Intra-fractional dose rate effect in continuous and interrupted irradiation of the MCF-7 cell line: Possible radiobiological implications for breath-hold techniques in breast radiotherapy?

PURPOSE: To investigate the effects of different dose rates (DRs) in continuous and interrupted irradiation on in-vitro survival of the MCF-7 cell line, towards finding possible radiobiological effects of breath-hold techniques in breast radiotherapy (RT), in which intra-fractional beam interruptions and delivery prolongation can occur. MATERIALS AND METHODS: MCF-7 cells were irradiated continuously or with regular interruptions using 6 MV x-rays at different accelerator DRs (50-400 cGy/min) to deliver a 2 Gy dose. The interrupted irradiation was delivered in a 10 s on, 10 s off manner. Then, cell survival and viability were studied using colony and MTT assays, respectively. RESULTS: Survival and viability with continuous and interrupted irradiation were similar ( P > 0.5). A significant increase in survival at 50, 100, and 400 cGy/min compared to 200 and 300 cGy/min was observed, also a significant decreasing and then increasing trend from 50 to 200 cGy/min and 200 to 400 cGy/min, respectively ( P < 0.04). Relative to 200 cGy/min, the survival fractions at 50, 100, 300, and 400 cGy/min were 1.24, 1.23, 1.05, and 1.20 times greater, respectively. Cell viability did not show significant differences between the DRs, despite following the same trend as cell survival. CONCLUSION: Our results suggest that for continuous irradiation of in-vitro MCF-7 cells, with increasing DR within the 50-400 cGy/min range, sensitivity increases and then decreases (inverse effect), also that up to doubling of treatment time in breath-hold techniques does not affect in-vitro radiobiological efficacy with 200-400 cGy/min accelerator DRs. Further confirmatory studies are required.

Full modulation transfer functions of thick parallel- and focused-element scintillator arrays obtained by a Monte Carlo optical transport model.

BACKGROUND: Arrays of thick segmented crystalline scintillators are useful x-ray converters for image-guided radiation therapy using electronic portal imaging (EPI) and megavoltage cone-beam computed tomography (MV-CBCT). Ionizing-radiation-only simulations previously showed relatively low modulation transfer function (MTF) in parallel-element arrays because of beam divergence. Hence, a focused-element geometry (matching the beam divergence) has been proposed. The "full" (ionizing and optical) MTF performance of such a focused geometry compared to its radiation-only MTF has, however, not been fully investigated. PURPOSE: To study the full MTF performance of such arrays in a more realistic situation in which optical characteristics are also included using an in-house detector model that supports light transport, and quantify the errors in MTF estimation when the optical stage is ignored. METHODS: First, radiation (x-ray and electron) transport was simulated. Then, transport of the generated optical photons was modeled using ScintSim2, an optical Monte Carlo (MC) code developed in MATLAB for simulation of two-dimensional (2D) parallel- and focused-element scintillator arrays. The full-MTF responses of focused- and parallel-element geometries, for a large array of 3 × 3 mm2 CsI:Tl detector elements of 10, 40, and 60 mm thicknesses, were examined. For each configuration, a composite line spread function (LSF) was calculated to obtain the MTF. RESULTS: At the Nyquist frequency, for 10 mm-thick central elements and 60 mm-thick peripheral parallel elements, full-MTF exhibited a drop of up to 15 and 79 times, respectively, compared with radiation-only MTF. This was found to be partly attributable to the angular distribution of the light emerging from the detector-element exit face and the dependence on its aspect ratio, since the light exiting thicker scintillators exhibited a more forward-directed distribution. Focused elements provided an increase of up to nine times in peripheral-area full MTF values. CONCLUSIONS: Full MTF was up to 79 times lower than radiation-only MTF. Focused arrays preserved full MTF by up to nine times compared to parallel elements. The differences in the results obtained with and without inclusion of optical photons emphasize the need to include light transport when optimizing thick segmented scintillation detectors. Besides their application in detector optimization for radiotherapy megavoltage photon imaging, these findings can also be useful for other segmented-scintillator-based imaging systems, for example, in nuclear medicine, or in 2D detection systems for quality assurance of MR-linacs.

Metal artifact reduction in cervix brachytherapy with titanium applicators using dual-energy CT through virtual monoenergetic images and an iterative algorithm: A phantom study.

