Early detection reduces mortality in lung cancer, but it is also considered as a challenge for oncologists and for healthcare systems. In addition, screening modalities like CT-scans come with undesired effects, many suspected patients are wrongly diagnosed with lung cancer. This thesis contributes to solve the challenge of early lung cancer detection by utilizing unique data consisting of self-reported symptoms. The proposed method is a predictive machine learning algorithm based on natural language processing, which handles the data as an unstructured data set. A replication of a previous study where a prediction model based on a conventional multivariate machine learning using the same data is done and presented, for comparison. After evaluation, validation and interpretation, a set of variables were highlighted as early predictors of lung cancer. The performance of the proposed approach managed to match the performance of the conventional approach. This promising result opens for further development where such an approach can be used in clinical decision support systems. Future work could then involve other modalities, in a multimodal machine learning approach. / Tidig lungcancerdiagnostisering kan öka chanserna för överlevnad hos lungcancerpatienter, men att upptäcka lungcancer i ett tidigt stadie är en av de större utmaningarna för onkologer och sjukvården. Idag undersöks patienter med riskfaktorer baserat på rökning och ålder, dessa undersökningar sker med hjälp av bland annat medicinskt avbildningssystem, då oftast CT-bilder, vilket medför felaktiga och kostsamma diagnoser. Detta arbete föreslår en maskininlärninig algoritm baserad på Natural language processing, som genom analys och bearbetning av ostrukturerade data, av patienternas egna anamneser, kan prediktera lungcancer. Arbetet har genomfört en jämförelse med en konventionell maskininlärning algoritm baserat på en replikering av ett annat studie där samma data behandlades som strukturerad. Den föreslagna metoden har visat ett likartat resultat samt prestanda, och har identifierat riskfaktorer samt symptom för lungcancer. Detta arbete öppnar upp för en utveckling mot ett kliniskt användande i form av beslutsstödsystem, som även kan hantera elektriska hälsojournaler. Andra arbeten kan vidareutveckla metoden för att hantera andra varianter av data, så som medicinska bilder och biomarkörer, och genom det förbättra prestandan.

Inadequate metabolic conditions in solid tumors lead to the formation of quiescent cancer cells that are suspended in a transient cell cycle arrest. When conditions change, quiescent cancer cells can re-enter the cell cycle and cause recurrence. Drug screening efforts have revealed mitochondrial oxidative phosphorylation as a unique metabolic dependency in quiescent cancer cells. The anthelmintic drug nitazoxanide is an inhibitor of oxidative phosphorylation and preferentially active against quiescent cancer cells in multicellular tumor spheroids.  In this thesis, we employed current and developed new models of quiescent cancer cells and applied live cell imaging for improved preclinical evaluation of cancer drugs in hepatocellular and colorectal carcinoma cell lines. As part of this work, a new assay to measure mitochondrial membrane potential in three-dimensional cell models was developed, an application of the JC-1 assay, and we demonstrated that the preferential activity against quiescent cancer cells of nitazoxanide is shared by two kinase inhibitors: sorafenib and regorafenib. The sensitivity of quiescent cancer cells to nitazoxanide, sorafenib, and regorafenib correlated with the disruption of the mitochondrial membrane potential. Nitazoxanide and sorafenib, in combination, caused an additive decrease in viability, mitochondrial membrane potential, and colony regrowth capacity.  Furthermore, we developed a quiescent hollow fiber assay and implemented an improved analysis using live cell imaging and adenosine triphosphate analysis. Hypoxia and cancer cell quiescence were enriched in hollow fiber macrocapsules over time, and the culture conditions affected nitazoxanide sensitivity. Additionally, we used basement membrane extract gel to support cell growth in hollow fiber macrocapsules and implanted macrocapsules in mice. We observed that the in vivo environment was favorable to cell growth. Through this characterization of the quiescent hollow fiber assay, we were able to outline important paths for future research.

