Mixed Beam Therapy Research Articles

Cost-effectiveness analysis of advanced radiotherapy techniques for post-mastectomy breast cancer patients

BackgroundPrior cost-effectiveness studies of post-mastectomy radiotherapy (PMRT) only compared conventional radiotherapy versus no radiotherapy and only considered tumor control. The goal of this study was to perform cost-effectiveness analyses of standard of care (SOC) and advanced PMRT techniques including intensity-modulated radiotherapy (IMRT), standard volumetric modulated arc therapy (STD-VMAT), non-coplanar VMAT (NC-VMAT), multiple arc VMAT (MA-VMAT), Tomotherapy (TOMO), mixed beam therapy (MIXED), and intensity-modulated proton therapy (IMPT).MethodsUsing a Markov model, we estimated the cost-effectiveness of various techniques over 15 years. A cohort of women (55-year-old) was simulated in the model, and radiogenic side effects were considered. Transition probabilities, utilities, and costs for each health state were obtained from literature and Medicare data. Model outcomes include quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER).ResultsFor the patient cohort, STD-VMAT has an ICER of $32,617/QALY relative to SOC; TOMO is dominated by STD-VMAT; IMRT has an ICER of $19,081/QALY relative to STD-VMAT; NC-VMAT, MA-VMAT, MIXED are dominated by IMRT; IMPT has an ICER of $151,741/QALY relative to IMRT. One-way analysis shows that the probability of cardiac toxicity has the most significant impact on the model outcomes. The probability sensitivity analyses show that all advanced PMRT techniques are more cost-effective than SOC at a willingness-to-pay (WTP) threshold of $100,000/QALY, while almost none of the advanced techniques is more cost-effective than SOC at a WTP threshold of $50,000/QALY.ConclusionAdvanced PMRT techniques are more cost-effective for breast cancer patients at a WTP threshold of $100,000/QALY, and IMRT might be a cost-effective option for PMRT patients.

Postmastectomy radiotherapy for left-sided breast cancer patients: Comparison of advanced techniques

Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients, and many advanced radiotherapy technologies were adopted for PMRT. The purpose of our study is to compare various advanced PMRT techniques including fixed-beam intensity-modulated radiotherapy (IMRT), non-coplanar volumetric modulated arc therapy (NC-VMAT), multiple arc VMAT (MA-VMAT), and tomotherapy (TOMO). Results of standard VMAT and mixed beam therapy that were published by our group previously were also included in the plan comparisons. Treatment plans were produced for nine PMRT patients previously treated in our clinic. The plans were evaluated based on planning target volume (PTV) coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP) of pneumonitis, lifetime attributable risk (LAR) of second cancers, and risk of coronary events (RCE). All techniques produced clinically acceptable PMRT plans. Overall, fixed-beam IMRT delivered the lowest mean dose to contralateral breast (1.56 ± 0.4 Gy) and exhibited lowest LAR (0.6 ± 0.2%) of secondary contralateral breast cancer; NC-VMAT delivered the lowest mean dose to lungs (7.5 ± 0.8 Gy), exhibited lowest LAR (5.4 ± 2.8%) of secondary lung cancer and lowest NTCP (2.1 ± 0.4%) of pneumonitis; mixed beam therapy delivered the lowest mean dose to heart (7.1 ± 1.3 Gy) and exhibited lowest RCE (8.6 ± 7.1%); TOMO plans provided the most optimal target coverage while delivering higher dose to OARs than other techniques. Both NC-VMAT and MA-VMAT exhibited lower values of all OARs evaluation metrics compare to standard VMAT. Fixed-beam IMRT, NC-VMAT, and mixed beam therapy could be the optimal radiation technique for certain breast cancer patients after mastectomy.

