Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: Results from eight European centres.

PURPOSE: To compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer. MATERIALS AND METHODS: All centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions. Target volume receiving 95% of prescribed dose (V95%iCTVtotal) should be >99%. Robustness towards setup, range, and respiration was evaluated. The plans were recalculated on a surveillance 4DCT (sCT) acquired at fraction ten and robustness evaluation was performed to evaluate the effect of respiration and inter-fractional anatomical changes. RESULTS: All PT and XT plans complied with V95%iCTVtotal >99% for the nominal plan and V95%iCTVtotal >97% for all respiratory and robustness scenarios. Lung and heart dose varied considerably between centres for both modalities. The difference in mean lung dose and mean heart dose between each pair of XT and PT plans was in median [range] 4.8 Gy [1.1;7.6] and 8.4 Gy [1.9;24.5], respectively. Patients B and C showed large inter-fractional anatomical changes on sCT. For patient B, the minimum V95%iCTVtotal in the worst-case robustness scenario was 45% and 94% for XT and PT, respectively. For patient C, the minimum V95%iCTVtotal was 57% and 72% for XT and PT, respectively. Patient A and D showed minor inter-fractional changes and the minimum V95%iCTVtotal was >85%. CONCLUSION: Large variability in dose to the lungs and heart was observed for both modalities. Inter-fractional anatomical changes led to larger target dose deterioration for XT than PT plans.

''It was the end of the world" - The lifeworld of elite male rugby union players living with injury. An interpretative phenomenological analysis.

BACKGROUND: Professional rugby is an aggressive sport. Consequently, injuries are an inevitable part of a rugby player's career. It is therefore crucial for sports medicine professionals to understand the subjective experience of injured athletes in order to optimize their care. OBJECTIVES: The purpose of this study was to take a lifeworld perspective to explore how living with injury was meaningful to professional rugby players. METHODS: A purposive sample of five participants were recruited and data collection undertaken via semi-structured interviews. Audio-recordings were transcribed verbatim and analyzed using interpretative phenomenological analysis methodology to develop the themes. FINDINGS: Three master themes emerged from the analysis, each comprising of two subthemes; 1) Sense of Uncertainty (1a. Fear of the Unknown, 1b. Lack of Control), 2) Experienced Change in Relationships (2a. Lived Human Relations, 2b. Coping), 3) Sense of Self (3a. Isolation and Belonging, 3b. ''Being" an Athlete). CONCLUSION: Participants described the challenge to their sense of self and 'being' athletes', as the isolation from the team deprived them of their sense of belonging. Participants illustrated the experienced significance of their relationships, the uncertainty over their lives and the unique strategies to cope. Emotions of anxiety, grief, anger, and shock reverberate throughout their accounts.

Pain Education in the Context of Non-Specific Low Back Pain: The Lived Experience of the Physiotherapist. An Interpretive Phenomenological Analysis.

OBJECTIVES: The aim of this study was to explore the physiotherapists' lived experiences of providing pain education (PE), to people living with non-specific low back pain (NSLBP). In previous studies, PE has been associated with positive clinical outcomes within the physiotherapeutic management of NSLBP. However, the meaning of providing PE, as experienced by physiotherapists, has not been specifically explored. METHODS: This study adopted a hermeneutic phenomenological approach to explore PE experiences. Six semi-structured interviews were conducted, interviews were transcribed and analysed in line with the 'interpretative phenomenological analysis' framework. RESULTS: Five main thematic meaning structures emerged: Experienced significance of assessment in understanding NSLBP, PE as explaining the nature of NSLBP, Experienced challenges in providing PE, individualisation as key to PE for NSLBP and Reassurance as central to PE for people living with NSLBP. CONCLUSIONS: The significance of subjective assessment, was a key component of PE, as experienced by participants. However, differences were noted between participants in addressing the sense of assessment; in seeking a physiotherapeutic understanding of the NSLBP, and in seeking to understand the situation of those who are in pain. Within the participant experience, the significance of 'patient' reassurance was highlighted, related to the individualisation and outcome of PE. Reassurance, as described by participants, was emotive and practically grounded and linked with physical activity promotion. Individualisation in PE was meaningfully related to language modification and developing positive therapeutic relationships. Physiotherapists described PE particularly challenging related to pain chronicity and psychosocial factors, which may have significant implications to practice.

Local delivery of angiogenesis-inhibitor minocycline combined with radiotherapy and oral temozolomide chemotherapy in 9L glioma.

OBJECT: Over the past several years, there has been increasing interest in combining angiogenesis inhibitors with radiotherapy and temozolomide chemotherapy in the treatment of glioblastoma. Although the US FDA approved bevacizumab for the treatment of glioblastoma in 2009, the European Medicines Agency rejected its use due to its questionable impact on patient survival. One factor contributing to the failure of angiogenesis inhibitors to increase overall patient survival may be their inability to cross the blood-brain barrier. Here the authors examined in a 9L glioma model whether intracranial polymer-based delivery of the angiogenesis inhibitor minocycline potentiates the effects of both radiotherapy and temozolomide chemotherapy in increasing median survival. The authors also investigated whether the relative timing of minocycline polymer implantation with respect to radiotherapy affects the efficacy of radiotherapy. METHODS: Minocycline was incorporated into the biodegradable polymer polyanhydride poly(1,3-bis-[p-carboxyphenoxy propane]-co-[sebacic anhydride]) (CPP:SA) at a ratio of 50:50 by weight. Female Fischer 344 rats were implanted with 9L glioma on Day 0. The minocycline polymer was then implanted on either Day 3 or Day 5 posttumor implantation. Cohorts of rats were exposed to 20 Gy focal radiation on Day 5 or were administered oral temozolomide (50 mg/kg daily) on Days 5-9. RESULTS: Both minocycline polymer implantations on Days 3 and 5 increased survival from 14 days to 19 days (p < 0.001 vs control). Treatment with a combination of both minocycline polymer and radiotherapy on Day 5 resulted in a 139% increase in median survival compared with treatment with radiotherapy alone (p < 0.005). There was not a statistically significant difference in median survival between the group that received minocycline implanted on the same day as radiotherapy and the group that received minocycline polymer 2 days prior to radiotherapy. Lastly, treatment with a combination of minocycline polymer with oral temozolomide resulted in a 38% extension of median survival compared with treatment of oral temozolomide alone (p < 0.001). CONCLUSIONS: These results show that minocycline delivered locally potentiates the effects of both radiotherapy and oral temozolomide in increasing median survival in a rodent glioma model. More generally, these results suggest that traditional therapy in combination with local, as opposed to systemic, delivery of angiogenesis inhibitors may be able to increase median survival for patients with glioblastoma.