Highly Conformal Craniospinal Radiotherapy Techniques Can Underdose the Cranial Clinical Target Volume if Leptomeningeal Extension through Skull Base Exit Foramina is not Contoured.

AIMS: Craniospinal irradiation (CSI) remains a crucial treatment for patients with medulloblastoma. There is uncertainty about how to manage meningeal surfaces and cerebrospinal fluid (CSF) that follows cranial nerves exiting skull base foramina. The purpose of this study was to assess plan quality and dose coverage of posterior cranial fossa foramina with both photon and proton therapy. MATERIALS AND METHODS: We analysed the radiotherapy plans of seven patients treated with CSI for medulloblastoma and primitive neuro-ectodermal tumours and three with ependymoma (total n = 10). Four had been treated with a field-based technique and six with TomoTherapy™. The internal acoustic meatus (IAM), jugular foramen (JF) and hypoglossal canal (HC) were contoured and added to the original treatment clinical target volume (Plan_CTV) to create a Test_CTV. This was grown to a test planning target volume (Test_PTV) for comparison with a Plan_PTV. Using Plan_CTV and Plan_PTV, proton plans were generated for all 10 cases. The following dosimetry data were recorded: conformity (dice similarity coefficient) and homogeneity index (D2 - D98/D50) as well as median and maximum dose (D2%) to Plan_PTV, V95% and minimum dose (D99.9%) to Plan_CTV and Test_CTV and Plan_PTV and Test_PTV, V95% and minimum dose (D98%) to foramina PTVs. RESULTS: Proton and TomoTherapy™ plans were more conformal (0.87, 0.86) and homogeneous (0.07, 0.04) than field-photon plans (0.79, 0.17). However, field-photon plans covered the IAM, JF and HC PTVs better than proton plans (P = 0.002, 0.004, 0.003, respectively). TomoTherapy™ plans covered the IAM and JF better than proton plans (P = 0.000, 0.002, respectively) but the result for the HC was not significant. Adding foramen CTVs/PTVs made no difference for field plans. The mean Dmin dropped 3.4% from Plan_PTV to Test_PTV for TomoTherapy™ (not significant) and 14.8% for protons (P = 0.001). CONCLUSIONS: Highly conformal CSI techniques may underdose meninges and CSF in the dural reflections of posterior fossa cranial nerves unless these structures are specifically included in the CTV.

Quantifying uncertainty in radiotherapy demand at the local and national level using the Malthus model.

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.

The Malthus Programme: developing radiotherapy demand models for breast and prostate cancer at the local, regional and national level.

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.

Radiotherapy demand and activity in England 2006-2020.

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.

Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors.

BACKGROUND: Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk. METHODS: We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case-control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956-2003. RESULTS: Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97-15.46)), and increased significantly with proximity of sRT to menarche (Ptrend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35-0.85)), and increased with number of premenopausal years after treatment (Ptrend=0.003). CONCLUSION: In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk.

The value of image-guided intensity-modulated radiotherapy in challenging clinical settings.

OBJECTIVE: To illustrate the wider potential scope of image-guided intensity-modulated radiotherapy (IG-IMRT), outside of the "standard" indications for IMRT. METHODS: 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). RESULTS: 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 by >3 mm in 19% of fractions, and by >5 mm in 9%. CONCLUSION: 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. ADVANCES IN KNOWLEDGE: IG-IMRT can offer improved outcomes in less common clinical situations, where conventional techniques would provide suboptimal treatment.

The management of lung cancer: a UK survey of oncologists.

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.

Primary testicular lymphoma.

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.

Development of an electronic medical record based intervention to improve medical care of osteoporosis.

UNLABELLED: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. An EMR-based intervention (osteoporosis order set) was developed with physician and patient input. There was a trend toward greater calcium supplementation from July 2008 to April 2009 (s = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. INTRODUCTION: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. The study population consisted of patients over 50 years of age. METHODS: Northwestern Memorial Hospital is a tertiary care academic hospital in Chicago. This study was conducted from September 1, 2007 through June 30, 2009. RESULTS: Physicians reported that barriers to care comprised nonacute nature of osteoporosis, belief that osteoporosis should be addressed by the PCP, low awareness of recurrent fractures, and radiographs with terms such as "compression deformity", "wedge deformity", or "vertebral height loss" which in their opinion were not clearly indicative of vertebral fractures. An EMR-based intervention was developed with physician and patient input. Over the evaluation period, 295 fracture cases in individuals over the age of 50 years in the medicine floors were analyzed. Mean age was 72 ± 11 years; 74% were female. Sites of fracture included hip n = 78 (27%), vertebral n = 87 (30%), lower extremity n = 61 (21%), upper extremity n = 43 (15%) and pelvis n = 26 (9%). There was no increase in documentation of osteoporosis in the medical record from pre- to post-EMR implementation (p = 0.89). There was a trend toward greater calcium supplementation from July 2008 to April 2009 (p = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. CONCLUSION: An electronic medical record intervention without electronic reminders created with physician input achieves an increase in calcium supplementation but fails to increase diagnosis or treatment for osteoporosis at the time of hospitalization for a fragility fracture.

Clinical examination does not assist in the detection of systemic relapse of testicular germ cell tumour.

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.

Lung spirometry parameters and diffusion capacity are decreased in patients with Type 2 diabetes.

