Lyn Oliver

Volumetric-modulated Arc Therapy in Head and Neck Radiotherapy: A Planning Comparison using Simultaneous Integrated Boost for Nasopharynx and Oropharynx Carcinoma

AIMS Volumetric-modulated arc therapy (VMAT) allows rapid delivery of radiotherapy. The aim of this planning study was to evaluate VMAT and dynamic intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique PATIENTS AND METHODS Planning computed tomography data from 10 patients with locoregionally advanced oropharynx or nasopharynx carcinoma were selected. The prescription dose was 70, 63 and 56Gy to the high-dose, intermediate-dose and low-dose planning target volume (PTV), respectively, and planning parameters were according to Radiation Therapy Oncology Group IMRT protocols. VMAT and IMRT plans were calculated, and dose-volume histograms were created for plan evaluation and comparison. RESULTS Clinically acceptable plans were achieved for both IMRT and VMAT plans, although IMRT plans typically required three times the number of monitor units. The coverage of 95% of the PTV70 was between 96 and 100% of the prescribed dose for IMRT plans and 100% for all VMAT plans. There was a trend of improved dose conformity for IMRT plans. Both IMRT and VMAT achieved acceptable plans in terms of sparing of the spinal cord and brainstem. Contralateral parotid sparing was improved with VMAT, with a mean dose of 25.08Gy (range 21.35-30.02Gy) for oropharynx and 31.37Gy (range 23.47-35.52Gy) for nasopharynx cases. CONCLUSION Simultaneous integrated boost VMAT achieved comparable plans to dynamic IMRT in complex head and neck cases and used two-thirds less monitor units.

The accuracy of the pencil beam convolution and anisotropic analytical algorithms in predicting the dose effects due to attenuation from immobilization devices and large air gaps.

When a photon beam passes through the treatment couch or an immobilization device, it may traverse a large air gap (up to 15 cm or more) prior to entering the patient. Previous studies have investigated the ability of various treatment planning systems to calculate the dose immediately beyond small air gaps, typically less than 5 cm thick, such as those within the body. The aim of this study is to investigate the ability of the Eclipse anisotropic analytical algorithm (AAA) and pencil beam convolution (PBC) algorithm to calculate the dose beyond large air gaps. Depth dose data in water for a 6 MV photon beam, 10 x 10 cm2 field size, and 100 cm SSD were measured beyond a range of air gaps (1-15 cm). The thickness of the water equivalent material positioned before the air gap ranged from 0.2 to 4 cm. Dose was calculated with the Eclipse PBC algorithm and AAA. The scattered and primary dose components were calculated from the measurements. The measured results indicate that as the air gap increases (from 1 to 15 cm) the dose reduces at the water surface and that beyond an air gap a secondary buildup region is required to re-establish electronic equilibrium. The dose beyond the air gap is also reduced at depths beyond the secondary buildup region. The PBC algorithm did not predict any reduction in dose beyond the air gap. AAA predicted the secondary buildup region but did not predict the reduction in dose at depths beyond it. The reduction in dose beyond the secondary buildup region was shown to be particularly relevant for air gaps of 5 cm or more when there was a 2 cm of water equivalent material positioned before the air gap. For these cases, where electronic equilibrium is established in the material positioned before the air gap, both algorithms were found to overestimate the dose by 2.0%-5.5%. It was concluded that the dose to depths of up to 15 cm beyond a large air gap is reduced due to a decrease in scattered radiation, produced in the material positioned before the air gap, reaching the point of interest. This effect is not well modeled by the Eclipse AAA and PBC algorithm and may result in dose calculation errors greater than 2.5%. Due to the contribution of other uncertainties in the radiation therapy treatment planning and delivery process, dose calculation errors of this magnitude are not consistent with the recommendation of the International Commission on Radiation Units and Measurements that the absorbed dose to the target volume be delivered with an uncertainty of less than +/- 5%.

