W. Beckham

A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis

PURPOSE Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution. PATIENTS AND METHODS A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy. RESULTS A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003). CONCLUSION Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.

Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy

PURPOSE To report interim cosmetic and toxicity results of a multicenter randomized trial comparing accelerated partial-breast irradiation (APBI) using three-dimensional conformal external beam radiation therapy (3D-CRT) with whole-breast irradiation (WBI). PATIENTS AND METHODS Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were randomly assigned after breast-conserving surgery to 3D-CRT APBI (38.5 Gy in 10 fractions twice daily) or WBI (42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score. After a planned interim cosmetic analysis, the data, safety, and monitoring committee recommended release of results. There have been too few IBTR events to trigger an efficacy analysis. RESULTS Between 2006 and 2011, 2,135 women were randomly assigned to 3D-CRT APBI or WBI. Median follow-up was 36 months. Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses (29% v 17%; P < .001), by patients (26% v 18%; P = .0022), and by physicians reviewing digital photographs (35% v 17%; P < .001). Grade 3 toxicities were rare in both treatment arms (1.4% v 0%), but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI (P < .001). CONCLUSION 3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with standard WBI. Clinicians and patients are cautioned against the use of 3D-CRT APBI outside the context of a controlled trial.

VOLUMETRIC MODULATED ARC THERAPY IMPROVES DOSIMETRY AND REDUCES TREATMENT TIME COMPARED TO CONVENTIONAL INTENSITY-MODULATED RADIOTHERAPY FOR LOCOREGIONAL RADIOTHERAPY OF LEFT-SIDED BREAST CANCER AND INTERNAL MAMMARY NODES

PURPOSE Volumetric modulated arc therapy (VMAT) is a novel extension of conventional intensity-modulated radiotherapy (cIMRT), in which an optimized three-dimensional dose distribution may be delivered in a single gantry rotation. VMAT is the predecessor to RapidArc (Varian Medical System). This study compared VMAT with cIMRT and with conventional modified wide-tangent (MWT) techniques for locoregional radiotherapy for left-sided breast cancer, including internal mammary nodes. METHODS AND MATERIALS Therapy for 5 patients previously treated with 50 Gy/25 fractions using nine-field cIMRT was replanned with VMAT and MWT. Comparative endpoints were planning target volume (PTV) dose homogeneity, doses to surrounding structures, number of monitor units, and treatment delivery time. RESULTS For VMAT, two 190 degrees arcs with 2-cm overlapping jaws were required to optimize over the large treatment volumes. Treatment plans generated using VMAT optimization resulted in PTV homogeneity similar to that of cIMRT and MWT. The average heart volumes receiving >30 Gy for VMAT, cIMRT, and MWT were 2.6% +/- 0.7%, 3.5% +/- 0.8%, and 16.4% +/- 4.3%, respectively, and the average ipsilateral lung volumes receiving >20 Gy were 16.9% +/- 1.1%, 17.3% +/- 0.9%, and 37.3% +/- 7.2%, respectively. The average mean dose to the contralateral medial breast was 3.2 +/- 0.6 Gy for VMAT, 4.3 +/- 0.4 Gy for cIMRT, and 4.4 +/- 4.7 Gy for MWT. The healthy tissue volume percentages receiving 5 Gy were significantly larger with VMAT (33.1% +/- 2.1%) and IMRT (45.3% +/- 3.1%) than with MWT (19.4% +/- 3.7%). VMAT reduced the number of monitor units by 30% and the treatment time by 55% compared with cIMRT. CONCLUSIONS VMAT achieved similar PTV coverage and sparing of organs at risk, with fewer monitor units and shorter delivery time than cIMRT.

Dosimetric validation of Acuros® XB with Monte Carlo methods for photon dose calculations

PURPOSE The dosimetric accuracy of the recently released Acuros XB advanced dose calculation algorithm (Varian Medical Systems, Palo Alto, CA) is investigated for single radiation fields incident on homogeneous and heterogeneous geometries, and a comparison is made to the analytical anisotropic algorithm (AAA). METHODS Ion chamber measurements for the 6 and 18 MV beams within a range of field sizes (from 4.0 x 4.0 to 30.0 x 30.0 cm2) are used to validate Acuros XB dose calculations within a unit density phantom. The dosimetric accuracy of Acuros XB in the presence of lung, low-density lung, air, and bone is determined using BEAMnrc/DOSXYZnrc calculations as a benchmark. Calculations using the AAA are included for reference to a current superposition/convolution standard. RESULTS Basic open field tests in a homogeneous phantom reveal an Acuros XB agreement with measurement to within +/- 1.9% in the inner field region for all field sizes and energies. Calculations on a heterogeneous interface phantom were found to agree with Monte Carlo calculations to within +/- 2.0% (sigmaMC = 0.8%) in lung (p = 0.24 g cm(-3)) and within +/- 2.9% (sigmaMC = 0.8%) in low-density lung (p = 0.1 g cm(-3)). In comparison, differences of up to 10.2% and 17.5% in lung and low-density lung were observed in the equivalent AAA calculations. Acuros XB dose calculations performed on a phantom containing an air cavity (p = 0.001 g cm(-3)) were found to be within the range of +/- 1.5% to +/- 4.5% of the BEAMnrc/DOSXYZnrc calculated benchmark (sigmaMC = 0.8%) in the tissue above and below the air cavity. A comparison of Acuros XB dose calculations performed on a lung CT dataset with a BEAMnrc/DOSXYZnrc benchmark shows agreement within +/- 2%/2mm and indicates that the remaining differences are primarily a result of differences in physical material assignments within a CT dataset. CONCLUSIONS By considering the fundamental particle interactions in matter based on theoretical interaction cross sections, the Acuros XB algorithm is capable of modeling radiotherapy dose deposition with accuracy only previously achievable with Monte Carlo techniques.

