Carbonic anhydrase IX expression and outcome after radiotherapy for muscle-invasive bladder cancer

Aims: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. Materials and methods: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. Results: CA IX immunostaining was detected in 89 (∼81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. Conclusions: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy. © 2007 The Royal College of Radiologists.

Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer : a retrospective analysis of a tertiary institute experience

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

Constructing a clinical decision-making framework for image-guided radiotherapy using a Bayesian Network

A decision-making framework for image-guided radiotherapy (IGRT) is being developed using a Bayesian Network (BN) to graphically describe, and probabilistically quantify, the many interacting factors that are involved in this complex clinical process. Outputs of the BN will provide decision-support for radiation therapists to assist them to make correct inferences relating to the likelihood of treatment delivery accuracy for a given image-guided set-up correction. The framework is being developed as a dynamic object-oriented BN, allowing for complex modelling with specific sub-regions, as well as representation of the sequential decision-making and belief updating associated with IGRT. A prototype graphic structure for the BN was developed by analysing IGRT practices at a local radiotherapy department and incorporating results obtained from a literature review. Clinical stakeholders reviewed the BN to validate its structure. The BN consists of a sub-network for evaluating the accuracy of IGRT practices and technology. The directed acyclic graph (DAG) contains nodes and directional arcs representing the causal relationship between the many interacting factors such as tumour site and its associated critical organs, technology and technique, and inter-user variability. The BN was extended to support on-line and off-line decision-making with respect to treatment plan compliance. Following conceptualisation of the framework, the BN will be quantified. It is anticipated that the finalised decision-making framework will provide a foundation to develop better decision-support strategies and automated correction algorithms for IGRT.

A practical and theoretical definition of very small field size for radiotherapy output factor measurements

Purpose This work introduces the concept of very small field size. Output factor (OPF) measurements at these field sizes require extremely careful experimental methodology including the measurement of dosimetric field size at the same time as each OPF measurement. Two quantifiable scientific definitions of the threshold of very small field size are presented. Methods A practical definition was established by quantifying the effect that a 1 mm error in field size or detector position had on OPFs, and setting acceptable uncertainties on OPF at 1%. Alternatively, for a theoretical definition of very small field size, the OPFs were separated into additional factors to investigate the specific effects of lateral electronic disequilibrium, photon scatter in the phantom and source occlusion. The dominant effect was established and formed the basis of a theoretical definition of very small fields. Each factor was obtained using Monte Carlo simulations of a Varian iX linear accelerator for various square field sizes of side length from 4 mm to 100 mm, using a nominal photon energy of 6 MV. Results According to the practical definition established in this project, field sizes < 15 mm were considered to be very small for 6 MV beams for maximal field size uncertainties of 1 mm. If the acceptable uncertainty in the OPF was increased from 1.0 % to 2.0 %, or field size uncertainties are 0.5 mm, field sizes < 12 mm were considered to be very small. Lateral electronic disequilibrium in the phantom was the dominant cause of change in OPF at very small field sizes. Thus the theoretical definition of very small field size coincided to the field size at which lateral electronic disequilibrium clearly caused a greater change in OPF than any other effects. This was found to occur at field sizes < 12 mm. Source occlusion also caused a large change in OPF for field sizes < 8 mm. Based on the results of this study, field sizes < 12 mm were considered to be theoretically very small for 6 MV beams. Conclusions Extremely careful experimental methodology including the measurement of dosimetric field size at the same time as output factor measurement for each field size setting and also very precise detector alignment is required at field sizes at least < 12 mm and more conservatively < 15 mm for 6 MV beams. These recommendations should be applied in addition to all the usual considerations for small field dosimetry, including careful detector selection.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity-modulated and volumetric-modulated arc radiotherapy

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across 5 centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity-modulated radiotherapy (IMRT) and 47 treated with volumetric-modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organ-at-risk sparing, through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each organ-at-risk. Statistical significance was evaluated using two-tailed Welch’s T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the organs-at-risk: with increased compliance with recommended organ-at-risk dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

A simple method for EPID-based in vivo dosimetry for radiotherapy treatments of head-and-neck cancers