About 12 to 17 percent of all breast cancers are triple-negative breast cancer (TNBC). In TNBC, estrogen, progesterone, and human epidermal growth factor receptor two are not expressed, or copies of the HER2 gene are decreased (or both). This makes TNBC hard to treat in comparison with other kinds of breast cancers. New studies have made some interesting observations on how some monoclonal antibodies can help to treat TNBC. One of the monoclonal antibodies that can be useful for treating TNBC is pembrolizumab. Pembrolizumab inhibits programmed death ligand 1 (PD-1), which is located on the surface of T cells from connecting to immune checkpoint proteins such as programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) located on the surface of the cancer cell. Breaking this connection enables continued activation of T cells and attack of the cancer cells. This thesis aimed to evaluate if pembrolizumab was safe and effective as monotherapy or as a combination therapy with chemotherapy for patients with different stages of TNBC. This study was based on scientific articles identified from the database PubMed. Five randomized controlled trial studies were selected for further study in this project. Two publications were chosen from keynote-355, which studied the effect and safety of Pembrolizumab in combination with chemotherapy and compared it to chemotherapy monotherapy in patients with metastatic TNBC. The first study included patients from different countries as it was a multi-center study, and the second one focused only on patients who enrolled in Japan. One study was chosen from keynote-119 studies, which compared health-related quality of life for patients who were treated with pembrolizumab monotherapy or with monotherapy of chemotherapy. The last two articles which were chosen were about keynote-522. The first article about keynote-522 compared was a multicenter study enrolled in 21 countries. In this study, patients had early-stage TNBC and received neoadjuvant placebo chemotherapy or pembrolizumab chemotherapy. After the breast operation, either adjuvant pembrolizumab or placebo was received. The other study looked at Asian patients who enrolled in keynote-522. Results showed that monotherapy with pembrolizumab did not make a massive difference in overall survival compared to chemotherapy. Still, it led to better health- related quality of life for patients (Combined Positive Score (CPS) ≥ 10) treated with pembrolizumab. Results from keynote-355 showed that combination therapy with pembrolizumab and chemotherapy led to better and longer progression-free survival and overall survival in patients with CPS ≥ 10 treated with pembrolizumab. The analysis of Japanese patients showed even better progression-free survival and overall survival results than the global population. The study from keynote-522 showed that neoadjuvant pembrolizumab and chemotherapy followed by adjuvant pembrolizumab had a better effect than only neoadjuvant chemotherapy. The second keynote-522 study showed the same results as the global study and better results at event-free survival for the Asian population than the overall population. After reviewing the articles, it was found that pembrolizumab proves to be a safe and effective treatment for TNBC. To enhance understanding of the drug's effects, measures such as extending follow-up periods, conducting further studies to assess its effectiveness, and exploring new research methodologies are proposed.

The structure, function and accessibility of epidermal skin provide aunique opportunity to study the DNA damage response (DDR) of a normaltissue. The in vivo response can be examined in detail, at a molecularlevel, and further associated to the structural changes, observed at atissue level. We collected an extensive skin biopsy material frompatients undergoing fractionated radiotherapy for 5 to 7 weeks. Several end-points inthe DDR pathways were examined before, during and after the treatment. Quantification of DNA double strand break (DSB) signalling focirevealed a hypersensitivity to doses below 0.3Gy. Furthermore, aconsiderable amount of foci persisted between fractions. The low dosehypersensitivity was observed throughout the treatment and was alsoobserved for several key parameters further downstream in the DDR-pathway, such as p21-associated checkpoint activation, apoptosisinduction and reduction in basal keratinocyte density (BKD).Furthermore, for dose fractions above 1.0 Gy, a distinct acceleration inDDR was observed half way into treatment. This was manifested as anaccelerated loss of basal keratinocytes, mirrored by a simultaneousincrease in DSBs and p21 expression. Quantifications of mitotic events revealed a pronounced suppression ofmitosis throughout the treatment which was clearly low dosehypersensitive. Thus, no evidence of accelerated repopulation could beobserved for fraction doses ranging from 0.05 to 2Gy. Our results suggest that the keratinocyte response primarily isdetermined by checkpoints, which leads to pre-mitotic cell elimination by permanent growth arrest and apoptosis. A comparison between the epidermal and dermal sub-compartments revealsa consistent up-regulation of the DDR response during treatment. Adifference was however observed in the recovery phase after treatment,where miR-34a and p21 remain up-regulated in dermis more persistentlythan in epidermis. Our observations suggest that the recovery phaseafter treatment can provide important clues to understand clinicalobservations such as the early and late effects observed in normaltissues during fractionated radiotherapy.