AIMS: In cohort studies, Type 2 diabetes mellitus has been associated with decreased forced 1 s expiratory volume and forced vital capacity. We examined if forced vital capacity, forced 1 s expiratory volume and diffusion lung capacity correlate with diabetes mellitus across different races in a clinical setting. METHODS: We examined the medical records of 19,882 adults 18-97 years of age in our centre from 1 January 2000 to 1 May 2009. After excluding patients with diseases causing abnormal lung function, 4164 subjects were available for analysis. We used multiple linear regressions to examine cross-sectional differences in forced vital capacity, forced 1 s expiratory volume and carbon monoxide diffusing capacity between patients with and without diabetes mellitus, after adjustment for age, sex, race, height, smoking, BMI and heart failure. RESULTS: Patients with diabetes (n = 560) were older (62 ± 12 vs. 55 ± 16 years), more likely to be men (56 vs. 43%), overweight (BMI 31.7 ± 8.5 vs. 27.3 ± 6.7 kg/m2 ), have heart failure (33 vs. 14%) and less likely to be Caucasians (65 vs. 76%) and never smokers (66 vs. 72%) compared with patients without diabetes (n = 3604). The mean unadjusted values in patients with diabetes vs. those without were: forced vital capacity 2.78 ± 0.91 vs. 3.19 ± 1.03 l; forced 1 s expiratory volume 2.17 ± 0.74 vs. 2.49 ± 0.0.83; and carbon monoxide diffusing capacity 16.67 ± 5.53 vs. 19.18 ± 6.72 ml(-1) min(-1) mmHg, all P < 0.0001. These differences remained significant after adjustment for covariates. After race stratification, only Caucasians with diabetes had a significant decrease in all lung function measures. CONCLUSIONS: Patients with diabetes have decreased lung function compared with those without diabetes. Caucasians with diabetes have more global lung function impairment compared with African-Americans and Hispanics.

Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour.

BACKGROUND: We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. METHODS: Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP. RESULTS: Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72-1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1-6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64-100%). CONCLUSION: Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data.

Organisational culture: variation across hospitals and connection to patient safety climate.

CONTEXT: Bureaucratic organisational culture is less favourable to quality improvement, whereas organisations with group (teamwork) culture are better aligned for quality improvement. OBJECTIVE: To determine if an organisational group culture shows better alignment with patient safety climate. DESIGN: Cross-sectional administration of questionnaires. Setting 40 Hospital Corporation of America hospitals. PARTICIPANTS: 1406 nurses, ancillary staff, allied staff and physicians. MAIN OUTCOME MEASURES: Competing Values Measure of Organisational Culture, Safety Attitudes Questionnaire (SAQ), Safety Climate Survey (SCSc) and Information and Analysis (IA). RESULTS: The Cronbach alpha was 0.81 for the group culture scale and 0.72 for the hierarchical culture scale. Group culture was positively correlated with SAQ and its subscales (from correlation coefficient r = 0.44 to 0.55, except situational recognition), ScSc (r = 0.47) and IA (r = 0.33). Hierarchical culture was negatively correlated with the SAQ scales, SCSc and IA. Among the 40 hospitals, 37.5% had a hierarchical dominant culture, 37.5% a dominant group culture and 25% a balanced culture. Group culture hospitals had significantly higher safety climate scores than hierarchical culture hospitals. The magnitude of these relationships was not affected after adjusting for provider job type and hospital characteristics. CONCLUSIONS: Hospitals vary in organisational culture, and the type of culture relates to the safety climate within the hospital. In combination with prior studies, these results suggest that a healthcare organisation's culture is a critical factor in the development of its patient safety climate and in the successful implementation of quality improvement initiatives.

Patterns of nurse-physician communication and agreement on the plan of care.

BACKGROUND: Interdisciplinary communication is critically important to provide safe and effective care, yet it has been inadequately studied for hospitalised medical patients. Our objective was to characterise nurse-physician communication and their agreement on patients' plan of care. METHODS: During a one-month period, randomly selected hospitalised patients, their nurses and their physicians were interviewed. Nurses and physicians were asked to identify one another, whether communication had occurred, and about six aspects of the plan of care. Two internists rated nurse-physician agreement on aspects of the plan of care as none, partial or complete agreement. Measures included the percentage of nurses and physicians able to identify one another and reporting communication and the percentage of nurse-physician pairs in agreement on aspects of the plan of care. RESULTS: 310 (91%) and 301 (88%) of 342 eligible nurses and physicians completed interviews. Nurses correctly identified patients' physicians 71% of the time and reported communicating with them 50% of the time. Physicians correctly identified the patients' nurses 36% of the time and reported communicating with them 62% of the time. Physicians and nurses showed no agreement on aspects of the plan of care ranging from 11% for planned procedures to 42% for medication changes. CONCLUSIONS: Nurses and physicians did not reliably communicate with one another and were often not in agreement on the plan of care for hospitalised medical patients.

Teamwork on inpatient medical units: assessing attitudes and barriers.

BACKGROUND: Discrepant attitudes about teamwork among nurses and physicians exist in operating rooms and intensive care units. Little is known about teamwork attitudes on general medical services. OBJECTIVE: To assess ratings of teamwork by providers on inpatient medical units and barriers to collaboration. DESIGN AND PARTICIPANTS: Nurses, primary hospital physicians and medical subspeciality consultants on four general medical units were surveyed. MEASUREMENTS: Providers rated the quality of communication and collaboration experienced with their own and other disciplines. Providers also rated potential barriers to collaboration. Differences between providers in ratings of collaboration and barriers were tested using analysis of variance. RESULTS: Of 230 eligible providers, 159 (69%) completed the survey. Teamwork ratings of nurses were similarly high across provider types. Ratings of physicians differed considerably by provider type (p

Radiotherapy in England in 2007: modelled demand and audited activity.

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.