage I NSCLC are warranted.

Results of a multicentric in silico clinical trial (ROCOCO): comparing radiotherapy with photons and protons for non-small cell lung cancer.

INTRODUCTION: This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). METHODS: Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. RESULTS: Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. CONCLUSIONS: The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities.

Uncertainties and correction methods when modeling passive scattering proton therapy treatment heads with Monte Carlo.

Nowadays, Monte Carlo models of proton therapy treatment heads are being used to improve beam delivery systems and to calculate the radiation field for patient dose calculations. The achievable accuracy of the model depends on the exact knowledge of the treatment head geometry and time structure, the material characteristics, and the underlying physics. This work aimed at studying the uncertainties in treatment head simulations for passive scattering proton therapy. The sensitivities of spread-out Bragg peak (SOBP) dose distributions on material densities, mean ionization potentials, initial proton beam energy spread and spot size were investigated. An improved understanding of the nature of these parameters may help to improve agreement between calculated and measured SOBP dose distributions and to ensure that the range, modulation width, and uniformity are within clinical tolerance levels. Furthermore, we present a method to make small corrections to the uniformity of spread-out Bragg peaks by utilizing the time structure of the beam delivery. In addition, we re-commissioned the models of the two proton treatment heads located at our facility using the aforementioned correction methods presented in this paper.

Accuracy of proton beam range verification using post-treatment positron emission tomography/computed tomography as function of treatment site.

PURPOSE: For 23 patients, an off-line positron emission tomography scan and a computed tomography scan after proton radiotherapy was performed at the Massachusetts General Hospital to assess in vivo treatment verification. A well-balanced population of patients was investigated to assess the effect of the tumor location on the accuracy of the technique. METHODS AND MATERIALS: Range verification was achieved by comparing the measured positron emission tomography activity distributions with the corresponding Monte Carlo-simulated distributions. Observed differences in the distal end of the activity distributions were analyzed as potential indicators for the range differences between the actual delivered and planned dose. RESULTS: The average spatial agreement between the measured and simulated activity distribution was within ±3 mm, and the corresponding average absolute agreement was within ±45% (derived from gamma index analysis). The mean absolute range deviation at 93 randomly chosen positions in 17 treatment fields delivered to 11 patients was 3.6 mm. Characteristic differences in the agreement of the measured and simulated activity distribution for the different tumor/target sites were found. This resulted from the different effect of factors such as biologic washout effects, motion, or limitations in the Monte Carlo-simulated activity patterns. CONCLUSION: We found that intracranial and cervical spine patients can greatly benefit from off-line positron emission tomography and computed tomography range verification. However, for the successful application of the method to patients with abdominopelvic tumors, major technological and methodologic improvements are needed. Among the intracranial and cervical spine target sites, patients with arteriovenous malformations or metal implants represent groups that could especially benefit from the approach.

Proton radiotherapy: the biological effect of treating alternating subsets of fields for different treatment fractions.

PURPOSE: Common practice in proton radiotherapy is to deliver a subset of all fields in the treatment plan on any given treatment day. We investigate using biological modeling if the resulting variation in daily dose to normal tissues has a relevant detrimental biological effect. METHODS AND MATERIALS: For four patient groups, the cumulative normalized total dose (NTD) was determined for normal tissues (OARs) of each patient using the clinically delivered fractionation schedule (FS(clin)), and for hypothetical fractionation schedules delivering all fields every day (FS(all)) or only a single field each day (FS(single)). Cumulative three-dimensional NTD distributions were summarized using the generalized equivalent uniform dose (gEUD) model. RESULTS: For the skull base/cervical spine chordoma group, the largest effect is a 4-Gy increase in gEUD of the chiasm when treating only a subset of fields on any day. For lung cancer and pancreatic cancer patients, the variation in the gEUD of normal tissues is <0.2 Gy. For the prostate group, FS(clin) increases the gEUD of the femoral heads by 9 Gy compared with FS(all). Use of FS(single) resulted in the highest NTD to normal tissues for any patient. FS(all) resulted in an integral NTD to the patient that is on average 5% lower than FS(clin) and 10% lower than FS(single). CONCLUSION: The effects of field set of the day treatment delivery depend on the tumor site and number of fields treated each day. Modeling these effects may be important for accurate risk assessment.

Interfractional variations in the setup of pelvic bony anatomy and soft tissue, and their implications on the delivery of proton therapy for localized prostate cancer.

PURPOSE: To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and setup approaches employed in proton therapy. METHODS: We used series of computed tomography data, which included the pretreatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription isodose were evaluated. RESULTS: In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7-3.6 mm for individual patients, variations of >5 mm from the planning computed tomography observed in all series), and femur rotation angle (standard deviation between 1.3° and 4.8°, with the maximum excursion exceeding 10° in 6 of 10 datasets). Shifts in the position of treated volume (98% isodose) were correlated with the variations in the lateral tissue thickness. CONCLUSIONS: Analysis suggests that, combined with image-guided setup verification, the range compensator expansion technique prevents loss of dose to target from femur rotation and soft-tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.