The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL. In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL. In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.

Within the field of radiotherapy treatments of tumour diseases, the hunt for more accurate and effective treatment methods is a continuous process. For some years ion-beam based radiotherapy, especially the proton-beam based applications, has increased in popularity and availability. The main reason behind this is the fact that ion-beam based applications make it possible to modulate the dose after the planning target volume (PTV) defined by the radiation oncologist. This means that it becomes possible to spare tissue in another way, which might result in more effective treatments, especially in the vicinity of radio sensitive organs. Ion-beam based treatments are however more sensitive to uncertainties in PTV position and beam range as ion-beams have a fixed range depending on target media and initial energy, as opposed to the conventional x-ray beams that do not really have a defined range. Instead their intensity decreases exponentially at a rate dependent of the initial energy and target media. Therefore density heterogeneities result in uncertainties in the planned treatments. As the plans normally are created using a CT-images, for which metallic implants can yield increased heterogeneities both from the implants themselves and so called metal artifacts (distortions in the images caused by different processes as the X-rays used in image acquisition goes through metals). Metallic implants affects the accuracy of a treatment, and therefore also the related risks, so it is important to have an idea of the magnitude of the impact. Therefore the aim of this study is to estimate the impact on a proton-beam based treatment plan for six cranial implants. These were one Ti-mesh implant, one temporal plate implant, one burr-hole cover implant and three craniofix implants of different sizes, which all are commonly seen at the Skandion clinic. Also the ability of the treatment planning system (TPS), used at the clinic, to simulate the effects on the plans caused by the implants is to be studied. From this result it should be estimated if the margins and practices in place at the clinic, for when it is required to aim the beam through the implant, are sufficient or if they should be changed. This study consisted of one test on the range shift effects and one test on the lateral dose distribution changes, with one preparational test in the form of a calibration of Gafchromic EBT3 films. The range shift test was performed on three of the implants, excluding the three craniofix implants using a water phantom and a treatment plan created to represent a standard treatment in the cranial area. The lateral dose distribution change test was performed as a solid phantom study using radiochromic film, for two treatment plans (one where the PTV was located \SI{2}{\centi\metre} below surface, for all implants, and one where it was located at the surface, only for the Ti-mesh and the temporal plate). The results of both tests were compared to simulations performed in the Eclipse treatment planing system (TPS) available at Skandion. The result of the range shift test showed a maximum range shift of \SI{-1.03 +- 0.01}{\milli\metre}, for the burr-hole cover implant, and as the related Eclipse simulations showed a maximal shift of \SI{-0.17 +- 0.01}{\milli\metre} there was a clear problem with the simulation. However, this might not be because of the TPS but due to errors in the CT-image reconstruction, such as, for example, geometrical errors in the representation of the implants. As the margin applied for a similar situation at the Skandion clinic (in order to correct for several uncertainty factors) is \SI{4.2}{\milli\metre} there might be a need to increase this margin depending on the situation. For the lateral distribution effects no definite results were found as the change varied in magnitude, even if it tended to manifest as a decreasing dose for the first plan and a increasing dose for the second. It was therefore concluded that further studies are needed before anything clear can be said.

