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The Malthus programme produces a model for the local and national level of radiotherapy demand for use by commissioners and radiotherapy service leads in England. The accuracy of simulation is dependent on the population cancer incidence, stage distribution and clinical decision data used by the model. In order to quantify uncertainty in the model, a global sensitivity analysis of the Malthus model was undertaken. As predicted, key decision points in the model relating to stage distribution and indications for surgical or non-surgical initial management of disease were observed to yield the strongest effect on simulated radiotherapy demand. The proportion of non-small cell lung cancer patients presenting with stage IIIB/IV disease had the largest effect on fraction burden in the four most common cancer types treated with radiotherapy, where a 1% change in stage IIIb/IV disease yielded a 1.3% change in fraction burden for lung cancer patients. A 1% change in mastectomy rate yielded a 0.37% change in fraction burden for breast cancer patients. The model is also highly sensitive to changes in the radiotherapy indications in colon and gastric cancer. Broadly, the findings of the sensitivity analysis mirror those previously published by other groups. Sensitivity analysis of the local-level population and cancer incidence data revealed that the cancer registration rate in the 50-64 year female population had the highest effect on simulation results. The analysis reveals where additional effort should be undertaken to provide accurate estimates of important parameters used in radiotherapy demand models.

Aims This paper compares the predictions of radiotherapy demand for England from the Malthus model with those from the earlier National Radiotherapy Advisory Group (NRAG) model, from the international literature and also with observed radiotherapy usage in England as a whole as recorded in the English radiotherapy dataset (RTDS). Materials and methods We reviewed the evidence base for radiotherapy for each type and stage of cancer using national and international guidelines, meta-analyses, systematic reviews and key clinical trials. Twenty-two decision trees were constructed and radiotherapy demand was calculated using English cancer incidence data for 2007, 2008 and 2009, accurate to the Primary Care Trust (PCT) level (population 91 500–1 282 384). The stage at presentation was obtained from English cancer registry data. In predictive mode, the model can take account of changes in cancer incidence as the population grows and ages. Results The Malthus model indicates reduced indications for radiotherapy, principally for lung cancer and rarer tumours. Our estimate of the proportion of patients who should receive radiotherapy at some stage of their illness is 40.6%. This is lower than previous estimates of about 50%. Nevertheless, the overall estimate of demand in terms of attendances is similar for the NRAG and Malthus models. The latter models that 48 827 attendances should have been delivered per million population in 2011. National data from RTDS show 32 071 attendances per million in 2011. A 50% increase in activity would be required to match estimated demand. This underprovision extends across all cancers and represents reduced access and the use of dose fractionation at odds with international norms of evidence-based practice. By 2016, demand is predicted to grow to about 55 206 attendances per million and by 2020 to 60 057. Discussion Services have increased their activity by 14% between 2006 and 2011, but estimated demand has increased by 11%. Access remains low and English radiotherapy dose fractionation still does not comply with international evidence-based practice.

$\textbf{OBJECTIVE}$: There is no consensus approach to covering skull base meningeal reflections-and cerebrospinal fluid (CSF) therein-of the posterior fossa cranial nerves (CNs VII-XII) when planning radiotherapy (RT) for medulloblastoma and ependymoma. We sought to determine whether MRI and specifically fast imaging employing steady-state acquisition (FIESTA) sequences can answer this anatomical question and guide RT planning. $\textbf{METHODS}$: 96 posterior fossa FIESTA sequences were reviewed. Following exclusions, measurements were made on the following scans for each foramen respectively (left, right); internal acoustic meatus (IAM) (86, 84), jugular foramen (JF) (83, 85) and hypoglossal canal (HC) (42, 45). A protocol describes measurement procedure. Two observers measured distances for five cases and agreement was assessed. One observer measured all the remaining cases. $\textbf{RESULTS}$: IAM and JF measurement interobserver variability was compared. Mean measurement difference between observers was -0.275 mm (standard deviation 0.557). IAM and JF measurements were normally distributed. Mean IAM distance was 12.2 mm [95% confidence interval (CI) 8.8-15.6]; JF was 7.3 mm (95% CI 4.0-10.6). The HC was difficult to visualize on many images and data followed a bimodal distribution. $\textbf{CONCLUSION}$: Dural reflections of posterior fossa CNs are well demonstrated by FIESTA MRI. Measuring CSF extension into these structures is feasible and robust; mean CSF extension into IAM and JF was measured. We plan further work to assess coverage of these structures with photon and proton RT plans. $\textbf{Advances in knowledge}$: We have described CSF extension beyond the internal table of the skull into the IAM, JF and HC. Oncologists planning RT for patients with medulloblastoma and ependymoma may use these data to guide contouring.

Aims This report reviews current radiotherapy practice across the UK in the management of lung cancer, and the way new treatments and technologies are being introduced, where improvements have occurred, and where work is still required. We wanted to determine adherence to both National Radiotherapy Advisory Group and National Institute for Health and Clinical Excellence (NICE) guidance. This survey was conducted on behalf of the Department of Health Lung Cancer & Mesothelioma Advisory Group. Materials and methods We sent a questionnaire to all UK radiotherapy departments. It covered radical radiotherapy dose fractionation, the use of concurrent or sequential chemotherapy for both non-small cell and small cell lung cancers, the use of continuous hyperfractionated accelerated radiotherapy, new radiotherapy techniques, the use of positron emission tomography/computed tomography for planning purposes and patient accrual into current National Cancer Research Network UK trials. Results This UK-wide survey of radiotherapy practice for lung cancer showed broad compliance with NICE clinical guidance, but highlighted significant variation in fractionation schedules and the use of concomitant chemoradiotherapy. Clinical trial entry into lung cancer radiotherapy trials was variable and many centres are not fully participating in recruitment into these trials. Conclusions This report has shown the variability of radiotherapy provision nationally. Current practice is largely consistent with current and updated NICE recommendations and best practice and should be recognised as such. It has also highlighted areas where improvements are still needed, particularly fractionation and new technologies. One particular aspect of concern is the poor recruitment to current UK-based clinical trials in lung cancer.

