Models for the bystander effect in gradient radiation fields: Range and signalling type.

Bystander responses to radiation are responsible for a significant fraction of cell death, but are not included in the conventional linear-quadratic (LQ) radiobiological model. Strong dose gradients in radiation fields affect the distribution of bystander signals and can be used to decrease the survival of cancer cells. Predictive models incorporating bystander effects are needed to design the dose gradients in modulated fields to improve cancer treatments. Fundamental questions concern the nature and range of bystander signalling. Some authors propose bystander signals are carried by diffusing molecular factors expressed into the extracellular medium and that strong dose gradients drive their diffusion. Others propose bystander effects occur between neighbouring cells through gap-junctions, leaving no universal agreement. Here we test three assumptions concerning the effective range of bystander signals using both average and local measures of survival. Model 1 assumes short range signalling (e.g. gap-junction mediated) proportional to the local dose gradient, without relying on diffusion across the extracellular medium; Model 2 assumes metabolite diffusion governed by Fick's second law with either negative or both signs of bystander effect; Model 3 assumes that the extent of signal production is dependent on the average of the dose gradient over the field and that the signals have long range distribution. A single bystander parameter for each model was fitted to observed average survival of cancer cells in uniform and modulated fields. All models gave better fits than the classical LQ model. Model 2 fitted best with one sign of bystander effect on survival. Model 3 gave the best overall fit of average survival. The models were then used to predict local survival and survival as a function of dose in modulated fields, using independent datasets, without changing the bystander parameter. Model 3 gave the best overall prediction. This study demonstrates that the bystander effect can be controlled by design of the radiation field modulation.

Grid therapy using high definition multileaf collimators: realizing benefits of the bystander effect.

BACKGROUND: In microbeam radiotherapy (MRT), parallel arrays of high-intensity synchrotron x-ray beams achieve normal tissue sparing without compromising tumor control. Grid-therapy using clinical linacs has spatial modulation on a larger scale and achieves promising results for palliative treatments of bulky tumors. The availability of high definition multileaf collimators (HDMLCs) with 2.5 mm leaves provides an opportunity for grid-therapy to more closely approach MRT. However, challenges to the wider implementation of grid-therapy remain because spatial modulation of the target volume runs counter to current radiotherapy practice and mechanisms for the beneficial effects of MRT are not fully understood. Without more knowledge of cell dose responses, a quantitative basis for planning treatments is difficult. The aim of this study is to determine if therapeutic benefits of MRT can be achieved using a linac with HDMLCs and if so, to develop a predictive model to support treatment planning. MATERIAL AND METHODS: HD120-MLCs of a Varian Novalis TXTM were used to generate grid patterns of 2.5 and 5.0 mm spacing, which were characterized dosimetrically using GafchromicTM EBT3 film. Clonogenic survival of normal (HUVEC) and cancer (NCI-H460, HCC-1954) cell lines following irradiation under the grid and open fields using a 6 MV photon beam were compared in-vitro for the same average dose. RESULTS AND CONCLUSIONS: Relative to an open field, survival of normal cells in a 2.5 mm striped field was the same, while the survival of both cancer cell lines was significantly lower. A mathematical model was developed to incorporate dose gradients of the spatial modulation into the standard linear quadratic model. Our new bystander extended LQ model assumes spatial gradients drive the diffusion of soluble factors that influence survival through bystander effects, successfully predicting the experimental results that show an increased therapeutic ratio. Our results challenge conventional radiotherapy practice and propose that additional gain can be realized by prescribing spatially modulated treatments to harness the bystander effect.

Improving motion management in radiation therapy: findings from a workshop and survey in Australia and New Zealand.

