Background and purpose: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. Materials and methods: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. Results: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. Conclusions: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome. (C) 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.

OBJECTIVE:To determine if meaningful patient characteristics pertaining to pressure ulcers (PU) can be derived from routinely collected community health data.METHODS:A retrospective cohort analysis of records was carried out. To provide a detailed dataset on PU for the community of interest, demographic, general medical and PU data were extracted from mandatory incident reports and audit of electronic and paper medical records. This study is reported in accordance with the RECORD Guidelines from the Equator Network. Adult patients were enrolled from a district nursing service in the target region (n=1085) during 2015. The target region was based on a geographical region bounded by a single postcode district (target region) consisting of 62,000 people of whom approximately 50,000 were adults, 3000 of whom were aged >75 years.RESULTS:The total number of recorded PUs was n=137 in 103 individuals. Data from mandatory incident reports was obtainable for nearly all variables. Electronic and paper medical records were less reliable due to missing data.CONCLUSION:Detailed characteristics of community-dwelling PU patients can be derived from routinely collected data, and provides various forms and levels of information which could feed into different projects. The use of mandatory reporting fields increases the level of reporting and reduces missing data. Data enriched with information from electronic and paper records could inform the addition of variables to mandatory forms to improve characterisation of community dwellers with PUs.

Background: Pressure injury is a common problem. Its prevention and treatment is predominantly focussed on views, perceptions and knowledge of healthcare staff rather than on patient experience, particularly those patients living in their own homes. Aim: This paper reports findings on patients experiences and perceptions of loss associated with PI. These findings are drawn from a larger study of pressure injury patients living and receiving care in the community. Methods: Qualitative interviews with 12 participants with pressure injury and five carers. Data was audio recorded and thematically analysed. The study is reported in accordance with the COREQ guidelines. Findings: Having a pressure injury negatively affected many aspects of life for our participants resulting in multiple losses. These losses included loss of mobility and independence, privacy and dignity, and social engagement and ability to engage in preferred activities. Discussion: Although the effects of a pressure injury may be similar for many people, the most important issues will differ from person-to-person thus treatment and prevention of pressure injury requires a multidisciplinary team having a holistic care approach. Some patients' pressure injury will never heal and it is increasingly important to involve the patient to find out what matters most to them and how their wound is impacting on them, to jointly develop a holistic, person-centred plan. Conclusion: Policy and practice should recognise and reflect that patients living with a pressure injury at home have different challenges and needs to those in acute or long term care. Pragmatic solutions in the delivery of pressure injury care are needed to compliment the drive to move healthcare from the hospital-to-home. (C) 2017 Australian College of Nursing Ltd. Published by Elsevier Ltd.

The present study, drawn from a larger mixed-methods case study, provides insights into the health literacy of community-based patients with pressure injuries, and their carers, and critically analyzes the patient information resources available; crucial because health literacy is associated with patient care and outcomes for patients. Two datasets were used to better understand patient literacy in relation to pressure injury: (i) narratives from patients and carers; and (ii) analysis of patient education resources. Narratives were subject to content analysis and patient education resources available to the patients were analyzed drawing on the Simplified Measure of Gobbledygook, the National Health Service Toolkit for Producing Patient Resources, and compared to an internationally-advocated pressure injury leaflet. The study findings indicated that despite leaflets broadly meeting required production and content guidelines, patients appeared to poorly engage with these materials and demonstrated limited health literacy in relation to pressure injury. Although improvements in leaflet production and readability might be advantageous, emphasis should remain on quality patient-health-care professional relationships to enable tailored patient education that can enhance awareness and engagement with treatment and prevention interventions.

AIMSThe aim of this study was to provide deep insights into the pain associated with pressure injuries in home-dwelling individuals using narrative accounts.BACKGROUNDPressure injuries or pressure ulcers are burdensome and costly. Prevalence data, surveys and systematic reviews demonstrate that pain associated with pressure injury is widespread, but voices of home-dwelling patients have remained largely unheard.DESIGNConcurrent mixed methods case study of a UK community of approximately 50,000 adults.METHODSQualitative interviews, conducted in 2016, of 12 home-dwelling adult participants with a current pressure injury (n = 10), or a recently healed pressure injury (n = 2).FINDINGSPain had an adverse impact on activities of daily living, mobility and sleep. Participants described days that were clouded in pain; a pain they felt was poorly understood and often out of control. Thematic content analysis revealed two major themes; these are: Poorly controlled pain: "I just want the pain to go away"; and, Uncertainty for the future: "it almost seems insurmountable."CONCLUSIONFindings of our study support the need to develop an appropriate assessment tool for pressure injury patients in the community to enable healthcare professionals and patients to recognize and manage pressure injury-related pain effectively.

