Association Between Thyroid Radiation Dose and Hypothyroidism in Breast Cancer Patients Undergoing Volumetric Modulated Arc Therapy for Regional Nodal Irradiation.

BACKGROUND/AIM: To investigate the association between the thyroid dysfunction and thyroid radiation dose in regional nodal irradiation (RNI) using volumetric modulated arc therapy (VMAT) for breast cancer. PATIENTS AND METHODS: We reviewed medical data of 67 patients with breast cancer who underwent curative surgery followed by adjuvant radiotherapy, including RNI using VMAT, between 2018 and 2021. All patients had normal thyroid functional test results, including thyroid stimulating hormone (TSH), T3, and free-T4. We defined subclinical hypothyroidism as increased TSH with or without decreased levels of free-T4 and T3 after the completion of VMAT. We calculated dose-volume histogram parameters (DVHPs), including the mean dose and relative thyroid volume receiving at least 10, 20, 30, and 40 Gy. RESULTS: The median follow-up time was 23.2 months. The 3-year locoregional failure-free survival, progression-free survival, and overall survival rates were 96.3%, 94.7%, and 96.2%, respectively. The mean thyroid dose was 21.4 Gy (range=11.5-29.4 Gy). Subclinical hypothyroidism was noted in 14 patients (20.9%) and the median time to the event was 4.1 months. Among the DVHPs, the relative volume receiving ≥20 Gy (V20Gy) was associated with subclinical hypothyroidism. The 2-year rates of subclinical hypothyroidism were 24.8% and 59.1% in patients with V20Gy ≤46.3% and >46.3%, respectively. CONCLUSION: A significant proportion of patients with breast cancer developed subclinical hypothyroidism after undergoing VMAT for RNI. Our findings highlight the importance of considering the thyroid as an organ at risk for VMAT planning, and suggest that V20Gy could be a useful dose-volume constraint.

Mask dependency of the lacrimal gland dose under whole brain radiotherapy when the six-degrees of freedom couch is not available.

BACKGROUND: Dry eye syndrome has been recently reported in patients who underwent whole brain radiotherapy (WBRT). WBRT based on a couch with three-degrees of freedom (3D) can occasionally be performed in which the rotational head motion is not corrected. This study assessed the dependency of the rotational errors on the mask and the dose variation of the lens and lacrimal gland in WBRT patients. METHODS: Translational and rotational setup errors were obtained at the first treatment with cone-beam CT (CBCT) for patients under WBRT and frameless stereotactic radiosurgery (SRS) (n = 20 each) immobilized using a conventional WB mask and an SRS mask with a bite block, respectively. For the CT sets of SRS cases, WBRT plans were generated for the study. To simulate the rotational error, rotated CT images were created with each rotational error, on which initial WBRT plans were copied and doses were recalculated. The lens and lacrimal gland doses with and without rotation errors were compared. RESULTS: Despite similar translational setup errors for the two masks, the SRS mask showed a dramatic reduction in rotational errors compared to those of the WB mask. The errors varied within -2.9° to 2.9° and -1.2° to 0.7° for the WB and SRS masks, respectively. Accordingly, the SRS mask confined the change in the maximum lens dose, mean dose of the lacrimal gland, and lacrimal volume receiving 15 Gy to one-third of those using the WB mask. CONCLUSION: When the six-degrees of freedom (6D) couch is not available, the frameless SRS mask is beneficial to WBRT for the faithful treatment as it was planned.

Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer.

We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.

Effects of Radiation Dose on Liver After Free-breathing Volumetric Modulated Arc Therapy for Breast Cancer.