Aims Patients on follow-up after orchidectomy or chemotherapy for testicular germ cell tumours follow a protocol of outpatient appointments and investigations designed to detect relapse. We wanted to investigate the contribution of clinical examination to patient management. Materials and methods The notes of 70 consecutive patients who suffered a first systemic relapse of their germ cell tumour within the last 10 years were studied to determine how the relapse was detected. Second testicular tumours were excluded. Results Of the 69 patients whose notes were available, only one had a significant finding on physical examination, concurrent with abnormal markers. Conclusions We suggest that, for patients following a planned programme of appointments and investigations, physical examination rarely contributes to the detection of systemic relapse in the follow-up of testicular germ cell tumours. It may therefore be possible to reconfigure follow-up to focus on investigations and telephone contact. We estimate that this change might be appropriate for 40% of attendances and might be welcomed by patients, many of whom find follow-up burdensome. If such a change were considered, patient education would be essential to ensure continuing compliance with the follow-up protocol.

Radiotherapy in the UK lags behind that in much of Europe in terms of both the low proportion of cancer patients gaining access to treatment and the long waiting times [1] and [2]. The technical quality of radiotherapy is also a cause for concern. The National Radiotherapy Advisory Group (NRAG) report published in May 2007 had an overall aim of developing world class radiotherapy [3]. The NRAG technology subgroup report envisaged that within 10 years 50% of patients would be treated by four-dimensional image-guided, adaptive radiotherapy, of which intensity-modulated radiotherapy [IMRT] is a vital component [4]. This paper summarises the work of the National Radiotherapy Implementation Group (NRIG) in supporting the implementation of IMRT.

Aims Modelling of demand has indicated substantial underprovision of radiotherapy in England. We have used national audit data to understand the differences between theory and practice. Materials and methods We used a web-based tool to collect data on all National Health Service patients in England starting a course of radiotherapy in the week commencing 24 September 2007. We also collected information on cancer site, so that patients could be triaged into the 22 categories used by the National Radiotherapy Advisory Group (NRAG). Results In England, excluding skin cancer other than melanoma, 2114 patients were prescribed 27 420 fractions during that week. Comparison of the audit data with the NRAG model showed that the shortfall in provision was a mixture of a lack of access (67%) and reduced fractionation (33%). The largest contributions to the overall gap were seen in the treatment of cancers of the breast (6%) (modelled at 15 fractions), head and neck (10%), lung (28%) and prostate (14%), together accounting for 58% of the difference. Others (including sarcoma and unknown primary) accounted for 19% of the difference. Limited access to radiotherapy for patients with stomach and pancreatic cancer contributed 10% and reduced fractionation for oesophageal cancer accounted for 6% of the overall gap. Fewer patients than expected were treated for rectal cancer, but they received 25 fraction regimens rather than short-course preoperative treatment. Patients with leukaemia and cancers of the brain, colon, corpus uteri and ovary received radiotherapy more often than expected, but because they are relatively rare none of these had an overall impact exceeding 1.2% of the gap in provision. Conclusions This audit confirms the underprovision of radiotherapy in England and shows that it is largely accounted for by low access rates of 37% rather than the 50% accepted in the literature. In consequence we estimate that 33 881 patients (13.9%) of the 243 748 patients diagnosed with cancer in England during 2006/2007 did not receive the radiotherapy we would have expected. Some of this gap in provision may be accounted for by differences in stage and performance status, which limit treatment options, for example in lung cancer. The NRAG model should be updated to take account of new data from this and other national audits, to ensure that it describes the stage and performance status of English patients and is sensitive to the range of professional opinion about treatment options. This will be essential for long-term planning as cancer incidence increases over the next decade, but it does not weaken the conclusion that there is a substantial current shortfall to be addressed immediately to improve timely access to treatment and thus the outcomes of therapy. As more resource becomes available, it should be possible to consider changing dose fractionation to comply with evidence-based practice and national guidelines from the National Institute for Health and Clinical Excellence and other bodies without disadvantaging patients by increasing waiting times.

Aims To document UK practice in radiotherapy fractionation. Methods All radiotherapy centres in the UK participated in a 1-week audit from 29 September 2003. Fractionation data were collected for all patients starting external beam radiotherapy. This included 2498 patients who were prescribed 32 547 fractions. Results For the radical treatment of non-skin malignancy ( n =708), the prescribed dose ranged from a single fraction of 8Gy for total-body irradiation to 75Gy in 43 fractions for prostate cancer. Postoperative treatment for breast cancer was dominated by three regimens: 40Gy in 15 fractions; 45Gy in 20 fractions; and 50Gy in 25 fractions. Palliative treatment was given in a single fraction to 393 patients (36%) with doses of up to 15Gy. Three hundred and ninety patients (36%) received four to seven fractions delivering 20–25Gy. Only 89 patients (8%) received more than 10 fractions with palliative intent but used 29% of such fractions. In the treatment of bone metastases, the most common prescriptions were 8–10Gy in a single fraction and 20Gy in five fractions. Conclusion UK radiotherapy practice has become more uniform and moved closer to practice in North America and Europe over the past 15 years. For radical radiotherapy, 54% of prescriptions were for a fraction size of 1.8–2.0Gy but the distribution was bi-modal and 20% of patients were prescribed fraction sizes of 2.7–3.0Gy. Evidence-based practice now supports hypo-fractionated palliative treatment favouring single fractions for bone metastases and one or two fractions for many patients with advanced lung cancer. Two fractions are advised for some patients with brain metastasis. If these guidelines had been applied uniformly, then the number of treatments prescribed for palliation could have fallen by 36% from 5197 to 3313. This would have represented a 6% reduction in the overall radiotherapy workload. Not all patients are suitable for such hypo-fractionated treatments, but this is an area in which resource use can be improved. In the postoperative management of breast cancer, a change in practice to use 15 fractions uniformly would reduce overall radiotherapy workload by 4%. By contrast, a change to 25 fractions would increase overall workload by 7%.

