Bakgrund: Under 2020 fick 7570 kvinnor i Sverige diagnosen bröstcancer. Under sjukdomsförloppet kommer behandling sättas in för att bota cancern och förebygga att den ska sprida sig och komma tillbaka i framtiden. De vanligaste behandlingarna vid bröstcancer är mastektomi, strålbehandling samt cytostatika. Det är viktigt att sjuksköterskan har rätt resurser, förutsättningar samt kunskap för att kunna möta kvinnan i sin sjukdom och förstå hur hennes sexualitet, självbild och identitet förändras under behandlingstiden vid bröstcancer. Syfte: Syftet var att beskriva hur kvinnans sexualitet, självbild och identitet förändras under behandlingstiden vid en bröstcancerdiagnos. Metod: Studien genomfördes med en kvalitativ design med induktiv ansats. Litteraturstudien utgick från tre patografier och analysen genomfördes i enlighet med Graneheim och Lundmans (2017) kvalitativa innehållsanalys. Resultat: Resultatet i denna studie baserades på två huvudkategorier/ teman och fyra underkategorier/ teman. De olika kategorierna/ teman beskriver hur tre kvinnor med en bröstcancerdiagnos upplever att deras självbild förändras under behandlingsperioden. Huvudkategorierna/ teman i studien är att inte känna igen sig själv, kroppsliga förändringar samt emotionella reaktioner. Under behandlingen förändras kvinnans självbild och identitet. Saker så som självständighet, kroppsuppfattning samt känsla av sexualitet omvärderas i relation till hur kvinnans liv var innan dess att hon fick bröstcancerdiagnosen  Slutsats: Slutsatsen som kan dras efter att ha studerat resultatet är att kvinnors självbild förändras under behandling av bröstcancer. I resultatet framkom det att flera aspekter av självbilden förändras. Bland dessa fanns förändrad identitet samt upplevelsen av kvinnans sexualitet. Resultatet i denna studie är riktat till den grundutbildade sjuksköterskan men kan med fördel också intressera övrig sjukvårdspersonal och bröstcancerdrabbade kvinnor.

Objectives: Quality of life (QoL) has been the focus of increasing interest in oncology. QoL assessment instruments implicitly assume that each QoL domain has the same meaning for each patient. The objective of this study was to analyze the importance of and the satisfaction with QoL domains and to analyze the relationship between the two. Methods: A sample of 308 breast cancer survivors was examined twice with a three-month time interval. The women completed the two QoL questionnaires Questions of Life Satisfaction (FLZ-M), which measures participants’ satisfaction with eight QoL domains and the subjective importance of those domains to them, and the EORTC QLQ-C30. A sample of 1,143 women from the general population served as controls. Results: Compared with the general population sample, the patients were less satisfied with their health andmore satisfied with all other QoL domains. The subjective importance of health was lower in the patients’ sample (Effect size: d = 0.38). Satisfaction with health and importance of health were slightly positively correlated (r between 0.05 and 0.08). The effect of QoL domain importance on general QoL was small (beta between −0.05 and 0.11), and interaction effects between domain importance and satisfaction on the prediction of global QoL were negligible. Conclusion: In addition to satisfaction with QoL dimensions, the subjective importance of these dimensions is relevant for psychooncological research and treatment. Health is not the only relevant QoL domain in breast cancer survivors, other domains such as finances also deserve health care providers’ attention.

Umeå University Hospital has acquired a new treatment planning system, RayStation, for radiotherapy. It has a different set of dose calculation algorithms that require new planning strategies for stereotactic lung cancer treatments. This \paper{} has two parts and the first investigates the Monte Carlo algorithm, recalculating doses for 21 historical treatments, and finds that it is slow but fast enough to be used and that it reports dose coverage that is usually lower than that of simpler algorithms, particularly for small tumours in low density lungs. The second part investigates the performance of four alternative planning methods: a straight forward PTV/ITV based method, a method using density override of the PTV, an ITV based semi-robust method and a fully robust method treating both setup margins and breathing motion robustly. The new methods are tested on 12 historical cases and are compared, using robust evaluation, to each other and the original plans. The first three are found to all be viable alternatives, while the fully robust method, while impressive, is found not to be a practical alternative at this time. / Norrlands Universitetssjukhus har skaffat ett nytt dosplaneringssystem, RayStation, till radioterapin. Det har en annan uppsättning dosberäkningsalgoritmer som kräver en ny planeringsstrategi för stereotaktisk lungcancerbehandling. Den här rapporten innehåller två delar och den första undersöker Monte Carlo-algoritmen genom att räkna om doserna för 21 tidigare behandlingar. Den visar sig vara långsam men snabb nog för att vara användbar och den rapporterar lägre dostäckning än enklare algoritmer, särskilt för små tumörer i lungor med låg densitet. Den andra delen undersöker fyra alternativa planeringsmetoder: en baserad på PTV och ITV utan krusiduller, en dito med s.k. override av PTVs densitet, en ITV-baserad med robust hantering av setup-marginaler och en helt robust metod med robust hantering av både marginaler och andningsrörelser. De nya metoderna testas på 12 tidigare behandlingar och jämförs, medelst robust utvärdering, med varandra och originalplanerna. De tre första visar sig alla vara goda alternativ medan den helt robusta, som visserligen är imponerande, inte är praktiskt användbar än.