Motion management has become an integral part of radiation therapy. Multiple approaches to motion management have been reported in the literature. To allow the sharing of experiences on current practice and emerging technology, the University of Sydney and the New South Wales/Australian Capital Territory branch of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) held a two-day motion management workshop. To inform the workshop program, participants were invited to complete a survey prior to the workshop on current use of motion management techniques and their opinion on the effectiveness of each approach. A post-workshop survey was also conducted, designed to capture changes in opinion as a result of workshop participation. The online workshop was the most well attended ever hosted by the ACPSEM, with over 300 participants and a response to the pre-workshop survey was received from at least 60% of the radiation therapy centres in Australia and New Zealand. Motion management is extensively used in the region with use of deep inspiration breath-hold (DIBH) reported by 98% of centres for left-sided breast treatments and 91% for at least some right-sided breast treatments. Surface guided radiation therapy (SGRT) was the most popular session at the workshop and survey results showed that the use of SGRT is likely to increase. The workshop provided an excellent opportunity for the exchange of knowledge and experience, with most survey respondents indicating that their participation would lead to improvements in the quality of delivery of treatments at their centres.

A survey of compliance with stereotactic ablative body radiotherapy quality recommendations.

INTRODUCTION: Many publications have proposed quality standards for stereotactic ablative body radiotherapy (SABR). However, data on the level of compliance with these guidelines is lacking in the literature. This study aimed to understand how these guidelines are applied in the clinic and to identify barriers to implementing such recommendations. METHODS: Interviews were conducted with multidisciplinary staff at radiation oncology centres across New South Wales formulated around the RANZCR Guidelines for Safe Practice of Stereotactic Body (Ablative) Radiation Therapy. The interview responses were grouped into 20 topics, assessed against the guidelines and thematically analysed. RESULTS: Good compliance with the guidelines was found, with more than 80% of centres achieving satisfactory results in more than half the topics. The areas with the lowest compliance were auditing, risk assessment and reporting recommendations. Barriers to the quality of SABR treatments included limited training opportunities, low patient numbers and a lack of clear requirements on comprehensive auditing and reporting. CONCLUSION: Overall, the centres surveyed reported good compliance with most of the RANZCR SABR guidelines. The tasks with the lowest compliance were those that monitor quality outcomes. Potential strategies for improvement include inclusion in clinical trials and the use of databases which link treatment parameters, dosimetry and outcomes. Further work will focus on the barriers identified in this survey and propose practical solutions to improve compliance in these areas.

Optimisation of exposure conditions for in vitro radiobiology experiments.

Despite the long history of using cell cultures in vitro for radiobiological studies, there is to date no study specifically addressing the dosimetric implications of flask selection and exposure environment in clonogenic assays. The consequent variability in dosimetry between laboratories impedes the comparison of results. In this study we compare the dose to cells adherent to the base of three types of commonly used culture flasks or plates. The cells are exposed to a 6MV clinical photon beam using either an open or a half blocked field. The depth of medium in each flask is varied with the medium surrounding the flask either water or air. The results show that the dose to the cells is more affected by the scattering conditions surrounding the flasks than by the level of filling within the flask. It is recommended that water or a water equivalent phantom material is used to surround the flasks or plates to approximate full scatter conditions at the cell layer. However for modulated fields, surrounding the 24 well plates with water-equivalent material is inadequate because of the large volume of air surrounding individual wells. Our results stress the importance of measuring the dose for new experimental configurations.

SEAFARER - A new concept for validating radiotherapy patient specific QA for clinical trials and clinical practice.

BACKGROUND: The quality of radiotherapy delivery has been shown to significantly impact clinical outcomes including patient survival. To identify errors, institutions perform Patient Specific Quality Assurance (PSQA) assessing each individual radiotherapy plan prior to starting patient treatments. Externally administered Dosimetry Audits have found problems despite institutions passing their own PSQA. Hence a new audit concept which assesses the institution's ability to detect errors with their routine PSQA is needed. METHODS: Purposefully introduced edits which simulated treatment delivery errors were embedded into radiation treatment plans of participating institutions. These were designed to produce clinically significant changes yet were mostly within treatment delivery specifications. Actual impact was centrally assessed for each plan. Institutions performed PSQA on each plan, without knowing which contained errors. RESULTS: Seventeen institutions using six radiation treatment planning systems and two delivery systems performed PSQA on twelve plans each. Seventeen erroneous plans (across seven institutions) passed PSQA despite causing >5% increase in spinal cord dose relative to the original plans. Six plans (from four institutions) passed despite a >10% increase. CONCLUSIONS: This novel audit concept evolves beyond testing an institution's ability to deliver a single test case, to increasing the number of errors caught by institutions themselves, thus increasing quality of radiation therapy and impacting every patient treated. Administered remotely this audit also provides advantages in cost, environmental impact, and logistics.