BACKGROUND/AIM: To evaluate the early effect of radiation dose on liver function in breast cancer patients undergoing free-breathing volumetric modulated arc therapy (FB-VMAT). PATIENTS AND METHODS: Medical records of 125 patients with breast cancer who underwent curative surgery followed by postoperative radiotherapy using FB-VMAT during 2018-2021 were reviewed. Results of the liver function test (LFT), performed within 1-week before and 6-months after radiotherapy, were collected and compared. The LFTs analyzed albumin, total and direct bilirubin, aspartate transaminase, alanine transferase, and alkaline phosphatase levels. The mean dose and relative liver volume receiving at least 10 Gy, 20 Gy, or 30 Gy were calculated. RESULTS: Median follow-up time was 21.4 months. One patient experienced locoregional and distant failures. The mean liver irradiation dose was 325.9 centigray (cGy) for all patients. The liver irradiation dose was higher in patients with right breast cancer than in those with left breast cancer (mean, 434.1 cGy vs. 260.6 cGy, p<0.001). Direct bilirubin and aspartate transaminase levels showed significant differences after FB-VMAT. LFT results outside normal limits were noted in 31 patients at follow-up, but nobody met the criteria of radiation-induced liver disease. Underlying liver disease, breast laterality, systemic treatment, or dose-volume histogram parameters were not associated with abnormal LFT results. CONCLUSION: FB-VMAT can deliver radiation doses safely without adversely affecting the liver. The mean dose ≤4 Gy could be a useful dose criterium of the liver for FB-VMAT plans.

Combined effect of dose gradient and rotational error on prescribed dose coverage for single isocenter multiple brain metastases in frameless stereotactic radiotherapy.

BACKGROUND: To evaluate the combined effect of rotational error and dose gradient on target dose coverage in frameless stereotactic radiotherapy. METHODS: Three spherical targets of different diameters (1, 1.5, and 2 cm) were drawn and placed equidistantly on the same axial brain computed tomography (CT) images. To test the different isocenter-target distances, 2.5- and 5-cm configurations were prepared. Volumetric modulated arc therapy plans were created for different dose gradients from the target, in which the dose gradients were modified using the maximum dose inside the target. To simulate the rotational error, CT images and targets were rotated in two ways by 0.5°, 1°, and 2°, in which one rotation was in the axial plane and the other was in three dimensions. The initial optimized plan parameters were copied to the rotated CT sets, and the doses were recalculated. The coverage degradation after rotation was analyzed according to the target dislocation and 12-Gy volume. RESULTS: A shallower dose gradient reduced the loss of target coverage under target dislocation, and the effect was clearer for small targets. For example, the coverage of the 1-cm target under 1-mm dislocation increased from 93 to 95% by increasing the Paddick gradient index from 5.0 to 7.9. At the same time, the widely accepted necrosis indicator, the 12-Gy volume, increased from 1.2 to 3.5 cm3, which remained in the tolerable range. From the differential dose volume histogram (DVH) analysis, the shallower dose gradient ensured that the dose-deficient under-covered target volume received a higher dose similar to that in the prescription. CONCLUSIONS: For frameless stereotactic brain radiotherapy, the gradient, alongside the margin addition, can be adjusted as an ancillary parameter for small targets to increase target coverage or at least limit coverage reduction in conditions with probable positioning error.

Interobserver variability in clinical target volume delineation in anal squamous cell carcinoma.

We evaluated the inter-physician variability in the target contouring of the radiotherapy for anal squamous cell carcinoma (ASCC). Clinical target volume (CTV) of three patients diagnosed with ASCC was delineated by seven experienced radiation oncologists from multi-institution. These patients were staged as pT1N1a, cT2N0, and cT4N1a, respectively, according to 8th edition of the American Joint Committee on Cancer staging system. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). The maximum distance from the boundaries of the STAPLE generated volume with confidence level of 80% to those of the contour of each CTV in 6 directions was compared. CTV of pelvis which includes primary tumor, perirectal tissue and internal/external iliac lymph node (LN) area (CTV-pelvis) and CTV of inguinal area (CTV-inguinal) were obtained from the seven radiation oncologists. One radiation oncologist did not contain inguinal LN area in the treatment target volume of patient 2 (cT2N0 stage). CTV-inguinal displayed moderate agreement for each patient (overall kappa 0.58, 0.54 and 0.6, respectively), whereas CTV-pelvis showed substantial agreement (overall kappa 0.66, 0.68 and 0.64, respectively). Largest variation among each contour was shown in the inferior margin of the CTV-inguinal. For CTV-pelvis, anterior and superior margin showed the biggest variation. Overall, moderate to substantial agreement was shown for CTV delineation. However, large variations in the anterior and cranial boarder of the CTV-pelvis and the caudal margin of the CTV-inguinal suggest that further studies are needed to establish a clearer target volume delineation guideline.

