In the cohort analyzed, identified changes in adjuvant breast radiotherapy resulted in overall savings due to updated indications for boost and the implementation of ultra-hypofractionated radiotherapy. We are now analyzing the impact of introducing simultaneous integrated boost and partial breast radiotherapy.

According to the Dutch Health Council, proton referrals aiming at toxicity reduction make up for 85% of total referrals. Considering the limited availability of proton installations, a model-based method of patient selection has been proposed by Dutch centres. In this retrospective study, we apply the Dutch model to determine how many SLRON head&neck patients would qualify for proton treatment planning.

Low gain avalanche detectors can measure charged particle fluences with high speed and spatial precision, and are a promising technology for radiation monitoring and dosimetry. A detector has been tested in a medical linac where single particles were observed with a time resolution of 50 ps. The integrated response is similar to a standard ionising chamber but with a spatial precision twenty times finer, and a temporal precision over 100 million times better, with the capability to measure the charge deposited by a single linac pulse. The unprecedented resolving power allows the structure of the ∼3 μs linac pulses to be viewed and the 350 ps sub-pulses in the train to be observed.

Purpose or ObjectiveA technique using analysis of on-board CBCT images to adapt the dose to the target on a fraction-by-fraction basis was developed.This new approach involves using the upper limit of dose volume constraints (DVCs) as the objective to be met at each fraction by tracking and accumulating dose voxels.The aim was to adapt the dose per fraction such that it was optimised each day without any organ at risk (OAR) DVCs being exceeded.The impact on tumour control probability (TCP) and normal tissue complication probability (NTCP) was evaluated.Material and Methods 31 patients who underwent prostate treatment were retrospectively investigated for this study.Initial VMAT plans consisting of 2 arcs were designed to deliver 74 Gy in 37 fractions of 2 Gy each to the target.The patients had on-board CBCT scans taken prior to treatment for between 9 and 33 fractions (436 in total).An in-house registration algorithm based on phase correlation[1] was used to retrospectively register CBCT images to the planning CT to determine the transformations and deformations in patients' anatomy.This allowed the original plan to be recalculated on the registered CT image that provided the position of the target and OARs for that fraction.By tracking individual voxels throughout treatment, the dose was accumulated and the DVHs and DVC values were determined for each fraction.

A means of reducing Patient Specific QA (PSQA) measurements for VMAT is currently a popular topic due to the resource burden it generates. The reluctance to reduce PSQA may be due to the difficulty in identifying the cause/s of plans that fail. Plans may fail due to a number of potential factors caused by the TPS, linac or measurement device. The goal of this study was to uncover the reason/s why a selection of VMAT plans have failed. PSQA was performed with SNC ArcCHECK. Five failing plans and two passing plans were analysed. The control points for each plan were broken up into separate static fields. The fields were delivered to ArcCHECK and compared to the TPS using a Python program. Dose-differences were tracked field-by-field for each diode and categorised according to the location of the diode to the beam: In-field, penumbra and out-of-field. A composite measurement of individual control point fields compared with the conventional PSQA measurement showed minimal difference indicating that the reason for PSQA fail was not due to dynamic delivery. Dose differences due to the out-of-field component had the greatest impact on the overall pass-rates. The latest version of the SNC Patient software provides corrections for diode over-response out-of-field and was investigated as a potential solution. The impact of applying the correction resulted in all previously failing plans passing. Deconstructing PSQA measurements identified out-of-field dose differences as the main cause of plans failing. The results of this study indicate the new out-of-beam correction should be applied. A means of reducing Patient Specific QA (PSQA) measurements for VMAT is currently a popular topic due to the resource burden it generates. The reluctance to reduce PSQA may be due to the difficulty in identifying the cause/s of plans that fail. Plans may fail due to a number of potential factors caused by the TPS, linac or measurement device. The goal of this study was to uncover the reason/s why a selection of VMAT plans have failed. PSQA was performed with SNC ArcCHECK. Five failing plans and two passing plans were analysed. The control points for each plan were broken up into separate static fields. The fields were delivered to ArcCHECK and compared to the TPS using a Python program. Dose-differences were tracked field-by-field for each diode and categorised according to the location of the diode to the beam: In-field, penumbra and out-of-field. A composite measurement of individual control point fields compared with the conventional PSQA measurement showed minimal difference indicating that the reason for PSQA fail was not due to dynamic delivery. Dose differences due to the out-of-field component had the greatest impact on the overall pass-rates. The latest version of the SNC Patient software provides corrections for diode over-response out-of-field and was investigated as a potential solution. The impact of applying the correction resulted in all previously failing plans passing. Deconstructing PSQA measurements identified out-of-field dose differences as the main cause of plans failing. The results of this study indicate the new out-of-beam correction should be applied.

influence of dose resolution (re-sempling of the simulated dose distribution to the detector resolution) on gamma result.Clinical relevance of such MLC errors should be also investigated.

