No abstract

BackgroundDose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Relatively few studies to date have investigated the dose rate effect in RNT. Therefore, the aim of this study was to benchmark 90Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes.ResultsThree human colorectal carcinoma (CRC) cell lines (HT29, HCT116, SW48) were exposed to 90Y doses in the ranges 1–10.4 and 6.2–62.3 Gy with initial dose rates of 0.013–0.13 Gy/hr (low dose rate, LDR) and 0.077–0.77 Gy/hr (high dose rate, HDR), respectively. Results were compared to a 6-MV photon beam doses in the range from 1–9 Gy with constant dose rate of 277 Gy/hr. The cell survival parameters from the linear quadratic (LQ) model were determined. Additionally, Monte Carlo simulations were performed to calculate the average dose, dose rate and the number of hits in the cell nucleus.For the HT29 cell line, which was the most radioresistant, the α/β ratio was found to be ≈ 31 for HDR–90Y and ≈ 3.5 for EBRT. LDR–90Y resulting in insignificant cell death compared to HDR–90Y and EBRT. Simulation results also showed for LDR–90Y, for doses ≲ 3 Gy, the average number of hits per cell nucleus is ≲ 2 indicating insufficiently delivered lethal dose. For 90Y doses  3 Gy the number of hits per nucleus decreases rapidly and falls below ≈ 2 after ≈ 5 days of incubation time. Therefore, our results demonstrate that LDR–90Y is radiobiologically less effective than EBRT. However, HDR–90Y at ≈ 56 Gy was found to be radiobiologically as effective as acute ≈ 8 Gy EBRT.ConclusionThese results demonstrate that the efficacy of RNT is dependent on the initial dose rate at which radiation is delivered. Therefore, for a relatively long half-life radionuclide such as 90Y, a higher initial activity is required to achieve an outcome as effective as EBRT.

The clinical implementation of real-time image-guided adaptive radiotherapy on a standard linear accelerator using KIM and MLC tracking is feasible. This achievement paves the way for real-time IGART to be a mainstream treatment option.

SummaryPrior to introducing intensity modulated radiotherapy (IMRT) for whole breast radiotherapy (WBRT) into our department we undertook a comparison of the dose parameters of several IMRT techniques and standard wedged tangents (SWT). Our aim was to improve the dose distribution to the breast and to decrease the dose to organs at risk (OAR): heart, lung and contralateral breast (Contra Br). Treatment plans for 20 women (10 right-sided and 10 left-sided) previously treated with SWT for WBRT were used to compare (a) SWT; (b) electronic compensators IMRT (E-IMRT); (c) tangential beam IMRT (T-IMRT); (d) coplanar multi-field IMRT (CP-IMRT); and (e) non-coplanar multi-field IMRT (NCP-IMRT). Plans for the breast were compared for (i) dose homogeneity (DH); (ii) conformity index (CI); (iii) mean dose; (iv) maximum dose; (v) minimum dose; and dose to OAR were calculated (vi) heart; (vii) lung and (viii) Contra Br. Compared with SWT, all plans except CP-IMRT gave improvement in at least two of the seven parameters evaluated. T-IMRT and NCP-IMRT resulted in significant improvement in all parameters except DH and both gave significant reduction in doses to OAR. As on initial evaluation NCP-IMRT is likely to be too time consuming to introduce on a large scale, T-IMRT is the preferred technique for WBRT for use in our department.

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Cone‐beam computed tomography (CBCT) is used for external‐beam radiation therapy setup and target localization. As with all medical applications of ionizing radiation, radiation exposure should be managed safely and optimized to achieve the necessary image quality using the lowest possible dose. The present study investigates doses from standard kilovoltage kV radiographic and CBCT imaging protocol, and proposes two novel reduced dose CBCT protocols for the setup of breast cancer patients undergoing external beam radiotherapy. The standard thorax kV and low‐dose thorax CBCT protocols available on Varian's On‐Board Imaging system was chosen as the reference technique for breast imaging. Two new CBCT protocols were created by modifying the low‐dose thorax protocol, one with a reduced gantry rotation range (“Under breast” protocol) and the other with a reduced tube current‐time product setting (“Low dose thorax 10ms” protocol). The absorbed doses to lungs, heart, breasts, and skin were measured using XRQA2 radiochromic film in an anthropomorphic female phantom. The absorbed doses to lungs, heart, and breasts were also calculated using the PCXMC Monte Carlo simulation software. The effective dose was calculated using the measured doses to the included organs and the ICRP 103 tissue weighting factors. The deviation between measured and simulated organ doses was between 3% and 24%. Reducing the protocol exposure time to half of its original value resulted in a reduction in the absorbed doses of the organs of 50%, while the reduced rotation range resulted in a dose reduction of at least 60%. Absorbed doses obtained from “Low dose thorax 10ms” protocol were higher than the doses from our departments orthogonal kV‐kV imaging protocol. Doses acquired from “Under breast” protocol were comparable to the doses measured from the orthogonal kV‐kV imaging protocol. The effective dose per fraction using the CBCT for standard low‐dose thorax protocol was 5.00±0.30 mSv; for the “Low dose thorax 10ms” protocol it was 2.44±0.21 mSv; and for the “Under breast” protocol it was 1.23±0.25 mSv when the image isocenter was positioned at the phantom center and 1.17±0.30 mSv when the image isocenter was positioned in the middle of right breast. The effective dose per fraction using the orthogonal kV‐kV protocol was 1.14±0.16 mSv. The reduction of the scan exposure time or beam rotation range of the CBCT imaging significantly reduced the dose to the organs investigated. The doses from the “Under breast” protocol and orthogonal kV‐kV imaging protocol were comparable. Simulated organ doses correlated well with measured doses. Effective doses from imaging techniques should be considered with the increase use of kV imaging protocols in order to support the use of IGRT.PACS numbers: 87.55.Qr, 87.55.ne, 87.53Bn, 87.55.kh

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.

IntroductionWe report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal.MethodsPlans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs.ResultsThe hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05).ConclusionHybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.