On-beam computed tomography reconstruction for radiotherapy verification from projection image differences caused by motion during treatment.

The purpose of this study is to propose a reconstruction method of a target and its neighborhood, representative of the moment of radiotherapy delivery, based on differences in its transit images between the time of planning computed tomography (pCT) and the time of treatment beam delivery. To validate the method, a lung phantom with a target object was constructed, and CT-scanned before and after making a shift of the target. The latter scan was intended to simulate a potential organ movement at the time of treatment, and to serve as ground-truth images. Treatment planning using arc-beam delivery was done on the first pCT images. The planned beams were irradiated to the phantom after the shift, while cine transit images were acquired. Cine transit images were also calculated through the pCT images before the shift. From the ratio of the measured and calculated transit images, the amount of image changes due to the organ movement between the time of pCT and that of treatment was three-dimensionally reconstructed. By adding the reconstructed images to the pCT images before the shift, the CT images of the phantom at the time of the beam delivery were generated and compared with the ground truth images. The phantom after the shift was also scanned by on-board cone-beam computer tomography (CBCT) and reconstructed from the measured transit images (MVCT) for comparison. The proposed method reconstructed images that are very close to the ground-truth images in the volume and HU values of the target and the dose-volume coverage of the target and lung. Similar agreement was not found in the CBCT and MVCT images. The method may be used for 4D target image reconstruction, and, combined with the reconstructed image of un-irradiated areas, may offer clinically useful images of the entire region of interest.

Enhancement of megavoltage electronic portal images for markerless tumor tracking.

PURPOSE: The poor quality of megavoltage (MV) images from electronic portal imaging device (EPID) hinders visual verification of tumor targeting accuracy particularly during markerless tumor tracking. The aim of this study was to investigate the effect of a few representative image processing treatments on visual verification and detection capability of tumors under auto tracking. METHODS: Images of QC-3 quality phantom, a single patient's setup image, and cine images of two-lung cancer patients were acquired. Three image processing methods were individually employed to the same original images. For each deblurring, contrast enhancement, and denoising, a total variation deconvolution, contrast-limited adaptive histogram equalization (CLAHE), and median filter were adopted, respectively. To study the effect of image enhancement on tumor auto-detection, a tumor tracking algorithm was adopted in which the tumor position was determined as the minimum point of the mean of the sum of squared pixel differences (MSSD) between two images. The detectability and accuracy were compared. RESULTS: Deblurring of a quality phantom image yielded sharper edges, while the contrast-enhanced image was more readable with improved structural differentiation. Meanwhile, the denoising operation resulted in noise reduction, however, at the cost of sharpness. Based on comparison of pixel value profiles, contrast enhancement outperformed others in image perception. During the tracking experiment, only contrast enhancement resulted in tumor detection in all images using our tracking algorithm. Deblurring failed to determine the target position in two frames out of a total of 75 images. For original and denoised set, target location was not determined for the same five images. Meanwhile, deblurred image showed increased detection accuracy compared with the original set. The denoised image resulted in decreased accuracy. In the case of contrast-improved set, the tracking accuracy was nearly maintained as that of the original image. CONCLUSIONS: Considering the effect of each processing on tumor tracking and the visual perception in a limited time, contrast enhancement would be the first consideration to visually verify the tracking accuracy of tumors on MV EPID without sacrificing tumor detectability and detection accuracy.

The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer.

