Malignant melanoma (MM) is the deadliest skin cancer with an ever-increasing incidence. New treatments have improved the prognosis for patients with advanced MM. Still, most patients do not respond, and the side effects can be severe, underlining the need for better therapies. The overall aim of this thesis was to evaluate new means to improve the treatment for patients with advanced MM. Immunostimulatory gene therapy (AdCD40L) was evaluated in a clinical study and BRAF-inhibitory treatment in rare cases of BRAF-mutated MM. Due to its immunogenicity, MM is an attractive target for immunostimulatory gene therapy. AdCD40L is an adenovirus carrying the human gene for CD40 ligand, which in different ways can stimulate the immune system to combat cancer. We conducted a Phase I/IIa study with AdCD40L in patients with metastatic MM having received established treatments. In cohort 1 (n=6), four weekly, intratumoural AdCD40L injections were given. In cohort 2 (n=9), low dose cyclophosphamide was added to increase the immune response. Since irradiation may act synergistically with immunotherapy, patients in cohort 3 (n=9) also received a single fraction of radiotherapy (8 Gy). This fraction was given towards the lesion selected for injections. The primary objectives were to assess the feasibility and safety of AdCD40L-treatment and secondarily its anti-tumour effects. Patients were thoroughly assessed for toxicity. The anti-tumour response was evaluated by imaging techniques (FDG-PET/CT, DW-MRI scans), tumour biopsies and blood tests. Plasma protein markers were measured with a multiplex platform. Another objective was to evaluate the potential of DW-MRI and FDG-PET/CT for prediction of AdCD40L treatment response, in terms of overall survival (OS). AdCD40L was well tolerated with mild transient reactions. Local and distant responses in PET/CT scans along with a significantly better 6-month survival in the cohorts that received cyclophosphamide conditioning were observed. Effector lymphocyte responses were elicited. All patients had an increased T effector/T regulatory-cell ratio and death receptors were significantly up-regulated post therapy. Inflammatory cytokines and other plasma proteins were altered in favourable ways by the AdCD40L treatment. The analyses support that the functional DWI parameters may be better early predictors of OS than the established metabolic and morphologic criteria of FDG-PET/CT and CT/MRI, respectively. In conclusion, the stimulation of the CD40 pathway to initiate anti-tumour immunity is a promising treatment alternative for MM patients. However, further studies with developed treatment schemes are warranted. In the first report ever on treatment of a pregnant patient with a BRAF-inhibitor, the therapy was initiated in the second trimester. The treatment with vemurafenib enabled prolonged gestation, hence reducing the risk of immaturity-related complications. Further, we report the first case worldwide of a patient with metastatic conjunctival melanoma who benefitted from treatment with vemurafenib. Additional studies are needed to assess the efficacy of BRAF -inhibitors in the different subtypes of ocular melanoma.

Acute lymphoblastic leukemia (ALL) has poor prognosis in older/elderly adults and in high-risk/relapsed disease. Recommended treatment of ALL was evaluated (study I-IV). Data was obtained from the Swedish Acute Leukemia registries and from patient records. I. We assessed ALL relapse treatment and outcome in 76 patients aged 15-65 years (y). Complete remission (CR) was achieved in 50/71 patients (70%). Of them, 29 underwent allogeneic hematopoietic stem cell transplantation (hSCT). Five year overall survival (OS) was 15%, but close to 50% in 19 patients <35y after hSCT. II. We studied outcome of treatment with the Hyper-CVAD protocol in 19 of 24 patients with T-ALL aged 18-72y. CR was reached in 89%, but 5y leukemia-free survival was only 29%, and 20% in 15 patients not transplanted in CR1. Six patients received hSCT in CR2. Finally, 5y OS in all 19 patients was 47%. The only negative prognostic factor found was age ≥35y. III. We evaluated minimal residual disease (MRD) monitoring in 35 patients with Philadelphia (Ph) negative B-ALL aged 46-79y and treated with the ABCDV protocol. The CR rate was 91%. MRD was measured by flow cytometry in 73% in CR1 (MRD1) and omitted in those >70y or with high-risk ALL. Five patients received hSCT (only one due to MRD). Five year OS in the whole cohort was 47%. Continuous CR but not OS was improved in patients with MRD1 <0.1 %. IV. We studied 155 patients with ALL (Ph+ in 35%) aged 55-85y and treated with remission induction/palliation (124/31). Both, intensive, and palliative treatment resulted in the CR rates of 70/83/16% and 3y OS of 26/32/3%. OS was negatively influenced by age and platelet count ≤35×109/L (but not Ph+). OS was not enhanced by introduction of an age-adapted protocol. We concluded that intensive treatment with subsequent allogeneic hSCT is the most reasonable option in younger patients with ALL recurrence (I). Hyper-CVAD has low relapse-preventing efficacy (II). MRD guided intensification is probably feasible in only a minority of older patients (III). Prognosis in elderly ALL is poor, but no longer impaired by Ph+ (IV).

Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment. Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991.  Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made.  Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs. PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective. A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients. The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.

Bakgrund: Varje år diagnostiseras mer än 9000 personer med bröstcancer i Sverige. En vanlig upplevelse är förlust av kontroll samt rädsla inför framtiden. Kvinnors existens påverkas till följd av sjukdom och biverkningar av behandling. Genom stöd kan kvinnor hantera oro, sorg och rädslor som uppkommer. Syfte: Syftet med denna litteraturbaserade studie var att undersöka hur kvinnor med bröstcancer upplevde sitt dagliga liv efter diagnos och behandling. Metod: En litteraturbaserad studie med nio kvalitativa artiklar. Resultat: Ur analysen framkom tre kategorier; Osäkerhet efter diagnosen, Relationernas betydelse och När livet får en ny innebörd, samt sju underkategorier. Konklusion: Kvinnor som drabbas av bröstcancer var en grupp med ökad risk för psykisk ohälsa, där osäkerhet och ett informationsbehov inte tillgodosågs. Sjukdomen gjorde att kvinnor genomgick olika former av kriser och behov av stöd var viktigt samt nödvändigt för vissa kvinnor för att orka kämpa vidare. Stöd från sjukvården och hög patientdelaktighet kunde leda till en känsla av kontroll och minskad sårbarhet. Sjukdomen gjorde även att kvinnor upplevde att livet fick en ny innebörd och blev mer värdefullt. / Background: In Sweden, more than 9000 people are diagnosed with breast cancer annually. A common experience are a loss of control and fear of the future. Furthermore, the cancer affect women's whole existence and side effects from treatment are common. With support, women are able to cope with anxiety, grief and fears that arise. Purpose: The aim of this litterature-based study was to examine how women with breast cancer experienced their daily life after diagnosis and treatment. Method: A litterature-based study with nine qualitative articles. Result: Three categories revealed; The uncertainty of the diagnosis; The meaning of relationships and When life gets a new meaning, and seven subcategories. Conclusion: Women with breast cancer were a group exposed to a greater risk of developing mental illness, where uncertainty and the need for information were unmet. The disease lead women to undergo a variety of crisis's and the need for support were important and necessary for some women in order to fight the disease. Support from healthcare and high patient-involvement facilitates and lead to a sense of control and reduced vulnerability. The disease could also cause women to experience a new meaning in life and that it became more valuable to them.

Respiratory motion during PET acquisition degrades image quality. It is mainly the area around the thorax and abdomen which is affected. External devices do provide respiratory gating solutions but are time-consuming to set up on patients and may not always be available. A data-driven gating (DDG) method based on principal component analysis (PCA) was found to provide a reliable respiratory gating signal, discriminating the need for external gating systems with FDG, but it remains to be investigated how well it performs with other PET tracers. The HER2-targeting radiotracer 68Ga-ABY-025 is currently in phase 3 development and is aimed to develop methods to select breast cancer patients that benefit from HER2-targeted treatment. Hence, absolute quantification is important. Respiratory motion correction will be important for improved quantitative accuracy since many patients have metastases in the lower part of the lungs or the liver.  DDG was applied to PET/CT list mode data retrospectively using quiescent period gating. Gated images were then compared to reconstructions without gating with a matched number of coincidences. Two iterative reconstructions were evaluated, TOF OSEM (3 iterations, 16 subsets, and a 5 mm gaussian postprocessing filter) and TOF BSREM β 400. Images were evaluated for standardized uptake value (SUV) changes for well-defined lesions in thorax and abdomen where respiratory motion is prevalent. Respiratory motion was detected in a mean 2.1 bed positions per examination. DDG application resulted in a mean increase of 12.7% in SUVmax for TOF OSEM reconstruction (p=0.0156).