The number of children and young adolescents diagnosed with cancer is increasing, leading to a need for new therapeutic strategies with diminished neurodegenerative side- effects. This report presents preliminary observations on glioma-initiating cells (GICs) in the way to develop a strategy that induces cell-cycle arrest or quiescence in neural stem cells (NSCs). To test how changes in membrane potential due to pharmacological treatments have effects on localization and levels of REV-ERBα protein, proneural (PN) and mesenchymal (MES) cells were treated with varying concentrations of REV-ERBα agonist SR9009 drug and T-type calcium channel blocker mibefradil. Treatments showed that both drugs do not relocalize REV-ERBα to the nucleus. However, SR9009 decreases the levels of REV-ERBα protein, whereas mibefradil does not have a similar effect.  Our preliminary data on mouse NSCs showed they engage with REV-ERBα protein while going into contact inhibition. Therefore, we investigated whether high confluency put PN and MES GICs into quiescence and the role of the main molecular clock protein REV-ERBα in this process. Cells were grown up to certain confluency, and following qPCR gene expression analysis revealed PN cells go into contact inhibition whereas MES cells continue proliferating even after they are grown to confluency. Moreover, REV-ERBα protein does not have any role in both outcomes.

Background: Neuroblastoma is the most common extracranial solid tumor in children. The survival rate in high-risk neuroblastoma is less than 50 % despite intensive multimodal therapy, and there is thus an immense need for new treatment options. In a previous preclinical study conducted at Uppsala University, treatment with sunitinib was found to inhibit tumor growth and angiogenesis in an orthotopic model of high-risk neuroblastoma.  Aim: The present study aimed to further explore the effect of sunitinib on tumor stroma, focusing on whether it was possible to detect and quantify tumor-associated neutrophils (TANs) in tumor sections from the above-mentioned study using immunohistochemistry (IHC). Methods: Tissue sections from formalin-fixated paraffin-embedded tumors were stained with anti-Ly-6G/Ly-6C, anti-ITGAM, or hematoxylin-eosin, and the number of granulocytes was quantified manually using a light microscope. An independent samples two-tailed t-test was used for statistical analysis. Results: The average number of granulocytes increased by 40 % in animals treated with sunitinib compared to control animals (p = 0.003) in hematoxylin-eosin stained tumor sections of orthotopic neuroblastomas. The results from the staining with anti-Ly-6G/Ly-6C or anti-ITGAM, on the other hand, were impossible to quantify due to the high background staining despite the concentration of antibody used. Conclusion: In conclusion, this report indicates that the density of TANs in an orthotopic murine neuroblastoma model is increased by treatment with sunitinib. However, to confirm this result, the study should be repeated once a reliable IHC method for the detection of TANs has been developed.

Background: Every year, hundreds of children are diagnosed with cancer. This affects the whole child's family, which means that the nurse during the child's cancer care must be there to support the whole family. The parent needs to feel involved in the child's care and have a trusting relationship with the nurse. As a parent, you have to go through a great deal of suffering, which requires the nurse to adapt her support to the needs of the parent and the child. Aim: The purpose of this study was to shed light on how a parent with a child with cancer experiences the nurse's support during and after cancer care. Method: A literature-based study was conducted. Ten qualitative articles were selected and analyzed, based on Friberg's analysis step model. This participates in three categories and a total of eight subcategories. Results: The results showed that the nurse's support was an important factor in an attempt to reduce the parent's suffering. This support could be divided into three categories: Cooperation between nurse and parent, parent's need for support and accessibility and communication. Conclusion: Pediatric cancer affects the whole child's family, and the parent is in great need of support to deal with their suffering and at the same time support their child. During their child’scancer care, the parent goes through many feelings of no longer recognizing their own child, as well as being helpless in their parenting role. By the nurse working in an empathetic and inclusive way where there is an opportunity to build meaningful and strengthening relationships between the parent and the nurse and that the parent's needs are also met, the parent's suffering can be reduced with the help of the nurse's support.