A fluence-convolution method to calculate radiation therapy dose distributions that incorporate random set-up error

The International Commission on Radiation Units and Measurements Report 62 (ICRU 1999) introduced the concept of expanding the clinical target volume (CTV) to form the planning target volume by a two-step process. The first step is adding a clinically definable internal margin, which produces an internal target volume that accounts for the size, shape and position of the CTV in relation to anatomical reference points. The second is the use of a set-up margin (SM) that incorporates the uncertainties of patient beam positioning, i.e. systematic and random set-up errors. We propose to replace the random set-up error component of the SM by explicitly incorporating the random set-up error into the dose-calculation model by convolving the incident photon beam fluence with a Gaussian set-up error kernel. This fluence-convolution method was implemented into a Monte Carlo (MC) based treatment-planning system. Also implemented for comparison purposes was a dose-matrix-convolution algorithm similar to that described by Leong (1987 Phys. Med. Biol. 32 327-34). Fluence and dose-matrix-convolution agree in homogeneous media. However, for the heterogeneous phantom calculations, discrepancies of up to 5% in the dose profiles were observed with a 0.4 cm set-up error value. Fluence-convolution mimics reality more closely, as dose perturbations at interfaces are correctly predicted (Wang et al 1999 Med. Phys. 26 2626-34, Sauer 1995 Med. Phys. 22 1685-90). Fluence-convolution effectively decouples the treatment beams from the patient. and more closely resembles the reality of particle fluence distributions for many individual beam-patient set-ups. However, dose-matrix-convolution reduces the random statistical noise in MC calculations. Fluence-convolution can easily be applied to convolution/superposition based dose-calculation algorithms.

Absolute dose calculations for Monte Carlo simulations of radiotherapy beams.

Monte Carlo (MC) simulations have traditionally been used for single field relative comparisons with experimental data or commercial treatment planning systems (TPS). However, clinical treatment plans commonly involve more than one field. Since the contribution of each field must be accurately quantified, multiple field MC simulations are only possible by employing absolute dosimetry. Therefore, we have developed a rigorous calibration method that allows the incorporation of monitor units (MU) in MC simulations. This absolute dosimetry formalism can be easily implemented by any BEAMnrc/DOSXYZnrc user, and applies to any configuration of open and blocked fields, including intensity-modulated radiation therapy (IMRT) plans. Our approach involves the relationship between the dose scored in the monitor ionization chamber of a radiotherapy linear accelerator (linac), the number of initial particles incident on the target, and the field size. We found that for a 10 x 10 cm2 field of a 6 MV photon beam, 1 MU corresponds, in our model, to 8.129 x 10(13) +/- 1.0% electrons incident on the target and a total dose of 20.87 cGy +/- 1.0% in the monitor chambers of the virtual linac. We present an extensive experimental verification of our MC results for open and intensity-modulated fields, including a dynamic 7-field IMRT plan simulated on the CT data sets of a cylindrical phantom and of a Rando anthropomorphic phantom, which were validated by measurements using ionization chambers and thermoluminescent dosimeters (TLD). Our simulation results are in excellent agreement with experiment, with percentage differences of less than 2%, in general, demonstrating the accuracy of our Monte Carlo absolute dose calculations.

Comparing planning time, delivery time and plan quality for IMRT, RapidArc and tomotherapy

The purpose of this study is to examine plan quality, treatment planning time, and estimated treatment delivery time for 5‐ and 9‐field sliding window IMRT, single and dual arc RapidArc, and tomotherapy. For four phantoms, 5‐ and 9‐field IMRT, single and dual arc RapidArc and tomotherapy plans were created. Plans were evaluated based on the ability to meet dose‐volume constraints, dose homogeneity index, radiation conformity index, planning time, estimated delivery time, integral dose, and volume receiving more than 2 and 5 Gy. For all of the phantoms, tomotherapy was able to meet the most optimization criteria during planning (50% for P1, 67% for P2, 0% for P3, and 50% for P4). RapidArc met less of the optimization criteria (25% for P1, 17% for P2, 0% for P3, and 0% for P4), while IMRT was never able to meet any of the constraints. In addition, tomotherapy plans were able to produce the most homogeneous dose. Tomotherapy plans had longer planning time, longer estimated treatment times, lower conformity index, and higher integral dose. Tomotherapy plans can produce plans of higher quality and have the capability to conform dose distributions better than IMRT or RapidArc in the axial plane, but exhibit increased dose superior and inferior to the target volume. RapidArc, however, is capable of producing better plans than IMRT for the test cases examined in this study. PACS number: 87.55.x, 87.55.D, 87.55.de, 87.55.dk