PURPOSE: It has been reported that the abnormal activation of receptor tyrosine kinases is associated with the development of many human carcinomas and the high activation of EGFR and Met mediates the tumorigenicity of laryngeal carcinoma. In this study, we have done the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) in laryngeal carcinoma in vitro and in vivo was thoroughly evaluated. METHODS: The effects of ME22S on cell viability was assessed through MTT assays, and then Western blotting and immunocytochemistry were used to determine the expression of EGFR and Met. Also, wound healing and invasion assays were performed to observe the inhibitory effects of ME22S. RESULTS: We found the ability of ME22S reducing the expression of both EGFR and Met and significantly inhibiting the cell migration, invasion, and proliferation of SNU899 and HN3 in vitro. Also, the notably reduced levels of p-Met, p-ERK, and p-AKT were found when the cells were treated with only ME22S alone or with HGF together. Meanwhile, ME22S, interestingly enough, caused caspase-3-dependent apoptotic cell death when HN3 cells were treated with ME22S for 72 h, decreased the HGF-induced Slug expression, and also inhibited the tumor growth of HN3 cells in a xenograft model in vivo. CONCLUSIONS: Taken together, our findings suggest that the dual inhibition of EGFR and Met through ME22S largely suppresses the invasion and growth of laryngeal carcinoma both in vitro and in vivo, hence, can be a practical approach as a novel therapeutic strategy for the treatment of laryngeal carcinoma.

Electron dose distributions caused by the contact-type metallic eye shield: Studies using Monte Carlo and pencil beam algorithms.

A metallic contact eye shield has sometimes been used for eyelid treatment, but dose distribution has never been reported for a patient case. This study aimed to show the shield-incorporated CT-based dose distribution using the Pinnacle system and Monte Carlo (MC) calculation for 3 patient cases. For the artifact-free CT scan, an acrylic shield machined as the same size as that of the tungsten shield was used. For the MC calculation, BEAMnrc and DOSXYZnrc were used for the 6-MeV electron beam of the Varian 21EX, in which information for the tungsten, stainless steel, and aluminum material for the eye shield was used. The same plan was generated on the Pinnacle system and both were compared. The use of the acrylic shield produced clear CT images, enabling delineation of the regions of interest, and yielded CT-based dose calculation for the metallic shield. Both the MC and the Pinnacle systems showed a similar dose distribution downstream of the eye shield, reflecting the blocking effect of the metallic eye shield. The major difference between the MC and the Pinnacle results was the target eyelid dose upstream of the shield such that the Pinnacle system underestimated the dose by 19 to 28% and 11 to 18% for the maximum and the mean doses, respectively. The pattern of dose difference between the MC and the Pinnacle systems was similar to that in the previous phantom study. In conclusion, the metallic eye shield was successfully incorporated into the CT-based planning, and the accurate dose calculation requires MC simulation.

USP8 modulates ubiquitination of LRIG1 for Met degradation.

The Met receptor tyrosine kinase is an attractive target for cancer therapy as it promotes invasive tumor growth. SAIT301 is a novel anti-Met antibody, which induces LRIG1-mediated Met degradation and inhibits tumor growth. However, detailed downstream mechanism by which LRIG1 mediates target protein down-regulation is unknown. In the present study, we discovered that SAIT301 induces ubiquitination of LRIG1, which in turn promotes recruitment of Met and LRIG1 complex to the lysosome through its interaction with Hrs, resulting in concomitant degradation of both LRIG1 and Met. We also identified USP8 as a LRIG1-specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time. SAIT301 triggers degradation of LRIG1 by inhibiting the interaction of LRIG1 and USP8, which regulates ubiquitin modification and stability of LRIG1. In summary, SAIT301 employs ubiquitination of LRIG1 for its highly effective Met degradation. This unique feature of SAIT301 enables it to function as a fully antagonistic antibody without Met activation. We found that USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of Met degradation. The relation of Met, LRIG1 and USP8 strongly supports the potential clinical benefit of a combination treatment of a USP8 inhibitor and a Met inhibitor, such as SAIT301.

Analysis of predictive factors for lung injury after forward-planned intensity-modulated radiotherapy in whole breast irradiation.

