Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers.

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men With Locally Advanced Prostate Cancer: 10-Year Data From the TROG 03.04 RADAR Trial.

PURPOSE: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer. METHODS AND MATERIALS: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group. RESULTS: A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups. CONCLUSIONS: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.

Sustainability of the Australian radiation oncology workforce: A survey of radiation therapists and radiation oncology medical physicists.

This study aimed to determine and compare Radiation Therapists' (RTs') and Radiation Oncology Medical Physicists' (ROMPs') perspectives about their profession and workplace, satisfaction with career progression opportunities, and leaving the current workplace. RTs and ROMPs who were currently or had previously worked in Australia were invited to complete an online survey. Univariate and multivariate methods were used for analysis. Participants were 342 RTs and 112 ROMPs with estimated response rates of 14% and 26% respectively. Both professions rated workload poorly and identified the need for improvement in: communication between professions' members, support for junior staff/new graduates, staff morale, on-site training and multidisciplinary communication. RTs, more than ROMPs, perceived their profession was recognised and respected, but RTs were less likely to be satisfied with career progression/advancement, job promotion prospects and opportunities to specialise. At least 20% of RTs and ROMPs were thinking about leaving their workplace and 13% of RTs and 8% of ROMPs were thinking about leaving their profession. Different factors contributed to workforce satisfaction and retention within each profession. Staff satisfaction and career progression are critical to retain RTs and ROMPs. Further research is required to explore strategies to address workplace dissatisfaction, recruitment and retention.

Association between measures of treatment quality and disease progression in prostate cancer radiotherapy: An exploratory analysis from the TROG 03.04 RADAR trial.

INTRODUCTION: Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. The study's purpose was to determine whether post-treatment disease progression is associated with measures of the quality of radiotherapy treatment. METHODS: The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose-escalated external beam radiation therapy. The trial incorporated a plan-review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan-Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality-related variables and the participant outcome local composite progression. RESULTS: Increased 'dose-difference' at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality-related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression. CONCLUSIONS: This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality-indicator outliers, and thus reduce the chance of observing significant associations with progression rates.

Radiation therapists' perspectives on participating in research.

INTRODUCTION: The objectives of this research were to: (1) determine the extent of Australian radiation therapists (RTs) research participation; (2) evaluate the impact of research involvement on career perceptions (3) explore which research topics require investigation and (4) identify benefits and barriers to research participation. METHODS: This study used mixed methods to collect qualitative and quantitative data using an online survey from a larger workforce study of RTs and radiation oncology medical physicists. Participants practising in Australia completed questions about their research involvement. Chi-square tests and logistic regression were used to analyse quantitative data and content analysis was used to explore qualitative data. RESULTS: Two hundred and ninety-six RTs answered the research questions. Forty-six percent had been involved in research. Of these, 91% had been involved in departmental, 28% in national, 14% in international and 29% in informal or self-directed research studies. Eleven RTs (8%) had received funding as a chief/principal investigator. Involvement in research was associated with a desire to make a career change. However, it also appeared to be associated with greater satisfaction with career progression and staying in the career. Respondents identified a range of potential research topics, benefits of participating in research and barriers which included lack of time, support and cost. CONCLUSION: Almost half of the RT participants identified that they were participating in research. Our data suggest that continued involvement in research, and opportunities to participate, improve RT job satisfaction. RTs' research activities are likely to be extended through provision of additional time and support.

A randomised comparison of three different immobilisation devices for thoracic and abdominal cancers.

INTRODUCTION: Patient immobilisation is critically important for both highly conformal conventionally fractionated radiotherapy and for stereotactic body radiotherapy. Different immobilisation devices are available to maintain patient position for radiotherapy but the most suitable one remains unknown. METHODS: Forty-five patients were randomly allocated to one of three immobilisation devices; the Q fix arm shuttle, BodyFIX without wrap or BodyFIX with wrap. Patients were imaged before and after treatment to ascertain intra-fraction and inter-fraction motion. Bony anatomy was used for matching to determine the positional accuracy of each device. Treatments were timed using a standard method. Patient comfort and staff satisfaction questionnaires were also issued to determine comfort, ease of use and preferences for each device. RESULTS: The BodyFIX without wrap was the more accurate device; however, the differences between the devices were not statistically significant. The BodyFIX with wrap was found to take significantly longer to set up and set down compared to the arm shuttle and the BodyFIX without wrap (all P < 0.001). Patients (37%) marginally preferred the BodyFIX with wrap. Most (81%) staff preferred the BodyFIX without wrap. CONCLUSION: Immobilisation using the BodyFIX without wrap was deemed to be suitable for clinical use. It was a clinically accurate device, the more efficient in terms of set up and set down time, the most preferred by staff and was accepted by patients.

