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This paper takes the academically unorthodox form of personal correspondence. This method, of letters between two educators writing to one another across the distance of two continents and different experiences, seeks to create an inclusive, confessional tone, one that invites the reader to get closer to the lived experience of those struggling within the educational and environmental crises. Critically, this correspondence also seeks to open discussion about the difficult demands of state secondary and tertiary education. The authors explore issues regarding their denuded experiences of working in formal education settings while bearing witness to environmental degradation and ecological collapse. In light of their exploration, the authors argue for an ‘agrios’, a wilder, more expansive polis, coupled with more ecologically-inclusive governance, to address the current potentially catastrophic political leadership that has seemingly turned away from ecological responsibility. This paper culminates in direct letters that focus on a series of practical proposals for action and on four premises for developing agriocy – the policy that supports the agrios/agriocity.

This paper begins with a very short overview of the environmental and educational challenges that exist today. It proceeds through three pedagogical strands – the relational, the critical, and the existential – that have been woven through the practices of many outdoor and environmental educators for the last 60 years. After each strand is described the paper offers a considered push with the goal of inspiring possibility and taking pedagogy further. Each push is described within the context of a Wild Pedagogies touchstone. The conclusion suggests that gathering all three strands, along with their proposed extensions, offers some promise towards responding to the global environmental challenges at hand. In fact, what might be needed is a comprehensive educational practice that draws best practices from all three along with their respective rich amalgam of skills. The paper ends with a call to outdoor and environmental educators.

To compare the modalities used to treat muscle-invasive bladder cancer (MIBC) and assess response to fractionated neoadjuvant chemotherapy. We retrospectively reviewed patients with MIBC that were treated with neoadjuvant fractionated gemcitabine–cisplatin (GC) and subsequently received radical treatment. Disease-free interval and overall survival curves were constructed using the Kaplan–Meier method. A Cox proportional hazards model was used to obtain hazard ratios, confidence intervals and associated p value in a univariate analysis. A total of 122 patients were included, of which 21 (17%) patients were treated with radiotherapy (RT), 27 (22%) were given chemo-radiotherapy (CRT) and (61%) 74 had surgery only. Median follow-up is 4.8 years (range 0.7–11.8 years). Definitive treatment did not significantly affect overall survival (p = 0.16) or disease-free interval (p = 0.74). The 5 year overall survival rates were 44% for RT, 54% for CRT and 55% for surgery and 47, 49 and 58% respectively, for disease-free interval. Ninety-six percent of patients received at least three cycles of fractionated neoadjuvant GC. Twenty-six percent of patients achieved a pathological complete response post cystectomy and only two patients progressed during this treatment. Patients with MIBC can potentially be treated with surgery, or with bladder preserving techniques—RT and CRT. No randomised evidence exists to directly compare radical options and a frequently used neoadjuvant chemotherapy regime also lacks randomised data. Patients responded well to and tolerated fractionated gemcitabine and cisplatin. This regime can be used in patients with an eGFR as low as 40 ml/min. Our results support the use of chemo-radiotherapy or surgery as radical treatments in suitable patients with MIBC. All patients should be considered for and be given the option of both cystectomy and chemo-radiotherapy.

Purpose Cabazitaxel 25 mg/m2 (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m2 (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 v mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the hazard ratio (HR) for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included progression-free survival, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Results Overall, 1,200 patients were randomly assigned (C20, n = 598; C25, n = 602). Baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P < .001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 v C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Conclusion The efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed. The noninferiority end point was met; C20 maintained ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.