Varje år diagnostiseras över 50 000 individer med cancer i Sverige. Ett cancerbesked väcker blandade känslor och associeras ofta med lidande och död. Ett svårt besked kan leda till en förändrad livssituation och kan även ses som början på en lång och mödosam resa. En vetenskaplig litteraturstudie baserad på 15 originalartiklar genomfördes med syftet att belysa patientens upplevelse av ett cancerbesked och därmed öka sjuksköterskans förståelse för patientens situation samt fördjupa kunskaperna inom ämnet. Genom litteraturgranskningen identifierades tre teman: information, emotionella reaktioner samt psykosocialt stöd. Patienten upplever att det är viktigt att informationen ges på ett öppet och ärligt sätt. Vidare framkom det betydelsefullt att uppmärksamma patientens emotionella reaktioner i samband med beskedet. Eftersom upplevelsen av ett cancerbesked påverkar patientens fortsatta upplevelse av sin sjukdom, har sjuksköterskan en viktig roll att fylla genom att erbjuda psykosocialt stöd i de olika tänkbara situationer som kan uppkomma i samband med ett livsavgörande besked. Fortsatt forskning behövs för att jämföra hur de rekommendationer som finns angående delgivandet av ett svårt besked överensstämmer med patienternas egna upplevelser och önskemål. / Every year, over 50 000 individuals in Sweden are diagnosed with cancer. The disclosure of the cancer diagnosis arouses emotions and is often associated with suffering and death. Receiving bad news may lead to changes in life and can also be seen as the beginning of a long and difficult journey. A scientific study based on 15 original articles was carried out with the purpose to identify the patient’s experience of receiving a cancer diagnosis and therefore increase the nurse’s understanding for the patient’s situation and deepen the knowledge of the subject. When examining the articles three themes were identified: information, emotional reactions and psychosocial support. The patient experience that it is important that the information is given in an open and honest manner. Patients also find it important that their emotional reaction is being observed as receiving the diagnosis. As the disclosure of the cancer diagnosis affects the patient’s further perception of the disease the nurse has an important role providing psychosocial support in various situations that may arise in connection with the disclosure. Continued research is needed to compare how guidelines for giving bad news to a patient correspond with the patient’s own experiences and preferences.

Prostate cancer (PC) is the most common cancer in Sweden. Most patients have slow growing tumors that will not cause them any harm within their lifetime, but some have aggressive tumors and will die from their disease. The ability of current clinical practice to predict tumor behavior and disease outcome is limited leading to both over- and undertreatment of PC patients. The men who die from their disease are those that develop metastases. It is therefore of great value to find better and more sensitive prognostic techniques, so that metastatic spread can be detected (or predicted) at an early time point, and so that appropriate treatment can be offered to each subgroup of patients. The aim of this thesis was to investigate if, and by what means, highly aggressive prostate tumors influence extratumoral tissues such as the non-malignant parts of the prostate and regional lymph nodes (LN), and also if any of our findings could be of prognostic importance. Gene- and protein expression analysis were the main methods used to address these questions. Our research group has previously introduced the expression Tumor Instructed (Indicating) Normal Tissue (TINT), and we use the term TINT-changes when referring to alterations in non-malignant tissue due to the growth of a tumor nearby or elsewhere in the body. In the Dunning rat PC-model we found that MatLyLu (MLL)-tumors, having a high metastatic ability, caused pre-metastatic TINT-changes that differ from those caused by AT1-tumors who have low metastatic ability. Prostate-TINT surrounding MLL-tumors had elevated immune cell infiltration, and gene ontology enrichment analysis suggested that biological functions promoting tumor growth and metastasis were activated in MLL- while inhibited in AT1-prostate-TINT. In the regional LNs we found signs of impaired antigen presentation, and decreased quantity of T cells in the MLL-model. One of the downregulated genes in the MLL-LNs was Siglec1 (also known as Cd169), expressed by LN resident macrophages that are important for antigen presentation. When examining metastasis-free LN tissue from PC patients we found CD169 expression to be a prognostic factor for PC-specific survival, and reduced