This study used a homogeneous water-equivalent model of an electronic portal imaging device (EPID), contoured as a structure in a radiotherapy treatment plan, to produce reference dose images for comparison with in vivo EPID dosimetry images. Head and neck treatments were chosen as the focus of this study, due to the heterogeneous anatomies involved and the consequent difficulty of rapidly obtaining reliable reference dose images by other means. A phantom approximating the size and heterogeneity of a typical neck, with a maximum radiological thickness of 8.5 cm, was constructed for use in this study. This phantom was CT scanned and a simple treatment including five square test fields and one off-axis IMRT field was planned. In order to allow the treatment planning system to calculate dose in a model EPID positioned a distance downstream from the phantom to achieve a source-to-detector distance (SDD) of 150 cm, the CT images were padded with air and the phantom’s “body” contour was extended to encompass the EPID contour. Comparison of dose images obtained from treatment planning calculations and experimental irradiations showed good agreement, with more than 90% of points in all fields passing a gamma evaluation, at γ (3%, 3mm )Similar agreement was achieved when the phantom was over-written with air in the treatment plan and removed from the experimental beam, suggesting that water EPID model at 150 cm SDD is capable of providing accurate reference images for comparison with clinical IMRT treatment images, for patient anatomies with radiological thicknesses ranging from 0 up to approximately 9 cm. This methodology therefore has the potential to be used for in vivo dosimetry during treatments to tissues in the neck as well as the oral and nasal cavities, in the head-and-neck region.

Commissioning of a new commercial plastic scintillator system for radiotherapy

Introduction Since 1992 there have been several articles published on research on plastic scintillators for use in radiotherapy. Plastic scintillators are said to be tissue equivalent, temperature independent and dose rate independent [1]. Although their properties were found to be promising for measurements in megavoltage X-ray beams there were some technical difficulties with regards to its commercialisation. Standard Imaging has produced the first commercial system which is now available for use in a clinical setting. The Exradin W1 scintillator device uses a dual fibre system where one fibre is connected to the Plastic Scintillator and the other fibre only measures Cerenkov radiation [2]. This paper presents results obtained during commissioning of this dosimeter system. Methods All tests were performed on a Novalis Tx linear accelerator equipped with a 6 MV SRS photon beam and conventional 6 and 18 MV X-ray beams. The following measurements were performed in a Virtual Water phantom at a depth of dose maximum. Linearity: The dose delivered was varied between 0.2 and 3.0 Gy for the same field conditions. Dose rate dependence: For this test the repetition rate of the linac was varied between 100 and 1,000 MU/min. A nominal dose of 1.0 Gy was delivered for each rate. Reproducibility: A total of five irradiations for the same setup. Results The W1 detector gave a highly linear relationship between dose and the number of Monitor Units delivered for a 10 9 10 cm2 field size at a SSD of 100 cm. The linearity was within 1 % for the high dose end and about 2 % for the very low dose end. For the dose rate dependence, the dose measured as a function of repetition the rate (100–1,000 MU/min) gave a maximum deviation of 0.9 %. The reproducibility was found to be better than 0.5 %. Discussion and conclusions The results for this system look promising so far being a new dosimetry system available for clinical use. However, further investigation is needed to produce a full characterisation prior to use in megavoltage X-ray beams.

Prostate radiotherapy treatment plan quality : effects of hip prostheses

Introduction This study aimed to examine the geometric and dosimetric results when radiotherapy treatment plans are designed for prostate cancer patients with hip prostheses. Methods Ten EBRT treatment plans for localised prostate cancer, in the presence of hip prostheses, were analysed and compared with a reference set of 196 treatment plans for localised prostate cancer in patients without prostheses. Crowe et al.’s TADA code [1] was used to extract treatment plan parameters and evaluate doses to target volumes and critical structures against recommended goals [2] and constraints [3, 4]. Results The need to avoid transmitting the radiation beam through the hip prostheses limited the range of gantry angles available for use in both the rotational (VMAT) and the non-rotational (3DCRT and IMRT) radiotherapy treatments. This geometric limitation (exemplified in the VMAT data shown in Fig. 1) reduced the overall quality of the treatment plans for patients with prostheses compared to the reference plans. All plans with prostheses failed the PTV dose homogeneity requirement [2], whereas only 4 % of the plans without prostheses failed this test. Several treatment plans for patients with hip prostheses also failed the QUANTEC requirements that less than 50 % of the rectum receive 50 Gy and less than 35 % of the rectum receive 60 Gy to keep the grade 3 toxicity rate below 10 % [3], or the Hansen and Roach requirement that less than 25 % of the bladder receive 75 Gy [4]. Discussion and conclusions The results of this study exemplify the difficulty of designing prostate radiotherapy treatment plans, where beams provide adequate doses to targeted tissues while avoiding nearby organs at risk, when the presence of hip prostheses limits the available treatment geometries. This work provides qualitative evidence of the compromised dose distributions that can result, in such cases.