Background Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care. Methods Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histopathology, and clinical information were reviewed. Final diagnosis was agreed on by the tumor board at study end. Results Five cases were excluded for lack of documented MRI diagnosis. The principal MRI diagnosis by pediatric radiologists was correct in 59%, increasing to 73% with addition of MRS. Of the 73%, 19.1% (95% CI, 9.1%-33.3%) were incorrectly diagnosed with MRI alone. MRS led to a significant improvement in correct diagnosis over all tumor types (P = .012). Of diagnoses correctly made with MRI, confidence increased by 37% when adding MRS, with no patients incorrectly re-diagnosed. Indolent lesions were diagnosed noninvasively in 85% of cases, with MRS a major contributor to 91% of these diagnoses. Of all patients, 39% were managed without histopathological diagnosis. MRS contributed to diagnosis in 68% of this group, modifying it in 12%. MRS influenced management in 33% of cases, mainly through avoiding and guiding biopsy and aiding tumor characterization. Conclusion MRS can improve accuracy and confidence in noninvasive diagnosis of pediatric brain lesions in clinical practice. There is potential to improve outcomes through avoiding biopsy of indolent lesions, aiding tumor characterization, and facilitating earlier family discussions and treatment planning.

BACKGROUND Treatment of medulloblastoma has evolved substantially with more chemotherapy, risk-adapted dosing of radiotherapy (RT) and new RT techniques. We present the endocrine profile for our patients treated over a 20-year period. METHODS The charts of patients treated for medulloblastoma between 1/1/00 and 31/12/19 were reviewed. 105 were available. Group 1 received chemotherapy alone, Group 2 received 23.4 Gy whole CNS RT with a posterior fossa (PF) boost to 54 Gy, Group 3 received > 35 Gy whole CNS RT with PF boost to 54–59 Gy, Group 4 received PF RT to 54 Gy. All received chemotherapy according to national guidelines or clinical trials relevant at the time. RESULTS Group 1 (M:F 11:6, 7 survivors mean age 2 years range 1–7) had no endocrinopathies. At 5 years from diagnosis Group 2 (M:F 15:13) and Group 3 (M:F 35:14) had the following % RESULTS Survival 77:61; Growth Hormone deficiency 92:100; Thyroid deficiency 75:81; ACTH deficiency 42:33. Girls were more likely to need sex hormone replacement than boys. Group 4 (M:F 7:5 mean age 2) were all treated in the first decade. 3 survivors, one GH deficiency, one thyroxine deficiency, one both. CONCLUSIONS There is a trend to earlier endocrinopathies in the group 3 vs group 2 patients, but it does not reach statistical significance. Girls are more likely to need sex hormone replacement than boys. This investigation provides a contemporary profile of endocrinopathy after treatment for medulloblastoma that can be used for future comparisons.

Tetrahydrocannabinidiol (THC; one of the main psychoactive components of cannabis) has been shown to suppress REM sleep1-4 and affect sleep latency,4 5 although these findings are not consistently replicated.3 4 6 Cannabis use is also reported to affect dreaming frequency.7 Most studies investigating cannabis use and sleep have been laboratory-based, while only a limited body of research exists on dream occurrence and cannabis use. This study aimed to pilot the measurement of participants sleeping at home in their usual surroundings, in order to assess effects of cannabis use compared to non-use, on objective sleep measures, dream reports, and self-reported anxiety, memory, and sleep quality. Eleven frequent cannabis users versus 8 non-users proceeded in their usual routines, and wore Hypnodyne Zmax portable sleep acquisition headbands (recording EEG, EOG and EMG) while sleeping at home over two consecutive nights. Participants gave dream reports in three awakenings, set at two-hourly intervals on each night, and once upon morning awakening, reporting dream content and subjective ratings of the dream’s bizarreness, emotionality, and sensory experience. In addition, participants completed problem cannabis use, lifetime and nightly cannabis use, PSQI, everyday memory and trait anxiety measures. No differences were reported by participants in sleep quality, anxiety or memory between the two groups; predictably, cannabis users reported significantly more problems in relation to use of the drug. Cannabis users demonstrated significantly longer sleep latency and less REM sleep overall; no other differences occurred in objective sleep measures between groups. Cannabis users reported higher bizarreness in their dreams, but no differences were reported in dream recall or other dream measures. It is noted that small sample sizes limit the generality of findings in this study. The procedure provides a useful paradigm and encouraging initial results, however, for contemporary research related to cannabis use and sleep in naturalistic conditions, in this ongoing project. References Babson K A, Sottile J, Morabito D. Cannabis, cannabinoids, and sleep: a review of the literature. Current psychiatry reports 2017;19(4):23. Bonn-Miller MO, Babson KA, Vandrey R. Using cannabis to help you sleep: heightened frequency of medical cannabis use among those with PTSD. Drug and alcohol dependence 2014;136:162–165. Bowles N P, Herzig M X, Shea S A. Recent legalisation of cannabis use: effects on sleep, health, and workplace safety. Nature and Science of Sleep 2017;19(9):249–51 Feinberg I, Jones R, Walker J M, Cavness C, March J. Effects of high dosage delta-9-tetrahydrocannabinol on sleep patterns in man. Clinical Pharmacology Therapy 1975;17(4):458–66. Karacan I, Fernandez-Salas A, Coggins W J, Carter W E, Williams R L, Thornby J I, Villaume J P. Sleep electroencephalographic-electrooculographic characteristics of chronic marijuana users: Part I. Annals of the New York Academy of Sciences 1976;282(1):348–74. Schierenbeck T, Riemann D, Berger M, Hornyak M. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Medicine Reviews 2008;12(5):381–389. Tassinari CA, Ambrosetto G, Peraita-Adrado MR, Gastaut H. The neuropsychiatric syndrome of δ9-tetrahydrocannabinol and cannabis intoxication in naive subjects. In: Nahas G G, Sutin K M, Harvey D, Agurell S, Pace N, Cancro R. (Eds), Marihuana and Medicine 1999 (1st edition 649–664).