Purpose: The use of radiotherapy fields smaller than 3 cm in diameter has resulted in the need for accurate detector correction factors for small field dosimetry. However, published factors do not always agree and errors introduced by biased reference detectors, inaccurate Monte Carlo models, or experimental errors can be difficult to distinguish. The aim of this study was to provide a robust set of detector-correction factors for a range of detectors using numerical, empirical, and semiempirical techniques under the same conditions and to examine the consistency of these factors between techniques. Methods: Empirical detector correction factors were derived based on small field output factor measurements for circular field sizes from 3.1 to 0.3 cm in diameter performed with a 6 MV beam. A PTW 60019 microDiamond detector was used as the reference dosimeter. Numerical detector correction factors for the same fields were derived based on calculations from a geant4 Monte Carlo model of the detectors and the Linac treatment head. Semiempirical detector correction factors were derived from the empirical output factors and the numerical dose-to-water calculations. Results: The PTW 60019 microDiamond was found to over-respond at small field sizes resulting in a bias in the empirical detector correction factors. The over-response was similar in magnitude to that of the unshielded diode. Good agreement was generally found between semiempirical and numerical detector correction factors except for the PTW 60016 Diode P, where the numerical values showed a greater over-response than the semiempirical values by a factor of 3.7% for a 1.1 cm diameter field and higher for smaller fields. Conclusions: Detector correction factors based solely on empirical measurement or numerical calculation are subject to potential bias. A semiempirical approach, combining both empirical and numerical data, provided the most reliable results.

_____________________________________________________________________________________________________DCA 10FFF and reduced treatment times when compared to FF.Further study on the role of tumor location is recommended to establish more conclusive results.A concern with the use of VMAT with SBRT is whether the motion of the tumor leads to significant dosing discrepancies.DCA remains immune to the MLC interplay effect.

The use of Raman spectroscopy to measure the biochemical profile of healthy and diseased cells and tissues may be a potential solution to many diagnostic problems in the clinic. Although extensively used to identify changes in the biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been used less often for analyzing changes to the cellular environment by external factors such as ionizing radiation. In tandem with this, the biological impact of low doses of ionizing radiation remains poorly understood. Extensive studies have been performed on the radiobiological effects associated with radiation doses above 0.1 Gy, and are well characterized, but recent studies on low-dose radiation exposure have revealed complex and highly variable responses. We report here the novel finding that demonstrate the capability of Raman spectroscopy to detect radiation-induced damage responses in isolated lymphocytes irradiated with doses of 0.05 and 0.5 Gy. Lymphocytes were isolated from peripheral blood in a cohort of volunteers, cultured ex vivo and then irradiated. Within 1 h after irradiation spectral effects were observed with Raman microspectroscopy and principal component analysis and linear discriminant analysis at both doses relative to the sham-irradiated control (0 Gy). Cellular DNA damage was confirmed using parallel γ-H2AX fluorescence measurements on the extracted lymphocytes per donor and per dose. DNA damage measurements exhibited interindividual variability among both donors and dose, which matched that seen in the spectral variability in the lymphocyte cohort. Further evidence of links between spectral features and DNA damage was also observed, which may potentially allow noninvasive insight into the DNA remodeling that occurs after exposure to ionizing radiation.