Stereotactic ablative body radiation therapy (SABR) in NSW.

A survey was conducted to establish the current utilisation of stereotactic ablative radiation therapy (SABR) services in NSW. The objective of the survey was to generate baseline data to inform requirements for a networked approach to the implementation of new radiation therapy techniques and technologies. All radiation therapy services in NSW were contacted by email with a request to complete a SABR service survey. Questions were designed to identify equipment used, treatment techniques in place, clinical sites treated with a SABR technique and plans to expand the current services offered. Each professional group was asked to identify areas of service delivery they would most like to improve. Sixteen responses were received representing 24 of 27 (89%) of NSW radiation therapy centres. The results indicate that most centres now treat with SABR, however the number of centres and the treatment sites are still increasing. VMAT treatments and 3D imaging are now commonplace. Liver was the most commonly reported treatment site where confidence in service delivery needed improvement. Data from the survey will be useful in formulating future collaborative and educational activities aimed at improving safety and efficacy in SABR service delivery to all patients in NSW and potentially the rest of the country.

Women and men in the Australasian College of Physical Scientists and Engineers in Medicine: workforce survey.

A survey was designed to determine aspirations, motivations and workplace experiences of both female and male members of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM). The survey collected both quantitate and qualitative data, including open ended questions. This paper reports the survey's qualitative results. The research was approved by Ethics at University of South Australia and endorsed by ACPSEM. All 205 women (30% of total membership) and 440 men were invited to complete the survey online. The data for the qualitative analysis were responses to open-ended questions within the survey. 102 women and 150 men completed surveys were received, with 66 surveys analysed, before data saturation was reached. The survey revealed a number of themes that reflect concerns and opportunities identifying the direction for improving work-life balance and gender equity within the medical physics profession in Australasia. Issues around managing challenging workloads and professional development were amplified for women with children and child-rearing responsibilities, directly contributing to a reduction in work capacity and a reorientation of work-life priorities. The survey provides direction for strategies to improve work-life balance and enable equitable engagement in the profession. The first is to identify and develop role models that actively model successful work-life balance and flexibility in gender roles and in professional conduct. The second is to improve the management skills of current and emerging administrators, advocating for improved work conditions for medical physics professionals at an organisation level. Finally, efforts need to be made to establish flexible professional development and career progression opportunities amongst those that are unable to commit to large workloads, which is common for those with child-rearing responsibilities. The realisation of these strategic goals will reduce the identified barriers to full female participation in the workforce, and shift gender-based subcultures within the workplace.

In-vivo dosimetry comparison of supraclavicular junction dose for breast and chest-wall patients with and without deep inspiration breath hold (DIBH).

PURPOSE: The use of deep inspiration breath-hold (DIBH) for patients with left-sided breast cancer reduces cardiac dose, with the aim of reducing the risk of major coronary events. However, this technique has not been universally adopted for patients requiring regional nodal irradiation (RNI) with one concern related to the junction dose. This study evaluates the dose received at the junction for both DIBH and free-breathing patients having tangential breast/chest wall radiation and regional nodal radiation treated with 3D-conformal or hybrid IMRT radiotherapy. METHODS: In-vivo dosimetry measurements utilizing EBT3 GafChromic™ film were performed for 19 patients during three fractions over their course of treatment. The mean junction dose and variability in junction dose were compared between the DIBH and free breathing patients. RESULTS: Our results show that for voluntary DIBH (v-DIBH) patients the junction dose is more variable between fractions. However, when comparing the average junction dose for DIBH and free breathing patients over the three measurements, the difference was small and not statistically significant. A larger difference was seen when patient measurements were analysed based on treatment linac. CONCLUSIONS: These results show that the mean junction dose is not significantly compromised by the use of v-DIBH. The small possibility of a change in junction dose due to breathing technique should be weighed against the proven increased risks associated with excess cardiac dose received by free-breathing patients. If junction dose is of concern, an in-vivo study, such as this one, could allow cautious introduction of DIBH for patients requiring supraclavicular irradiation.