Bakgrund: Bröstcancer är idag den vanligaste cancersjukdomen bland kvinnor globalt. När en kvinna drabbas av bröstcancer tar ofta anhöriga ett stort ansvar för kvinnans omsorg i hemmet. Problematiken med anhörigomsorg är att anhörigas förutsättningar för att ge omsorg ser olika ut och att deras egen hälsa riskerar att påverkas. Syfte: Syftet var att belysa anhörigas upplevelser av att ge omsorg till en kvinnlig familjemedlem med bröstcancer. Metod: Metoden var en allmän kvalitativ litteraturöversikt med 11 artiklar som analyserades genom en kvalitativ innehållsanalys. Resultat: Två kategorier identifierades; Omsorgens utmaningar och Stöd i omsorgen. Under Omsorgens utmaningar identifierades två sub-kategorier; Svårigheter att ge omsorg och Känsla av att vardagen prövades. Under Stöd i omsorgen identifierades två sub-kategorier; Känsla av att stärka kvinnan och Behov av att vägledas. Slutsats: Anhöriga upplevde flera svårigheter med att ge omsorg. Den ökade belastningen på dagens hälso- och sjukvård gör att ansvaret för patientens omsorg ökar för anhöriga, vilket var svårt att ta sig an. Anhöriga upplever likväl att deras insatser gör skillnad. Trots att forskning understryker vikten av att se till alla familjemedlemmars behov och öka utrymmet för familjefokuserad omvårdnad, finns ett fortsatt behov av ytterligare forskning kring anhörigas upplevelser av familjefokuserad omvårdnad i dagens vård och omsorg. / Background: Breast cancer is the most common type of cancer among women globally. When a woman suffers from breast cancer the main responsibility of care is often taken by her relatives. The problem with relative care is that the relatives' conditions for providing care look different and that their own health risks being affected. Aim: The aim was to highlight relatives' experiences of providing care to a female family member with breast cancer. Method: The method was a general qualitative literature review with 11 articles that were analyzed through a qualitative content analysis. Result: Two categories were identified; The challenges of care and Support in care. Within The challenges of care two sub-categories were identified; The difficulties of providing care and The feeling that everyday life was tested. Within Support in care two sub-categories were identified; The feeling of strengthening the woman and Need to be guided. Conclusion: Relatives experienced several difficulties in providing care. The increased burden on today´s health care means that the responsibility for the patient's care increases for relatives, which was difficult to handle. Relatives still feel that their efforts make a difference. Although research emphasizes the importance of looking after the needs of all family members and increasing the scope for family-focused nursing, there is a continuing need for further research on relatives' experiences of family-focused nursing in today's care and nursing.

No description available.

Neuroblastoma (NB), an extracranical solid tumor, is among the most prevalent cancers affecting children, particularly those under the age of five. High-risk NB presents a survival rate just below 50 %. Angiogenesis, a crucial process in NB, is induced by various pro-angiogenic factors. The compound SU11657 has demonstrated efficacy in inhibiting angiogenesis and tumor progression. Tumor-associated macrophages (TAMs) and Tumor-associated neutrophils (TANs) contribute to tumor progression, including angiogenesis, and their heightened levels within the tumor has been correlated with a poor clinical prognosis. This study aimed to quantify TANs and TAMs in NB tumors through manual assessment and the development of an automated digital image analysis. Unfortunately, due to time constraints, TAMs were not subjected to detailed analysis. Immunohistochemistry using antibody ab2557 and DAB staining was employed, and cell content analysis was performed through both manual assessment and digital analysis using QuPath. Successful differentiation of TANs was achieved with ab2557. The manual assessment observed a decrease of TANs between the control and treatment groups in UB7 and UB8, with UB7 being statistically significant (p<0.05), based on a two-tailed t-test. QuPath analysis noted increases in the percentages of TANs between the control and treatment groups, with the t-tests being non-significant (p>0.05). While digital image analysis is gaining importance in clinical applications, imperfections persist, underscoring the imperative for further research and development to accurately distinguish biomarkers.