Experimental investigation of the response of an amorphous silicon EPID to intensity modulated radiotherapy beams

The aim of this work was to experimentally determine the difference in response of an amorphous silicon (a-Si) electronic portal imaging device (EPID) to the open and multileaf collimator (MLC) transmitted beam components of intensity modulated radiation therapy (IMRT) beams. EPID dose response curves were measured for open and MLC transmitted (MLCtr) 10 x 10 cm2 beams at central axis and with off axis distance using a shifting field technique. The EPID signal was obtained by replacing the flood-field correction with a pixel sensitivity variation matrix correction. This signal, which includes energy-dependent response, was then compared to ion-chamber measurements. An EPID calibration method to remove the effect of beam energy variations on EPID response was developed for IMRT beams. This method uses the component of open and MLCtr fluence to an EPID pixel calculated from the MLC delivery file and applies separate radially dependent calibration factors for each component. The calibration procedure does not correct for scatter differences between ion chamber in water measurements and EPID response; these must be accounted for separately with a kernel-based approach or similar method. The EPID response at central axis for the open beam was found to be 1.28 +/- 0.03 of the response for the MLCtr beam, with the ratio increasing to 1.39 at 12.5 cm off axis. The EPID response to MLCtr radiation did not change with off-axis distance. Filtering the beam with copper plates to reduce the beam energy difference between open and MLCtr beams was investigated; however, these were not effective at reducing EPID response differences. The change in EPID response for uniform sliding window IMRT beams with MLCtr dose components from 0.3% to 69% was predicted to within 2.3% using the separate EPID response calibration factors for each dose component. A clinical IMRT image calibrated with this method differed by nearly 30% in high MLCtr regions from an image calibrated with an open beam calibration factor only. Accounting for the difference in EPID response to open and MLCtr radiation should improve IMRT dosimetry with a-Si EPIDs.

An experimental investigation into the radiation field offset of a dynamic multileaf collimator

In this study we investigate the characteristics of a rounded leaf end multileaf collimator (MLC) that is used for delivering intensity-modulated radiotherapy (IMRT) with a Varian linear accelerator. The rounded leaf end MLC design results in an offset between the radiation field edge (the physical leaf position) and the light field (the geometric leaf position). We call this the radiation field offset (RFO). The leaf position is calibrated to the leaf tip at the mid-leaf plane. There is an additional offset between the geometric leaf position and the projected leaf tip position that varies as a function of distance from the collimator central axis due to the MLC geometry. We call this the leaf position offset (LPO). There is a lack of consistency in the interpretation and implementation of the RFO and the LPO in the literature. We investigated the RFO and the LPO on Varians 600 C/D and 21 EX linear accelerators. We used a combination of film and ion chamber measurements of static, segmental MLC (SMLC) and dynamic MLC (DMLC) fields to quantify the leaf offsets across the range of leaf positions. We were able to improve the dosimetry at large off-axis positions with minor adjustments to the vendors LPO file. The RFO was determined to within 0.1 mm accuracy at the collimator central axis. The measured RFO value depends on whether the method is based on the radiation field edge position or on an integral dose measurement. The integral dose method results in an RFO that is approximately 0.2 mm greater than the radiation field edge method. The difference is due to the MLC penumbra shape. We propose a methodology for measuring and implementing MLC leaf offsets that is suitable for both SMLC and DMLC IMRT. In addition, we propose some definitions that more clearly describe the MLC leaf position for accurate IMRT dosimetry.