Uracil-DNA glycosylase (UNG) is the primary enzyme responsible for removing uracil residues from DNA. Increasing evidence suggests that UNG may be a potential target for the development of novel antiviral and/or anticancer agents. To determine whether the uracil-DNA glycosylase inhibitor protein (UGI) could be used to specifically target UNGs intracellularly, we developed a construct that expresses UGI as a fusion protein with the TAT-protein transduction domain and described a novel method for the purification of recombinant TAT-UGI. Treatment of several cell types with TAT-UGI resulted in a dose- and time-dependent decrease in UNG activity. A somewhat surprising effect of TAT-UGI treatment was the decrease in cell proliferation, but not in cell viability. The results of this study support the premise that UNG can be used as a potential therapeutic target and also demonstrate that protein transduction can be used to modulate UNG activity.

Aims Current treatment for primary central nervous system lymphoma (PCNSL) involves high-dose methotrexate (HDMTX) with or without radiotherapy. Many published studies describing this approach include a highly selected group of patients. We report a single-centre experience of unselected cases of PCNSL. Materials and methods We retrospectively reviewed the case notes of 55 consecutive patients diagnosed with biopsy-proven PCNSL between 1995 and 2003 at Addenbrooke's Hospital Cambridge, UK. We describe the treatment and outcome, including survival, treatment-related toxicity and long-term functional disability. Results At diagnosis, 45% of patients were considered unfit to receive treatment with HDMTX, owing to poor performance status or comorbidity. These patients had a median survival of 46 days and may not have been included in other published studies. The remaining patients were treated with a chemotherapy regimen, which included HDMTX. Patients who received at least one cycle of a chemotherapy containing HDMTX had a median survival of 31 months. Forty per cent did not complete planned chemotherapy owing to toxicity, disease progression or death. The median survival of patients treated with HDMTX aged 60 years compared with patients aged under 60 years was 26 months vs 41 months ( P =0.07), respectively. Younger patients treated with HDMTX, who achieved complete remission with chemotherapy, had a median survival of 56 months. We identified a high incidence of functional disability among survivors, resulting from a combination of the tumour itself, the neurosurgical procedure required for diagnosis and the late neurotoxicity of combined chemoradiotherapy. Conclusion The treatment of PCNSL is associated with significant early and late toxicity. Further attempts to improve treatment should address mechanisms to reduce this toxicity. In particular, the benefit of radiotherapy in patients who achieve complete remission with HDMTX will remain uncertain until it is addressed in a multicentre, randomised trial.

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is responsible for maintaining low intracellular levels of dUTP, thus preventing the incorporation of dUTP into DNA. A 21 bp double-stranded RNA molecule (siRNAdUT3) targeted against motif 3 of human dUTPase resulted in a time- and dose-dependent decrease in dUTPase activity in transfected cells. dUTPase activity was reduced approximately 95 ± 5% in all cell lines tested 48 h after transfection with 2 μg siRNAdUT3 and it was maintained at this decreased level for at least 72 h. Down-regulation of dUTPase resulted in a significant increase in intracellular dUTP and a decreased proliferation of the transfected cells. Therefore, we conclude that dUTPase activity/expression can be down-regulated using siRNA specifically targeted to dUTPase mRNA and that this approach can be used to elucidate the role of dUTPase in DNA metabolism, as well as, to determine whether dUTPase is a valid target for drug development.

Background and purpose : To assess inter-clinician variability amongst specialist paediatric radiation oncologists in delineating clinical target volumes for treating medulloblastoma as a quality assurance exercise prior to the introduction of the SIOP PNET 4 trial protocol of conformal radiotherapy to the posterior fossa and tumour bed. Patients and methods : Participants from 17 UK centres attended an educational meeting and then completed a clinical planning exercise to outline: (1) the whole posterior fossa and (2) the tumour bed. Quantitative analysis of the volumes, lengths, spatial positioning and axial planes for each individual was carried out and variation between individuals analysed. Results : Outlining of the posterior fossa was reasonably consistent, although most variation was seen in defining the superior border of the tentorium. A major difference was the decision whether or not to include the post-surgical meningocoele in the clinical target volume (CTV). The CTV for the tumour bed was under treated by all participants due to lack of inclusion of pre-operative tumour extent. Conclusions : This exercise demonstrated several ambiguities in the draft protocol and highlighted particular areas of inter-clinician variation. Consequently the protocol was revised and improved to take account of these findings. We recommend that planning exercises, in conjunction with education and training, should be implemented before the start of any new radiotherapy trial. In the future, the use of image transfer will allow prospective peer review of target volumes before treatment commences. These measures are essential to ensure that alterations in clinical practice are achieved in a uniform way.

Although recent trials have raised concerns about the toxicity of raltitrexed monotherapy in patients with advanced colorectal cancer (aCRC), similar concerns have also been raised with other chemotherapy regimens in aCRC. The lessons learnt form our previous experiences with raltitrexed are, therefore, still important as they offer practical guidances to optimise tolerability of chemotherapy for CRC in general. The aims of the study were to report the low-toxicity profile in 58 patients receiving raltitrexed when a rigorous patient information and education strategy was implemented together with an intensive supportive adjuvant drugs regimen from the start. After a discussion with the consultant, all patients received a further consultation with a specialist nurse, a series of bespoke information tools, including an information video and written guidelines on how to avoid, prevent and deal promptly with the side-effects of raltitrexed. They all received intravenous adjuvant ondansetron and dexamethasone, then oral domperidone, ranitidine and nystatin from cycle one. The dose intensity was 98% over 307 cycles. Toxicity associated with raltitrexed comprised grade 1/2 diarrhoea (31.6% of treatment cycles), nausea (12.4%) and vomiting (8.4%), with no grade 3/4 events; grade 1/2 alopecia (17.9%); grade 1 (only) stomatitis (2.3%) and grade 1/2/3 lethargy (70.3%, only 2.3% grade 3), anaemia (14.3%, only 0.3% grade 3) and neutropenia (3.3%, only 0.3% grade 3). There were no treatment-related deaths. The low toxicity, despite high-dose intensity, suggests that intensive supportive education and drugs should have a role in the future design of regimens containing raltitrexed and other chemotherapy regimens for colorectal carcinoma.