491 Background: Chemoradiotherapy (cRT) with 5FU and Mitomycin C (5FU/MMC) is an accepted standard of care for muscle invasive bladder cancer. Cetuximab is an approved radio-sensitiser in head and neck cancer and EGFR is over-expressed in bladder cancer. We report a phase 1/2 trial of the addition of cetuximab to standard cRT. Methods: Phase 1/2 single-arm, multicentre, open-label study conducted in 5 UK centres. Treatment: RT: 64 Gy/32 fractions, 5FU 2.5g/m2 over days 1-5 & 22-26, MMC 12g/m2 day 1, cetuximab 400mg/m2 day -8, 200mg/m2 day 1 and weekly x7. Main inclusion criteria: T2-4aN0M0 urothelial cancer, PS 0-1; prior neoadjuvant therapy permitted. Endpoints: Phase 1; feasibility and safety of cRT with cetuximab + 5FU/MMC in combination. Phase 2; local control (LC) at 3 months. Secondary outcomes: invasive loco-regional progression free survival (LPFS), noninvasive LPFS, metastasis free survival (MFS), overall survival (OS) & patient reported outcomes (PROMs). Sample size; phase 1 between 6 and 18, phase 2 up to 45 including those recruited in phase 1. Results: Between Sept 2012 and Oct 2016, 33 patients were recruited; 7 in phase 1 26 in phase 2. Median age 70.1 (IQR 65.4-80.2) yrs, 60.6% WHO Performance Status 0; 81.8% male, 26/33 neoAd chemotherapy. 3 patients ineligible post registration. 30 evaluable pts started RT, 1 patient didn’t complete RT due to serious adverse event (interstitial pneumonitis), 3 with delays. Phase 1, 6/7 pts completed Cetux therapy, 1 omitted 1 dose for grade 3 rash. LC was 77% (95% CI 58, 90). Overall median dose intensities Cetux 100%, MMC 99% 5FU 99.8%. 8 pts developed recurrence; 2 MIBC. The 6 & 12 month muscle-invasive LPFS was 93 &; non-invasive LPFS 97% & 85%, MFS 90% & 90%, OS 97% & 87%. PROMs showed a transient dip at 1 mo, back to baseline at 3 mo. Conclusions: Phase 1 data demonstrate it’s feasible and safe to add cetuximab to cRT with 5FU/MMC with high delivered dose intensities. Although recruitment failed to reach the pre-specified target for phase 2 exploratory analysis indicate the 3 month bladder control rates and recurrence rates are above those reported in BC2001 with good PROMs provides evidence to consider further evaluation of cetuximab. Clinical trial information: 80733590.

