Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

Exercise intensity influences NEAT in overweight and obese adults

PURPOSE: To determine the effect of acute bouts of moderate- and high-intensity walking exercise on non-exercise activity thermogenesis (NEAT) in overweight and obese adults. ---------- METHOD: 16 participants performed a single bout of either moderate-intensity walking exercise (MIE) or high-intensity walking exercise (HIE) on two separate occasions. The MIE consisted of walking for 60 minutes on a motorized treadmill at 6 km.h. The 60-minute HIE session consisted of walking in 5-min intervals at 6 km.h and 10% grade followed by 5-min at 0% grade. NEAT was assessed by accelerometer on three days before, the day of, and three days following the exercise sessions. ---------- RESULTS: There was no significant difference in NEAT vector magnitude (counts.min) between the pre-exercise period (days 1-3) and the exercise day (day 4) for either MIE or HIE protocol. In addition, there was no change in NEAT during the three days following the MIE session, however NEAT increased by 16% on day 7 (post-exercise) compared with exercise day (P = 0.32). However during the post-exercise period following the HIE session, NEAT was increased by 25% on day 7 compared with the exercise day (P = 0.08), and by 30-33% compared with pre-exercise period (day 1, day 2 and day 3); P = 0.03, 0.03, 0.02, respectively. ---------- CONCLUSION: A single bout of either MIE or HIE did not alter NEAT on the exercise day or on the first two days following the exercise session. However, monitoring NEAT on a third day allowed the detection of a 48-h delay in increased NEAT after performing HIE. A longer-term intervention is needed to determine the effect of accumulated exercise sessions over a week on NEAT.

Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells

Background The androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis. Results Comparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR. Conclusion Taken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.

A research opportunity : “3D-ROSE” : virtual reality preparation for children having radiotherapy or imaging procedures

Professor Christian Langton is a medical physicist at Queensland University of Technology in Brisbane. He has developed a way of preparing children who are about to have either radiotherapy or MRI imaging procedures and is seeking research partners to develop and test these further. This is a great opportunity for nurses interested in research, and who have access to a children’s hospital, to work with Professor Langton on some truly innovative, multidisciplinary research.

Civic engagement and associationalism : the impact of group membership scope versus intensity of participation

The relationship between participation in civic and political activities and membership of voluntary associations is now well established. What is less clear is the relative impacts of how much time people spend on group activities (associational intensity), and the number and type of groups that individuals are involved with (associational scope). Does it matter in terms of civic engagement, for example, whether one is a member of a quilting-circle or trade union? Does it matter whether association ‘membership’ is simply an annual payment or a major commitment of time and energy? In this article, we use a large survey to explore these questions empirically by focusing on the membership patterns and civic engagement practices of 4,001 citizens drawn from eight suburbs across Greater Melbourne, Australia. Our findings indicate that, while associational intensity is positively related to civic engagement, associational scope (the number of group memberships per person), is a more influential determinant of the level of civic and political participation. The results also suggest that while all forms of associationalism are important in terms of fostering greater levels of civic activity, not all forms have the same impact.

Internet usage, internet marketing intensity and international marketing growth

This paper examines the role of the Internet in international marketing growth. Evidence of a positive relationship between e-mail, website usage, online marketing and advertising with international market growth was found, in terms of increased sales from new customers in new countries, new customers in existing countries, and existing customers.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Low intensity CBT by mail

Introduction: There are many low intensity (LI) cognitive behavoural therapy (CBT) solutions to the problem of limited service access. In this chapter, we aim to discuss a relatively low-technology approach to access using standard postal services-CBT by mail, or M-CBT. Bibliotherapies including M-CBT teach key concepts and self-management techniques, together with screening tools and forms to structure home practice. M-CBT differs from other bibliotherapies by segmenting interventions and mailing them at regular intervals. Most involve participants returning copies of monitoring forms or completed handouts. Therapist feedback is provided, often in personal letters that accompany the printed materials. Participants may also be given access to telephone or email support. ----- ----- M-CBT clearly fulfills criteria for an LI CBT (see Bennett-Levy et al., Chapter 1, for a definition of LI interventions). Once written, they involve little therapist time and rely heavily on self-management. However, content and overall treatment duration need not be compromised. Long-term interventions with multiple components can be delivered via this method, provided their content can be communicated in letters and engagement is maintained.

Implementing low intensity CBT in case management of clients with severe mental illness

In a previous chapter (Dean and Kavanagh, Chapter 37), the authors made a case for applying low intensity (LI) cognitive behaviour therapy (CBT) to people with serious mental illness (SMI). As in other populations, LI CBT interventions typically deal with circumscribed problems or behaviours. LI CBT retains an emphasis on self-management, has restricted content and segment length, and does not necessarily require extensive CBT training. In applying these interventions to SMI, adjustments may be needed to address cognitive and symptomatic difficulties often faced by these groups. What may take a single session in a less affected population may require several sessions or a thematic application of the strategy within case management. In some cases, the LI CBT may begin to appear more like a high-intensity (HI) intervention, albeit simple and with many LI CBT characteristics still retained. So, if goal setting were introduced in one or two sessions, it could clearly be seen as an LI intervention. When applied to several different situations and across many sessions, it may be indistinguishable from a simple HI treatment, even if it retains the same format and is effectively applied by a practitioner with limited CBT training. ----- ----- In some ways, LI CBT should be well suited to case management of patients with SMI. treating staff typically have heavy workloads, and find it difficult to apply time-consuming treatments (Singh et al. 2003). LI CBT may allow provision of support to greater numbers of service users, and allow staff to spend more time on those who need intensive and sustained support. However, the introduction of any change in practice has to address significant challenges, and LI CBT is no exception. ----- ----- Many of the issues that we face in applying LI CBT to routine case management in a mnetal health service and their potential solutions are essentially the same as in a range of other problem domains (Turner and Sanders 2006)- and, indeed, are similar to those in any adoption of innovation (Rogers 2003). Over the last 20 years, several commentators have described barriers to implementing evidence-based innovations in mental health services (Corrigan et al. 1992; Deane et al. 2006; Kavanagh et al. 1993). The aim of the current chapter is to present a cognitive behavioural conceptualisation of problems and potential solutions for dissemination of LI CBT.