Design of and technical challenges involved in a framework for multicentric radiotherapy treatment planning studies.

This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data.

A rapid communication from the AAPM Task Group 201: recommendations for the QA of external beam radiotherapy data transfer. AAPM TG 201: quality assurance of external beam radiotherapy data transfer.

The transfer of radiation therapy data among the various subsystems required for external beam treatments is subject to error. Hence, the establishment and management of a data transfer quality assurance program is strongly recommended. It should cover the QA of data transfers of patient specific treatments, imaging data, manually handled data and historical treatment records. QA of the database state (logical consistency and information integrity) is also addressed to ensure that accurate data are transferred.

Clinical implementation of full Monte Carlo dose calculation in proton beam therapy.

The goal of this work was to facilitate the clinical use of Monte Carlo proton dose calculation to support routine treatment planning and delivery. The Monte Carlo code Geant4 was used to simulate the treatment head setup, including a time-dependent simulation of modulator wheels (for broad beam modulation) and magnetic field settings (for beam scanning). Any patient-field-specific setup can be modeled according to the treatment control system of the facility. The code was benchmarked against phantom measurements. Using a simulation of the ionization chamber reading in the treatment head allows the Monte Carlo dose to be specified in absolute units (Gy per ionization chamber reading). Next, the capability of reading CT data information was implemented into the Monte Carlo code to model patient anatomy. To allow time-efficient dose calculation, the standard Geant4 tracking algorithm was modified. Finally, a software link of the Monte Carlo dose engine to the patient database and the commercial planning system was established to allow data exchange, thus completing the implementation of the proton Monte Carlo dose calculation engine ('DoC++'). Monte Carlo re-calculated plans are a valuable tool to revisit decisions in the planning process. Identification of clinically significant differences between Monte Carlo and pencil-beam-based dose calculations may also drive improvements of current pencil-beam methods. As an example, four patients (29 fields in total) with tumors in the head and neck regions were analyzed. Differences between the pencil-beam algorithm and Monte Carlo were identified in particular near the end of range, both due to dose degradation and overall differences in range prediction due to bony anatomy in the beam path. Further, the Monte Carlo reports dose-to-tissue as compared to dose-to-water by the planning system. Our implementation is tailored to a specific Monte Carlo code and the treatment planning system XiO (Computerized Medical Systems Inc.). However, this work describes the general challenges and considerations when implementing proton Monte Carlo dose calculation in a clinical environment. The presented solutions can be easily adopted for other planning systems or other Monte Carlo codes.

Comparison between the lateral penumbra of a collimated double-scattered beam and uncollimated scanning beam in proton radiotherapy.

Intensity modulated proton radiotherapy (IMPT) can reduce the dose to critical structures by optimizing the distribution and intensity of individual pencil beams. The IMPT can be delivered by dynamically scanning a pencil beam with variable intensity and energy across the tumor target volume. The lateral penumbra of an uncollimated pencil beam is compromised, however, by the scattering in air between the vacuum window and the patient, and by the initial beam size. In this study, we compare the transversal penumbra of a pencil beam to the one of a collimated Gaussian broad divergent beam, such as the one produced by the double scattering system, for different range compensator thicknesses, collimator-to-surface distances (CSD), proton range and pencil beam sizes (sigma0). The effect of vacuum and helium in the nozzle on the pencil beam lateral profile further downstream is also investigated. The lateral spatial intensity distribution for the collimated Gaussian broad divergent proton beam is modeled using the generalized Fermi-Eyges theory. The model is validated with measurements of the lateral profile in water at different depths for two different ranges (7.7 cm and 22.1 cm, respectively). Nearly 2500 treatment fields are analyzed to establish typical clinical beam configurations, such as the range compensator thicknesses, CSD and range, which we use to predict the 80%-20% lateral penumbra. The penumbra of the collimated broad divergent beam is calculated for fixed source-to-surface distance (SSD) of 220 cm and source size of 2.5 cm (sigma). The results show that the model predicts the penumbra at different water depths with accuracy better than 0.2 mm. At depths larger than 7.6 cm (minimum range of the clinical fields analyzed), the accuracy is better than 3%. The treatment fields feature the following average configuration: the range compensator thickness of 6.5+/-2.8 cm (max 19.4 cm), CSD 11.9+/-3.8 cm (max 29.4 cm) and range of 16.0+/-6.1 cm. The penumbra of a pencil beam at shallow depth is in general larger (i.e., worse) than the penumbra of a collimated beam, but better at larger depths. The depth at which the two penumbras are identical exhibits only a small dependence on the proton range, but is strongly affected by the collimator-to-surface distance. For CSD 10 cm, range compensator thickness 6 cm, SSD 220 cm and source size 2.5 cm, this depth is 11.5 cm for a 5 mm pencil beam, and 9.1 cm for a 3 mm pencil beam. For most of the clinical sites considered, assuming the beam configurations of this study, the pencil beam penumbra is larger (i.e., worse). By moving the vacuum window downstream or by replacing air with helium in the gantry nozzle, the dosimetrical benefit of scanning would be drastically improved, especially for small sigma0 (5 mm or less).

