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Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history ofprostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial.Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localized prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n ¼ 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era.Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outliningreview showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of theprostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints inProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent.Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Aims The outcome of patients with pancreatic cancer from an unselected population within a UK region has not previously been reported. We undertook a review of pancreatic cancer in southeast Wales, with an emphasis on locally advanced non-metastatic pancreatic cancer (LANPC) in an attempt to define a subgroup of patients who would probably benefit from multi-modality treatment. Materials and methods Case notes of patients referred to Velindre Hospital between 1 January 2002 and 31 December 2005 were reviewed. Data on patient demographics, tumour characteristics, treatment, treatment response and overall survival were collected. The Log-rank test was used to compare survival between groups and Cox regression was used to evaluate whether age, gender, tumour site and treatment response correlated with overall survival in LANPC. Results Of the 354 referrals (complete data on 315 patients), 93% were inoperable and 51% of inoperable patients received active treatment (149/294). One hundred and fourteen patients out of 315 (36%) had LANPC and 72/114 (64%) were fit for active treatment, including chemotherapy (n = 66) and chemoradiotherapy (CRT) (n = 6). The median survival of patients with LANPC was 7.4 months (95% confidence interval 6.4–8.5). Survival for patients receiving chemotherapy, CRT and no treatment was 9.2 (7.5–10.7), 12.6 (6.1–19.1) and 4.5 (3.7–5.3) months, respectively. Overall survival of patients who had non-progressive disease after initial chemotherapy was significantly better than those who progressed (11.8 vs 6.6 months, P = 0.01). Of the 180/315 (57%) patients presenting with metastatic disease, 43% received active treatment. Overall survival of metastatic patients was 2.8 months (2.3–3.2 months); for those receiving active treatment, this was 5.6 months (5.1–6.1 months) and for those receiving active supportive care 1.8 months (1.6–2.0 months). Conclusions In this UK network, about half of the patients received active treatment. Although the overall outcome was poor, that of treated patients was comparable with published studies. For patients with LANPC, the initial response or disease stabilisation on chemotherapy defined a subset of patients who had better outcome. The role of CRT over and above chemotherapy needs to be defined through trials that should include a neoadjuvant ‘chemotherapy-only’ phase to select out patients who benefit from multi-modality treatment.

Clinicians may be forgiven for thinking that Stage I seminoma is one of the 'simpler' situations to manage; adjuvant radiotherapy has been used with great success for many years. After irradiation to the para-aortic and ipsilateral pelvic nodes (the classic 'dog-leg' field) to a dose upwards of 30-35 Gy (in 1.5-2.0 Gy fractions), only 2%-3% of patients will relapse. Most of these can be salvaged with chemotherapy, resulting in an overall cure rate of 99% [1,2]. Why should any departure from this policy be entertained? All treatments have their drawbacks, and adjuvant dog-leg radiotherapy is no exception. Planning a dog-leg field can be time-consuming and cumbersome; some centres will supplement the information already obtained from abdominal CT scans with intravenous urography in the simulator. Usually, customized lead blocks will be required, and the patient will consequently require two visits to the simulator before beginning treatment. Once treatment is underway, daily visits to hospital for 3-4 weeks are required. For a young man with work commitments, all of this is time-consuming, particularly when the acute morbidity of treatment is also taken into account.

Locally advanced prostate cancer remains as controversial as ever. On the one hand, large numbers of patients worldwide with T3-4 N0 disease are treated with androgen deprivation therapy alone, acknowledging that the disease is associated with a high incidence of subsequent bone metastases and death from prostate cancer. On the other hand, recent technological developments have made it possible to treat locoregional disease with unprecedented ferocity, and have encouraged a new generation of enthusiasts who lament the ‘failures’ of the past and the perceived ‘under-treatment’ of this disease. Apart from hormone therapy, the options for a man with T3 prostate cancer now include high-dose radiotherapy (with a brachytherapy ‘boost’ [1]) with or without high-dose radiation to pelvic lymph nodes (by conventional, conformal or intensity-modulated radiotherapy) [2–6], and even surgery (the subject of an EORTC phase II study [7,8]). Indeed, when faced with a relatively young patient, it is hard to resist ‘throwing the book’ at him, therapeutically speaking. Is it, however, right to do so? That such a patient needs treatment is beyond question (in terms of his being faced with a ‘significant’ cancer), but, that does not mean that the treatment is effective. Is the poorer prognosis of such patients related to the presence of sub-clinical metastatic disease or is the metachronous development of metastatic disease due to failure to eradicate the primary tumour? Even if the latter is the case, is locally advanced disease really curable with current technological wizardry? We don’t know the answer in this patient group, any more than we do for organ-confined disease. Among the clamour for giving more and different forms of treatment, stands the clinical trial NCIC CTG PR.3/MRC PR07 (ISRCTN24991896). In this trial, men