Background: Health care within the home setting is a vital and growing component of pressure injury (PI) prevention and management. Objectives: To describe the use of health services and pressure-redistributing devices in community dwelling patients with PI's. Design: Mixed-methods collective case study of a defined, diverse geographic postcode area in the United Kingdom. Methods: Quantitative retrospective analysis of electronic and paper medical records of adult PI patients from 2015 district nursing reports. Qualitative semi-structured interviews of community dwelling adult patients receiving, or received, treatment for PI in 2016. Results: Mandatory reports (n = 103) revealed that 90 patients were supplied with a variety of pressure-redistributing devices but only one-third of patients used the equipment as recommended. Qualitative interviews (n = 12), reported to COREQ guidelines, revealed that patients felt reliant on community health services, and were concerned about the consistency of their care. Conclusions: Authentic patient involvement is required to provide care and interventions that are acceptable to PI patients and can be incorporated into self-care strategies and effectively monitored.

Background and purpose: Intensity modulated radiotherapy requires all target areas to be treated by a single radiotherapy plan. In anal cancer, the pelvic nodes, inguinal nodes and primary tumour represent three different targets. We aim to calculate target-specific motion in anal cancer radiotherapy, when delivered using a single pelvic online auto-match.Materials and methods: Twenty consecutive patients treated using IMRT at a single institution were studied. CBCTs were retrospectively re-matched around the inguinal nodes and primary tumour. Match values were recorded relative to origin, defined as pelvic CBCT auto-match. Systematic and random errors were quantified to determine target-specific motion and suggested margins calculated using van Herk formulae.Results: The suggested margins to cover the independent motion of the inguinal and anal targets for LR, CC and AP set up around the inguinal nodes were 1.5 mm, 2.7 mm and 2.8 mm; and the primary tumour were, 4.6 mm, 8.9 mm and 5.2 mm respectively.Conclusions: Target-specific set up will likely result in reduced treatment volumes and as such reduced toxicity. This is the first time a relationship has been described between pelvic bones, inguinal nodes and primary tumour. The PLATO study will prospectively assess the toxicity and outcomes of this target-specific margins strategy. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Background and purposeNelfinavir can enhance intrinsic radiosensitivity, reduce hypoxia and improve vascularity. We conducted a phase II trial combining nelfinavir with chemoradiotherapy (CRT) for locally advanced inoperable pancreatic cancer (LAPC).Materials and methodsRadiotherapy (50.4Gy/28 fractions; boost to 59.4Gy/33 fractions) was administered with weekly gemcitabine and cisplatin. Nelfinavir started 3–10days before and was continued during CRT. The primary end-point was 1-year overall survival (OS). Secondary end-points included histological downstaging, radiological response, 1-year progression free survival (PFS), overall survival (OS) and treatment toxicity. An imaging sub-study (n=6) evaluated hypoxia (18F-Fluoromisonidazole-PET) and perfusion (perfusion CT) during induction nelfinavir.ResultsThe study closed after recruiting 23 patients, due to non-availability of Nelfinavir in Europe. The 1-year OS was 73.4% (90% CI: 54.5–85.5%) and median OS was 17.4months (90% CI: 12.8–18.8). The 1-year PFS was 21.8% (90% CI: 8.9–38.3%) and median PFS was 5.5months (90% CI: 4.1–8.3). All patients experienced Grade 3/4 toxicity, but many were asymptomatic laboratory abnormalities. Four of 6 patients on the imaging sub-study demonstrated reduced hypoxia and increased perfusion post-nelfinavir.ConclusionsCRT combined with nelfinavir showed acceptable toxicity and promising survival in pancreatic cancer.

Background and purposeTo determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).Methods and materialsTwo groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats).Percent volume of PBM and sub structures receiving 5–25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.ResultsPMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p < 0.05).ConclusionWhilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.

Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused significant radiosensitization in cancer but not normal tissue cell lines. Other means of blocking this pathway, knockdown of thiamine transporter-1 (THTR1) or treatment with the thiamine analogue pyrithiamine hydrobromide (PyrH) caused significant tumor specific radiosensitization. There was persistent DNA damage in cells irradiated after TPK1 and THTR1 knockdown or PyrH treatment. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitization target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumor specific radiosensitization.

e15279 Background: In LAPC, additional benefit of CRT over chemotherapy is uncertain. Optimising local therapy for a subset that never develops distant disease may prolong survival. Nelfinavir is thought to enhance radiosensitivity through hypoxia reduction by increasing tumour blood flow. Methods: A non-randomised, single centre phase II study, in FDG-PET-selectedpatients withhistologically proven LAPC. CRT consisted of: nelfinavir 1250 mg bd (days -3 to 45); gemcitabine 300 mg/m2 & cisplatin 30 mg/m2 (days 2, 9, 23 & 30); concurrent radiotherapy: 59.4 Gy/33# to primary tumour, 50.4 Gy/28# to regional nodes. Adjuvant gemcitabine was given for 6 months. Primary endpoint: 1 year overall survival (OS); secondary endpoints included: toxicity, response rate, resectability, median progression free survival (PFS), OS and local PFS. 6 patients had sequential dynamic 18fluoromisonidazole PET (FMISO-PET) and perfusion CT (pCT) before and after 6-7 days of nelfinavir (given from day -8). Results: 23 patients entered between Feb 2010-July2014. The trial was stopped because of unavailability of nelfinavir in Europe. 3 patients did not complete treatment (1 each of PE, biliary sepsis, stroke). Common G3/4 toxicities: thrombocytopenia/leukopenia (both 35%), diarrhoea (17%), nausea/vomiting (17%), fatigue (13%). 1 yr and median OS: 76.7% (95% CI 52.8-89.6) and 17.4 months (95% CI 12.7-22.8) respectively. 1 yr PFS and Local PFS: 36.8% (16.5-57.5) and 52.9% (95% CI 25.2-74.4) respectively. Mean FDG SUVmax reduction was 39% (p < 0.001) and was ≥60% in 29% of patients. 2 patients became resectable. 4/6 patients had reduced FMISO retention and increased pCT derived blood flow (BF) post-nelfinavir. Mean change in FMISO-k3 (2 tissue compartmental model) -50.3% vs 6% and BF 20.1 vs -7.1% in responders vs non-responders. 8/13 demonstrated a reduction in pAKT in peripheral blood mononuclear cells. Conclusions: Nelfinavir with CRT is well tolerated with promising outcomes, as these patients were not pre-selected through induction chemotherapy. Modulation of hypoxia & BF by nelfinavir was demonstrated. A randomised phase II study, SCALOP2, opens in 2015. Clinical trial information: 2008-006302-42.

576 Background: Definitive chemoradiotherapy is standard of care in anal squamous cell carcinoma. The ACT II trial set the standard achieving three year overall survival rates of 73%. However patients with locally advanced disease have a ~50% local relapse rate. Studies have failed to demonstrate an improvement in local relapse rate by altering the systemic therapy. Although 2/3 of relapses are local as opposed to regional or distant, there is limited knowledge on the 3D position of these relapses. We aim to retrospectively review the patterns of local failure in three dimensions, relative to the radiotherapy plan. Methods: Between February 2007 and April 2012, 77 patients were treated for squamous cell carcinoma of the anus with radical chemoradiotherapy. Early stage (T0/2) and locally advanced (T3/4) tumours constituted 53% and 44% respectively. 37% of patients had nodal disease. As per ACT II protocol we used a gross tumour volume (GTV) to PTV margin of 3cm and prescribed to a dose of 50.4Gy. In patients with a local recurrence, imaging from the time of recurrence was imported into the radiotherapy planning system. The volume and site of gross recurrence was noted relative to the previous GTV and 95% isodose line. The mean dose delivered to the relapsed area was calculated. Results: Median follow-up was 42 months (range 14 to 78 months). Eight (10%) patients failed to respond. Six (8%) patients developed an isolated local relapse, 2 (3%) distant metastatic disease alone and 1 both local and distant relapse. Of those that relapsed locally, 5 patients were T2N0, one T3N0 and 1 node positive. There were no regional relapses. The entire macroscopic relapse lay within the 95% isodose line of the 50.4Gy in all patients. The median percentage of relapse that lay within GTV was 63% (range 29 to 100%). A GTV to PTV margin of 2cm would have encompassed all macroscopic relapses. The median doses to relapsed area was 52Gy (range 51Gy to 53Gy) with the minimum dose to any relapsed area being 49Gy. Conclusions: The majority of relapses centred on the GTV suggesting the gross tumour was uncontrolled with current doses in these patients. A reduction of GTV to PTV margin may be appropriate, facilitating trials of dose escalation with the aim of improving outcomes.