Sensitivities in the production of spread-out Bragg peak dose distributions by passive scattering with beam current modulation.

A spread-out Bragg peak (SOBP) is used in proton beam therapy to create a longitudinal conformality of the required dose to the target. In order to create this effect in a passive beam scattering system, a variety of components must operate in conjunction to produce the desired beam parameters. We will describe how the SOBP is generated and will explore the tolerances of the various components and their subsequent effect on the dose distribution. A specific aspect of this investigation includes a case study involving the use of a beam current modulated system. In such a system, the intensity of the beam current can be varied in synchronization with the revolution of the range-modulator wheel. As a result, the weights of the pulled-back Bragg peaks can be individually controlled to produce uniform dose plateaus for a large range of treatment depths using only a small number of modulator wheels.

Four-dimensional proton treatment planning for lung tumors.

PURPOSE: In proton radiotherapy, respiration-induced variations in density lead to changes in radiologic path lengths and will possibly result in geometric misses. We compared different treatment planning strategies for lung tumors that compensate for respiratory motion. METHODS AND MATERIALS: Particle-specific treatment planning margins were applied to standard helical computed tomography (CT) scans as well as to "representative" CT scans. Margins were incorporated beam specific laterally by aperture widening and longitudinally by compensator smearing. Furthermore, treatment plans using full time-resolved 4D-computed tomography data were generated. RESULTS: Four-dimensional treatment planning guaranteed target coverage throughout a respiratory cycle. Use of a standard helical CT data set resulted in underdosing the target volume to 36% of the prescribed dose. For CT data representing average target positions, coverage can be expected but not guaranteed. In comparison to this strategy, 4D planning decreased the mean lung dose by up to 16% and the lung volume receiving 20 Gy (prescribed target dose 72 Gy) by up to 15%. CONCLUSION: When the three planning strategies are compared, only 4D proton treatment planning guarantees delivery of the prescribed dose throughout a respiratory cycle. Furthermore, the 4D planning approach results in equal or reduced dose to critical structures; even the ipsilateral lung is spared.

Intra- and interfractional patient motion for a variety of immobilization devices.

The magnitude of inter- and intrafractional patient motion has been assessed for a broad set of immobilization devices. Data was analyzed for the three ordinal directions--left-right (x), sup-inf (y), and ant-post (z)--and the combined spatial displacement. We have defined "rigid" and "non-rigid" immobilization devices depending on whether they could be rigidly and reproducibly connected to the treatment couch or not. The mean spatial displacement for intrafractional motion for rigid devices is 1.3 mm compared to 1.9 mm for nonrigid devices. The modified Gill-Thomas-Cosman frame performed best at controlling intrafractional patient motion, with a 95% probability of observing a three-dimensional (3D) vector length of motion (v95) of less than 1.8 mm, but could not be evaluated for interfractional motion. All other rigid and nonrigid immobilization devices had a v95 of more than 3 mm for intrafractional patient motion. Interfractional patient motion was only evaluated for the rigid devices. The mean total interfractional displacement was at least 3.0 mm for these devices while v95 was at least 6.0 mm.

The prediction of output factors for spread-out proton Bragg peak fields in clinical practice.

The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoc, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process.

Levetiracetam use and pregnancy outcome.

Prenatal exposure to levetiracetam (LEV) has been shown to cause skeletal abnormalities and growth retardation in animal studies, but the teratogenicity of this new antiepileptic drug in humans is still unknown. We detected no malformations in a series of 11 pregnancies with LEV exposure, although it was striking that three cases had a low birth weight. There may be an association between maternal LEV use and reduced birth weight, but too few cases have been monitored so far. We recommend that the outcomes of all pregnancies exposed to LEV should be carefully registered.

Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas.

BACKGROUND: For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local therapy, depending on the site and type of sarcoma, the surgical approach, and the efficacy of chemotherapy. METHODS: The authors review the current status of advanced technology radiation therapy in the management of bone and soft tissue sarcoma. RESULTS: Advances in radiotherapy have resulted in improved treatment for bone and soft tissue sarcomas. Intensity-modulated radiation therapy (IMRT) uses modifications in the intensity of the photon-beam from a linear accelerator across the irradiated fields to enhance dose conformation in three dimensions. For proton-beam radiation therapy, the nuclei of hydrogen atoms are accelerated in cyclotrons or synchrotrons, extracted, and transported to treatment rooms where the proton beam undergoes a series of modifications that conform the dose in a particular patient to the tumor target. Brachytherapy and intraoperative radiation therapy have generally been used to treat microscopic residual disease in patients with sarcomas. These technologies deliver dose to tumor cells with irradiation of limited volumes of normal tissue. Patients who may benefit from technically advanced radiotherapy include those with skull base and spine/paraspinal sarcomas, Ewing's sarcoma, and retroperitoneal/extremity sarcomas. CONCLUSIONS: Advances in radiation therapy technology, particularly IMRT, proton-beam or other charged-particle radiation therapy, brachytherapy, and intraoperative radiation therapy, have led to improved treatment for patients with bone and soft tissue sarcomas.