1 Background: External beam radiotherapy (EBRT) is a curative treatment for LPCa. Large randomised controlled trials (RCTs) have shown moderately hypofractionated regimens (2.5–3 Gy/fraction(f)) as non-inferior to conventionally fractionated regimens (2 Gy/f). PACE-B aims to demonstrate non-inferiority of SBRT compared to CFMHRT for biochemical or clinical failure. Compared to CFMHRT, SBRT reduces patient (pt) attendances but compressed overall treatment time may influence acute toxicity severity. Methods: PACE is a phase III open-label multiple-cohort RCT. Men with LPCa, stage T1-T2, ≤ Gleason 3 + 4, PSA ≤ 20 ng/mL, unsuitable for surgery or preferring EBRT, were eligible for the PACE-B cohort. Between 08/12-01/18, 874 pts (38 centres) were randomised (1:1) to SBRT or CFMHRT. SBRT dose was 36.25 Gy/5f in 1-2 weeks (wks), CFMHRT as 78 Gy/39f over 7.5 wks, or 62 Gy/20f in 4 wks. Androgen deprivation therapy was not permitted. Clinician reported acute toxicity was assessed at baseline, 2-weekly during CFMHRT and at 2, 4, 8 & 12 wks post-treatment. Key toxicity outcomes were worst grade 2+ Radiation Therapy Oncology Group (RTOG) genitourinary (GU) and gastrointestinal (GI) acute toxicities, compared by Chi-square test with alpha 0.05 divided between the two measures. Results: By per protocol analysis n=430 received CFMHRT, n=414 received SBRT. Key characteristics seen in the CFMHRT and SBRT groups respectively were: mean age: 69.5 vs 69.3 years; T-stage ≥T2b: 51.8% vs 56.6%; Gleason Score 3+4: 80.2% vs 85.0%; PSA 10-20 ng/mL: 30.9% vs 31.6%. RTOG G2+ toxicity was not significantly different for GI events (CMFHRT 52/430 (12.1%) vs SBRT 42/414 (10.1%), p=0.368), nor GU events (CFMHRT 117/430 (27.2%) vs SBRT 96/414 (23.2%), p=0.179). Conclusions: Despite an accelerated treatment schedule, RTOG assessments show similar rates of acute GI and GU toxicity for SBRT and CFHFRT. Pt follow-up in PACE-B continues and results of late toxicity and biochemical/clinical failure are awaited. Clinical trial information: NCT01584258.

Background TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. Trial registration EU-CTR 2009-012097-12 2009-09-03

Introduction: This chapter describes the characteristics of adult patients on renal replacement therapy (RRT) in the UK in 2008 and the prevalence rate per million population (pmp) in Primary Care Trusts and local authorities (Council Areas or District Councils) (PCT/LAs) were calculated. Methods: Complete data were electronically collected from all 72 renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of prevalent RRT patients in 2008 at centre and national level in the UK. Age and gender standardised ratios of actual to expected for prevalence rates in PCT/LAs were calculated. Results: There were 47,525 adult patients receiving RRT in the UK on 31/12/2008, equating to a UK prevalence of 774 pmp. This represents an annual increase in prevalence of approximately 4.4% although there was significant variation between PCT/LA areas. The pmp growth rate from 2007 to 2008 for prevalent patients by treatment modality in the UK was 5.9% for haemodialysis (HD), a fall of 9.2% for peritoneal dialysis (PD) and growth of 4.6% with a functioning transplant. Over the long term (1982–2007), the steady growth in transplant prevalent numbers was maintained at 4%. There was a slow but steady decline in PD patient numbers from 1999 onwards. Median RRT vintage was 5.3 years. The median age of prevalent patients was 57.3 years (HD 65.5 years, PD 61.0 years and transplant 50.4 years). For all ages, prevalence rates in males exceeded those in females peaking in the 75–79 years age group at 2,582 pmp for males and 70–74 years age group at 1,408 pmp for females. The most common identifiable renal diagnosis was biopsy-proven glomerulonephritis (16.0%), followed by diabetes (14.1%). Transplantation was the most common treatment modality (47%) followed closely by HD (43%). However, HD was increasingly common with increasing older age at the expense of transplantation. Conclusions: The HD and transplant population continued to expand whilst the PD population contracted. There was national, regional and dialysis centre level variation in prevalence rates. This has implications for service planning and ensuring equity of care for RRT patients.