PURPOSE: To evaluate an iterative metal-artifact reduction (iMAR) algorithm, dual-energy CT (DECT) through virtual monoenergetic images (VMI), and a combination of iMAR and DECT for reducing metal artifact severity (AS) induced by Fletcher titanium applicators used in cervix brachytherapy, the efficacy of which are hitherto unreported. METHODS AND MATERIALS: 120 kVp single-energy CT (SECT) (Siemens) of BEBIG tandem applicators, varying in shape (straight or curved) and diameter (3.5 mm or 5 mm) in a custom-made water-filled phantom, and their DECT images obtained from extrapolation of 80 kVp and 140 kVp, were reconstructed using four methods: DECT through VMI±iMAR, and SECT±iMAR. The DECT images were reconstructed monoenergetically at 70, 150, and 190 keV. AS was evaluated using measured values and statistical analysis. RESULTS: iMAR, DECT, and combined DECT and iMAR reduced AS (p < 0.05). DECT had a lower AS than SECT, even without iMAR (p < 0.025). SECT+iMAR was more effective than DECT-iMAR with VMI at 70 and 190 keV (p < 0.05), whereas showing no statistically significant difference at 150 keV. With DECT and iMAR combined, AS was reduced more effectively compared to the SECT+iMAR or DECT alone. It also reduced the mean interobserver uncertainty by 0.2 mm. CONCLUSIONS: These findings indicate that iMAR reduces the AS caused by Fletcher titanium applicators for both SECT and DECT, a combination of iMAR and DECT is superior to either strategy alone, and at low energies, DECT+iMAR also produces similar artifact reduction. These practical strategies promise more accurate source-position and structure definitions in CT-based gynecological brachytherapy treatment planning.

Intraoperative radiation therapy in non-breast cancer patients: A report of 26 cases from Shiraz, south of Iran.

Background: Intraoperative radiation therapy (IORT) is the delivery of radiation at the time of surgery. Whereas the dose delivered by external beam radiation therapy (EBRT) is limited by the tolerance of the surrounding normal tissues, IORT allows exclusion of a part or all of the dose-limiting sensitive structures by operative mobilization and/or direct shielding of these structures. The aim of the present study was to report the non-breast cancer patients' outcomes after receiving IORT in Shiraz, Iran. Methods: In this retrospective study, all cases who had received IORT and had non-breast malignancies were selected. Diagnosis was confirmed by biopsy. Additional imaging was done by sonography, magnetic resonance imaging (MRI) and computed tomography (CT). IORT was applied by self-shielded, LIAC 6-12 MeV Sordina mobile linear accelerator. Typically, a single dose of 10-21 Gy was given for maximally resected tumors. The statistical analyses were carried out using SPSS (version 21). Results: Twenty-six patients were treated with IORT alone or combined with EBRT. Different tumors were treated, including colorectal adenocarcinoma (10 cases, 38.4 %), Soft Tissue Sarcomas (STS, 11 cases, 42.3 %), head and neck cancers (3 cases, 11.5 %), one cervix malignancy case and one paravertebral fibromatosis case. Mean ± SD overall survival was 15±14.89 (0-38) and 34.3±15.72 (14-53) months for colorectal cancer and STS, respectively. Conclusion: IORT is mostly useful for pelvic and abdominal malignancies where normal bowel limits the dose that can be delivered with EBRT. However, the dose delivered in a single fraction with IORT is rarely sufficient for tumor control; therefore, IORT is usually preceded or followed by additional EBRT which should be further evaluated preferably in prospective randomized trials.

Independent assessment of source transit time for the BEBIG SagiNova® cobalt-60 high dose rate brachytherapy afterloader.

Independent verification of transit time and the methodology employed in commercial high dose rate (HDR) afterloaders to compensate its effect is an important part of their commissioning and quality assurance. This study aimed to independently evaluate the Co-60 source transit time of the new BEBIG SagiNova® HDR afterloader unit by employing a dosimetric approach using a well-type ionization chamber. The source was placed at three dwell positions (DPs) to mimic a variety of clinical situations with different distances from the afterloader unit. The distances of the DPs to the afterloader were 129.37 cm, 124.50 cm and 118.57 cm. Plans were generated using the SagiPlan® treatment planning system to produce 3, 5, 10, 15, 20, 30, 40, 60 and 120 s dwell times (DTs). The residual transit times (following any possible system compensation) were assessed using the ESTRO-recommended approach of obtaining transit time compensation factors and another strategy established for teletherapy sources. The mean residual transit time depended on the distance between the afterloader and the DP, ranging from 0.43 to 1.10 s. The transit dose contribution was case-specific, ranging from 0.4% for a 60 s DT at the nearest DP to the afterloader up to 15.6% for a 3 s DT at the furthest DP from the unit. The results show that currently SagiNova® afterloader does not apply transit time compensation and suggest a 0.2-0.5 s compensation for each arrival and departure DP from/to the afterloader, depending on position in an 11 cm active length.

