The outcome of a multi-centre feasibility study of online adaptive radiotherapy for muscle-invasive bladder cancer TROG 10.01 BOLART.

PURPOSE: To assess whether online adaptive radiotherapy for bladder cancer is feasible across multiple Radiation Oncology departments using different imaging, delivery and recording technology. MATERIALS AND METHODS: A multi-centre feasibility study of online adaptive radiotherapy, using a choice of three "plan of the day", was conducted at 12 departments. Patients with muscle-invasive bladder cancer were included. Departments were activated if part of the pilot study or after a site-credentialing visit. There was real time review of the first two cases from each department. RESULTS: 54 patients were recruited, with 50 proceeding to radiotherapy. There were 43 males and 7 females with a mean age of 78 years. The tumour stages treated included T1 (1 patient), T2 (35), T3 (10) and T4 (4). One patient died of an unrelated cause during radiotherapy. The three adaptive plans were created before the 10th fraction in all cases. In 8 (16%) of the patients, a conventional plan using a 'standard' CTV to PTV margin of 1.5cm was used for one or more fractions where the pre-treatment bladder CTV was larger than any of the three adaptive plans. The bladder CTV extended beyond the PTV on post treatment imaging in 9 (18%) of the 49 patients. CONCLUSIONS: From a technical perspective an online adaptive radiotherapy technique can be instituted in a multi-centre setting. However, without further bladder filling control or imaging, a CTV to PTV margin of 7mm is insufficient.

Introduction of online adaptive radiotherapy for bladder cancer through a multicentre clinical trial (Trans-Tasman Radiation Oncology Group 10.01): Lessons learned.

Online adaptive radiotherapy for bladder cancer is a novel radiotherapy technique that was found feasible in a pilot study at a single academic institution. In September 2010 this technique was opened as a multicenter study through the Trans-Tasman Radiation Oncology Group (TROG 10.01 bladder online adaptive radiotherapy treatment). Twelve centers across Australia and New-Zealand registered interest into the trial. A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists represented the trial credentialing and technical support team. To provide timely activation and proper implementation of the adaptive technique the following key areas were addressed at each site: Staff education/training; Practical image guided radiotherapy assessment; provision of help desk and feedback. The trial credentialing process involved face-to-face training and technical problem solving via full day site visits. A dedicated "help-desk" team was developed to provide support for the clinical trial. 26% of the workload occurred at the credentialing period while the remaining 74% came post-center activation. The workload was made up of the following key areas; protocol clarification (36%), technical problems (46%) while staff training was less than 10%. Clinical trial credentialing is important to minimizing trial deviations. It should not only focus on site activation quality assurance but also provide ongoing education and technical support.

Movie making as a cognitive distraction for paediatric patients receiving radiotherapy treatment: qualitative interview study.

OBJECTIVES: To establish the outcomes achieved by using an innovative movie-making programme designed to reduce fear of radiotherapy among paediatric patients. DESIGN: Qualitative descriptive evaluation based on semistructured, qualitative interviews with purposeful sampling and thematic analysis. SETTING: Tertiary Cancer Centre. PARTICIPANTS: 20 parents of paediatric patients who had produced a movie of their radiation therapy experience and were in a follow-up phase of cancer management. RESULTS: Participants attributed a broad range of outcomes to the movie-making program. These included that the programme had helped reduce anxiety and distress exhibited by paediatric patients and contributed to a willingness to receive treatment. Other outcomes were that the completed movies had been used in school reintegration and for maintaining social connections. CONCLUSIONS: Allowing children to create a video of their experience of radiotherapy provided a range of benefits to paediatric patients that varied according to their needs. For some patients, movie-making offered a valuable medium for overcoming fear of the unknown as well as increasing understanding of treatment processes. For others, the development of a personalised video offered an important cognitive/attentional distraction through engaging with an age-appropriate activity. Together these outcomes helped children maintain self-control and a positive outlook.