Development of a dose assessment tool for the auditing of radiotherapy treatment dosimetric quality

The reporting and auditing of patient dose is an important component of radiotherapy quality assurance. The manual extraction of dose-volume metrics is time consuming and undesirable when auditing the dosimetric quality of a large cohort of patient plans. A dose assessment application was written to overcome this, allowing the calculation of various dose-volume metrics for large numbers of plans exported from treatment planning systems. This application expanded on the DICOM-handling functionality of the MCDTK software suite. The software extracts dose values in the volume of interest by using a ray casting point-in-polygon algorithm, where the polygons have been defined by the contours in the RTSTRUCT file...

Gel dosimetry—it’s been the next big thing in radiotherapy for the past 25 years

Gel dosimetry and plastic chemical dosimeters such as PresageTM are capable of very accurately mapping dose distributions in three dimensions. Combined with their near tissue equivalence one would expect that after several decades of development they would be the dosimeter of choice for dosimetry, however they have not achieve widespread clinical use. This presentation will include a brief description and history of developments in gels and 3D plastics for dosimetry, the limitations and advantages, and their role in the future.

CTCombine : rotating and combining CT data with an accurate detector model to simulate radiotherapy portal imaging at non-zero beam angles

Established Monte Carlo user codes BEAMnrc and DOSXYZnrc permit the accurate and straightforward simulation of radiotherapy experiments and treatments delivered from multiple beam angles. However, when an electronic portal imaging detector (EPID) is included in these simulations, treatment delivery from non-zero beam angles becomes problematic. This study introduces CTCombine, a purpose-built code for rotating selected CT data volumes, converting CT numbers to mass densities, combining the results with model EPIDs and writing output in a form which can easily be read and used by the dose calculation code DOSXYZnrc...

4DCT radiotherapy for NSCLC: A review of planning methods

Purpose To establish whether the use of a passive or active technique of planning target volume (PTV) definition and treatment methods for non-small cell lung cancer (NSCLC) deliver the most effective results. This literature review assesses the advantages and disadvantages in recent studies of each, while assessing the validity of the two approaches for planning and treatment. Methods A systematic review of literature focusing on the planning and treatment of radiation therapy to NSCLC tumours. Different approaches which have been published in recent articles are subjected to critical appraisal in order to determine their relative efficacy. Results Free-breathing (FB) is the optimal method to perform planning scans for patients and departments, as it involves no significant increase in cost, workload or education. Maximum intensity projection (MIP) is the fastest form of delineation, however it is noted to be less accurate than the ten-phase overlap approach for computed tomography (CT). Although gating has proven to reduce margins and facilitate sparing of organs at risk, treatment times can be longer and planning time can be as much as 15 times higher for intensity modulated radiation therapy (IMRT). This raises issues with patient comfort and stabilisation, impacting on the chance of geometric miss. Stereotactic treatments can take up to 3 hours to treat, along with increases in planning and treatment, as well as the additional hardware, software and training required. Conclusion Four-dimensional computed tomography (4DCT) is superior to 3DCT, with the passive FB approach for PTV delineation and treatment optimal. Departments should use a combination of MIP with visual confirmation ensuring coverage for stage 1 disease. Stages 2-3 should be delineated using ten-phases overlaid. Stereotactic and gated treatments for early stage disease should be used accordingly; FB-IMRT is optimal for latter stage disease.