Evaluation of the validity of a convolution method for incorporating tumour movement and set-up variations into the radiotherapy treatment planning system

Modern radiotherapy techniques have developed to a point where the ability to conform to a particular tumour shape is limited by organ motion and set-up variations. The result is that dose distributions displayed by treatment planning systems based on static beam modelling are not representative of the dose received by the patient during a fractionated course of radiotherapy. The convolution-based method to account for these variations in radiation treatment planning systems has been suggested in previous work. The validity of the convolution method is tested by comparing the dose distribution obtained from this convolution method with the dose distribution obtained by summing the contribution to the total dose from each fraction of a fractionated treatment (for increasing numbers of fractions) and simulating random target position variations between fractions. For larger numbers of fractions (approximately or > 15) which are the norm for radical treatment schemes, it is clear that incorporation of movement by a convolution method could potentially produce a more accurate dose distribution. There are some limitations that have been identified, however, especially in relation to the heterogeneous nature of patient tissues, which require further investigation before the technique could be applied clinically.

Clinical significance of multi-leaf collimator positional errors for volumetric modulated arc therapy.

BACKGROUND AND PURPOSE Multi-leaf collimator (MLC) positional errors occur during intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) deliveries. The impact of such errors has been evaluated for IMRT but not VMAT. The purpose of this work is to understand how random and systematic VMAT MLC positional errors affect the patient dose distribution. MATERIALS AND METHODS Eight head and neck single arc (360°) VMAT treatment plans were created. Random and two types of systematic MLC errors were simulated for error magnitudes of 0.25, 0.5, 1, 2 and 5mm. The two types of systematic MLC errors were: (1) MLC banks are shifted in the same direction (left or right) and (2) MLC banks are shifted in opposing directions resulting in smaller or larger field shapes. The MLC errors were simulated, for all control points, on both banks of active MLC leaves only. RESULTS There is a linear correlation of MLC errors with gEUD for all error types. The gEUD dose sensitivities with MLC error for the PTV70 were -0.2, -0.9, -2.8 and 1.9 Gy/mm for random, systematic shift, systematic close and systematic open MLC errors, respectively. The sensitivity of VMAT plans to MLC positional errors was similar to those of IMRT plans with less than 50 segments but much less than those created for a step and shoot with more than 50 segments or sliding-window delivery technique. To maintain the PTV70 to within 2% would require that MLC open/close errors be within 0.6mm. CONCLUSIONS Radiation therapy centers should have adequate quality assurance programs in place to assess open/close MLC errors (i.e. leaf gap errors) as they tend to be more impactful than random or systematic MLC shift errors.

A Monte Carlo evaluation of RapidArc dose calculations for oropharynx radiotherapy.

RapidArc, recently released by Varian Medical Systems, is a novel extension of IMRT in which an optimized 3D dose distribution may be delivered in a single gantry rotation of 360 degrees or less. The purpose of this study was to investigate the accuracy of the analytical anisotropic algorithm (AAA), the sole algorithm for photon dose calculations of RapidArc treatment plans. The clinical site chosen was oropharynx and the associated nodes involved. The VIMC-Arc system, which utilizes BEAMnrc and DOSXYZnrc for particle transport through the linac head and patient CT phantom, was used as a benchmarking tool. As part of this study, the dose for a single static aperture, typical for RapidArc delivery, was calculated by the AAA, MC and compared with the film. This film measurement confirmed MC modeling of the beam aperture in water. It also demonstrated that the AAA dosimetric error can be as high as 12% near isolated leaf edges and up to 5% at the leaf end. The composite effect of these errors in a full RapidArc calculation in water involving a C-shaped target and the associated organ at risk produced a 1.5% overprediction of the mean target dose. In our cohort of six patients, the AAA was found, on average, to overestimate the PTV60 coverage at the 95% level in the presence of air cavities by 1.0% (SD = 1.1%). Removing the air cavities from the target volumes reduced these differences by about a factor of 2. The dose to critical structures was also overestimated by the AAA. The mean dose to the spinal cord was higher by 1.8% (SD = 0.8%), while the effective maximum dose (D2%) was only 0.2% higher (SD = 0.6%). The mean dose to the parotid glands was overestimated by approximately 9%. This study has shown that the accuracy of the AAA for RapidArc dose calculations, performed at a resolution of 2.5 mm or better, is adequate for clinical use.