Background: The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. Aims: To determine the extent to which the guidelines for anaemia management are met in the UK. Methods: Quarterly data (haemoglobin (Hb) and factors that influence Hb) extracts from renal centres in England, Wales, Northern Ireland (EWNI), and annual data from the Scottish Renal Registry for incident and prevalent renal replacement therapy (RRT) cohorts for 2008 were analysed by the UK Renal Registry (UKRR). Results: In the UK, in 2008 57% of patients commenced dialysis therapy with Hb ≥ 10.0 g/dl (median Hb 10.2 g/dl). For incident patients the Hb at 3 and 6 months of dialysis treatment was 11.4 and 11.7 g/dl respectively. The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6–12.5 g/dl. Of HD patients 85% had a Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.8–12.6 g/dl). Of UK PD patients 89% had a Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 436 mg/L (IQR 289–622) and 95% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 246 mg/L (IQR 141–399) with 84% of PD patients having a ferritin ≥ 100 mg/L. In EWNI the mean ESA dose was higher for HD than PD patients (9,166 vs. 6,302 IU/week). Conclusions: Last year for the flrst time a small fall (from 85.9% in 2006 to 85.6% in 2007) in the % of HD patients with a Hb of ≥ 10 g/dl which was thought to be related to the implementation of the new Hb Standard which has a target range of 10.5–12.5 g/dl was seen. This year attainment of Hb ≥ 10 g/dl in HD patients fell again slightly to 85.3%. In HD patients, 54% of patients had a Hb ≥ 10.5 and ≤ 12.5 g/dl compared with 53% in the 2008 Report.

Background: International comparisons between renal registries are important to highlight epidemiological and practice differences in RRT provision between countries. This report aims to compare the rates of RRT incidence and prevalence in the UK with a number of different countries. Methods: Data from 19 countries or regions between 2003 and 2007 from four international renal registries were analysed. Rates of RRT incidence, prevalence, transplantation and dialysis modality were compared. A crude mortality rate for each country was calculated. Results: Despite continued growth, the UK ranked 16th highest in incidence rate and 15th in prevalence rate in 2007. This may partly be related to successful primary care preventing stage 5 CKD. The UK had the 8th fastest rate of increase in RRT prevalence of 18 countries (4.2%/ year). The age profile of UK RRT patients was comparable with other countries. The UK had the 6th highest use of home dialysis therapies. The UK has the 8th highest incidence and 9th highest prevalence rate of kidney transplantation of 16 countries. Conclusion: Meeting the growing demand for RRT is a problem for all countries that choose to offer it. The UK continues to provide for growth in demand for RRT.

Background: A preliminary review of the UK Renal Registry (UKRR) pre-RRT study data revealed results suggesting that, for some patients, the date of start of renal replacement thera

These analyses examine survival from the start of renal replacement therapy (RRT), based on the total incident UK dialysis population reported to the Registry, including the 21% who started on PD and the 5% who received a pre-emptive transplant. Survival of prevalent patients and changes in survival between 1997-2006 are reported. The article includes a discussion on the technical definition for the date of start of both PD and HD.Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting during 2006) was calculated with and without a 90 day RRT start cut off. Survival of incident patients is shown with and without censoring at transplantation. Both the Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. Relative risk of death was calculated compared with the general UK population.The 2006 unadjusted 1 year after 90 day survival for patients starting RRT was 86%. In incident 18-64 year olds the unadjusted 1 year survival had risen from 85.9% in 1997 to 91.5% in 2006 and for those agedor = 65 it had risen from 63.8% to 72.9%. The age adjusted survival of prevalent dialysis patients rose from 85% in 2000 to 89% in 2007. Diabetic patient survival rose from 76.6% in 2000 to 84.0% in 2007. The relative risk of death on RRT compared with the general population was 30 at age 30 years compared with 3 at age 80 years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 34% of deaths, infection 20% and treatment withdrawal 14%.Incident and prevalent patient survival on RRT in all the UK countries for all age ranges and also for patients with diabetes continued to improve. The relative risk of death on RRT compared with the general population has fallen since 2001. Death rates on dialysis in the UK remained lower than when compared with a similar aged population on dialysis in the USA.