An assessment of radiation oncology medical physicists' perspectives on undertaking research.

As part of a study of the radiation oncology workforce, radiation oncology medical physicists (ROMPs) who had worked in Australia were surveyed regarding their attitudes to participating in research. Responses from 88 ROMPs were available for analysis, representing a broad mix of employment situations and research experience. Greater than 70% of ROMPs described their involvement in research as "liking it" or "loving it", with associated identified benefits including skills development, job satisfaction and career progression. Over half of respondents agreed that involvement in research inspired them to stay in their profession. However, lack of time, support and motivation were all identified as barriers to participation in research. Areas of research interest were identified. This study highlights the importance of a research culture for job satisfaction and staff retention.

Radiation therapy staffing model 2014.

INTRODUCTION: In 2001, the Radiation Therapy Advisory Panel (RTAP) of the Australian Society of Medical Imaging and Radiation Therapy (ASMIRT) (formerly known as Australian Institute of Radiography) published a model for radiation therapist staffing in Australian radiation oncology departments. Between 2012-2013, the model was reviewed to ensure it reflected current radiation therapy practice, technology, and to facilitate forward planning of the radiation therapy workforce. METHOD: Twenty-four sites from all states participated and provided data on megavoltage simulation, planning and treatment delivery. For simulation and planning activity, the length of time to complete was collected against relevant Medicare Benefits Schedule (MBS) items. For treatment delivery, time to complete activities was collected against a common set of activities. Modelling assumptions are clearly identified in the methodology. RESULTS: A new model was developed retaining the essential model parameter of full-time equivalent (FTE) radiation therapists (RTs) per linear accelerator operating hour as in the 2001 model but based on contemporary practice and data. The model also includes significant refinements that improve the model's overall utility and flexibility for both workforce planning purposes and for individual services to use the model according to their own organisational needs and service delivery profiles. CONCLUSION: The ASMIRT believes that the 2014 RT staffing model provides the utility and flexibility for radiation oncology services to best plan RT staffing establishments according to their needs and reflecting the diversity between services and within the sector. It should also provide a robust and valid basis for governments and service planners to use as a guide in workforce planning into the future.

Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial.

BACKGROUND: The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. METHODS: We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. RESULTS: Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. CONCLUSION: RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration.

Technical quality assurance during the TROG 03.04 RADAR prostate radiotherapy trial: are the results reflected in observed toxicity rates?

INTRODUCTION: Multicentre radiotherapy clinical trials can incorporate quality assurance (QA) procedures for ensuring consistent application of the trial protocol in the planning, delivery and reporting of participant treatments. Subsequently detected variations from trial protocol have previously been shown to reduce treatment efficacy, although little has been shown for toxicity rates. The purpose of this study was to investigate the association of QA measures and protocol variations on toxicity incidence in the context of a prostate radiotherapy trial. METHODS: Using QA records from the TROG 03.04 RADAR trial, the impact of variations on gastrointestinal (GI) and genito-urinary (GU) toxicities was investigated. RESULTS: Protocol variation rates were lower than reported in previous studies, and showed little correlation with GI toxicity outcomes. Variations classified as 'major' showed a non-significant trend for increased toxicity relative to those classified as 'minor'. Results from a Level III phantom-based dosimetry study showed some correlation with GI toxicity, whereas ranking on a set-up accuracy study did not impact on toxicity. Toxicity in general increased with the number of participants accrued per centre, at odds with previous reports relating to disease progression, with a potential link to increases in low-mid-range rectal doses in the cohort from higher-accruing centres. No QA-related variables correlated with GU toxicities. CONCLUSIONS: Besides non-significant trends, minimal association was observed between QA variables and toxicity rates for the RADAR trial. The intention of the trial's QA programme was to reduce treatment variations and minimise toxicity in the context of a relevantly advanced treatment approach.