Purpose/Objective: Measuring, calculating, and reducing non-target doses present unique challenges with which many medical physicists may have limited experience.The American Association of Physicists in Medicine Task Group (TG) 158 report: 'Measurement and calculation of doses outside the treatment volume from external-beam radiation therapy' provides guidance for physicists in assessing and managing non-target doses.The primary objectives of this presentation are to (1) highlight major concerns with nontarget radiation, (2) provide a rough estimate of doses associated with different treatment approaches in clinical practice, and (3) to highlight techniques that may be considered for reducing non-target doses and (4) summarize TG-158 recommendations for both clinical and research practice. Materials and Methods:The TG-158 report reviewed approximately 300 publications in the literature to provide guidance on management of non-target doses.This presentation will summarize key components of the report and its recommendations.Results: The Task Group 158 report generated guidance for physicists in terms of doses to non-target structures, dosimetry and computational techniques for assessing nontarget doses, as well as potential treatment and patient management options for minimizing non-target doses.This was done by addressing the following charges: 1. Highlight major concerns with non-target radiation 2. Provide a rough estimate of doses associated with different treatment approaches in clinical practice 3. Discuss the uses of dosimeters and phantoms for measuring photon, electron, and neutron exposures 4. Discuss the use of calculation techniques (including Monte Carlo) for dosimetric evaluations 5. Highlight techniques that may be considered for reducing non-target doses 6. Make recommendations for clinical and research practice This presentation will summarize the Task Group report's findings on topics 1, 2, 5, and 6 from the list above.Topics 3 and 4, measurement and calculation of non-target doses, are each broad topics and separate abstracts detailing these topics are separate submitted abstracts at this meeting.Conclusions: This presentation will summarize key components of the AAPM TG-158 report and its recommendations.

The use of Raman spectroscopy to measure the biochemical profile of healthy and diseased cells and tissues may be a potential solution to many diagnostic problems in the clinic. Although extensively used to identify changes in the biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been used less often for analyzing changes to the cellular environment by external factors such as ionizing radiation. In tandem with this, the biological impact of low doses of ionizing radiation remains poorly understood. Extensive studies have been performed on the radiobiological effects associated with radiation doses above 0.1 Gy, and are well characterized, but recent studies on low-dose radiation exposure have revealed complex and highly variable responses. We report here the novel finding that demonstrate the capability of Raman spectroscopy to detect radiation-induced damage responses in isolated lymphocytes irradiated with doses of 0.05 and 0.5 Gy. Lymphocytes were isolated from peripheral blood in a cohort of volunteers, cultured ex vivo and then irradiated. Within 1 h after irradiation spectral effects were observed with Raman microspectroscopy and principal component analysis and linear discriminant analysis at both doses relative to the sham-irradiated control (0 Gy). Cellular DNA damage was confirmed using parallel γ-H2AX fluorescence measurements on the extracted lymphocytes per donor and per dose. DNA damage measurements exhibited interindividual variability among both donors and dose, which matched that seen in the spectral variability in the lymphocyte cohort. Further evidence of links between spectral features and DNA damage was also observed, which may potentially allow noninvasive insight into the DNA remodeling that occurs after exposure to ionizing radiation.

There is much evidence supporting the existence of bystander effects in cells that were never exposed to radiation. Directly irradiated cells and bystander cells can communicate with each other using gap junctional intercellular communication or by releasing soluble factors into the surrounding medium. Exosomes and microvesicles are also known to mediate communication between cells. The main aim of this study is to establish whether exosomes and microvesicles are involved in radiation induced bystander signaling. Human keratinocytes, HaCaT cells, were irradiated (0.005, 0.05 and 0.5 Gy) using γ rays produced from a cobalt 60 teletherapy unit. After irradiation, the cells were incubated for 1 h and the irradiated cell conditioned medium (ICCM) was harvested. Exosomes were isolated from the ICCM using ultracentrifugation. Exosomes were characterized using light scattering analysis (LSA) and scanning transmission electron microscopy (STEM). Cytotoxicity and reactive oxygen species assays and real time calcium imaging were performed either with ICCM from which exosomes and microvesicles were removed or with the exosome fraction resuspended in cell culture media. The characterization data showed a particle size distribution indicative of both exosomes (30–100 nm) and microvesicles (>100 nm) and the light scattering analysis showed increased concentration of both exosomes and microvesicles with increasing dose. Western blotting confirmed the presence of an exosomal protein marker, TSG 101. Treatment of unirradiated cells with ICCM in which exosomes and microvesicles were removed resulted in abrogation of ICCM induced effects such as reduction in viability, calcium influx and production of reactive oxygen species. Addition of exosomes to fresh media produced similar effects to complete ICCM. These results suggest a role for exosomes and microvesicles in radiation induced bystander signaling.

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells is not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant increase in γ-H2AX foci formation when irradiated to 20 cGy in-field in comparison to out-of-field. However, no significant difference in cell survival or colony volume was observed whether the PNT1A cells were irradiated in-field or out-of-field. Out-of-field radiation dose alone can have a damaging effect on the proliferation of PNT1A cells when a clinically relevant dose of 2 Gy is delivered in in-field. Out-of-field radiation with the transfer of bystander factors induces an adaptive response in the PNT1A cells.