PURPOSE: This study was performed to assess frequency, timings of occurrence, and predictors of radiologic lung damage (RLD) after forward-planned intensity-modulated radiotherapy (FIMRT) for whole breast irradiation. METHODS: We retrospectively reviewed medical records of 157 breast cancer patients and each of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months after completion of breast radiotherapy (RT). FIMRT was administered to whole breast only (n=152), or whole breast and supraclavicular regions (n=5). Dosimetric parameters, such as mean lung dose and lung volume receiving more than 10 to 50 Gy (V10-V50), and clinical parameters were analyzed in relation to radiologic lung damage. RESULTS: In total, 104 patients (66.2%) developed RLD after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4 months, and 15.3% at 10 months after completion of RT. More patients of 47 or younger were found to have RLD at 10 months after RT than patients older than the age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47 and V40 >7.2% were significant predictors for higher risk of RLD. CONCLUSION: RLD were not infrequently detected in follow-up CT after whole breast FIMRT. More detected cases of RLD among younger patients are believed to have developed at later points after RT than those of older patients. Age and V40 were significant predictors for RLD after whole breast intensity-modulated radiotherapy.

Application of a dummy eye shield for electron treatment planning.

Metallic eye shields have been widely used for near-eye treatments to protect critical regions, but have never been incorporated into treatment plans because of the unwanted appearance of the metal artifacts on CT images. The purpose of this work was to test the use of an acrylic dummy eye shield as a substitute for a metallic eye shield during CT scans. An acrylic dummy shield of the same size as the tungsten eye shield was machined and CT scanned. The BEAMnrc and the DOSXYZnrc were used for the Monte Carlo (MC) simulation, with the appropriate material information and density for the aluminum cover, steel knob and tungsten body of the eye shield. The Pinnacle adopting the Hogstrom electron pencil-beam algorithm was used for the one-port 6-MeV beam plan after delineation and density override of the metallic parts. The results were confirmed with the metal oxide semiconductor field effect transistor (MOSFET) detectors and the Gafchromic EBT2 film measurements. For both the maximum eyelid dose over the shield and the maximum dose under the shield, the MC results agreed with the EBT2 measurements within 1.7%. For the Pinnacle plan, the maximum dose under the shield agreed with the MC within 0.3%; however, the eyelid dose differed by -19.3%. The adoption of the acrylic dummy eye shield was successful for the treatment plan. However, the Pinnacle pencil-beam algorithm was not sufficient to predict the eyelid dose on the tungsten shield, and more accurate algorithms like MC should be considered for a treatment plan.

A new anti-c-Met antibody selected by a mechanism-based dual-screening method: therapeutic potential in cancer.

c-Met, the high affinity receptor for hepatocyte growth factor (HGF), is one of the most frequently activated tyrosine kinases in many human cancers and a target for cancer therapy. However, inhibitory targeting of c-Met with antibodies has proven difficult, because most antibodies have intrinsic agonist activity. Therefore, the strategy for reducing the agonism is critical for successful development of cancer therapies based on anti-c-Met antibodies. Here we developed a mechanism-based assay method for rapid screening of anti-c-Met antibodies, involving the determination of Akt phosphorylation and c-Met degradation for agonism and efficacy, respectively. Using the method, we identified an antibody, F46, that binds to human c-Met with high affinity (Kd = 2.56 nM) and specificity, and induces the degradation of c-Met in multiple cancer cells (including MKN45, a gastric cancer cell line) with minimal activation of c-Met signaling. F46 induced c-Met internalization in both HGF-dependent and HGF-independent cells, suggesting that the degradation of c-Met results from antibody-mediated receptor internalization. Furthermore, F46 competed with HGF for binding to c-Met, resulting in the inhibition of both HGF-mediated invasion and angiogenesis. Consistently, F46 inhibited the proliferation of MKN45 cells, in which c-Met is constitutively activated in an HGF-independent manner. Xenograft analysis revealed that F46 markedly inhibits the growth of subcutaneously implanted gastric and lung tumors. These results indicate that F46, identified by a novel mechanism-based assay, induces c-Met degradation with minimal agonism, implicating a potential role of F46 in therapy of human cancers.

MET signaling regulates glioblastoma stem cells.

Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level of MET in human primary GBM specimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target.

Variations in dose distribution and optical properties of Gafchromic(TM) EBT2 film according to scanning mode.