Background Muscle invasive bladder cancer is a serious clinical problem and is fatal for the majority of patients. Alternative treatments for this condition are radical cystectomy or radical radiotherapy. The choice of treatment varies according to the resident country. The ideal treatment would be a bladder preserving therapy with total eradication of the tumour without compromising survival. Objectives The objective of this review was to compare the overall survival after radical surgery (cystectomy) versus radical radiotherapy in patients with muscle invasive cancer. Search methods We searched the Cochrane Controlled Trials Register (July 2001), MEDLINE (July 2001), EMBASE (July 2001), CancerLIT (July 2001), Healthstar (July 2001) and the Database of Abstracts of Reviews of Effectiveness (July 2001). Attempts to contact authors of unpublished data were undertaken. Selection criteria Randomised trials comparing surgery versus radiotherapy were eligible for assessment. Data collection and analysis Three reviewers assessed trial quality based on the Cochrane Guidelines. Data were extracted from the text of the article or extrapolated from the Kaplan-Meier plot. The Peto odds ratio was determined to compare the overall survival and disease-specific survival. Analysis was performed on an intention-to-treat basis and treatment actually received. Main results Three randomised trials comparing pre-operative radiotherapy followed by radical cystectomy (surgery) versus radical radiotherapy with salvage cystectomy (radical radiotherapy) were eligible for assessment. These trials represented a total of 439 patients, 221 randomised to surgery and 218 to radical radiotherapy. Three trials were combined for the overall survival results and one for the disease-specific analysis (Bloom 1982). The mean overall survival (intention-to-treat analysis) at 3 and 5 years were 45% and 36% for surgery, and 28% and 20% for radiotherapy, respectively. Peto odds ratio (95% confidence interval) analysis consistently favoured surgery in terms of overall survival. The results were significantly in favour of surgery at 3 years (OR = 1.91, 95% CI 1.30 to 2.82) and at 5 years (OR = 1.85 95% CI 1.22 to 2.82). On a 'treatment received' basis, the results were significantly in favour of surgery at 3 (OR = 1.84, 95% CI 1.17 to 2.90) and 5 years (OR = 2.17, 95% CI 1.39 to 3.38) for overall survival and at 3 years (OR = 1.96, 95% CI 1.06 to 3.65) for disease-specific survival. Authors' conclusions The analysis of this review suggests that there is an overall survival benefit with radical surgery compared to radical radiotherapy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patients numbers were small and that many patients did not receive the treatment they were randomised to. It must also be noted that many improvements in both radiotherapy and surgery have taken place since the initiation of these trials.

Introduction The standard - supine with arms abducted to 90o - position for breast radiotherapy is stable, but raises the sub-diaphragmatic organs superiorly. A volume of liver may consequently be included within the radiation portal. The novel aim of this report is to quantify the dose-volume characteristics of hepatic irradiation and to seek relationships with interleukin-6 soluble receptor (IL-6sR), an inflammatory mediator potentially induced by damaged hepatocytes. Methods Participants comprised 98 women with 0–IIa stage breast cancer; undergone breast conservation surgery; prescribed 4000cGy/15 fractions/3 weeks; no prior or concurrent systemic therapies. The liver was outlined on contiguous CT slices and the volume irradiated to 10 and 50% of the dose (Liver10,50) derived via dose-histogram analysis. Enzyme-linked immunosorbent assay kits determined sera concentrations of IL-6sR. Results Liver50 ranged between 0–92 cm3, mean (SD) = 11.7 cm3 (1.1). This was consistent with up to 8% of the liver being irradiated, with a mean of 1.7% and 0.03% for right and left-sided tumours respectively. For right-sided tumours (n = 52), the mean (SD) Liver10 was 56.3 cm3 (52.8). The maximal dose was 113.1% of the prescribed 40Gy, with a mean (SD) value of 87.1% (32.3). A correlation between IL-6sR and Liver10 was non-significant pre-radiotherapy (ρ = .17, p = 0.2), but significant during (ρ = .32, p = 0.02), and four weeks post-radiotherapy (ρ = .38, p = 0.007). No significant correlations were found for left-sided tumours. Conclusions Up to 8% of the liver is irradiated within the primary beam during breast conservation therapy. This volume is insufficient to precipitate radiation-induced liver disease. However, low-dose effects are evident for right-sided treatments, rendering moderate-strength positive associations with IL-6sR. Elevated IL-6sR is associated with fatigue and depression in women with breast cancer. Given the liver’s metabolic role, multi-modal therapy may enhance the findings.

We report the results of a prospective study to quantify inaccuracies in patient set-up during routine radiotherapy for tumours of the brain and bladder, which took place as part of our departmental development. Knowledge of these inaccuracies is required to put into practice the ICRU 50 recommendations regarding clinical target volume and planning target volume. We measured inaccuracies in two dimensions by comparing portal beam films with the simulator check film. Our method used manual measurements, proved to be a very laborious technique, and demonstrated the need for portal imaging. Ninety-five brain and 97 bladder portal films from 30 brain and 30 bladder patients were examined. Displacements greater than 0.5 cm were seen in 13% of brain treatments in the supero-inferior direction and 1% in the anteroposterior direction. With bladder treatments, displacements greater than 0.75 cm were seen in 12% in the supero-inferior direction and 5% in the lateral direction. These results are consistent with other previous studies. We identified a very small systematic error in the department, which was not [corrected] considered to be clinically significant. These results are discussed with reference to other similar studies and the ICRU 50 recommendations.