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Träfflista för sökning "AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) ;srt2:(2020-2021)"

Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) > (2020-2021)

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21.
  • Almstedt, Elin, 1988- (författare)
  • New targeted therapies for malignant neural tumors : From systematic discovery to zebrafish models
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cancers in the neural system presents a major health challenge. The most aggressive brain tumor in adults, glioblastoma, has a median survival of 15 months and few therapeutic options. High-risk neuroblastoma, a childhood tumor originating in the sympathetic nervous system, has a 5-year survival under 50%, despite extensive therapy. Molecular characterization of these tumors has had some, but so far limited, clinical impact. In neuroblastoma, patients with ALK mutated tumors can benefit from treatment with ALK inhibitors. In glioblastoma, molecular subgroups have not yet revealed any subgroup-specific gene dependencies due to tumor heterogeneity and plasticity. In this thesis, we identify novel treatment candidates for neuroblastoma and glioblastoma. In paper I, we discover novel drug targets for high-risk neuroblastoma by integrating patient data, large-scale pharmacogenomic profiles, and drug-protein interaction maps. Using a novel algorithm, TargetTranslator, we identify more than 80 targets for this patient group. Activation of cannabinoid receptor 2 (CNR2) or inhibition of mitogen-activated protein kinase 8 (MAPK8) reduces tumor growth in zebrafish and mice models of neuroblastoma, establishing TargetTranslator as a useful tool for target discovery in cancer. In paper II, we screen approximately 1500 compounds across 100 molecularly characterized cell lines from patients to uncover heterogeneous responses to drugs in glioblastoma. We identify several connections between pathway activities and drug response. Sensitivity to proteasome inhibition is linked to oxidative stress response and p53 activity in cells, and can be predicted using a gene signature. We also discover sigma receptors as novel drug targets for glioblastoma and find a synergistic vulnerability in targeting cholesterol homeostasis.In paper III, we systematically explore novel targets for glioblastoma using an siRNA screen. Downregulation of ZBTB16 decreases cell cycle-related proteins and transcripts in patient-derived glioblastoma cells. Using a zebrafish assay, we find that ZBTB16 promotes glioblastoma invasion in vivo. In paper IV, we characterized the growth of seven patient-derived glioblastoma cell lines in orthotopic zebrafish xenografts. Using automated longitudinal imaging, we find that tumor engraftment strongly correlates with tumor initiation capacity in mice xenografts and that the heterogeneous response to proteasome inhibitors is maintained in vivo. In summary, this thesis identifies novel targets for glioblastoma and neuroblastoma using systematic approaches. Treatment candidates are evaluated in novel zebrafish xenograft models that are developed for high-throughput glioblastoma and neuroblastoma drug evaluation. Together, this thesis provides promising evidence of new therapeutic options for malignant neural tumors.
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22.
  • Biganzoli, L., et al. (författare)
  • The requirements of a specialist breast centre
  • 2020
  • Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 51, s. 65-84
  • Tidskriftsartikel (refereegranskat)abstract
    • This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. The centrepiece of this article is the requirements section, comprising definitions; multidisciplinary structure; minimum case, procedure and staffing volumes; and detailed descriptions of the skills of, and resources needed by, members and specialisms in the multidisciplinary team in a breast centre. These requirements are positioned within narrative on European breast cancer epidemiology, the standard of care, challenges to delivering this standard, and supporting evidence, to enable a broad audience to appreciate the importance of establishing these requirements in specialist breast centres. (C) 2020 The Authors. Published by Elsevier Ltd.
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23.
  • Borrelli, P., et al. (författare)
  • AI-based detection of lung lesions in F-18 FDG PET-CT from lung cancer patients
  • 2021
  • Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background[F-18]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is a well-established modality in the work-up of patients with suspected or confirmed diagnosis of lung cancer. Recent research efforts have focused on extracting theragnostic and textural information from manually indicated lung lesions. Both semi-automatic and fully automatic use of artificial intelligence (AI) to localise and classify FDG-avid foci has been demonstrated. To fully harness AI's usefulness, we have developed a method which both automatically detects abnormal lung lesions and calculates the total lesion glycolysis (TLG) on FDG PET-CT.MethodsOne hundred twelve patients (59 females and 53 males) who underwent FDG PET-CT due to suspected or for the management of known lung cancer were studied retrospectively. These patients were divided into a training group (59%; n = 66), a validation group (20.5%; n = 23) and a test group (20.5%; n = 23). A nuclear medicine physician manually segmented abnormal lung lesions with increased FDG-uptake in all PET-CT studies. The AI-based method was trained to segment the lesions based on the manual segmentations. TLG was then calculated from manual and AI-based measurements, respectively and analysed with Bland-Altman plots.ResultsThe AI-tool's performance in detecting lesions had a sensitivity of 90%. One small lesion was missed in two patients, respectively, where both had a larger lesion which was correctly detected. The positive and negative predictive values were 88% and 100%, respectively. The correlation between manual and AI TLG measurements was strong (R-2 = 0.74). Bias was 42 g and 95% limits of agreement ranged from -736 to 819 g. Agreement was particularly high in smaller lesions.ConclusionsThe AI-based method is suitable for the detection of lung lesions and automatic calculation of TLG in small- to medium-sized tumours. In a clinical setting, it will have an added value due to its capability to sort out negative examinations resulting in prioritised and focused care on patients with potentially malignant lesions.