The radiotherapy delivery service in England is emerging from a 25 year blight on strategic planning and forecasting of radiotherapy demand. Two of the most influential documents used as evidence for renovation and expansion in radiotherapy services are the Royal College of Radiologists (RCR) equipment, workload and staffing survey [1] and the National Radiotherapy Advisory Group (NRAG) report [2]. Where the RCR survey quantified significant variation in allocation and consumption of radiotherapy resources across England and Wales, the NRAG 2007 report generated national targets for radiotherapy service provision in terms of fraction burden (40,000 fractions per million of population by 2010 and up to 54,000 fractions per million by 2016) and the proportion of cancer patients receiving radiotherapy at some point in their cancer journey (access rate), which was estimated at 52% [3]. Although the NRAG model has been instrumental in providing evidence of radiotherapy under provision, it has proven difficult for clinicians and local commissioning groups to apply the model at a regional level, just as the RCR report would have predicted. Independent of any differences in clinical practice among radiation oncologists across the country, local variation in radiotherapy demand is driven by differences in population demographics and age distribution, co-morbidity, disease incidence and variation in the diagnostic and surgical pathways leading to radiotherapy treatment. It clear that a national ‘best fit’ model cannot provide a good fit for commissioning and service provision at the local level.

BACKGROUND: Historically, the 5-year overall survival (OS) for metastatic medulloblastoma (MMB) was less than 40%. The strategy of post-operative induction chemotherapy (IC) followed by hyperfractionated accelerated radiotherapy (HART) and response directed high dose chemotherapy (HDC) was reported in a single center study to improve 5-year OS to 73%. We report outcomes of this strategy in UK. METHODS: Questionnaires were sent to all 20 UK pediatric oncology primary treatment centers to collect retrospective data on delivered treatment, toxicity and survival with this strategy in children aged 3-19 years with MMB. RESULTS: Between February 2009 and October 2011, 34 patients fulfilled the entry criteria of the original study. The median age was 7 years (range 3-15). Median interval from surgery to HART was 109 versus 85 days in the original series. The incidence of grade 3 or 4 hematological toxicities with IC and HDC was 83-100%. All 16 patients who achieved complete response by the end of the regimen remain in remission but only three of 18 patients with lesser responses are still alive (P

Radiotherapy workload is poorly represented by simple parameters of patients, fractions or fields treated because these do not contain any measure of treatment complexity. However, complexity is increasing and there is an urgent need to quantify this. We have evaluated the basic treatment equivalent (BTE) model as a measure of radiotherapy workload and complexity. Radiotherapy treatment times, from the patient entering to exiting the treatment room maze, were measured for 1298 treatment sessions on 269 patients. The data were used to assess the original model and derive three new models for predicting treatment duration. The most complicated, the 'Addenbrooke's complex model', contained two additional predictor variables, including 'site/technique', in a linear additive form. Before the study, the department used a standard treatment appointment time of 10 minutes. However, 50% of the measured treatments took longer than 10 minutes, (mean 10.9). Summed over the working day, this discrepancy indicates that a standard 10-minute appointment is a poor basis for scheduling radiotherapy. The original BTE model was effective in predicting treatment times, although this was improved by refinement of the model. The Addenbrooke's complex model correctly predicted 70% of treatment times to within 2 minutes (55% for the original BTE model), 80% to within 2.5 minutes and 95% to within 4.7 minutes. The percentage of the variation in observed times accounted for by the model is 59.4%. The models can represent radiotherapy complexity, can improve scheduling on linear accelerators, and are likely to be applicable to other departments. They are thus tools to assess the impact of changes in complexity from new techniques, trial protocols (e.g. the Medical Research Council prostate radiotherapy trial RTO1), and possible time saving from advanced technology such as multileaf collimators (MLCs) or automated machine set-up. The replacement of manually-lifted shielding blocks by MLCs should save 1.1-1.5 minutes for a three- or four-field pelvic plan (i.e. 12%-13%). The models could also be used to aid planning for future linear accelerator provision and for costing radiotherapy treatment.

Fifty-five patients with non- seminomatous germ cell tumours (NSGCT) who were referred to a regional clinical oncology centre over a 3-year period were assessed prospectively with assays of the serum tumour markers alpha-feto protein (AFP) and beta-human chorionic gonadotropin ( β hCG). Paired baseline β hCG assays were undertaken using a polyclonal radioimmunoassay (RIA) and a monoclonal fluoroimmuno assay (FIA). Serial paired measurements were undertaken in patients showing discordance on baseline assays. Four patients (7%; 95% confidence interval 0–14) showed discordance between the paired β hCG assays. Of these, two showed elevated β hCG on RIA, with normal levels on FIA; two showed elevated β hCG on FIA, with normal levels on RIA. No discordance was noted with AFP assays. Discordance persisted in two of the patients (50%) and disappeared on treatment in one (25%); one patient died during treatment. Discordant β hCG assays present difficulties in interpretation and have therapeutic implications in patients with NSGCT. No single currently available assay is conclusive in all patients and commercial assay kits should be chosen with care.

Aims The Malthus Programme has delivered a tool for modelling radiotherapy demand in England. The model is capable of simulating demand at the local level. This article investigates the local and regional level variation in predicted demand with respect to Breast and Prostate cancer, the two tumour types responsible for the majority of radiotherapy treatment workload in England. Materials and methods Simulations were performed using the Malthus model, using base population incidence data for the period from 2007–2009. Simulations were carried out at the level of Primary Care Trusts, Cancer Networks, and nationwide, with annual projections for 2012, 2016 and 2020. Benchmarking was undertaken against previously published models from the UK, Canada and Australia. Results For breast cancer, the fraction burden for 2012 varied from 5537 fractions per million in Tower Hamlets PCT to 18 896 fractions per million in Devon PCT (national mean - 13 592 fractions per million). For prostate cancer, the fraction burden for 2012 varied from 4874 fractions per million in Tower Hamlets PCT to 23 181 fractions per million in Lincolnshire PCT (national mean - 15 087 fractions per million). Predictions of population growth by age cohort for 2016 and 2020 result in the regional differences in radiotherapy demand becoming greater over time. Similar effects were also observed at the level of the cancer network. Conclusions Our model shows the importance of local population demographics and cancer incidence rates when commissioning radiotherapy services.