Impact of treatment planning and delivery factors on gastrointestinal toxicity: an analysis of data from the RADAR prostate radiotherapy trial.

BACKGROUND: To assess the impact of incremental modifications of treatment planning and delivery technique, as well as patient anatomical factors, on late gastrointestinal toxicity using data from the TROG 03.04 RADAR prostate radiotherapy trial. METHODS: The RADAR trial accrued 813 external beam radiotherapy participants during 2003-2008 from 23 centres. Following review and archive to a query-able database, digital treatment plans and data describing treatment technique for 754 patients were available for analysis. Treatment demographics, together with anatomical features, were assessed using uni- and multivariate regression models against late gastrointestinal toxicity at 18-, 36- and 54-month follow-up. Regression analyses were reviewed in the context of dose-volume data for the rectum and anal canal. RESULTS: A multivariate analysis at 36-month follow-up shows that patients planned using a more rigorous dose calculation algorithm (DCA) was associated with a lower risk of stool frequency (OR: 0.435, CI: 0.242-0.783, corrected p = 0.04). Patients using laxative as a method of bowel preparation had higher risk of having increased stool frequency compared to patients with no dietary intervention (OR: 3.639, CI: 1.502-8.818, corrected p = 0.04). Despite higher risks of toxicities, the anorectum, anal canal and rectum dose-volume histograms (DVH) indicate patients using laxative had unremarkably different planned dose distributions. Patients planned with a more rigorous DCA had lower median DVH values between EQD23 = 15 Gy and EQD23 = 35 Gy. Planning target volume (PTV), conformity index, rectal width and prescription dose were not significant when adjusted for false discovery rate. Number of beams, beam energy, treatment beam definition, positioning orientation, rectum-PTV separation, rectal length and mean cross sectional area did not affect the risk of toxicities. CONCLUSIONS: The RADAR study dataset has allowed an assessment of technical modifications on gastrointestinal toxicity. A number of interesting associations were subsequently found and some factors, previously hypothesised to influence toxicity, did not demonstrate any significant impact. We recommend trial registries be encouraged to record technical modifications introduced during the trial in order for more powerful evidence to be gathered regarding the impact of the interventions.

Quality improvements in prostate radiotherapy: outcomes and impact of comprehensive quality assurance during the TROG 03.04 'RADAR' trial.

INTRODUCTION: The Trans-Tasman Radiation Oncology Group 03.04 'Randomised Androgen Deprivation and Radiotherapy' multicentre prostate cancer trial examined the optimal duration of androgen deprivation in combination with dose-escalated radiotherapy. Rigorous quality assurance (QA) processes were undertaken to ensure the validity and reliability of the radiation therapy treatment plan data. METHOD: QA processes included a planning benchmarking exercise and a periodic audit of target and normal tissue delineation. Centralised electronic review of digital plan data for external-beam radiotherapy was undertaken to detect protocol variations. The impact of clinical factors and feedback to submitting centres during the trial on variation rates was investigated. RESULTS: Twenty-three centres across Australia and New Zealand recruited 1071 participants to the trial. Treatment plans for 754 participants receiving external-beam treatment alone were reviewed. From these, 1185 minor and 86 major variations were identified, leading to feedback to treating centres to reduce variations for subsequent patients' treatment and plans, suggesting improvement in treatment quality through these QA programs. Participant anatomical factors (delineated clinical target volume and rectal volume) and treatment planning factors (beam energy, beam definition and patient position orientation) were found to significantly impact variation rates. The dummy run demonstrated disagreement in identification of the base of the prostate and the superior extent of the rectum. Feedback from the periodic audit led to a change of practice at five contributing centres. CONCLUSION: The application of a suite of complementary QA activities allows the quality of trial data to be optimised and quantified, and can provide a catalyst for reforming treatment practices.