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24.
  • Hagström, Josefin, et al. (författare)
  • Heeding the psychological concerns of young cancer survivors : A single-arm feasibility trial of CBT and a cognitive behavioral conceptualization of distress
  • 2020
  • Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundA subgroup of adolescent and young adult (AYA) survivors of cancer during adolescence report high levels of psychological distress. To date, evidence-based psychological interventions tailored to the cancer-related concerns experienced by this population are lacking. The present study aimed to (1) examine the feasibility and preliminary efficacy of an individualized cognitive behavioral therapy (CBT) intervention for AYA survivors of cancer during adolescence; and (2) identify and conceptualize cancer-related concerns as well as maintaining factors using cognitive-behavioral theory.MethodsA single-arm trial, whereby AYA survivors of cancer during adolescence (aged 17–25 years) were provided individualized face-to-face CBT at a maximum of 15 sessions. Clinical outcomes were assessed at baseline, post-intervention, and three-month follow-up. Intervention uptake, retention, intervention delivery, and reliable change index scores were examined. An embedded qualitative study consisted of two unstructured interviews with each participant pre-intervention. Along with individual behavioral case formulations developed to guide the intervention, interview data was analyzed to identify and conceptualize cancer-related concerns and potential maintaining factors.ResultsTen out of 213 potential participants invited into the study were included, resulting in an overall participation rate of 4.7%. Nine participants completed the intervention, with respectively seven and eight participants completing the post-intervention and three month follow-up assessment. The majority of reported cancer-related concerns and maintaining factors were conceptualized into four themes: social avoidance, fear of emotions and bodily symptoms, imbalance in activity, and worry and rumination.ConclusionsGiven significant recruitment difficulties, further research is required to examine barriers to help-seeking in the AYA cancer survivor population. However, the conceptualization of cancer-related concerns and maintaining factors experienced by the population may represent an important first step in the development of psychological support tailored toward AYA cancer survivors’ unique needs.
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25.
  • Abrahams, Harriët J. G., et al. (författare)
  • Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer : Individual patient data meta-analyses
  • 2020
  • Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:11, s. 1772-1785
  • Forskningsöversikt (refereegranskat)abstract
    • ObjectivePsychosocial interventions can reduce cancer‐related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta‐analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention‐related characteristics on the effect of psychosocial interventions on cancer‐related fatigue in patients with non‐metastatic breast and prostate cancer.MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta‐analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed‐effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).ResultsStatistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = −0.19 [95% confidence interval (95%CI) = −0.30; −0.08]; prostate cancer: β = −0.11 [95%CI = −0.21; −0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention‐related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = −0.27 [95%CI = −0.40; −0.15]), fatigue‐specific interventions (β = −0.48 [95%CI = −0.79; −0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = −0.85 [95%CI = −1.40; −0.30]).ConclusionsOur findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.
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26.