The role of radiotherapy patients in provision of student interpersonal skills feedback

Background At Queensland University of Technology, student radiation therapists receive regular feedback from clinical staff relating to clinical interpersonal skills. Although this is of great value, there is anecdotal evidence that students communicate differently with patients when under observation. Purpose The aim of this pilot was to counter this perceived observer effect by allowing patients to provide students with additional feedback. Materials and methods Radiotherapy patients from two departments were provided with anonymous feedback forms relating to aspects of student interpersonal skills. Clinical assessors, mentors and students were also provided with feedback forms, including questions about the role of patient feedback. Patient perceptions of student performance were correlated with staff feedback and assessment scores. Results Results indicated that the feedback was valued by both students and patients. Students reported that the additional dimension focused them on communication, set goals for development and increased motivation. These changes derived from both feedback and study participation, suggesting that the questionnaires could be a useful teaching tool. Patients scored more generously than mentors, although there was agreement in relative grading. Conclusions The anonymous questionnaire is a convenient and valuable method of gathering patient feedback on students. Future iterations will determine the optimum timing for this method of feedback.

CT Anatomy for Radiotherapy

Knowledge of CT anatomy is increasingly vital in daily radiotherapy practice, especially with more widespread use of cross-sectional image-guided radiotherapy (IGRT) techniques. Existing CT anatomy texts are predominantly written for the diagnostic practitioner and do not always address the radiotherapy issues while emphasising structures that are not common to radiotherapy practice. CT Anatomy for Radiotherapy is a new radiotherapy-specific text that is intended to prepare the reader for CT interpretation for both IGRT and treatment planning. It is suitable for undergraduate students, qualified therapy radiographers, dosimetrists and may be of interest to oncologists and registrars engaged in treatment planning. All essential structures relevant to radiotherapy are described and depicted on 3D images generated from radiotherapy planning systems. System-based labelled CT images taken in relevant imaging planes and patient positions build up understanding of relational anatomy and CT interpretation. Images are accompanied by comprehensive commentary to aid with interpretation. This simplified approach is used to empower the reader to rapidly gain image interpretation skills. The book pays special attention to lymph node identification as well as featuring a unique section on Head and Neck Deep Spaces to help understanding of common pathways of tumour spread. Fully labelled CT images using radiotherapy-specific views and positioning are complemented where relevant by MR and fusion images. A brief introduction to image interpretation using IGRT devices is also covered. The focus of the book is on radiotherapy and some images of common tumour pathologies are utilised to illustrate some relevant abnormal anatomy. Short self-test questions help to keep the reader engaged throughout.

The automation of radiotherapy treatment planning assessment

Aim The assessment of treatment plans is an important component in the education of radiation therapists. The establishment of a grade for a plan is currently based on subjective assessment of a range of criteria. The automation of assessment could provide a number of advantages including faster feedback, reduced chance of human error, and simpler aggregation of past results. Method A collection of treatments planned by a cohort of 27 second year radiation therapy students were selected for quantitative evaluation. Treatment sites included the bladder, cervix, larynx, parotid and prostate, although only the larynx plans had been assessed in detail. The plans were designed with the Pinnacle system and exported using the DICOM framework. Assessment criteria included beam arrangement optimisation, volume contouring, target dose coverage and homogeneity, and organ-at-risk sparing. The in-house Treatment and Dose Assessor (TADA) software1 was evaluated for suitability in assisting with the quantitative assessment of these plans. Dose volume data were exported in per-student and per-structure data tables, along with beam complexity metrics, dose volume histograms, and reports on naming conventions. Results The treatment plans were exported and processed using TADA, with the processing of all 27 plans for each treatment site taking less than two minutes. Naming conventions were successfully checked against a reference protocol. Significant variations between student plans were found. Correlation with assessment feedback was established for the larynx plans. Conclusion The data generated could be used to inform the selection of future assessment criteria, monitor student development, and provide useful feedback to the students. The provision of objective, quantitative evaluations of plan quality would be a valuable addition to not only radiotherapy education programmes but also for staff development and potentially credentialing methods. New functionality within TADA developed for this work could be applied clinically to, for example, evaluate protocol compliance.