The utility of e-Learning to support training for a multicentre bladder online adaptive radiotherapy trial (TROG 10.01-BOLART).

BACKGROUND AND PURPOSE: An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial. The aim of this study is to demonstrate the utility of this e-Learning programme. MATERIALS AND METHODS: Modules were created on relevant pelvic anatomy, Cone Beam CT soft tissue recognition and trial details. Radiation therapist participants' knowledge and confidence were evaluated before, at the end of, and after at least 6 weeks of e-Learning (long term). RESULTS: One hundred and eighty-five participants were recruited from 12 centres, with 118 in the first, and 67 in the second cohort. One hundred and forty-six participants had two tests (pre and post e-Learning) and 39 of these had three tests (pre, post, and long term). There was an increase confidence after completion of modules (p<0.001). The first cohort pre scores increased from 67 ± 11 to 79 ± 8 (p<0.001) post. The long term same question score was 73 ± 14 (p=0.025, comparing to pre-test), and different questions' score was 77 ± 13 (p=0.014). In the second cohort, pre-test scores were 64 ± 10, post-test same question score 78 ± 9 (p<0.001) and different questions' score 81 ± 11 (p<0.001). CONCLUSIONS: e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge.

Optimising the dosimetric quality and efficiency of post-prostatectomy radiotherapy: a planning study comparing the performance of volumetric-modulated arc therapy (VMAT) with an optimised seven-field intensity-modulated radiotherapy (IMRT) technique.

PURPOSE: The purpose of this study was to compare and evaluate radiotherapy treatment plans using volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) for post-prostatectomy radiotherapy. METHODS AND MATERIALS: The quality of radiotherapy plans for 10 patients planned and treated with a seven-field IMRT technique for biochemical failure post-prostatectomy were subsequently compared with 10 prospectively planned single-arc VMAT plans using the same computed tomography data set and treatment planning software. Plans were analysed using parameters to assess for target volume coverage, dose to organs at risk (OAR), biological outcomes, dose conformity and homogeneity, as well as the total monitor units (MU), planning and treatment efficiency. RESULTS: The mean results for the study population are reported for the purpose of comparison. For IMRT, the median dose to the planning target volume, V(95%) and D(95%) was 71.1 Gy, 98.9% and 68.3 Gy compared with 71.2 Gy, 99.2% and 68.6 Gy for VMAT. There was no significant difference in the conformity index or homogeneity index. The VMAT plans achieved better sparing of the rectum and the left and right femora with a reduction in the median dose by 7.9, 6.3 and 3.6 Gy, respectively. The total number of monitor units (MU) was reduced by 24% and treatment delivery time by an estimated 3 min per fraction without a significant increase in planning requirements. CONCLUSIONS: VMAT can achieve post-prostatectomy radiotherapy plans of comparable quality to IMRT with the potential to reduce dose to OAR and improve the efficiency of treatment delivery.

Credentialing of radiotherapy centres for a clinical trial of adaptive radiotherapy for bladder cancer (TROG 10.01).

BACKGROUND: Daily variations in bladder filling make conformal treatment of bladder cancer challenging. On-line adaptive radiotherapy with a choice of plans has been demonstrated to reduce small bowel irradiation in single institution trials. In order to support a multicentre feasibility clinical trial on adaptive radiotherapy for bladder cancer (TROG 10.01) a credentialing programme was developed for centres wishing to participate. METHODS: The credentialing programme entails three components: a facility questionnaire; a planning exercise which tests the ability of centres to create three adaptive plans based on a planning and five cone beam CTs; and a site visit during which image quality, imaging dose and image guidance procedures are assessed. Image quality and decision making were tested using customised inserts for a Perspex phantom (Modus QUASAR) that mimic different bladder sizes. Dose was assessed in the same phantom using thermoluminescence dosimetry (TLD). RESULTS: All 12 centres participating in the full credentialing programme were able to generate appropriate target volumes in the planning exercise and identify the correct target volume and position the bladder phantom in the phantom within 3mm accuracy. None of the imaging doses exceeded the limit of 5 cGy with a CT on rails system having the lowest overall dose. CONCLUSION: A phantom mimicking the decision making process for adaptive radiotherapy was found to be well suited during site visits for credentialing of centres participating in a clinical trial of adaptive radiotherapy for bladder cancer. Combined with a planning exercise the site visit allowed testing the ability of centres to create adaptive treatment plans and make appropriate decisions based on the volumetric images acquired at treatment.

