Flattening filter free volumetric modulated arc therapy for extreme hypofractionation of prostate cancer - Decreasing the treatment time and reducing the impact of prostate motion

Purpose: This work examined the feasibility of flattening filter free (FFF) volumetric modulated arc therapy (VMAT) for extreme hypofractionation of prostate cancer. The aim was to investigate the potential gain in treatment time per fraction for extreme hypofractionation of prostate cancer, while preserving or improving the treatment plan quality and radiation delivery quality. The impact of intrafractional prostatic displacement was investigated in a motion study using six different prostate trajectories. Material and methods: Nine patients (CTV volume range: 35.1-82.5 cm3), who received VMAT in Lund between 2013-2015, were selected from the currently on-going HYPO-RT-PC trial. Using single arcs, treatment plans with photon beam qualities 10 MV, 6 MV FFF and 10 MV FFF were created for each patient for the conventional treatment arm, 78 Gy in 2 Gy fractions, and for the hypofractionated treatment arm, 42.7 Gy in 6.1 Gy fractions. Parameters from the dose-volume histograms (DVH) for the different beam qualities were statistically evaluated using a paired sample student’s t-test. Treatment delivery was evaluated through measurements on a Varian TrueBeamTM with a Delta4 pretreatment verification phantom (ScandiDos AB, Uppsala, Sweden). The required beam-on time for each plan was also recorded. A motion study was performed for the patient with the longest treatment times, for one flattened and one unflattened hypofractionated plan using the Hexamotion (ScandiDos AB, Uppsala, Sweden). Trajectory data of six different prostate movement patterns (Ng et al., 2012) were used for studying the dosimetric effects of prostate motion. All results were evaluated relative to a static delivery. Results: The treatment plans were visually reviewed and approved by a senior physician at the department. Evaluating the DVHs of the different treatment plans, no significant differences between beam qualities or between fractionation schedules were observed. All objectives were met for all plans. At the treatment delivery control all plans passed the gamma criterion 3%, 2 mm with a pass rate of 98.8% or higher. The beam-on time for all conventional treatment plans was 1.0 minute. The mean beam-on time was 2.3 minutes for the hypofractionated 10 MV standard plan, 1.3 minutes for the 6 MV FFF and 1.0 minute for the 10 MV FFF, respectively. In the motion study, no or little effect was observed on the pass rate for displacements ≤ 1mm, compared to the static delivery. The shorter treatment delivery was superior for three patterns, while the longer treatment was preferred in the case of a temporal displacement of the prostate. Conclusions: The treatment time for extreme hypofractionation of prostate cancer is reduced to less than half the time by combining FFF-technique with VMAT. The treatment plan quality and radiation delivery quality are equal to those observed for flattened beams. A shorter beam-on time also seems advantageous for the majority of prostate motion patterns investigated. Based on this work, it is feasible to implement FFF VMAT for extreme hypofractionation of prostate cancer (HYPO-RT-PC trial) at the radiotherapy department at Skåne University Hospital, Lund.I skrivande stund är sju olika cancercentra i Sverige, däribland Skånes Universitetssjukhus i Lund, mitt uppe i en gemensam randomiserad studie som undersöker behandling av prostatacancer med två olika strålningsscheman. Patienterna i studien blir slumpvis tilldelade antingen en standardbehandling, där de får en liten mängd strålning vid 39 olika tillfällen, eller en så kallad hypofraktionerad behandling, där de istället får ca tre gånger så mycket strålning per gång vid endast 7 tillfällen. Målet med studien är att testa om den hypofraktionerade behandlingen kan ge ett bättre resultat med ökad bot utan högre grad av biverkningar. Prostatacancer är den vanligaste cancerformen i Sverige och årligen diagnosticeras nära 10 000 män – motsvarande ungefär en man i timmen, dygnet runt, året om. Prostatan i sig är en körtel som sitter i nedre delen av buken, nära blåsa och ändtarm. Eftersom den inte är fixerad i någon fast struktur påverkas prostatans position av bland annat blåsfyllnad, ändtarms-aktivitet och ofrivilliga muskelrörelser i underkroppen. Detta innebär att prostatan även har en viss sannolikhet att röra sig under pågående strålbehandling, trots att positionen verifieras och, vid behov, justeras genom bildtagning innan varje behandling påbörjas. Studier har visat att avvikelsen i prostatans position blir större ju längre tid som går, varför många menar på att man bör hålla behandlingstiderna så korta som möjligt. Eftersom det vid hypofraktionering tar längre tid vid varje behandlingstillfälle, då en större mängd strålning ska levereras, har syftet med detta examensarbete varit att undersöka hur mycket behandlingstiden kan förkortas genom användning av en nyare teknik, så kallad flattening filter free (FFF) strålbehandling. Målet var även att säkerställa att de nya behandlingarna kunde planeras och levereras med minst lika bra kvalitet som de nuvarande. För detta valdes nio patienter ut från hypostudien och jämfördes på sex olika sätt. Slutligen genomfördes en rörelsestudie på en av patienterna, där några olika rörelsemönster och deras eventuella inverkan på strålleveransens precision undersöktes. Resultaten visade att genom att kombinera FFF-teknik med den redan befintliga rotationsbehandlingen, kunde tiderna för hypofraktioneringen mer än halveras för samtliga patienter. Efter noggrann utvärdering av behandlingsplanerna genererade med FFF, kunde dessa konstateras hålla samma höga kvalitet som de med nuvarande teknik. Vidare kunde även en högkvalitativ strålleverans säkerställas genom inmätning med kvalitetssäkringsutrustning. Den nya, korta behandlingstiden är densamma som för en standardbehandling, samtidigt som tre gånger mer strålning levereras. Med hypofraktionering behöver patienten bara behandlas vid 7 tillfällen, jämfört med annars 39, vilket gynnar både den individuella patienten men också sjukvården och samhället i stort, sett ur ett ekonomiskt perspektiv. Fördelen med att hålla nere tiden visade sig även i rörelsestudien, där en kort behandling gav bättre resultat än en lång för alla undersökta rörelsemönster utom ett, men där var skillnaden väldigt liten. Det var tydligt att prostatans drift ur position påverkade strålleveransen, även inom tidsramen av några få minuter. Baserat på detta arbete kunde slutsatsen dras att det är möjligt, och dessutom fördelaktigt, att minska behandlingstiden för hypofraktionerad strålbehandling av prostatacancer, genom införandet av FFFteknik, ner till samma tid som det tar att leverera en standardbehandling