Measurement and modeling of out-of-field doses from various advanced post-mastectomy radiotherapy techniques

More and more advanced radiotherapy techniques have been adopted for post-mastectomy radiotherapies (PMRT). Patient dose reconstruction is challenging for these advanced techniques because they increase the low out-of-field dose area while the accuracy of out-of-field dose calculations by current commercial treatment planning systems (TPSs) is poor. We aim to measure and model the out-of-field radiation doses from various advanced PMRT techniques. PMRT treatment plans for an anthropomorphic phantom were generated, including volumetric modulated arc therapy with standard and flattening-filter-free photon beams, mixed beam therapy, 4-field intensity modulated radiation therapy (IMRT), and tomotherapy. We measured doses in the phantom where the TPS calculated doses were lower than 5% of the prescription dose using thermoluminescent dosimeters (TLD). The TLD measurements were corrected by two additional energy correction factors, namely out-of-beam out-of-field (OBOF) correction factor KOBOF and in-beam out-of-field (IBOF) correction factor KIBOF, which were determined by separate measurements using an ion chamber and TLD. A simple analytical model was developed to predict out-of-field dose as a function of distance from the field edge for each PMRT technique. The root mean square discrepancies between measured and calculated out-of-field doses were within 0.66 cGy Gy−1 for all techniques. The IBOF doses were highly scattered and should be evaluated case by case. One can easily combine the measured out-of-field dose here with the in-field dose calculated by the local TPS to reconstruct organ doses for a specific PMRT patient if the same treatment apparatus and technique were used.

SU-E-T-536: A Simple Method for Optimal Field Abutment Between Photon and Electron Beams in Mixed Beam Radiation Therapy

Purpose: Significant efforts have been made to develop practical methods for the clinical implementation of advanced mixed beam therapy. One of the problems with the use of multiple adjacent electron radiation fields is the possibility of extreme dose inhomogeneity in the junction region. Because radiation beams are divergent, adjacent fields can overlap at depth and give rise to regions of excessive dose. Overlaps can be avoided by separating the electron fields but this in turn can give rise to areas of reduced dose at shallow depths. Thus the aim of this work is to find the optimal gap for different combined electron and photon beam situations. Method: Monte Carlo simulation was conducted for our Varian treatment head using the MCBEAM code, and the MCSIM code was used for modeling a water phantom to derive the dose distribution. Simulated PDDs and profiles were compared to measurements for photon and electron beams. Then isodose distributions were generated for adjacent fields with different separation gaps for different abutment situations such as photon‐photon, electron‐electron and photon‐electron combinations. Results: Good agreement was achieved between Monte Carlo simulation and measurement for all studied photon and electron beam energies. Separation gaps can be chosen that would Result in a flatter profile at a desired depth. Optimal gaps can be selected that compromise between the cold and hot spots inside the target. Conclusion: The Monte Carlo code used was capable of modeling our photon and electron beams accurately. We addressed a simple method to solve the field abutment problem in combined photon and electron treatments for advance mixed beam radiation therapy.

Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94.62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.

Characterization of an extendable multi-leaf collimator for clinical electron beams

An extendable x-ray multi-leaf collimator (eMLC) is investigated for collimation of electron beams on a linear accelerator. The conventional method of collimation using an electron applicator is impractical for conformal, modulated and mixed beam therapy techniques. An eMLC would allow faster, more complex treatments with potential for reduction in dose to organs-at-risk and critical structures. The add-on eMLC was modelled using the EGSnrc Monte Carlo code and validated against dose measurements at 6–21 MeV with the eMLC mounted on a Siemens Oncor linear accelerator at 71.6 and 81.6 cm source-to-collimator distances. Measurements and simulations at 8.4–18.4 cm airgaps showed agreement of 2%/2 mm. The eMLC dose profiles and percentage depth dose curves were compared with standard electron applicator parameters. The primary differences were a wider penumbra and up to 4.2% reduction in the build-up dose at 0.5 cm depth, with dose normalized on the central axis. At 90 cm source-to-surface distance (SSD)-–relevant to isocentric delivery-–the applicator and eMLC penumbrae agreed to 0.3 cm. The eMLC leaves, which were 7 cm thick, contributed up to 6.3% scattered electron dose at the depth of maximum dose for a 10 × 10 cm2 field, with the thick leaves effectively eliminating bremsstrahlung leakage. A Monte Carlo calculated wedge shaped dose distribution generated with all six beam energies matched across the maximum available eMLC field width demonstrated a therapeutic (80% of maximum dose) depth range of 2.1–6.8 cm. Field matching was particularly challenging at lower beam energies (6–12 MeV) due to the wider penumbrae and angular distribution of electron scattering. An eMLC isocentric electron breast boost was planned and compared with the conventional applicator fixed SSD plan, showing similar target coverage and dose to critical structures. The mean dose to the target differed by less than 2%. The low bremsstrahlung dose from the 7 cm thick MLC leaves had the added advantage of reducing the mean dose to the whole heart. Isocentric delivery using an extendable eMLC means that treatment room re-entry and repositioning the patient for SSD set-up is unnecessary. Monte Carlo simulation can accurately calculate the fluence below the eMLC and subsequent patient dose distributions. The eMLC generates similar dose distributions to the standard electron applicator but provides a practical method for more complex electron beam delivery.