Children who have survived a brain tumor often experience late consequences as a result of the tumor itself, and/or treatment. The child’s ability to engage in daily activities may be restricted by these late consequences. Examples of these late consequences are challenges with their activity levels and engagement in daily activities. Therefore, it is important to study these children’s late consequences over time. The aim of the thesis is to use data from medical and school records linked to ICF, to investigate how the participation problems/ restrictions of children that completed cancer directed treatment for a brain tumor tend to occur simultaneously with codes from other ICF components, over time. For the present research the inclusion criteria were children that were followed by the habilitation service, school and health care for at least 4 years after completing their brain tumor treatment. Seven children were included in the study. For each child, records were obtained from habilitation, school and health care and a complete retrospective screening was conducted between February 2022 and April 2022. Problems in relation to everyday life were identified and linked to ICF codes and domains. Descriptive statistics was used to analyze the data, in order to see the re-occurrences of the ICF domains during the time and observe the trajectory and intensity of the problems. The results revealed that the problems linked to body functions were the most frequently mentioned ICF domain by all three services as well as over time. Problems over time related to activity and participation were less focused and little emphasis were focused on problems related to the environment. The pattern over time was very individual. In order to more prominent focus on the child’s everyday functioning, follow-up guidelines should also include the child's functioning in everyday life, and not only areas related to body function. To conclude, when caring for these children, it is important to also focus on the child’s function in everyday life and to individualize the care since the pattern of problems over time seems to be very individual. / <p></p><p></p> / Using ICF to Describe Problems With Functioning in Everyday Life for Children Who Completed Treatment for Brain Tumor: An Analysis Based on Professionals' Documentation

Bakgrund: En stor livsförändring som en cancerdiagnos kan medföra förändrad sexualitet och sexuell hälsa. Sjuksköterskor har en roll att bemöta patienters behov av stöd och information, samt skapa förutsättningar för en god hälsa. Minst en av tre personer drabbas av cancer i Sverige, vilket medför att allt fler lever med konsekvenser av både diagnos och behandling.  Motiv: Hälso- och sjukvårdspersonal pratar inte om sexuell hälsa och sexualitet med patienter med cancer i den utsträckning som det önskas av patienter, trots att det anses vara viktigt. Studien kan skapa en förståelse av sjuksköterskors perspektiv, och bidra till en bättre omvårdnad av patienter med cancer.  Syfte: Att undersöka sjuksköterskors användning och uppfattning av samtal kring den sexuella hälsan och sexualitet med patienter inom onkologisk sluten- och öppenvård.Metod: Tvärsnittsstudie med kvantitativ design. En webbenkät genomfördes bland sjuksköterskor inom onkologisk verksamhet. Data analyserades med deskriptiv respektive analytisk statistik (signifikansanalys).  Resultat: Majoriteten av sjuksköterskorna angav att de har ett större behov av utbildning och otillräcklig kunskap inom ämnet. Majoriteten angav att det är både läkarens och sjuksköterskans ansvar att initiera samtalet. Sjuksköterskorna rapporterade hinder relaterat till att samtala om sexuell hälsa. Statistiskt signifikanta skillnader hittades mellan sjuksköterskor beroende på yrkeserfarenhet och vårdform. Konklusion: Sjuksköterskor inom cancervården (särskilt inom slutenvården) behöver mer utbildning och bättre förutsättningar för att kunna möta patienters behov kring sexuell hälsa. Vidare forskning behövs för att utvärdera utbildningsinsatser och implementering av kliniska rutiner. / Background: During life threating events, such as cancer, patients may face changes in sexuality and sexual health. Nurses have a role in meeting patients' needs of support and information, as well as health promoting. At least one in three people get cancer in Sweden, which indicate the large number of patients living with the consequences of both diagnosis and treatment, that may change both sexual health and sexuality.  Motive: Health care professionals do not discuss sexual health and sexuality to the extent desired by patients with cancer, even though it is considered to be important. The study can bring knowledge on nurses' perspectives, which could contribute to better cancer care. Purpose: To investigate nurse's use and perception of conversations about sexuality and sexual health with patients in oncology care.  Method: Cross-sectional study with quantitative design. A web survey was carried out among oncology nurses in Sweden. Collected data were analyzed using descriptive and analytical statistics (significance analysis).Results: The majority of nurses indicated a need for more training and not having sufficient knowledge to be able to address patients’ sexual health. The majority indicated that both nurse's and physicians were responsibility to initiate discussions. The nurses reported several barriers to conversations about sexual health. Statistically significant differences were found between nurses depending on professional experience and whether they work in outpatient or inpatient care.  Conclusion: Nurses in inpatient care have a greater need for training and clearer clinical routines. Further research is desirable regarding the implementation of routines and to understand nurses' needs for training.