In the UK over 10,000 new cases of bladder cancer were diagnosed in 2012, making it the seventh most common cancer in the UK. For those with advanced disease at presentation, prognosis is poor. Disease presenting with one pathological node (N1) is considered to be Stage 4 and is therefore considered the same as disease with widespread metastases. Pelvic lymph node dissection is considered standard when performing radical cystectomy; however, owing to potential toxicity, pelvic radiotherapy is not routine even when attempting radical treatment. We present five cases where radical treatment has been delivered to patients with node-positive bladder cancer. Treatment volumes included the whole bladder and bilateral pelvic nodes, and where it was felt appropriate, chemotherapy was delivered concurrently. Data has been collected by reviewing hospital notes including radiotherapy, volumes and dose distributions. Treatment was tolerated well with only minimal gastrointestinal and urinary symptoms reported. Three of the five patients had thrombocytopenia. This complication may be explained by the larger volume of radiation exposure. Local control appears to be good with all the patients having no pelvic relapse at the time of reporting. Two patients have relapsed with distant metastatic disease. No long-term side effects of therapy have been reported. Intensity-modulated radiotherapy techniques allow larger volumes to be treated owing to improved conformality and the resulting reduced toxicity. Treatment may be appropriate with both radical and adjuvant doses of radiation. More work is necessary to assess which patients would benefit and are most suitable for such treatment.

4527 Background: This phase I/II trial assessed the safety, feasibility and efficacy of cetuximab (Cet) in combination with 5-fluorouracil (5FU) and mitomycin C (MMC) with concurrent radiotherapy (RT) for the treatment of muscle invasive bladder cancer (MIBC). BC2001 trial has previously reported significant improvement in locoregional control in patients (pts) with MIBC who were randomised to synchronous chemo-RT compared to RT alone (James, Hussain, Hall et al NEJM 2012). Results for phase I have been reported previously. This abstract reports the combined results of phases I/II. Methods: From September 2012 to October 2016, 33 pts were recruited (7 pts to phase I from 2 UK centres and 26 patients to phase II from 5 UK centres). Pts received loading dose of Cet 400 mg/m2 followed by weekly Cet 250 mg/m2 for 7 weeks, continuous infusion 5FU 500mg/m2/day during fractions 1-5 and 16-20 of RT and MMC 12mg/m2on day 1 in combination with radical RT 64 Gy in 32 fractions. Neoadjuvant chemotherapy was mandatory in phase I but optional in phase II. Primary outcomes in phase I were feasibility and toxicity. Primary outcome in phase II was 3 month pathological complete response (CR) rate, secondary outcomes included toxicity, progression free survival (PFS) and overall survival (OS). Results: Median age of pts was 70 (range 46.9-85.6). Treatment completion rates in phase I were RT 100%, 5FU 100 %, MMC 100%, Cet 96%. Of the 28 analysable pts, phase II primary outcome data was available for 25 pts at the time of analysis with a 3 month pathological CR rate of 88%. 5 local progressions and 4 deaths were reported. 12 pts suffered at least one SAE. Grade 4 toxicities observed were dyspnoea, atrial fibrillation, interstitial pneumonitis, sepsis, thromboembolism, neutropenia and palpitations. The commonest grade 3 toxicities were skin rash, diarrhoea, low platelet count, low white blood cell count, fever and haematuria. The most common grade 1 and 2 toxicities were diarrhoea and skin rash. Data on PFS and OS will be presented. Conclusions: It was feasible and safe to add cetuximab to full dose chemo-RT with 5FU/MMC. The CR rate is encouraging and further randomised studies with this combination are warranted. Clinical trial information: ISRCTN80733590.