To illustrate the wider potential scope of image-guided intensity-modulated radiotherapy (IG-IMRT), outside of the "standard" indications for IMRT.Nine challenging clinical cases were selected. All were treated with radical intent, although it was accepted that in several of the cases the probability of cure was low. IMRT alone was not adequate owing to the close proximity of the target to organs at risk, the risk of geographical miss, or the need to tighten planning margins, making image-guided radiotherapy an essential integral part of the treatment. Discrepancies between the initial planning scan and the daily on-treatment megavoltage CT were recorded for each case. The three-dimensional displacement was compared with the margin used to create the planning target volume (PTV).All but one patient achieved local control. Three patients developed metastatic disease but benefited from good local palliation; two have since died. A further patient died of an unrelated condition. Four patients are alive and well. Toxicity was low in all cases. Without daily image guidance, the PTV margin would have been insufficient to ensure complete coverage in 49% of fractions. It was inadequate by3 mm in 19% of fractions, and by5 mm in 9%.IG-IMRT ensures accurate dose delivery to treat the target and avoid critical structures, acting as daily quality assurance for the delivery of complex IMRT plans. These patients could not have been adequately treated without image guidance.IG-IMRT can offer improved outcomes in less common clinical situations, where conventional techniques would provide suboptimal treatment.

Primary testicular non-Hodgkin lymphoma (PTL) comprises around 9% of testicular cancers and 1-2% of all non-Hodgkin lymphomas. Its incidence is increasing and it primarily affects older men, with a median age at presentation of around 67 years. By far the most common histological subtype is diffuse large B-cell lymphoma, accounting for 80-90% of PTLs. Most patients present with a unilateral testicular mass or swelling. Up to 90% of patients have stage I or II disease at diagnosis (60 and 30%, respectively) and bilateral testicular involvement is seen in around 35% of patients. PTL demonstrates a continuous pattern of relapse and propensity for extra-nodal sites such as the central nervous system and contralateral testis. Retrospective data have emphasised the importance of prophylactic radiotherapy in reducing recurrence rates within the contralateral testis. Recent outcome data from the prospective IELSG-10 trial have shown far better progression-free and overall survival than historical outcomes. This supports the use of orchidectomy followed by Rituximab- cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), central nervous system prophylaxis and prophylactic radiotherapy to the contralateral testis with or without nodal radiotherapy in patients with limited disease. Central nervous system relapse remains a significant issue and future research should focus on identifying the best strategy to reduce its occurrence. Here we discuss the evidence supporting combination chemotherapy and radiotherapy in PTL.

Aims Modelling of demand has shown substantial underprovision of radiotherapy in the UK. We used national audit data to study geographical differences in radiotherapy waiting times, access and dose fractionation across the four countries of the UK and between English strategic health authorities. Materials and methods We used a web-based tool to collect data on diagnosis, dose fractionation and waiting times on all National Health Service patients in the UK starting a course of radiotherapy in the week commencing 24 September 2007. Cancer incidence for the four countries of the UK and for England by primary care trust was used to model demand for radiotherapy aggregated by country and by strategic health authority. Results Across the UK, excluding skin cancer, 2504 patients were prescribed 33 454 fractions in the audit week. Waits for radical radiotherapy exceeded the recommended 4 week maximum for 31% of patients (range 0–62%). Fractions per million per year ranged from 17 678 to 36 426 and radical fractions per incident cancer ranged from 3.0 to 6.7. Patients who were treated received similar treatment in terms of fractions per radical course of radiotherapy (18.2–23.0). Access rates ranged from 25.2 to 48.8%, nearing the modelled optimum of 50.7% in three regions. Fractions per million prescribed as a first course of treatment varied from 43.9 to 90.3% of modelled demand. The percentage of patients failing to meet the 4 week Joint Council for Clinical Oncology target for radical radiotherapy rose as activity rates increased ( r =0.834), indicating a mismatch of demand and capacity. In England, a comparison between strategic health authorities showed that increasing deprivation was correlated with lower rates of access to radiotherapy ( r =−0.820). Conclusions There are substantial differences across the UK in the radiotherapy provided to patients and its timeliness. Radiotherapy capacity does not reflect regional variations in cancer incidence across the UK (3618–5800 cases per million per year). In addition, deprivation is a major unrecognised influence on radiotherapy access rates. In regions with higher levels of deprivation, fewer patients with cancer receive radiotherapy and the proportion treated radically is lower. This probably reflects late presentation with advanced disease, poor performance status and co-morbid illness. To provide an equitable, evidence-based service, the needs of the local population should be assessed using demand modelling based on local cancer incidence. Ideally this should include data on deprivation, performance status and stage at presentation. The results should be compared with local radiotherapy activity data to understand waits, access and dose fractionation in order to plan adequate provision for the future. The development of a mandatory radiotherapy data set in England will facilitate this, but to assist change it is essential that the results are analysed and fed back to clinicians and commissioners.

Four patients with seminoma of the testis and coexisting horseshoe kidney are presented. Three patients had stage one disease, which would conventionally be managed by abdominal nodal irradiation. However, because of the risk of radiation nephritis, a surveillance policy was adopted with regular computed tomography (CT). Two of these three patients have relapsed and are disease free after chemotherapy. The fourth patient had Stage IIC disease which initially responded to combined radiotherapy and chemotherapy. This patient's disease relapsed and he died despite further treatment. Because of the altered retroperitoneal anatomy, CT interpretation must be made with special care.

We present a case report of a patient who received adjuvant carboplatin for stage 1 seminoma and relapsed with abdominal lymph node metastasis at 48 months. In recent years, many oncologists have offered a single cycle of adjuvant carboplatin AUC7 as adjuvant treatment for stage 1 seminoma. The available data show a non-inferior relapse-free survival at 3 years compared with para-aortic radiotherapy. The rate of relapse beyond this point has not been reported. Patients with stage 1 seminoma represent a group of patients with excellent outcomes, and treatment options must also consider the late effects of treatment, of which there are increasing data of mortality for those treated with radiotherapy. Patients who opt for surveillance have a greater than 80% chance of remaining relapse free at 5 years, but those on surveillance require more CT examinations for follow-up. For those treated with single-agent carboplatin, our case report highlights that late relapse can occur, and we suggest that CT surveillance beyond 2 years is required given the lack of mature data on late relapse.