PURPOSE: The authors aim was to investigate the effects of using transmission and reflection scanning modes, the film orientation during scanning, and ambient room light on a dosimetry system based on the Gafchromic(TM) EBT2 film model. METHODS: For calibration, the films were cut to 3 × 3 cm(2) and irradiated from 20 to 700 cGy at the depth of maximum dose using 6 and 10 MV photon beams in a 10 × 10 cm(2) field size. Absolute dose calibration of the linear accelerator was done according to the TRS398 protocol. An FG65-G ionization chamber was used to monitor the dose while irradiating the films in solid water. The film pieces were scanned with an EPSON Expression 1680 Pro flatbed scanner in transmission and reflection modes. Authors investigated the effect of orientation on films and examined the optical properties of EBT2 film using an ellipsometer and an ultraviolet (UV)/visible spectrometer to explain the dosimetric dependence of the film on orientation during the scanning process. To investigate the effect of ambient room light, films were preirradiated in 6 and 10 MV photon beams with intensity-modulated radiotherapy (IMRT) quality assurance (QA) plans, and then exposed to room light, either directly for 2 days in a workroom or for 2 months in a film box. Gamma index pass criteria of (3%, 3 mm) were used. RESULTS: The dose response curves based on net optical density (NOD) indicated that the reflection scanning mode can provide a better dose sensitivity than the transmission scanning mode, whereas the standard deviation of the dose is greater in reflection mode than in transmission mode. When the film was rotated 90° from the portrait orientation, the average dose of the EBT2 film decreased by 11.5-19.6% in transmission mode and by 1.5-2.3% in reflection mode. Using an ellipsometer, variation of the refractive index of EBT2 film-the birefringence property-was found to be the largest between 45° (1.72 and 1.71) and 135° (1.8 and 1.77) for 300 and 800 cGy. Absorption spectra of EBT2 films measured with spectrometer were the function of film orientation. The readings in reflection scanning mode were more stable against room light than those in transmission scanning mode, although dose readings increased in both modes after the films were exposed to room light. CONCLUSIONS: The transmission scanning mode exhibited a strong dependence on film orientation during scanning and a change in optical density resulting from room light exposure, so a constant scanning orientation and minimal exposure to light can reduce uncertainty in the measured dose (23 ± 3%). The angular dependence was analyzed using Jones matrices and optical properties of EBT2 film were obtained using an ellipsometer and an UV/visible spectrometer. The reflection scanning mode has relatively good stability with respect to room light and film orientation on a scanner, although the large standard deviation of dose is a disadvantage in measurements of absolute dose. Reflection scanning mode can offer a potential advantage for film dosimetry in radiotherapy, although transmission scanning mode is still recommended for dosimetry as it provides better uncertainty results.

Comparison of film dosimetry techniques used for quality assurance of intensity modulated radiation therapy.

PURPOSE: Accurate dosimetry is essential to ensure the quality of advanced radiation treatments, such as intensity modulated radiation therapy (IMRT). Therefore, a comparison study was conducted to assess the accuracy of various film dosimetry techniques that are widely used in clinics. METHODS: A simulated IMRT plan that produced an inverse pyramid dose distribution in a perpendicular plane of the beam axis was designed with 6 MV x rays to characterize the large contribution of scattered photons to low dose regions. Three film dosimetry techniques, EDR2, EDR2 with low-energy photon absorption lead filters (EDR2 WF), and GafChromic EBT, were compared to ionization chamber measurements as well as Monte Carlo (MC) simulations. The accuracy of these techniques was evaluated against the ionization chamber data. Two-dimensional comparisons with MC simulation results were made by computing the gamma index (gamma) with criteria ranging from 2% of dose difference or 2 mm of distance to agreement (2%/2 mm) to 4%/4 mm on the central vertical plane (20 x 20 cm2) of a square solid water phantom. Depth doses and lateral profiles at depths of 5, 10, and 15 cm were examined to characterize the deviation of film measurements and MC predictions from ionization chamber measurements. RESULTS: In depth dose comparisons, the deviation between the EDR2 films was 9% in the low dose region and 5% in high dose region, on average. With lead filters, the average deviation was reduced to -1.3% and -0.3% in the low dose and high dose regions, respectively. EBT film results agreed within 1.5% difference on average with ionization chamber measurements in low and high dose regions. In two-dimensional comparisons with MC simulation, EDR2 films passed gamma tests with a 2%/2 mm criterion only in the high dose region (gamma < or = 1, total of 63.06% of the tested region). In the low dose region, EDR2 films passed gamma tests with 3%/3 mm criterion (gamma < or = 1, total of 98.4% of the tested region). For EDR2 WF and GafChromic EBT films, gamma tests with a 2% /2 mm criterion (gamma < or = 1) in the tested area was 97.3% and 96.8% of the tested region, respectively. CONCLUSIONS: The EDR2 film WF and GafChromic EBT film achieved an average accuracy level of 1.5% against an ionization chamber. These two techniques agreed with the MC prediction in 2%/2mm criteria evaluated by the gamma index, whereas EDR2 without filters achieved an accuracy level of 3%/3 mm with the decision criteria of agreement greater than 95% of the tested region. The overall results will provide a useful quantitative reference for IMRT verifications.