Influence of dwell time homogeneity error weight parameter on treatment plan quality in inverse optimized high-dose-rate cervix brachytherapy using SagiPlan.

PURPOSE: Restricting the gradients of dwell times between adjacent dwell positions can potentially be beneficial in reducing the probability of unwanted hot/cold spots occurring, if the planned applicators/anatomy relative positions change before or during treatment. This constraint, however, may degrade plan quality. This study, for the first time, aims to quantify the impact of modulation restriction on plan quality indices in inverse optimization for cervix high-dose-rate (HDR) brachytherapy using the BEBIG SagiPlan treatment planning system. MATERIAL AND METHODS: Ten cervical cancer patient plans were optimized for treatment with a BEBIG SagiNova 60Co HDR afterloader using the min/max inverse planning method, with dwell time homogeneity error weight (DTHEW) parameter values of 0 to 10. Dwell time homogeneity and gradients as well as various plan quality indices were analyzed. RESULTS: For DTHEW = 0, min/max-based optimization yielded higher HR-CTV D90 values than the variance-based option (p < 0.001) and was therefore selected for this study. Averaging over all patients, selecting non-zero DTHEWs resulted in a general increase in dwell time homogeneity and decrease in mean and maximum adjacent dwell time gradients, especially between DTHEWs of 0 and 1. For DTHEW > 1, an increase of this parameter did not always result in more homogeneous dwell times or reduced gradients in individual patients. There was a negative correlation between DTHEW and both HR-CTV D90 and V100 (p < 0.001, r = -0.91). Increasing DTHEW also negatively affected conformity index (p < 0.001, r = -0.99). Changes in rectum and sigmoid colon D2cc were insignificant. There was a strong positive relationship between bladder D2cc and DTHEW (p < 0.001, r = 0.99). CONCLUSIONS: Assuming a static geometry, statistically significant degradation of plan quality can result from restricting the dwell time homogeneity in min/max-based optimization of cervix HDR brachytherapy plans using SagiPlan. Therefore, setting DTHEW to zero is indicated for the type of patient plans considered in this study.

ScintSim1: A new Monte Carlo simulation code for transport of optical photons in 2D arrays of scintillation detectors.

Two-dimensional (2D) arrays of thick segmented scintillators are of interest as X-ray detectors for both 2D and 3D image-guided radiotherapy (IGRT). Their detection process involves ionizing radiation energy deposition followed by production and transport of optical photons. Only a very limited number of optical Monte Carlo simulation models exist, which has limited the number of modeling studies that have considered both stages of the detection process. We present ScintSim1, an in-house optical Monte Carlo simulation code for 2D arrays of scintillation crystals, developed in the MATLAB programming environment. The code was rewritten and revised based on an existing program for single-element detectors, with the additional capability to model 2D arrays of elements with configurable dimensions, material, etc., The code generates and follows each optical photon history through the detector element (and, in case of cross-talk, the surrounding ones) until it reaches a configurable receptor, or is attenuated. The new model was verified by testing against relevant theoretically known behaviors or quantities and the results of a validated single-element model. For both sets of comparisons, the discrepancies in the calculated quantities were all <1%. The results validate the accuracy of the new code, which is a useful tool in scintillation detector optimization.

A Monte Carlo and experimental investigation of the dosimetric behavior of low- and medium-perturbation diodes used for entrance in vivo dosimetry in megavoltage photon beams.

Full buildup diodes can cause significant dose perturbation if they are used on most or all of radiotherapy fractions. Given the importance of frequent in vivo measurements in complex treatments, using thin buildup (low-perturbation) diodes instead is gathering interest. However, such diodes are strictly unsuitable for high-energy photons; therefore, their use requires evaluation and careful measurement of correction factors (CFs). There is little published data on such factors for low-perturbation diodes, and none on diode characterization for 9 MV X-rays. We report on MCNP4c Monte Carlo models of low-perturbation (EDD5) and medium-perturbation (EDP10) diodes, and a comparison of source-to-surface distance, field size, temperature, and orientation CFs for cobalt-60 and 9 MV beams. Most of the simulation results were within 4% of the measurements. The results suggest against the use of the EDD5 in axial angles beyond ± 50° and exceeding the range 0° to +50° tilt angle at 9 MV. Outside these ranges, although the EDD5 can be used for accurate in vivo dosimetry at 9 MV, its CF variations were found to be 1.5-7.1 times larger than the EDP10 and, therefore, should be applied carefully. Finally, the MCNP diode models are sufficiently reliable tools for independent verification of potentially inaccurate measurements.