To evaluate the role of chest CT in the initial staging of testicular seminomatous germ cell tumours. All patients referred to Addenbrooke's Hospital with testicular seminoma from 1 January 2000 to 31 December 2005 were included and case notes retrospectively reviewed. One hundred and eighty-two patients with testicular seminoma were identified, with a median age of 37 years (range 19–74). Most patients had stage I disease (86%). Twenty-four patients had abnormal abdominal CT findings. One hundred and fifty-eight had normal abdominal CT findings but, on initial staging, chest CT reported abnormalities in 13 patients, which, on further follow-up CT were deemed to be irrelevant to the diagnosis of seminoma. There was a further patient with a normal CT abdomen in whom chest CT detected obvious metastatic disease, which was seen on chest x-ray. Overall 18 cases required additional investigations and follow-up for abnormalities subsequently found to be benign. There was a false-positive rate of 10% for initial staging with chest CT. This is the largest reported series of staging CT chest in testicular seminoma. In all patients with normal abdominal CT, normal chest x-ray and abnormal chest CT, subsequent follow-up investigations demonstrated that the lung lesions were incidental findings.

Aims The Royal College of Radiologists has published a review of the evidence base for radiotherapy dose fractionation. We modelled the implications of changes in practice on radiotherapy demand and compared it with current activity, access and waiting times across the countries of the UK. Materials and methods We collected data on diagnosis, dose fractionation and waiting times on all patients in the UK starting a course of radiotherapy in the week commencing 26 September 2005. Excluding skin cancer, 2610 patients were prescribed 34 194 fractions. Results Radiotherapy access rates were 38% in England, 43% in Scotland and 37% in Wales. These are all lower than the 52% of cancer patients recommended by modelling. To increase access to the recommended level, a 33% increase in activity is required across the UK. For each of 13 cancer diagnoses, we modelled optimum fractionation and compared it with current practice. To deliver the dose fractionation with the best evidence base, a further increase in activity of 37% is required. To take account of both access and optimal fractionation, the two factors should be multiplied (1.33×1.37=1.82) giving an overall increase of 82% for the UK. This would require 53 741 fractions per million population annually. The exact value depends on the cancer incidence in each country, but should be compared with current activity of 28 040 in England, 39 584 in Scotland and 31 228 in Wales. Limited capacity is reflected in waiting times. The percentage of patients exceeding the maximum recommended wait of 28 days for radical or adjuvant postoperative radiotherapy was 55% in England, 44% in Scotland and 74% in Wales. Conclusions To secure adequate access to treatment and optimal dose fractionation, substantial increases in radiotherapy activity of 92% in England, 61% in Scotland and 97% in Wales are required. Achieving this will require a planned programme of investment in staff, training and equipment.

Most patients with Stage IA and IIA supradiaphragmatic Hodgkin's disease are conventionally treated in the UK by radiotherapy. Traditionally, a mantle field is used. This encompasses the lymph nodes of the neck, axillae and mediastinum in continuity with appropriate shielding of sensitive structures, particularly the lungs. The overall relapse rate after mantle radiOtherapy is high (over 40% in clincially staged patients [1,2]), but the infield relapse rate is low (1% in the British National Lymphoma Investigation (BNLI) series). Salvage chemotherapy is highly successful, with over 70% of patients surviving to 14 years [2]. The following discussion relates to radiotherapy when used as the sole treatment modality. In combination with chemotherapy [3] and in paediatric practice [4], lower doses are used but there are less data in this area and the role of radiotherapy in combination treatment remains uncertain because no adequate randomized clinical trial has ever been completed [5,6]. To radiotherapists who are accustomed to prescribe doses of 60 Gy or more to treat the common solid malignancies, the radiation dose used to treat Hodgkin's disease and the moribidity associated with it appear low. The received wisdom that most radiotherapy trainees in Britain and elsewhere are taught is that 'the dose to involved sites of Hodgkin's disease is 40 Gy'. This view is supported by groups such as the BNLI [2,7] and the EORTC [8]. The 1990-1991 Patterns of Care newsletter recommended 36-44 Gy to involved regions and 30-40 Gy to uninvolved sites [9]. Treatment is normally given 5 days a week in fractions of 2 Gy or less. The acute morbidity seems low, but, in such a high dose necessary, and what are the long term effects?

Cranio-spinal irradiation for medulloblastoma can impair fertility in girls. The literature indicates that an ovarian dose of 4 Gy causes permanent infertility in 30% of young females and that doses of1.5 Gy over the whole treatment are desirable. We report a modified radiotherapy technique using a non-divergent beam edge inferiorly to reduce the ovarian dose.Eight female patients with medulloblastoma had magnetic resonance imaging (MRI) studies in the treatment position to identify the position of their ovaries relative to the radiation field. The information was transferred to the radiotherapy planning system and plans were generated using conventional spinal fields and modified fields with a half beam block at the inferior border.Identifying the position of the ovaries by MRI enabled the dose to be estimated for the two techniques. Using a non-divergent beam inferiorly, the mean ovarian dose was reduced in all cases by a median value of 2.45 Gy (range 0.6-19.5 Gy) and the median percentage reduction was 66.8% (range 2.6-84.6%). The position of the ovary relative to the beam edge was critical in determining the dose reduction for each case. The modified technique doubled the number of patients receiving4 Gy to a single ovary from three to six. With this alteration, three patients also had an ovary receiving1.5 Gy whereas all exceeded this dose with conventional treatment.We recommend using asymmetry at the inferior spinal border to achieve a non-divergent edge to the treatment field to reduce the dose to the ovary. Using MRI to localise the ovaries is important in estimating their dose and in assisting the counselling of patients and their families about future fertility.