The impact of MLC transmitted radiation on EPID dosimetry for dynamic MLC beams

The purpose of this study was to experimentally quantify the change in response of an amorphous silicon (a-Si) electronic portal imaging device (EPID) to dynamic multileaf collimator (dMLC) beams with varying MLC-transmitted dose components and incorporate the response into a commercial treatment planning system (TPS) EPID prediction model. A combination of uniform intensity dMLC beams and static beams were designed to quantify the effect of MLC transmission on EPID response at the central axis of 10 x 10 cm2 beams, at off-axis positions using wide dMLC beam profiles, and at different field sizes. The EPID response to MLC transmitted radiation was 0.79 +/- 0.02 of the response to open beam radiation at the central axis of a 10 x 10 cm2 field. The EPID response to MLC transmitted radiation was further reduced relative to the open beam response with off-axis distance. The EPID response was more sensitive to field size changes for MLC transmitted radiation compared to open beam radiation by a factor of up to 1.17 at large field sizes. The results were used to create EPID response correction factors as a function of the fraction of MLC transmitted radiation, off-axis distance, and field size. Software was developed to apply the correction factors to each pixel in the TPS predicted EPID image. The corrected images agreed more closely with the measured EPID images in areas of intensity modulated fields with a large fraction of MLC transmission and, as a result the accuracy of portal dosimetry with a-Si EPIDs can be improved. Further investigation into the detector response function and the radiation source model are required to achieve improvements in accuracy for the general case.

Initial evaluation of a commercial EPID modified to a novel direct‐detection configuration for radiotherapy dosimetry

Electronic portal imaging devices (EPIDs) integrated with medical linear accelerators utilize an indirect-detection EPID configuration (ID-EPID). Amorphous silicon ID-EPIDs provide high quality low dose images for verification of radiotherapy treatments but they have limitations as dosimeters. The standard ID-EPID configuration includes a high atomic number phosphor scintillator screen, a 1 mm copper layer, and other nonwater equivalent materials covering the detector. This configuration leads to marked differences in the response of an ID-EPID compared to standard radiotherapy dosimeters such as ion chambers in water. In this study the phosphor and copper were removed from a standard commercial EPID to modify the configuration to a direct-detection EPID (DD-EPID). Using solid water as the buildup and backscatter for the detector, dosimetric measurements were performed on the DD-EPID and compared to standard dose-in-water data for 6 and 18 MV photons. The sensitivity of the DD-EPID was approximately eight times less than the ID-EPID but the signal was sufficient to produce accurate and reproducible beam profile measurements for open beams and an intensity-modulated beam. Due to the lower signal levels it was found necessary to ensure that the dark field correction (no radiation) DD-EPID signal was stable or updated frequently. The linearity of dose response was comparable to the ID-EPID but with a greater under-response at low doses. DD-EPID measurements of field size output factors and beam profiles at the depth of maximum dose (dmax), and tissue-maximum ratios between the depths of 0.5 and 10 cm, were in close agreement with dose in water measurements. At depths beyond dmax the DD-EPID showed a greater change in response to field size than ionisation chamber measurements and the beam penumbrae were broader compared to diode scans. The modified DD-EPID configuration studied here has the potential to improve the performance of EPIDs for dose verification of radiotherapy treatments.

Paclitaxel sensitizes multidrug resistant cells to radiation.

The unique action of paclitaxel, to stabilize mlcrotubules and block cells at the radiosensitive G2M phase of the cell cycle, suggests it may sensitize tumors to radiotherapy. We have Investigated the potential of this Interaction to overcome multidrug resistance In vitro using the HL60 cell line and Its P-glycoprotein expressing, multidrug resistant H/E8 subllne. HL60 cells showed a modest 1.4-fold (p<0.01) Increase in sensitivity to 2 Qy radiation given 24 h after a 1 h treatment with paclitaxel. The H/E8 subllne, which has Increased radiation resistance and expresses an extended multidrug resistance phenotype, showed significant sensltizatlon to radiation (up to 2.3- fold sensitlzation; p<0.01) even with doses of paclitaxel which had no effect on cell viability or were associated with any Ga/M block In the cell cycle. In the presence of verapamll, an Inhibitor of P-glycoproteln mediated efflux, drug resistant cells could be sensitized to 2 Gy radiation by similar paclitaxel doses as the parental cell (>or =≥ 30 nM; p<0.01). These results Indicate a therapeutic advantage may be possible In the treatment of resistant tumors by the combined use of paclitaxel with radiation.