Prostate cancer (PCa) is the second most common cancer diagnosis for men and the fifth leading cause of cancer-related death worldwide. A common treatment strategy for PCa is external beam radiation therapy (EBRT), where high doses of radiation are used to kill cancer cells. Recent developments in RT include maintaining acceptable side effects during intensified treatment over fewer treatment occasions (hypofractionation) and boosting the level of radiation to the gross tumor volume (GTV) visible on multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET). Without a histopathological (HP) reference, the dose distribution cannot be compared to the varying grades of aggressivity within the cancer, known as ISUP grade groups (IGGs). The aim of this master thesis project was to explore the dose distribution over IGGs using a gold standard HP reference and investigate the mitigating effects of rectal spacers, following a hypofractionated RT schedule with focal boosts. The dataset consists of 15 patients, planned for radical prostatectomy. These patients harbored high-risk disease (IGG ≥ 4) in the GTV. HP evaluations following surgery resulted in physical slices of the prostate, showing the location and IGG of lesions. EBRT treatment plans that combined an ultra-hypofractionation strategy with a boost to the GTV were made. The dose distributions were evaluated by dose volume histograms (DVHs) over the target volumes, organs at risks (OARs) and the lesions. Robust evaluations of targets and OARs were performed by recalculating doses following translations of the patient by 2 mm in all directions. Similarly, lesions were shifted by 2 mm in all directions with respect to the nominal dose plan to estimate the sensitivity to motion. The effects of the translations were assessed by examining the impact on the DVHs and percentage of passed clinical goals. Two viable dose plans for each patient were produced, one for a 10 mm spacer and one for 8 mm. Both plans fulfill all rectum goals. For the 10 mm plan, the average median dose (D50) was greater than the prescribed prostate dose (42.7 Gy) for all IGGs by atleast 1.1 Gy. The D50 of the higher grades (IGG 3, 4 and 5) were 47.5, 46.4 and 48.7 Gy, meaning that they were closer to the desired GTV dose 49.0 Gy than the prescribed prostate dose. This thesis project showed that it is possible to reach high GTV doses while sparing the OARs and that the higher IGGs received a higher dose than the lower grades. Examining rectal dose depending on different spacer thicknesses allowed us to recommend a spacer thickness that is safe to use, which can provide increased patient comfort while saving time and resources.

Neuroblastoma is a childhood cancer of the peripheral sympathetic nervous system, emerging from cells of the neural crest. In Sweden, neuroblastoma accounts for 20 cases out of all, 300-350, pediatric cancer cases each year (Barncancerfonden 2019, Turup on behalf of Cancer Centrum 2019). This cancer often appears in the sympathetic ganglia and/or the adrenal gland and has a high rate of metastasis that often results in morbidity (Matthay et al. 2016). Recent findings implicating a mutation in the Rho/Rac signaling pathway, a pathway involved in neural crest differentiation and migration, were found in every fourth neuroblastoma patient (Dyberg et al. 2017) These mutations tend to shift Rho to a more active state which is believed to lead to more downstream Rho-associated Kinase (ROCK) activation. While inhibition of ROCK has been seen to promote MYCN protein degradation, induce neuroblastoma cell differentiation and repress neuroblastoma growth in vitro and in vivo (Dyberg et al. 2017). Rho/ROCK signaling pathway effects on cytoskeletal arrangement and cell shape have also been suggested to be involved in tumor promoted changes of the TME (Johan and Samuel, 2018). In this master’s thesis project, we explore the effects of the Rho/ROCK pathway on the tumor microenvironment (TME) and immune response (IR) in neuroblastoma. More specifically we are focusing on populations of T cells, macrophages and fibroblasts in tumors, and looking into tumor vascular structure (such as blood vessel) and extracellular matrix (ECM) formation after ROCK inhibitor treatment within neuroblastoma tumors from transgenic mice model TH-MYCN and multi-cellular tumor spheroids (MCTS), a three-dimensional (3D) in vitro model simulating TME in neuroblastoma cell lines. Through our studies we hope to find insights into the Rho/ROCK signaling pathway and involvement of the tumor microenvironment in cancer therapy, while elucidating potential new drugs and drug targets for improving outcomes in neuroblastoma treatment.

Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data. Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome. Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases. Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

Childhood cancer is a life-threatening disease with a profound impact on the family. Treatment side-effects and accompanied dietary difficulties are for example severe stressors, as appropriate nutrition is important for the treatment success and quality of life. In addition, (unhealthy) dietary patterns established in childhood tend to maintain in survivors. Parents are key players in feeding and establishing these pat-terns, though, systematic research on how parents experience these dietary difficulties is limited. This study aimed at exploring parental experiences of children’s dietary changes and difficulties during cancer treatment and after completion: what feelings do parents experience regarding their child’s dietary changes and difficulties, what feeding strategies to they apply to handle these difficulties, and how did they experience professional support and what are parental support needs. A systematic literature review was conducted and resulted in 21 suitable articles. The children were 0-21 years old, had various types of cancer, and received various types of therapy. Findings showed that parents reported many dietary changes (e.g. increase or decrease in food intake) and associated symptoms (e.g. nausea, changed tastes) during and after the cancer treatment course. Parents reported mainly negative feelings towards these dietary difficulties (e.g. distress and anxiety) and applied a wide range of behavioural feeding strategies, both negative (e.g. pressure to eat) and positive (e.g. provide healthy food) strategies. Parents also used complementary and alternative medicine. A high need for informational support regarding eating and feeding was expressed by parents during treatment, a need for emotional and practical support to a lower extent. These results showed how frequent and profound eating and feeding difficulties are in the childhood cancer and survivor population, and their (negative) impact on parents. Parents consequently need more support: they need oral and written information to set realistic expectations and install appropriate feeding strategies. This is important for the child’s nutritional status and general health both during and after cancer.