  • Latini, Francesco, M.D. 1982- (författare)
  • Significance of white matter anatomy in interpreting features and behaviour of low-grade gliomas and implications for surgical treatment
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Diffuse gliomas are extremely heterogeneous tumours characterized by slow growth but extensive infiltration. Their kinetic features reflect the complex interaction over time with the surrounding brain, influencing treatment planning and outcome. Indeed, resection of diffuse gliomas present a surgical challenge due to their invasiveness and the preferential location in eloquent regions. White matter bundles are the main eloquent limit to surgical resection, but this anatomical-functional information cannot be predicted preoperatively on the individual level. The incomplete description of the human brain connectome, the complex application of pathological/lesion model to the brain connectomic organization, and the underestimated role of white matter anatomy in radiological classification systems are among the major limitations for the comprehension of the glioma/white matter interaction. The overall aim of this thesis was to explore a new approach and new techniques to study the glioma/white matter interaction. A combination of white matter dissection and diffusion tensor tractography (DTT) was used to describe the connectomic organization of two major temporo-occipital connections, the inferior and the middle longitudinal fasciculus. This information was applied to patients with diffuse gliomas, demonstrating how white matter analysis was important to decode patient specific cognitive and language impairment. A new classification system for diffuse gliomas, the Brain-Grid, was created, merging local radiological anatomy with a DTT atlas for infiltration analysis. This standardized radiological tool provided information on subcortical extension (tumour invasiveness), speed, and preferential direction of glioma progression. Applied to a larger cohort of patients, differences were detected between diffuse gliomas subtypes. Tumour invasiveness and the preferential location, type, and extent of white matter involvement differed, impacting overall survival. Regional differences in white matter infiltration were detected among five major white matter bundles, and possible favourable morphological and diffusion features were investigated with transmission electron microscopy and DTT. Fibre diameter, myelin thickness, and the organization of the white matter fibres were different in regions with high infiltration frequency, providing a possible link to the preferential location of diffuse gliomas. Finally, the white matter connectivity, tumour-induced neuroplasticity, clinical and demographic information, preoperative assessment (neuropsychological and language evaluation) were compared with intraoperative findings during awake surgery. Neuropsychological impairment was associated with more invasive tumours and a higher risk of the intraoperative finding of eloquent tumour. The pattern of early cortical neuroplasticity seemed exhausted at the time of diagnosis, with age as a factor predicting the neuroplasticity potential. The combined use of these new techniques revealed new insights into the glioma/white matter interaction. The results provided in this thesis, describe a new way to structure the multidisciplinary perioperative management of these patients. This new information may improve the functional outcome at the individual level, resulting in prolonged survival for adults with diffuse gliomas.
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27.
  • Ohlsson-Nevo, Emma, et al. (författare)
  • Patients' perspective in the context of proton beam therapy : summary of a Nordic workshop
  • 2020
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 59:10, s. 1139-1144
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: On 15-16 November 2019, the Skandion Clinic in Sweden hosted the first Nordic workshop on 'Patients' perspective in proton beam therapy'. The workshop was conducted to describe and compare the patient care in PBT clinics in the Nordic countries and to initiate a collaboration, with the target to ensure patient participation and reduce the risk of inequity of access by lowering the barriers for accepting PBT in a distant clinic. The overarching aim of this workshop was to describe and compare the use of patients' perspectives in the Nordic PBT clinics.MATERIAL AND METHODS: Twelve participants attended the workshop, representing Denmark, Norway and Sweden. The participants were registered nurses working in patient care, researchers, physicist and leaders of the Skandion Clinic.RESULTS: The consensus of the workshop was that systematic use of patient experiences on individual and group level is essential for developing clinical practice and understanding the overall effects of PBT. A difference in how the Nordic countries use patient experiences in clinical practise was found. The importance of lowering the barriers for participation in national proton trials and proton treatment were emphasized, however, there is a lack of knowledge about individual and organizational barriers to accepting PBT, and further research is therefore needed.CONCLUSION: Collaboration between the Nordic countries regarding patients' perspectives in the context of PBT is of importance to compare national differences as well as to find similarities, but most importantly to learn from each other and to improve patient care. Nordic collaboration with focus on systematic collection of patient-reported outcomes in the context of PBT is unique. Collaboration in research offers the possibility to increase the inclusion of patients' perspectives in study protocols.
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28.
  • Hasselgren, Kristina, et al. (författare)
  • Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease
  • 2020
  • Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.
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29.
  • Shamoun, Levar, et al. (författare)
  • Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer
  • 2021
  • Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group. - 1007-9327 .- 2219-2840. ; 27:30, s. 5076-5087
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes. AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance. METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls. RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer. CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.
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30.
  • Razumova, Zoia, et al. (författare)
  • Report from the European Society of Gynaecological Oncology (ESGO) 2020 State-of-the-Art Virtual Meeting
  • 2021
  • Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 31:5, s. 658-669
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a report from the European Society of Gynaecological Oncology State-of-the-Art Virtual Meeting held December 14-16, 2020. The unique 3-day conference offered comprehensive state-of-the-art summaries on the major advances in the treatment of different types of gynecological cancers. Sessions opened with a case presentation followed by a keynote lecture and interactive debates with opinion leaders in the field. The speakers also presented scientific reviews on the clinical trial landscape in collaboration with the European Network of Gynecological Oncological Trial (ENGOT) groups. In addition, the new ESGO-ESRTO-ESP endometrial cancer guidelines were officially presented in public. This paper describes the key information and latest studies that were presented for the first time at the conference.
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