Assuring high quality treatment delivery in clinical trials - Results from the Trans-Tasman Radiation Oncology Group (TROG) study 03.04 "RADAR" set-up accuracy study.

BACKGROUND AND PURPOSE: A multi-centre clinical trial for prostate cancer patients provided an opportunity to introduce conformal radiotherapy with dose escalation. To verify adequate treatment accuracy prior to patient recruitment, centres submitted details of a set-up accuracy study (SUAS). We report the results of the SUAS, the variation in clinical practice and the strategies used to help centres improve treatment accuracy. MATERIALS AND METHODS: The SUAS required each of the 24 participating centres to collect data on at least 10 pelvic patients imaged on a minimum of 20 occasions. Software was provided for data collection and analysis. Support to centres was provided through educational lectures, the trial quality assurance team and an information booklet. RESULTS: Only two centres had recently carried out a SUAS prior to the trial opening. Systematic errors were generally smaller than those previously reported in the literature. The questionnaire identified many differences in patient set-up protocols. As a result of participating in this QA activity more than 65% of centres improved their treatment delivery accuracy. CONCLUSIONS: Conducting a pre-trial SUAS has led to improvement in treatment delivery accuracy in many centres. Treatment techniques and set-up accuracy varied greatly, demonstrating a need to ensure an on-going awareness for such studies in future trials and with the introduction of dose escalation or new technologies.

Detailed review and analysis of complex radiotherapy clinical trial planning data: evaluation and initial experience with the SWAN software system.

AIM: Contemporary radiotherapy clinical trials typically require complex three-dimensional (3D) treatment planning. This produces large amounts of data relating technique and dose delivery for correlation with patient outcomes. Assessment of the quality of this information is required to ensure protocol compliance, to quantify the variation in treatments given to patients and to enhance the power of studies to determine correlates of patient outcomes. MATERIALS AND METHODS: A software system ('SWAN') was developed to facilitate the objective analysis, quality-assurance and review of digital treatment planning data from multi-centre radiotherapy trials. The utility of this system was assessed on the basis of its functionality and our experience of its use in the context of multi-centre clinical trials and trials-support activities. RESULTS: The SWAN system has been shown to have the functionality required for use in several multi-centre trials, including automated review and archive processes. Approximately 800 treatment plans from over 30 participating institutions have so far been assessed with the system for several treatment planning scenarios. To illustrate this we include a description of the use of the system for a large-recruitment prostate radiotherapy trial being undertaken in Australasia, including examples of how the review process has changed clinical practice. CONCLUSION: The successful implementation of SWAN has been demonstrated in a number of clinical trials. The software provides an opportunity for comprehensive review of treatment parameters that could impact on clinical outcomes and trial results. Such quality-assurance (QA) has previously been difficult or impossible to achieve, particularly for a clinical trial involving large numbers of patients. Such reviews have highlighted inconsistencies in clinical practice that have since been addressed through feedback from the review process. The process of data collection and review should be undertaken by dedicated, experienced and skilled staff in order to ensure efficiency.

External respiratory motion for abdominal radiotherapy patients: implications for patient alignment.

Conformal external beam radiotherapy relies on accurate spatial positioning of the tumor and normal tissues during treatment. For abdominal patients, this is complicated by the motion of internal organs and the external patient contour due to respiration. As external motion influences the degree of accuracy achievable in patient setup, this motion was studied to provide indication of motions occurring during treatment, as well as to assess the technique of breath-holding at exhale (B-HEX). The motion of external abdominal points (anterior and right lateral) of a series of volunteers was tracked in real-time using an infrared tracking system, with the volunteers in treatment position. The resulting motion data was assessed to evaluate (1) the change in position of each point per breath/breath-hold, (2) the change in position between breaths/breath-holds, and (3) the change in position across the whole recording time. Analysis shows that, for the anterior abdominal point, there is little difference in the variation of position with time for free-breathing as opposed to the B-HEX technique. For the lateral point however, the B-HEX technique reduces the motion during each treatment cycle (i.e., during the breath-hold) and over an extended period (i.e., during a series of breath-holds). The B-HEX technique thus provides greater accuracy for setup to lateral markers and provides the opportunity to reduce systematic and random localization errors.