Prevalence of tail biting in pigs and associations to carcass condemnations - a Finnish pilot study

The aim of this study was to investigate the prevalence of tail biting in Finland and the relationship between tail biting and carcass condemnation

Symptoms and aspects on eosinophil activity in allergic rhinitis

Allergic rhinitis is a major atopic disease. Even if much is known about the pathophysiology of this condition, and despite the fact that good treatments are available, there is a need for new treatment options, particularly for such aiming at new targets and reduced side effects. Recruitment and activation of eosinophils is a key feature of allergic rhinitis. Eosinophils have different activation modes with subsequent mediator release. Before and during a natural birch pollen season we take nasal biopsies and utilize electron microscopy to assess eosinophil activity. We show that allergen exposure produces a marked increase in piecemeal degranulation and release of mediators (indicated by ECP). Variations in onset, intensity, and duration of natural pollen exposure make it difficult to compare treatments in allergic rhinitis. To overcome this, we demonstrate that repeated individualized allergen challenges can produce symptoms and signs that mimic seasonal disease. We indicate the usefulness of the model by demonstrating dose-dependent symptom-reducing effects of a topical corticosteroid. Preceding observations suggest that ß2-agonists may be treatment candidates for allergic inflammation. Utilizing the above-mentioned allergen challenge model, we examine whether or not a topical ß2-agonist (formoterol) affect eosinophilic inflammation in allergic rhinitis. We demonstrate that the ß2-agonist neither affects symptoms and eosinophilic inflammation in allergic rhinitis nor the efficacy of a topical corticosteroid. Employing the allergen challenge model, and a topical corticosteroid as experimental tool, we demonstrate that production of the eosinophil chemokine CCL5 is particularly corticosteroid sensitive, suggesting that it may be a valid treatment target

An Archaeological Picture of Iron Age Religions in Ancient Palestine

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Enjoying Work or Burdened by it? How Personal Assistants Experience and Handle Stress at Work.

A personal assistant has to promote equality in living conditions for persons with severe disabilities. The aim of this study was to explore how personal assistants experience their work and what strategies they employ to alleviate work-related stress. Thirty personal assistants were interviewed and latent content analysis was performed. The findings regarding the experiences of work-related stress could be brought together under the theme of "difficulties of being in a subordinate position," and those regarding management strategies could be brought together under the theme of "coming to terms with the work situation." There is a need to empower personal assistants through training programs including tailored education, working communities, and coaching