SU-FF-T-579: Comparison of Helical Tomotherapy and Mixed Beam Treatment Plans for Superficial Parotid Cancers

Purpose: To compare helical tomotherapy (HT) with mixed beam therapy (electron and IMRT) plans for a superficial parotid treatment. Method and Materials: Mixed beam and HT dose plans were developed for a patient with a superficial parotid gland tumor. Seven mixed beam plans included a 7‐field photonIMRT plan optimized on top of a single en‐face, 16‐MeV electron beam dose distribution. The ratio of photon to electron beam weights (at depth R100) were 1:0 (IMRT only), 2:1, 1:1, 1:2, 1:3, 1:4, and 0:1 (electrons only). Planning objectives for HT plans were set as closely as possible to those in the mixed beam plans, and were determined using our clinical planning protocol for head and neck cancers. The resulting dose distribution from each plan was evaluated using multiple dose metrics for the planning target volume (PTV) and normal tissues.Results: Dose homogeneity, D95%‐5%, was best for HT (0.94 Gy), and worst for electrons (7.19 Gy), but improved with mixed beam (0.99 Gy for 1:3) to nearly equal that of HT. Conformity index was 0.69 for HT and 0.78 for IMRT, but improved with mixed beam (0.80 for 2:1). Mean dose to the contralateral parotid was 16.0 Gy for HT and 20.1 Gy for IMRT, but improved with mixed beam (9.8 Gy for 1:4). Similar normal tissue results were found for the spinal cord, eyes, lens, optic nerves, and contralateral eye. Conclusions: Utilizing IMRT in mixed beam therapy improves dose homogeneity while taking advantage of the finite electron range to spare nearby critical structures. In this case, mixed beam therapy plans were comparable with or superior to HT and IMRT for the PTV and normal tissues.Conflict of Interest: This work was supported in part by TomoTherapy, Inc.

Electron Intensity Modulation with Multileaf Collimation for Mixed-beam Partial Breast Irradiation

Currently, patients undergoing partial breast irradiation are typically treated with 3-5 non-coplanar high energy photon beams. The addition of electron beams has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. The purpose of this work was to explore the use of mixed-beam therapy (MBT), with combined intensity-modulated electron and photon beams in the treatment of partial breast targets. Electron fields used in MBT were modulated using the X-ray MLC without an electron applicator.

TH-D-AUD B-05: Electron Intensity Modulation for Mixed-Beam Radiation Therapy with An X-Ray Multi-Leaf Collimator

Purpose: To explore the use of mixed‐beam therapy (MBT), i.e., combined intensity‐modulated electron and x‐ray beams using the x‐ray multileaf collimator(MLC), in the treatment of head and neck and breast cancers. For shallow head and neck and partial breast targets, the addition of electrons has the potential of improving target coverage and sparing of critical structures and reduction of integral dose due to rapid dose falloff with depth and reduced exit dose.Method and Materials:Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods and integrated into a commercially‐available treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2×2‐cm2 beamlets, which were beam‐weight optimized along with intensity modulation of x‐ray beams. MBT treatment plans were created for 8 shallow head and neck and 9 partial breast irradiation cases, and optimized to obtain equivalent target dose coverage compared to the original IMRT plans. MBT treatment plans were evaluated with respect to target conformality and integral dose in comparison with original clinical plans. Results: The shallow head and neck targets were shown to have reduced integral dose with MBT, on average 8% less than IMRT, as well as reductions in doses to critical structures distal to the target along the electron beam direction. MBT partial breast plans had an average reduction in integral dose of 14%, and also showed improvement in target conformality by an average of 24%. Conclusion: MBT shows promise for improving normal structure sparing and reducing integral dose, while maintaining target coverage and increasing target dose conformality.