expression was linked to an increased risk of PC-specific death. Some of our findings in prostate- and LN-TINT could be seen already when the tumors were very small suggesting that differences in TINT-changes between tumors with different metastatic capability can be detected early in tumor progression. However, before coming of use in the clinic more research is needed to better define a suitable panel of prognostic TINT-factors as well as the right time window of when to use them. / Populärvetenskaplig sammanfattning Prostatacancer är den i särklass vanligaste cancerformen hos män i Sverige. De flesta patienter har en mycket långsamt växande tumör som inte orsakar dem några större besvär under deras livstid, men enbart i Sverige dör ca 2500 patienter/år av sjukdomen. Det är först vid uppkomst av metastaser som sjukdomen blir dödlig. Befintliga diagnos- och prognosmetoder är otillräckliga när det gäller att uppskatta och förutse tumörens aggressivitet och risk för att bilda metastaser. Detta gör att vissa patienter inte får tillräcklig behandling eller behandlas försent medan andra behandlas i onödan. Behovet av förbättrad diagnostik är därför stort. Om vi kan hitta markörer för potentiellt metastaserande sjukdom, och i bästa fall också behandla innan metastaser uppstår, skulle det förbättra chansen för överlevnad markant. För att kunna växa och spridas behöver en tumör inte bara förbereda närliggande vävnader utan förmodligen hela kroppen. Vår hypotes är att potentiell dödliga tumörer sannolikt är bättre på detta än mer ofarliga. Man vet från studier av andra cancerformer att farliga tumörer orsakar förändringar i det organ dit cancern senare sprids. Dessa förändringar sker för att de tumörceller som senare anländer ska kunna överleva, och processen har fått namnet pre-metastatisk nisch. Bl.a. har man sett att immunsystemet hämmas och nybildning av kärl ökar. Det är vanligt att metastaser uppstår i närliggande lymfkörtlar innan uppkomst av metastaser i andra organ. Dock är väldigt lite känt om pre-metastatiska förändringar i lymfkörtlar eftersom den forskning som hittills är gjord främst har tittat på andra organ. Inom prostatacancer finns det förvånande få studier av premetastatiska nischer överhuvudtaget, och man vet därför inte om de alls förekommer eller vilka förändringar som i så fall sker. Vår grupp har tidigare myntat uttrycket TINT som står för Tumor Instructed (Indicating) Normal Tissue (TINT är ett engelskt verb som betyder färga) och syftar på förändringar i normal vävnad som inducerats av tumören, dvs. att tumörer färgar av sig på omgivningen. Det kan vara förändringar i normal vävnad nära tumören, som i det här fallet resten av prostatan, eller i vävnad långt ifrån tumören som till exempel regionala lymfkörtlar, lungor och benmärg. Syftet med det här avhandlingsarbetet var att undersöka TINT-förändringar inducerade av aggressiv cancer och se om dessa skiljer sig från TINT-förändringar inducerade av mindre farliga tumörer, samt att utvärdera om någon TINT-förändring skulle kunna användas för att prognostisera vilka patienter som har hög risk att få metastaser. Vi har använt oss av en prostatacancer-modell i råtta där vi analyserat genoch proteinuttryck i pre-metastatiska regionala lymfkörtlar, tumörer och prostata-TINT (dvs. prostatavävnad utanför tumören). TINT-förändringar inducerade av MatLyLu (MLL), en tumör med hög metastaserande förmåga, jämfördes mot TINT-förändringar inducerade av AT1, en snabbväxande tumör men med låg förmåga att bilda metastaser. Vi kunde vi se flera skillnader mellan modellerna. Genuttrycket i MLL-prostata-TINT indikerade en aktivering av cellulära funktioner som visat sig stimulera tumörväxt och spridning såsom celldelning, viabilitet, migration, invasion, och angiogenes (nybildning av kärl). I AT1-prostata-TINT var genuttrycket kopplat till samma funktioner men verkade istället inhibera dessa. Genom att titta på vävnaderna i mikroskop kunde vi se att MLL-tumörer rekryterade färre T-celler (som har en viktig funktion i immunsvaret mot tumören), men istället fler makrofager och granulocyter till både tumören och prostata-TINT (dessa typer av immunceller har visats kunna hjälpa tumörer att växa och sprida sig). MLL-tumörer hade också fler blodkärl och lymfkärl strax utanför tumören. I de regionala lymfkörtlarna från djur med MLL-tumörer visade genuttrycket tecken på försämrad antigenpresentation, samt immunhämning och/eller induktion av immuntolerans. Immuntolerans innebär att immuncellen inte längre reagerar mot det specifika antigen den blivit tolerant emot. Detta är vanligt förekommande hos individer med cancer och är ett sätt för tumören att undkomma immunförsvaret. I vävnadsprover av lymfkörtlarna kunde vi se färre antigenpresenterande