Objectives To study survival and late events after adjuvant chemotherapy in Stage 1 nonseminoma. Methods From 1978 to 1986, all patients had surveillance. From 1986, adjuvant chemotherapy (initially a 3-day regimen of etoposide, bleomycin, and cisplatin, but, more recently, bleomycin, Oncovin, and cisplatin) was offered to patients at a high risk of relapse (greater than 30%). Results A total of 382 patients with Stage 1 nonseminoma treated between 1978 and 2000 were reviewed. Of the 234 patients treated by surveillance, 71 (30%) had relapses (5 after 2 years), 6 died (2.6%) of germ cell cancer, and 3 developed second primary testicular cancer. Of the 148 men treated with adjuvant chemotherapy, 6 (4%) had relapses and 2 (1.4%) died of chemoresistant cancer. After one course of etoposide, bleomycin, and cisplatin, 3 (6.5%) of 46 developed a relapse; after two courses, 1 (3.6%) of 28 did so; and after bleomycin, Oncovin, and cisplatin every 10 days ×2, 2 (2.7%) of 74 patients did so. Of the high-risk patients who were offered adjuvant treatment, 24% declined. As a consequence, the relapse rate of the surveillance patients only fell from 36% to 27% after the introduction of adjuvant therapy, although for the total cohort treated in the adjuvant era, the relapse rate was 16%. Conclusions Adjuvant chemotherapy is more effective than retroperitoneal lymph node dissection for reducing the relapse risk in high-risk Stage 1 nonseminoma. However, given the uncertainty about the incidence of postchemotherapy late events, surveillance and retroperitoneal lymph node dissection remain justified alternatives. With positron emission tomography and laparoscopy showing increasing promise in these cases, quality-of-life studies and greater patient involvement in treatment selection are needed.

Background Primary testicular lymphoma (PTL) presents in most cases, histologically, as a diffuse large B-cell lymphoma. PTL has a propensity for metastases to the central nervous system (CNS) cited as 20% at 5 years. Bilateral testicular involvement is seen in 35% of cases. Treatment commonly consists of orchidectomy followed by Rituximab- cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), intrathecal methotrexate (IT-MTX) and prophylactic radiotherapy to the contralateral testis. Administration of systemic high-dose MTX (HD-MTX), at 3 g/m2, has been proposed as an approach to improve CNS parenchymal penetration and may prevent the need for scrotal irradiation. From 2005 within the Anglia Cancer Network, HD-MTX was incorporated into standard treatment for patients with PTL, who were fit enough to receive high dose therapy. Here we report outcomes from the 2 largest lymphoma centres within the network. Method A retrospective review was carried out using medical records of patients with PTL treated with HD-MTX at Cambridge University Hospitals (CUH) and Norfolk and Norwich University Hospital (NNUH), UK, from 2005 onwards. Histological diagnoses were made via orchidectomy or testicular biopsy. Factors reviewed included: age, stage, ECOG performance status, presence of B symptoms and IPI score at diagnosis, treatment regimen, grade 3/4 toxicity and clinical outcome. Stage IV disease was excluded as it cannot be distinguished from a non-testicular primary. Results 10 patients were identified who met the search criteria. 6 were treated at CUH and 4 at NNUH. Median age at diagnosis was 61.5 (49-71). All patients presented with scrotal swelling and 30% had bilateral tumours. ECOG PS was 0 (90%) and 1 (10%). 80% had stage IE disease and 20% stage IIE (paraaortic). Median IPI was 1. Patients were planned to receive 6 cycles of R-CHOP21 with 3-6 cycles IT-MTX with 3 cycles HD-MTX (3 g/m2) administered between or after R-CHOP21. Patients at NNUH only also received radiotherapy at 30 Gy in 15 fractions to the contralateral testis +/- PA nodes if stage IIE disease. One NNUH patient did not receive IT-MTX and one CUH patient only received 2 cycles HD-MTX for logistical reasons. No grade 3 or 4 toxicities were noted. At time of submission with a median follow-up of 4.27 years, only 1 patient has relapsed within the bone marrow. He died of systemic disease but was not shown to have CNS relapse. One patient died of a non-PTL related cause. 8 patients remain in ongoing first remission. No cases of CNS or testicular relapse have been noted in our 10 patients including the 6 patients who did not receive scrotal irradiation. One patient at CUH with bilateral disease was diagnosed on biopsies alone. He underwent unilateral orchidectomy after completing systemic treatment demonstrating a complete response, despite no radiotherapy. He declined a second orchidectomy and remains relapse free at 5.91 years follow-up. Conclusion Treating PTL with HD-MTX, IT-MTX and R-CHOP has shown encouraging clinical outcomes in terms of treatment tolerability and disease-free survival at a median follow-up of 4.27 years. Accepting the small numbers, the absence of CNS relapse with this follow-up suggests prophylactic efficacy of HD-MTX. The finding that disease was eliminated in an in situ testis following treatment is also significant, given the standard practice of contralateral testicular irradiation. These results highlight the need for further prospective research to determine the role of HD-MTX in the management of PTL. Disclosures: No relevant conflicts of interest to declare.

For ovarian ablation using radiotherapy, the pelvis is irradiated using generous fields sizes, as the position of the ovaries is uncertain. To assess the variation in ovarian position, we reviewed 81 sequential CT examinations of the pelvis performed in women under the age of 50 years. Women with pelvic malignancy or previous pelvic surgery were excluded from the analysis, leaving 30 eligible women. One or both ovaries could be clearly identified in 23 of these patients; in 19 (83%), the ovaries were located within the upper two-thirds of a ring defined by the sacroiliac joints, the bony side wall of the pelvis and the symphysis pubis. The ovaries were located outside this ring in four (17%) women. Ovarian position did not appear to be influenced by parity, uterine orientation, the degree of bladder filling or faecal loading within the rectum. The treatment volume for artificial radiation menopause has been variably defined; the upper part of the pelvis may not be included. The results from this retrospective study suggest that the treatment volume should extend from the inferior border of the fifth lumbar vertebra down to a level traversing the middle of the femoral heads and 1 cm lateral to the pelvic side walls.