Predicting the clonogenic survival of A549 cells after modulated x-ray irradiation using the linear quadratic model

In this study we present two prediction methods, mean dose and summed dose, for predicting the number of A549 cells that will survive after modulated x-ray irradiation. The prediction methods incorporate the dose profile from the modulated x-ray fluence map applied across the cell sample and the linear quadratic (LQ) model. We investigated the clonogenic survival of A549 cells when irradiated using two different modulated x-ray fluence maps. Differences between the measured and predicted surviving fraction were observed for modulated x-ray irradiation. When the x-ray fluence map produced a steep dose gradient across the sample, fewer cells survived in the unirradiated region than expected. When the x-ray fluence map produced a less steep dose gradient across the sample, more cells survived in the unirradiated region than expected. Regardless of the steepness of the dose gradient, more cells survived in the irradiated region than expected for the reference dose range of 1-10 Gy. The change in the cell survival for the unirradiated regions of the two different dose gradients may be an important factor to consider when predicting the number of cells that will survive at the edge of modulated x-ray fields. This investigation provides an improved method of predicting cell survival for modulated x-ray radiation treatment. It highlights the limitations of the LQ model, particularly in its ability to describe the biological response of cells irradiated under these conditions.

Requirements for radiation oncology physics in Australia and New Zealand.

This Position Paper reviews the role, standards of practice, education, training and staffing requirements for radiation oncology physics. The role and standard of practice for an expert in radiation oncology physics, as defined by the ACPSEM, are consistent with the IAEA recommendations. International standards of safe practice recommend that this physics expert be authorised by a Regulatory Authority (in consultation with the professional organisation). In order to accommodate the international and AHTAC recommendations or any requirements that may be set by a Regulatory Authority, the ACPSEM has defined the criteria for a physicist-in-training, a base level physicist, an advanced level physicist and an expert radiation oncology physicist. The ACPSEM shall compile separate registers for these different radiation oncology physicist categories. What constitutes a satisfactory means of establishing the number of physicists and support physics staff that is required in radiation oncology continues to be debated. The new ACPSEM workforce formula (Formula 2000) yields similar numbers to other international professional body recommendations. The ACPSEM recommends that Australian and New Zealand radiation oncology centres should aim to employ 223 and 46 radiation oncology physics staff respectively. At least 75% of this workforce should be physicists (168 in Australia and 35 in New Zealand). An additional 41 registrar physicist positions (34 in Australia and 7 in New Zealand) should be specifically created for training purposes. These registrar positions cater for the present physicist shortfall, the future expansion of radiation oncology and the expected attrition of radiation oncology physicists in the workforce. Registrar physicists shall undertake suitable tertiary education in medical physics with an organised in-house training program. The rapid advances in the theory and methodology of the new technologies for radiation oncology also require a stringent approach to maintaining a satisfactory standard of practice in radiation oncology physics. Appropriate on-going education of radiation oncology physicists as well as the educating of registrar physicists is essential. Institutional management and the ACPSEM must both play a key role in providing a means for satisfactory staff tuition on the safe and expert use of existing and new radiotherapy equipment.

A preliminary investigation of cell growth after irradiation using a modulated x-ray intensity pattern.

In this study we have investigated a spatial distribution of cell growth after their irradiation using a modulated x-ray intensity pattern. An A549 human non-small cell lung cancer cell line was grown in a 6-well culture. Two of the wells were the unirradiated control wells, whilst another two wells were irradiated with a modulated x-ray intensity pattern and the third two wells were uniformly irradiated. A number of plates were incubated for various times after irradiation and stained with crystal violet. The spatial distribution of the stained cells within each well was determined by measurement of the crystal violet optical density at multiple positions in the plate using a microplate photospectrometer. The crystal violet optical density for a range of cell densities was measured for the unirradiated well and this correlated with cell viability as determined by the MTT cell viability assay. An exponential dose response curve was measured for A549 cells from the average crystal violet optical density in the uniformly irradiated well up to a dose of 30 Gy. By measuring the crystal violet optical density distribution within a well the spatial distribution of cell growth after irradiation with a modulated x-ray intensity pattern can be plotted. This method can be used for in vitro investigation into the changes in radiation response associated with treatment using intensity modulated radiation therapy (IMRT).