TU‐A‐350‐01: Electron Monte Carlo: Clinical Impact

This presentation will facilitate participants with the clinical application of Monte Carlo dose calculation algorithms in radiotherapy treatment planning and dosimetry verification. Following a brief introduction to the clinical implementation and commissioning of the Monte Carlo dose calculation software detailed discussions will be given on the actual and potential impact of Monte Carlo dose calculation algorithms on conventional electron beam therapy and advanced mixed beam treatments.Comparisons of patient treatment plans generated using conventional dose calculation algorithms and Monte Carlo methods will be made with an emphasis on the causes of the dose discrepancies. Further discussions will be conducted on the use of Monte Carlo dose calculation as a radiotherapy treatment QA tool to validate individual patient plans and as an investigation tool to improve target dose conformity and normal tissue sparing using novel treatment techniques.Educational Objectives:1. To describe clinical implement and commissioning of Monte Carlo dose calculation algorithms for radiotherapy treatment planning.2. To discuss the impact of Monte Carlo dose calculation in electron therapy and advanced mixed beam therapy treatment planning.3. To describe the applications of Monte Carlo dose calculation in treatment planning and beam delivery QA for advanced radiotherapy treatments.

TH-D-AUD B-04: Developing Hardware and Software Tools for Advanced Mixed Beam Radiotherapy

Purpose: Intensity-modulated radiation therapy (IMRT) provides excellent lateral dose conformity while energy- and intensity-modulated electron therapy (MBRT) can spare distal critical structures for shallow targets. This work aims to combine IMRT and MERT for advanced mixed beam therapy (MBRT) of breast and head and neck cancers. Method and Materials: We have acquired a motorized electron-specific multileaf collimator (eMLC) for accurate beam delivery for both conventional electron therapy and MERT. The eMLC is retractable to provide large apertures for efficient photon and electron beam delivery for MBRT. Extensive measurements were performed to verify dose distributions collimated by the eMLC and to validate MBRT treatment plans. Monte Carlo based dose calculation, treatment optimization and leaf sequencing algorithms were investigated for efficient and accurate beam delivery. This technique is being implemented clinically for scalp, head and neck, and breast treatment through pilot studies that are specially designed for dose escalation and hypofractionation. Results: The eMLC provides similar electron beam characteristics to that obtained with a conventional electron applicator/cutout. The leakage is 1.8% for 16MeV electron beams and is less than 1% for other lower electron energies. A typical MERT has a 2–3 modulation-scaling factor, which results in a maximum 5% leakage dose that is similar to that from IMRT. The measurement results agreed with the planned dose distributions to 3%/3mm for both uniform and heterogeneous phantoms. Conclusion: We have developed a MBRT system for the treatment of shallow targets that consists of hardware tools and software tools for accurate and efficient beam delivery. The technique is being implemented clinically for partial breast, scalp and head and neck treatments.

Multileaf collimation of electrons—clinical effects on electron energy modulation and mixed beam therapy depending on treatment head design

The aim of this study was to explore the possibilities of using multileaf-collimated electron beams for advanced radiation therapy with conventional scattering foil flattened beams. Monte Carlo simulations were performed with the aim to improve electron beam characteristics and enable isocentric multileaf collimation. The scattering foil positions, monitor chamber thickness, the MLC location and the amount of He in the treatment head were optimized for three common commercial accelerators. The performance of the three optimized treatment head designs was compared for different SSDs in air, at treatment depth in water and for some clinical cases. The effects of electron/photon beam matching including generalized random and static errors using Gaussian one-dimensional (1D) error distributions, and also electron energy modulation, were studied at treatment depth in water. The modification of the treatment heads improved the electron beam characteristics and enabled the use of multileaf collimation in isocentric delivery of both electron and photon beams in a mixed beam IMRT procedure.