Summary points Radiotherapy plays an important role in the care of patients with cancer and forms part of the management of 40% of patients cured of their disease.1 Advances have been made in the past two decades, as improvements in engineering and computing have enabled technologies such as intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and stereotactic radiotherapy (SRT) to be used in routine clinical practice. This article explains newer radiotherapy techniques and aims to enable general practitioners and non-specialist clinicians to advise patients who come to them with questions. It will focus on external beam radiotherapy (EBRT), which is the most common form of treatment, delivered to 125 000 patients a year in England.2 #### Sources and selection criteria This article is an evidence based review of clinical radiotherapy. We searched PubMed and the Cochrane databases between 1990 and 2012 using the search terms radiotherapy, intensity modulated radiotherapy, image guided radiotherapy, stereotactic radiotherapy, and proton beam therapy to identify observational studies, randomised trials, meta-analyses, and systematic reviews. X rays are a form of electromagnetic radiation that deliver their energy through waves called photons. These photons are produced by accelerating a stream of electrons and colliding them with a metal target. High energy photons produce secondary electrons in human tissue. Electrons cause DNA damage which, if not repaired, proves fatal at cell division. Absorbed …

Aim In 2007, the National Radiotherapy Advisory Group (NRAG) issued a report with national targets for radiotherapy capacity based on cancer incidence and best clinical practice1. The model specified a national target of 54,000 fractions per million by 2016, and an access rate (percentage of cancer patients receiving radiotherapy treatment) of 52%. Whilst the model formed the basis of targets within the National Cancer Plan, it is difficult to apply the model at a local level, due to the variation in underlying population demographics and a 2.5 fold variation in cancer incidence within the country.

Purpose : Underpinned by increased confidence in cure of metastatic seminoma by chemotherapy during the past 12 years, three management strategies for Stage I seminoma have been evaluated by six collaborating centers within the Anglian Germ Cell Tumor Group. This paper evaluates the efficacy of surveillance, prophylactic radiotherapy and adjuvant chemotherapy, and discusses these differing management approaches. Methods and Materials : Patients were recruited into the study between 1982 and 1992. There was no randomization between treatment groups. Seventy-nine patients received prophylactic radiotherapy (median follow-up = 51 months), 67 patients had surveillance alone (median follow-up = 61 months) and 78 patients were treated with adjuvant single agent platinum (median follow-up = 44 months). Fifty-three of these patients received two courses of platinum (median follow-up = 51 months) and 25 patients received one course (median follow-up = 29 months, range 22–72 months). Results : There were 18 (27%) recurrences on surveillance, five (6%) after radiotherapy, one (1%) after two courses of adjuvant single agent platinum and none after one course of carboplatin. There was one death from testis cancer after radiotherapy and none after adjuvant chemotherapy treatments. Two patients died with drug resistant disease after relapse on surveillance. There was one death from a myocardial infarction after prophylactic radiotherapy and one death from suicide in the surveillance group. A retrospective quality of life questionnaire reviewing the incidence of early and late toxicity revealed no major differences though they suggest that those treated with one course adjuvant carboplatin had somewhat less sickness and an earlier return to work. Conclusion : Single agent carboplatin appears well tolerated and is an effective adjuvant treatment for Stage I seminoma. A multicenter randomized trial of the different treatment modalities is required to further evaluate its use.

To assess the value of prophylactic cipro-floxacin in reducing the incidence of neutropenic fever in men receiving intensive chemotherapy for germ cell tumours, we reviewed the case notes of 88 consecutive patients treated between January 1986 and December 1992. Nadir blood counts were performed in all patients on day 14. From 1989, prophylactic ciprofloxacin 250 mg b.d. was started when the neutrophil count was less than 1 × 10 9 /l and then prescribed for all subsequent courses of chemotherapy from day 7 to day 21. In total, 88 men received 429 courses of chemotherapy. Prophylactic ciprofloxacin was prescribed for 168 courses. This was associated with a trend towards reducing the risk of admission per course of chemotherapy from 8% (20/261) to 4% (6/168) ( P = 0.08 ). WHO grade ¾ neutropenia ( 9 /l) was documented for 240 (56%) courses of chemotherapy. The incidence of fever in these patients was significantly reduced from 15% (20/131) to 5% (6/109) ( P = 0.02 ) with prophylactic ciprofloxacin. Two patients, one of whom had received prophylactic ciprofloxacin, died of chest infection confirmed on post-mortem. The results of this non-randomized, retrospective study suggest that prophylactic ciprofloxacin 250 mg b.d. is effective in reducing the incidence of fever complicating neutropenia during chemotherapy for germ cell tumours. To be cost effective, it should be given only to neutropenic patients.

We have conducted three audits of the number of fractions used within our department to treat symptomatic bone metastases. The initial audit identified 133 patients treated for bone metastases in a 3-month period using 538 fractions (mean number of fraction=4.1, range 1–14). These figures were presented at our audit meeting along with a literature review which provided no evidence of any advantage of multiple fractions over single fractions. Departmental guidelines recommending the use of single fractions were established. A subsequent audit identified 149 patients treated with 520 fractions (mean number of fractions=3.5, range 1–11). A third audit identified 148 patients treated with 335 fractions (mean number of fractions=2.3, range 1–10). Audit has resulted in a reduction in the number of fractions used to treat bone metastases in our department. The major effect was seen after the second audit.

The British government has recently stated its aim of reducing deaths from cancer by a fifth over the next decade, with contributions from prevention, early diagnosis, and better treatments. British cancer cure rates are poorer than those of continental Europe and North America,1 and under—resourcing of radiotherapy services contributes to this.2 The government target could be accomplished by providing adequate radiotherapy facilities to deliver proved clinical treatments. After surgery, radiotherapy is the most effective curative treatment for cancer. Between 30% and 40% of the population will develop cancer, and at least half require radiotherapy at some time in their illness. Of patients having radiotherapy about 60% are treated with curative intent, often in combination with surgery and chemotherapy. Improving the effectiveness of radiotherapy would thus have a substantial impact on cancer cures in the United Kingdom. Provision of adequate radiotherapy facilities would improve the outcome of cancer treatment through three main mechanisms. The first is reduction of the waiting …