Evaluation of delivered monitor unit accuracy of gated step-and-shoot IMRT using a two-dimensional detector array.

PURPOSE: To overcome the problem of organ motion in intensity-modulated radiation therapy (IMRT), gated IMRT is often used for the treatment of lung cancer. In this study, the authors investigated the accuracy of the delivered monitor units (MUs) from each segment during gated IMRT using a two-dimensional detector array for user-specific verification purpose. METHODS: The authors planned a 6 MV photon, seven-port step-and-shoot lung IMRT delivery. The respiration signals for gated IMRT delivery were obtained from the one-dimensional moving phantom using the real-time position management (RPM) system (Varian Medical Systems, Palo Alto, CA). The beams were delivered using a Clinac iX (Varian Medical Systems, Palo Alto, CA) with the Millennium 120 MLC. The MatriXX (IBA Dosimetry GmbH, Germany) was validated through consistency and reproducibility tests as well as comparison with measurements from a Farmer-type ion chamber. The authors delivered beams with varying dose rates and duty cycles and analyzed the MatriXX data to evaluate MU delivery accuracy. RESULTS: There was quite good agreement between the planned segment MUs and the MUs computed from the MatriXX within +/- 2% error. The beam-on times computed from the MatriXX data were almost identical for all cases, and they matched well with the RPM beam-on and beam-off signals. A slight difference was observed between them, but it was less than 40 ms. The gated IMRT delivery demonstrated an MU delivery accuracy that was equivalent to ungated IMRT, and the delivered MUs with a gating signal agreed with the planned MUs within +/- 0.5 MU regardless of dose rate and duty cycle. CONCLUSIONS: The authors can conclude that gated IMRT is able to deliver an accurate dose to a patient during a procedure. The authors believe that the methodology and results can be transferred to other vendors' devices, particularly those that do not provide MLC log data for a verification purpose.

Feasibility study of radiophotoluminescent glass rod dosimeter postal dose intercomparison for high energy photon beam.

A radiophotoluminescent glass rod dosimeter (GRD) system has recently become commercially available. In this study we evaluated whether the GRD would be suitable for external dosimetric audit program in radiotherapy. For this purpose, we introduced a methodology of the absorbed dose determination with the GRD by establishing calibration coefficient and various correction factors (non-linearity dose response, fading, energy dependence and angular dependence). A feasibility test of the GRD postal dose intercomparison was also performed for eight high photon beams by considering four radiotherapy centers in Korea. In the accuracy evaluation of the GRD dosimetry established in this study, we obtained within 1.5% agreements with the ionization chamber dosimetry for the (60)Co beam. It was also observed that, in the feasibility study, all the relative deviations were smaller than 3%. Based on these results, we believe that the new GRD system has considerable potential to be used for a postal dose audit program.

Dosimetric characteristics of linear accelerator photon beams with small monitor unit settings.

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step-and-shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step-and-shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two-dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for 300 MU/min and 4.5% for 600 MU/min, showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step-and-shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start-up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step-and-shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step-and-shoot IMRT planning.