Treatment results of fast neutron irradiation in soft tissue sarcomas

Surgery is the standard treatment of soft-tissue sarcomas. Adjuvant radiotherapy with photons after less radical resection can improve local control. The rate of tumor control achieved in patients with G1 and G2 soft tissue sarcomas incompletely resected and treated postoperatively with neutron irradiation is similar to that seen in patients undergoing complete tumor resection and adjuvant photon irradiation. At the Department of Radiotherapy and Radiation Oncology of the University of Münster, 61 patients with soft tissue sarcomas were irradiated postoperatively with fast neutrons. Mainly tumors of low or intermediate malignancy (R0; 27%; R1, 21%; R2, 52%) were treated. Malignant fibrous histiocytoma, liposarcoma, and neurogenic sarcomas dominated. 46 patients were irradiated with fast neutrons alone, and 15 patients were treated with mixed beam therapy (photons and neutrons). The median follow-up period was 44 months. Overall five-year survival probability analysed by Kaplan-Meyer method was 42.5%. The local control rate was 57.7%. 15 patients showed complete remission, 18 patients had a partial remission. Only 11% of the patients showed grade III and IV side effects during neutron irradiation. Neutron irradiation is efficocious in treating highly and intermediately differentiated soft tissue sarcomas. The result of surgical resection seems to be a very important prognostic factor for patients with soft tissue sarcomas.

Normalization: What Does it Really Mean?

Attempts have been made to standardize normalization techniques, but it remains a confusing issue. As of late there are five different possible normalization tools consisting of normalizing: 1.1. to the isocenter,2.2. to a specific point other than the isocenter,3.3. to a minimum target absorbed dose whose area of maximum target absorbed dose is a 2 cm2 area,4.4. to an isodose value,5.5. to the dmax of the beams.The International Commission on Radiation Units and Measurements has updated its report number 29 to further recommend normalization standards to include planning to a specification point that: 1.1. is easy to define in an unambiguous way,2.2. is chosen in a region where the dose is rather homogeneous and representative of the dose distribution throughout the target volume,3.3. defined where the dose can be accurately determined,4.4. normalizes to the isocenter of the plan where the maximum absorbed dose is a 1.5 cm2 area,5.5. limits the dose variation to 10%.With increasing complexity involving three-dimensional planning, mixed-beam therapy, and heterogeneity compensation, a full understanding of dose determination is necessary to accurately implement treatment plans.

Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate

The records of 132 patients participating in clinical trials using fast neutron ( n = 94), mixed neutron and photon ( n = 16), or conventional photon ( n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31 132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients ( p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons ( 6 7 ) or mixed beam therapy ( 1 7 ).

Fast neutron radiotherapy for locally advanced prostate cancer: Update of a past trial and future research directions

Between June, 1977, and April, 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a phase III study comparing fast neutron radiotherapy as part of a mixed beam (neutron /photon) regimen with conventional photon (x-ray) radiotherapy for patients with locally advanced (Stages C and Dl) adenocarcinoma of the prostate. A total of 91 analyzable patients were entered into the study with the two treatment groups balanced in regard to all major prognostic variables. The current analysis is for a median follow-up of 6.7 years (range 3.4–9.0 yrs.). The results are statistically significant in favor of the mixed-beam group for all parameters mentioned. At five years the freedom from local/regional relapse rate is 81 percent on the mixed-beam arm compared with 60 percent on the photon arm. The actuarial overall survival rate at five years is 70 percent on the mixed beam compared with 56 percent on the conventional photon arm. The determinantal survival at five years (which excluded death due to intercurrent disease in patients clinically free o f cancer) was 82 percent on the mixed-beam arm compared with 61 percent on the photon arm. The type of therapy appeared to be the most important predictor of both local tumor control and patient survival in a step-wise Cox analysis. There was no difference in the treatmentrelated morbidity for the two patient groups. Mixed-beam therapy may be superior to standard photon radiotherapy for treatment of locally advanced prostate cancer.

Outcome analysis of patients treated for high grade gliomas: long term evaluation of mixed beam therapy

Outcome analysis of patients treated for high grade gliomas: long term evaluation of mixed beam therapy