Search

Aims Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC. Materials and methods Searches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC. Results Twenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival. Conclusion Docetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary.

Aims To determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers. Materials and methods In total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement. Results The mean intra-fraction prostate displacements were −0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and −0.86 ± 1.73 mm in the left–right, superior–inferior and anterior–posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43–0.77) and 0.47 (95% confidence interval 0.22–0.65) in the superior–inferior and anterior–posterior directions, respectively. There was no significant correlation in the left–right direction with a coefficient of –0.04 (95% confidence interval −0.31–0.23). Conclusions The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.

Aims We hypothesised that accelerated fractionated radiotherapy may provide a good palliative approach for dysphagia relief in patients with incurable oesophageal cancer, significantly reducing the overall duration of treatment, while providing symptom response with an acceptable toxicity profile. A phase I/II accelerated fractionation study was conducted to evaluate the efficacy and toxicity of this approach. Materials and methods Patients with incurable oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology Group performance status≤3, without fistula or oesophageal stent in situ , were eligible. Treatment consisted of 40Gy in 20 fractions, twice a day (2Gy per fraction, ≥6h apart), 5 days a week, over 2 weeks. Results Of the 39 evaluable patients, the dysphagia response rate was 69% (27/39) with a median response duration of 5.5 months. The median time to response was 4 weeks. Twenty-eight per cent (11/39) of patients had transient worsening in their dysphagia scores. Acute toxicity (weeks 1–8) occurred in 41% (16/39) of patients. An improvement in global quality of life by week 8 was seen in 42% of patients. There were no late neurological sequelae. The median overall survival was 8 (range 1.7–58+) months. Conclusion The ideal palliative regimen should be relatively short, with minimal toxicity, while offering a favourable response profile. Accelerated fractionation fulfils these criteria and is a suitable treatment alternative for the palliation of dysphagia, especially if the goal is to deliver a higher total biological dose within a shorter (2 week) period of time.

Design: Population-based cohort study. Background: Malignant spinal cord compression (MSCC) has long been recognized as an important complication of cancer, but its incidence is unknown. Objectives: To describe the incidence, the management, and the outcome of MSCC in the cancer population of the Canadian province of Ontario. Methods: Episodes of MSCC, and treatments used for each episode, were identified by linking electronic hospital separation records and cancer centre records to Ontario’s population-based cancer registry. The cumulative frequency of MSCC in the last 5 years of life was described in the 121 435 patients who died of cancer in Ontario between 1990 and 1995. Survival after the first episode of MSCC, and duration of hospitalization with MSCC, was described. Results: The cumulative probability of experiencing at least one episode of MSCC in the 5 years preceding death from cancer was 2.5% overall, and ranged from 0.2% in cancer of the pancreas to 7.9% in myeloma. Overall, 60.2% of first episodes of MSCC were treated with primary radiotherapy, and 16.1% with surgerypostoperative radiotherapy, while in the remaining 23.7%, there was no record of radiotherapy or surgery. Overall, the median survival following the first episode of MSCC was 2.9 months. The diagnosis of MSCC was associated with a doubling of the time spent in hospital in the last year of life. Conclusion: MSCC is a fairly common occurrence among patients dying of cancer. There is a 40-fold variation in the cumulative incidence of MSCC among different types of cancer. Loblaw, D. A. et al. (2003). Clinical Oncology 15, 211–217 2003 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.

Over the last few years, the management of prostate cancer has undergone many changes and due to substantial developments in the understanding of prostate cancer biology, functional imaging, technological radiotherapy and new systemic agents. There is an ever-growing spectrum of treatment strategies aimed at improving patient selection, treatment outcomes and disease evaluation. This special issue will explore some of these exciting and emerging new management schemes to understand the rationale and their methodology, evaluate the current data underpinning the basis of its development and future directions. The topics selected for this special issue on prostate cancer range from functional imaging to the use of new targeted therapies in the setting of non-metastatic prostate cancer. This issue begins with the use of functional and molecular imaging from Turkbey et al. [1]. Standard magnetic resonance imaging (MRI) sequences have been the recognised gold standard for pelvic imaging, particularly for appropriate T staging in prostate cancer. The development of MRI sequences such as diffusion-weighted MRI, dynamic contrast-enhanced MRI and MRI spectroscopy has provided greater assessment and functionality. Used together with standard MRI sequences, this multi-parametric MRI combination can greatly improve both the identification and the staging of prostate cancer to enable better patient selection for strategies that include focal therapy, dose escalation with simultaneous integrated boosting for the whole gland or treatment of the dominant intra-prostatic nodule, as well as the evaluation of treatment responses. The availability of higher strength MRI imagers and multi-channel phased array surface coils may provide equivalent imaging to endorectal coil probes and can have advantages for both patient comfort and image co-registration when used for radiotherapy treatment planning. In addition, there are many new positron emission tomography (PET) tracers that have been shown to provide greater sensitivity and specificity compared with the fluorine-18 labelled glucose analogue (FDG-PET) for prostate cancer imaging. These PET tracers include 11 C-acetate and 11 C-choline or 11 F-choline with newer tracers that target the amino acid transport, such as 11 C-methionine and 11 F-FACBC (synthetic L-leucine amino-acid analogue). These scans may provide useful information in recurrent local disease or the detection of early nodal involvement. There is renewed interest in the prostate-specific membrane antigen as an imaging biomarker. The opportunities that these new functional and molecular imaging modalities can offer are many, but there must be appropriate and careful clinical correlation in