celler, och liksom i tumörerna fanns det färre T-celler i MLL-modellen, något vi kunde se redan när tumörerna var väldigt små. CD169 är ett protein som bl.a. uttrycks av sinus-makrofager i lymfkörtlar. Dessa makrofager har en central funktion i att aktivera ett tumör-specifikt immunsvar. I råttmodellen kunde vi se att regionala lymfkörtlar från djur med MLL-tumörer hade lägre nivåer av CD169 än regionala lymfkörtlar från djur med AT1-tumörer, och då antalet sinus-makrofager visat sig ha prognostiskt värde i t.ex. tjocktarmscancer, ville vi se om det kunde vara så även i prostatacancer. Därför kvantifierade vi uttrycket av CD169 i metastasfria regionala lymfkörtlar från prostatacancerpatienter och såg att låga nivåer av CD169 medförde en ökad risk för att dö i prostatacancer. Sammantaget tyder resultaten på att MLL-tumören jämfört med AT1- tumören bättre lyckas förbereda omgivande vävnad för att gynna tumörväxt och spridning, både lokalt i prostatan men också längre bort från tumören i de regionala lymfkörtlarna. Våra fynd stämmer väl överens med aktuell tumörbiologisk forskning om hur tumörer påverkar sin omgivning. Något som inte visats tidigare är att miljön utanför tumören verkar skilja sig drastiskt beroende på tumörens metastaserande förmåga, samt att dessa skillnader går att se relativt tidigt under sjukdomsförloppet och förmodligen även långt bort från tumören. Vi har också visat att särskilt aggressiv prostatacancer verkar inducera en pre-metastatisk nisch i tumördränerande lymfkörtlar likt det som beskrivits i andra modellsystem och i andra cancertyper, men hittills inte i prostatacancer. Fler studier behövs för att bättre karaktärisera de förändringar som en potentiellt dödlig prostatacancer orsakar i andra vävnader, och för att ta reda på hur denna kunskap kan användas för att förbättra diagnostik och behandling.

Background: Glioblastoma (GBM) is the most common and malignant primary brain tumor. It is a rapidly progressing tumor that infiltrates the adjacent healthy brain tissue and is difficult to treat. Despite modern treatment including surgical resection followed by radiochemotherapy and adjuvant chemotherapy, the outcome remains poor. The median overall survival is 10-12 months. Neuroimaging is the most important diagnostic tool in the assessment of GBMs and the current imaging standard is contrast-enhanced magnetic resonance imaging (MRI). Positron emission tomography (PET) has been recommended as a complementary imaging modality. PET provides additional information to MRI, in biological behavior and aggressiveness of the tumor. This study aims to investigate if the combination of PET and MRI can improve the diagnostic assessment of these tumors. Patients and methods: In this study, 22 patients fulfilled the inclusion criteria, diagnosed with GBM, and participated in all four 18F-fluorothymidine (FLT)-PET/MR examinations. FLT-PET/MR examinations were performed preoperative (baseline), before the start of the oncological therapy, at two and six weeks into therapy. Optimization of an adaptive thresholding algorithm, a batch processing pipeline, and image feature extraction algorithms were developed and implemented in MATLAB and the analyzing tool imlook4d. Results: There was a significant difference in radiochemotherapy treatment response between long-term and short-term survivors’ tumor volume in MRI (p<0.05), and marginally significant (p<0.10) for maximum standard uptake value (SUVmax), PET tumor volume, and total lesion activity (TLA). Preoperative short-term survivors had on average larger tumor volume, higher SUV, and total lesion activity (TLA). The overall trend seen was that long-term survivors had a better treatment response in both MRI and PET than short-term survivors.  During radiochemotherapy, long-term survivors displayed shrinking MR tumor volume after two weeks, and almost no remaining tumor volume was left after six weeks; the short-term survivors display marginal tumor volume reduction during radiochemotherapy. In PET, long-term survivors mean tumor volumes start to decrease two weeks into radiochemotherapy. Short-term survivors do not show any PET volume reduction two and six weeks into radiochemotherapy. For patients with more or less than 200 days progression-free survival, PET volume and TLA were significantly different, and MR volume only marginally significant, suggesting that PET possibly could have added value. Conclusion: The combination of PET and MRI can be used to predict radiochemotherapy response between two and six weeks, predicting overall survival and progression-free survival using MR and PET volume, SUVmax, and TLA. This study is limited by small sample size and further research with greater number of participants is recommended.