Benchmarking dosimetric quality assessment of prostate intensity-modulated radiotherapy.

PURPOSE: To benchmark the dosimetric quality assessment of prostate intensity-modulated radiotherapy and determine whether the quality is influenced by disease or treatment factors. PATIENTS AND METHODS: We retrospectively analyzed the data from 155 consecutive men treated radically for prostate cancer using intensity-modulated radiotherapy to 78 Gy between January 2007 and March 2009 across six radiotherapy treatment centers. The plan quality was determined by the measures of coverage, homogeneity, and conformity. Tumor coverage was measured using the planning target volume (PTV) receiving 95% and 100% of the prescribed dose (V(95%) and V(100%), respectively) and the clinical target volume (CTV) receiving 95% and 100% of the prescribed dose. Homogeneity was measured using the sigma index of the PTV and CTV. Conformity was measured using the lesion coverage factor, healthy tissue conformity index, and the conformity number. Multivariate regression models were created to determine the relationship between these and T stage, risk status, androgen deprivation therapy use, treatment center, planning system, and treatment date. RESULTS: The largest discriminatory measurements of coverage, homogeneity, and conformity were the PTV V(95%), PTV sigma index, and conformity number. The mean PTV V(95%) was 92.5% (95% confidence interval, 91.3-93.7%). The mean PTV sigma index was 2.10 Gy (95% confidence interval, 1.90-2.20). The mean conformity number was 0.78 (95% confidence interval, 0.76-0.79). The treatment center independently influenced the coverage, homogeneity, and conformity (all p < .0001). The planning system independently influenced homogeneity (p = .038) and conformity (p = .021). The treatment date independently influenced the PTV V(95%) only, with it being better at the start (p = .013). Risk status, T stage, and the use of androgen deprivation therapy did not influence any aspect of plan quality. CONCLUSION: Our study has benchmarked measures of coverage, homogeneity, and conformity for the treatment of prostate cancer using IMRT. The differences seen between centers and planning systems and the coverage deterioration over time highlight the need for every center to determine their own benchmarks and apply clinical vigilance with respect to maintaining these through quality assurance.

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy.

BACKGROUND: Image-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically. METHODS: Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74 Gy in 37 fractions, to 78 Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment. RESULTS: In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference. CONCLUSIONS: In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.

Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study.

PURPOSE: To determine the advantages and disadvantages of daily online adaptive image-guided radiotherapy (RT) compared with conventional RT for muscle-invasive bladder cancer. METHODS AND MATERIALS: Twenty-seven patients with T2-T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided RT using cone-beam computed tomography (CBCT). From day 1 daily soft tissue-based isocenter positioning was performed using CBCT images acquired before treatment. Using a composite of the initial planning CT and the first five daily CBCT scans, small, medium, and large adaptive plans were created. Each of these adaptive plans used a 0.5-cm clinical target volume (CTV) to planning target volume expansion. For Fractions 8-32, treatment involved daily soft tissue-based isocenter positioning and selection of suitable adaptive plan of the day. Treating radiation therapists completed a credentialing program, and one radiation oncologist performed all the contouring. Comparisons were made between adaptive and conventional treatment on the basis of CTV coverage and normal tissue sparing. RESULTS: All 27 patients completed treatment per protocol. Bladder volume decreased with time or fraction number (p < 0.0001). For the adaptive component (Fractions 8-32) the small, medium, large, and conventional plans were used in 9.8%, 49.2%, 39.5%, and 1.5% of fractions, respectively. For the adaptive strategy, 2.7% of occasions resulted in a CTV V95 <99%, compared with 4.8% of occasions for the conventional approach (p = 0.42). Mean volume of normal tissue receiving a dose >45 Gy was 29% (95% confidence interval, 24-35%) less with adaptive RT compared with conventional RT. The mean volume of normal tissue receiving >5 Gy was 15% (95% confidence interval, 11-18%) less with adaptive RT compared with conventional RT. CONCLUSIONS: Online adaptive radiotherapy is feasible in an academic radiotherapy center. The volume of normal tissue irradiated can be significantly smaller without reducing CTV coverage.

Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre.

PURPOSE: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. METHODS AND MATERIALS: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5-8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8-years post treatment. RESULTS: All patients completed radiotherapy without any treatment breaks. The 8-year risks of ≥ Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of ≥ Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. CONCLUSIONS: These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting.

The dosimetric consequences of anatomic changes in head and neck radiotherapy patients.

INTRODUCTION: To investigate anatomical response-related changes in the head and neck region during a course of radical radiotherapy and their impact on the planned dosimetry. METHODS: The study consisted of 10 patients with primary mucosal carcinoma. Patients' nutritional requirements were managed as per departmental protocol to minimise weight loss during treatment. Kilovoltage computed tomography (CT) scans were acquired once 40 to 50 Gy had been delivered. Gross tumour volumes (GTV) and organs at risk were delineated and the initial optimised treatment plan was overlaid on the repeat CT. Comparisons were made between scans and absolute volume variations, centres of structures, dice similarity coefficients and the subsequent dosimetric impact were assessed. RESULTS: Median weight loss at second scan was 3%. Primary and lymph node GTVs reduced by 49.9% (range 21.3-82%) and 73.7% (range 61.7-88.6%), respectively, yet continued to receive the prescribed dose. Maximum dose to spinal cord and brainstem changed minimally. Spared and un-spared parotid gland volumes reduced by median 23.5% and 20.5%, respectively, with no consistent translational displacement direction and minimal change in the mean dose. CONCLUSIONS: Despite some significant geometric changes, nutritional management ensured patient size and shape was maintained in these consecutively selected patients and subsequently there was no apparent under-dosing of targets or over-dosing of normal structures with this technique. Further investigations which model gradual change and allow cumulative dosimetry are required to better characterise what occurs during the treatment course.

Adaptive radiotherapy for bladder cancer reduces integral dose despite daily volumetric imaging.

We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging.

A Phase II study of external-beam radiotherapy and endovascular brachytherapy with PTA and stenting for femoropopliteal artery restenosis.

PURPOSE: To assess the safety and seek evidence of efficacy of combined external-beam radiotherapy (EBRT) and endovascular brachytherapy in the treatment of stenotic vascular lesions. METHODS AND MATERIALS: Seventeen patients with high risk for restenosis of femoropopliteal arteries were enrolled in this study from February 2000 to August 2002. The external beam radiotherapy regimen consisted of 10 Gy in 5 fractions of 2 Gy, starting on Day 0. This was followed on Day 6 by angiography, stent placement, and intraluminal brachytherapy to a dose of 10 Gy at 1.2 mm from stent surface. The EBRT was continued from the same day to another 10 Gy in 2 Gy daily fractions for 5 days. RESULTS: The follow up ranged from 33 months to 60 months. At the time of analysis 15 of 17 patients were alive with patent stents. Of these, 10 were symptom-free. Two patients died of unrelated causes. CONCLUSIONS: The combination of EBRT and endovascular brachytherapy provided adequate dose distribution without any geographical miss or "candy wrapper" restenosis. No incidence of aneurysmal dilation of radiated vascular segment was observed. The treatment was feasible, well tolerated, and achieved 88% stenosis free survival.