4542 Background: There is a paucity of chemotherapy options for the treatment of patients who have relapsed following platinum based chemotherapy (CT). Cabazitaxel is a new taxane that showed in-vivo antiproliferative activity on resistant cell lines. Methods: CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients (pts) with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had received platinum based treatment and recurred within 12 months of the last cycle of CT. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes were Progression Free Survival (PFS), Overall Survival (OS), Quality of Life assessment, safety and tolerability. A total of 96 pts required to detect differences in ORR from 5% to 30%; 80% power; 5% alpha level; 10% dropouts. Stopping rules, using Simon’s two stage optimal design to assess the individual effectiveness of CAB, required at least 1 ORR from 10 pts on CAB during 1st stage (i.e. total of 20 pts randomised) and 4 from 29 CAB pts in 2nd stage (assuming lower ORR limit of 0.05, target ORR of 0.20, 80% power, 5% alpha level). The trial was supported by grant from Sanofi. Results: Between January 2013 and October 2016, 20 pts were randomised (10 on each arm). 75% males; median age 68 years; 65% had recurred within 6 months of previous CT. BSC included paclitaxel CT for 9 pts and radiotherapy for 1 pt. 8 pts completed 6 cycles of CT (3 on CAB; 5 on BSC). 6 pts on each arm were evaluated for response after having 2/3 cycles; 2 pts had an ORR on CAB and 1 pt on BSC. 14 pts have died of disease (8 on CAB; 6 on BSC).Median OS was 5.6 months (95% confidence interval (CI) 0.7-15.2) for CAB pts and 8.2 months (95% CI 1.0-8.8) for BSC pts. Median PFS was 4.4 months (95% CI 0.7-9.4) for CAB pts and 4.1 months (95% CI 1.0-6.8) for BSC pts. Conclusions: It has been hard to recruit these poorly patients within a single centre, but CAB-B1 successfully reached the efficacy target for the 1st stage, showing that there could be a role for CAB in these pts. Clinical trial information: NCT01668459.

5008Background: The Phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for C plus prednisone (P) (25 mg/m2once every 3 weeks plus 10 mg orally once daily) versus mitoxantrone plus P (Hazard Ratio [HR] 0.70; P < 0.0001) in pts with mCRPC previously treated with D. This PROSELICA study (NCT01308580) was designed to determine the relative efficacy and safety profile of C20 plus P compared with C25 plus P. Methods: In this randomized, open-label, multinational phase III study, pts with mCRPC and ECOG performance status 0–2, who progressed after treatment with D, were stratified (ECOG, RECIST, region) and randomized 1:1 to C20 or C25. To show that C20 could preserve ≥ 50% of the efficacy benefit showed by C25 in TROPIC, the HR of C20 vs C25 for the primary endpoint OS could not exceed 1.214 under 1-sided 98.89% confidence level adjusted after interim analyses. Secondary endpoints included progression free survival (PFS), safety, PSA, pain and tumor responses and qu...

Blood pressure (BP) control is assessed annually from patients on Renal Replacement Therapy at renal centres in England, Wales and Northern Ireland by the UK Renal Registry.Patients alive and receiving RRT on 31st December 2007 with a BP reading in either the fourth or third quarter of 2007 were included. Summary statistics were calculated for each renal centre, nation and renal disease category. Linear regression analyses were performed for prevalent patients between 2000 and 2007.Significantly more haemodialysis patients achieved the BP standard (44.6% pre-HD and 48.8% post-HD) than peritoneal dialysis (32.8%) or renal transplant patients (26.7%). Median BP fell significantly between 2000 and 2007 for each treatment modality. There was significant variability in BP control between renal centres (p0.0001) for haemodialysis and transplant patients. Hypertension was significantly more common in haemodialysis patients with vascular disorders such as diabetes and renovascular disease (56.8%) than in glomerulonephritis (51.0%) or tubular disorders (45.1%). The effect was less prominent in peritoneal dialysis and not evident in transplant patients where few achieved the BP standard.A minority of patients on RRT achieved BP standards in 2007. There remained a significant variation in achievement of standards between renal centres.