VALIDERING AV MAY-GRÜNWALD GIEMSA VID FÄRGNING AV CYTOLOGIPROVEROPTIMERING AV IN VITRO-DIAGNOSTIK, MED ANLEDNING AV NYA EU-KRAVKARIN SVANTESSONSvantesson, K. Validering av May-Grünewald Giemsa vid färgning av cytologiprover. Optimering av in vitro-diagnostik, med anledning av nya EU-krav. Examensarbete i biomedicinsk laboratorievetenskap, 15 högskolepoäng. Malmö Universitet: Fakulteten för hälsa och samhälle, institutionen för Biomedicinsk vetenskap, 2023.Cancer uppstår vid onormal celldelning, men uppkommer även vid kronisk inflammation. För att kunna konstatera om patienten har cancer krävs olika typer av diagnostik, där cytologidiagnostik ingår. Med hjälp av olika färglösningar kan cancerceller i serösa vätskor färgas för att upptäckas, således kan den cancerdrabbade patienten behandlas. May-Grünwald Giemsa (MGG) ingår i Romanowsky-färgningsteknikerna och har använts sedan 1800-talet.Färglösningen ger en högkvalitativ visualisering av cellernas morfologi. Färgen används inom histologi-, hematologi- och cytologidiagnostiken. Laboratorier som arbetar med in vitro-diagnostik (IVD) måste arbeta med märkta produkter som är reglerade för IVD. År 2017 fastställdes att inom fem år skall alla laboratorier i Europeiska unionen (EU) som utför IVD, arbeta med in vitro-diagnostik reglerade (IVDR) produkter för att uppnå EU-direktiven. Syftet med studien var att optimera en ny färgblandning av MGG vid färgning av cytologiprover, så att IVDR-kraven uppfylls på Patologen i Skövde. Studien omfattade flera försök för att fastställa vilket av färgprotokollen som gav bästa kvalité på cellerna i cytologiska preparat. Under studiens gång har det även visats att olika faktorer, exempelvis färskheten av provet kan påverka infärgningens kvalité av preparatet. Gammalt eller felhanterat provmaterial kan leda till försämrad infärgning av cellerna. Resultat från studien visade att färgprotokollet Histo Lab (HL) gav goda resultat efter en modifiering av sammansättningen och tiden vid infärgning. / VALIDATION OF MAY-GRÜNWALD GIEMSA IN THE STAINING OF CYTOLOGY SAMPLESOPTIMIZATION OF IN VITRO-DIAGNOSTICS, DUE TO NEW EU REQUIREMENTSKARIN SVANTESSONSvantesson, K. Validation of May-Grünwald Giemsa in the staining of cytology samples. Optimization of in vitro-diagnostics, due to new EU requirements. Degree project in biomedical laboratory science, 15 higher education credits. Malmö University: Faculty of Health and Society, Department of Biomedical Sciences, 2023.Cancer is caused by abnormal cell division, but also occurs by chronic inflammation. In order to determine whether the patient has cancer, different types of diagnostics are required, where cytology diagnostics are included. With thehelp of different dye solutions, cancer cells in serous fluids can be stained and detected, allowing for diagnosis and treatment. May-Grünwald Giemsa (MGG) is part of the Romanowsky staining techniques and has been used since the 19th century. The dye solution provides a high-quality visualization of the cells' morphology and is used in histology-, hematology- and cytology diagnostics.Laboratories that work with in-vitro diagnostics (IVD) must use products that are in vitro-diagnostics regulated (IVDR). In 2017 it was determined that within five years all laboratories in the European Union (EU) performing IVD must work with IVDR labeled products to achieve EU directives. The aim of the study was to optimize a new dye stain of MGG for cytology samples, so that the IVDR requirements are achieved at the pathology laboratory in Skövde. The study included several attempts to determine which of the staining protocols produced the best quality of the cells in cytology preparations. During the study, it has also been shown that various factors can negatively affect the results. If sample material is too old or mishandled, it can lead to poor staining of the cells. Results from the study showed that the Histo Lab (HL) staining protocol gave goodresults after modification of the composition and time of staining.