Radiation dosimetry in cell biology: comparison of calculated and measured absorbed dose for a range of culture vessels and clinical beam qualities.

PURPOSE: Cell culture studies are frequently used to evaluate the effects of cancer treatments such as radiotherapy, hormone therapy, chemotherapy, nanoparticle enhancement, and to determine any synergies between the treatments. To achieve valid results, the absorbed dose of each therapy needs to be well known and controlled. In this study, we aim to determine the uncertainty associated with radiation exposure in different experimental conditions. MATERIALS AND METHODS: We have performed an in-depth evaluation of the absorbed dose and dose distribution that would be delivered to a cell sample when cultivated in a number of the more popular designs of culture vessels. We focus on exposure to two beam types: a kilovoltage x-ray beam and a megavoltage photon beam, both of which are routinely used to treat cancer patients in the clinical environment. CONCLUSIONS: Our results identify large variations of up to 16% in the absorbed dose across multi-well culture plates, which if ignored in radiobiological experiments, have the potential to lead to erroneous conclusions.

Assessment of voluntary deep inspiration breath-hold with CINE imaging for breast radiotherapy.

Deep Inspiration Breath-Hold (DIBH) techniques for breast cancer radiation therapy (RT) have reduced cardiac dose compared to Free Breathing (FB). Recently, a voluntary deep inspiration breath-hold (vDIBH) technique was established using in-room lasers and skin tattoos to monitor breath-hold. An in-house quality assessment of positional reproducibility during RT delivery with vDIBH in patients with left-sided breast cancer was evaluated. The electronic portal imaging device (EPID) was used in cinematographic (CINE) mode to capture a sequence of images during beam delivery. Weekly CINE images were retrospectively assessed for 20 left-sided breast cancer patients receiving RT in vDIBH, and compared with CINE images of 20 patients treated in FB. The intra-beam motion was assessed and the distance from the beam central axis (CA) to the internal chest wall (ICW) was measured on each CINE image. These were then compared to the planned distance on digitally reconstructed radiograph (DRR). The maximum intra-beam motion for any one patient measurement was 0.30 cm for vDIBH and 0.20 cm for FB. The mean difference between the distance from the CA to ICW on DRR and the equivalent distance on CINE imaging (as treated) was 0.28 cm (SD 0.17) for vDIBH patients and 0.25 cm (SD 0.14) for FB patients (P = 0.458). The measured values were comparable for patients undergoing RT in vDIBH, and for those in FB. This quality assessment showed that using in-room lasers and skin tattoos to independently monitor breath-hold in vDIBH as detected by 'on-treatment' CINE imaging is safe and effective.

An imaging evaluation of the simultaneously integrated boost breast radiotherapy technique.

INTRODUCTION: To evaluate in-field megavoltage (MV) imaging of simultaneously integrated boost (SIB) breast fields to determine its feasibility in treatment verification for the SIB breast radiotherapy technique, and to assess whether the current-imaging protocol and treatment margins are sufficient. METHODS: For nine patients undergoing SIB breast radiotherapy, in-field MV images of the SIB fields were acquired on days that regular treatment verification imaging was performed. The in-field images were matched offline according to the scar wire on digitally reconstructed radiographs. The offline image correction results were then applied to a margin recipe formula to calculate safe margins that account for random and systematic uncertainties in the position of the boost volume when an offline correction protocol has been applied. RESULTS: After offline assessment of the acquired images, 96% were within the tolerance set in the current department-imaging protocol. Retrospectively performing the maximum position deviations on the Eclipse™ treatment planning system demonstrated that the clinical target volume (CTV) boost received a minimum dose difference of 0.4% and a maximum dose difference of 1.4% less than planned. Furthermore, applying our results to the Van Herk margin formula to ensure that 90% of patients receive 95% of the prescribed dose, the calculated CTV margins were comparable to the current departmental procedure used. CONCLUSION: Based on the in-field boost images acquired and the feasible application of these results to the margin formula the current CTV-planning target volume margins used are appropriate for the accurate treatment of the SIB boost volume without additional imaging.