| 281. |
- Wick, Wolfgang, et al.
(author)
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Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma
- 2016
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 18:10, s. 1434-1441
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Journal article (peer-reviewed)abstract
- Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma). MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory). Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, > 84%) and infiltrative profile (> 88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed. Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns.
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| 282. |
- Wikström, Christina, 1967-
(author)
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Criterion-referenced measurement for educational evaluation and selection
- 2005
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Doctoral thesis (other academic/artistic)abstract
- In recent years, Sweden has adopted a criterion-referenced grading system, where the grade outcome is used for several purposes, but foremost for educational evaluation on student- and school levels as well as for selection to higher education. This thesis investigates the consequences of using criterion-referenced measurement for both educational evaluation and selection purposes. The thesis comprises an introduction and four papers that empirically investigate school grades and grading practices in Swedish upper secondary schools. The first paper investigates the effect of school competition on the school grades. The analysis focuses on how students in schools with and without competition are ranked, based on their grades and SweSAT scores. The results show that schools that are exposed to competition tend to grade their students higher than other schools. This effect is found to be related to the use of grades as quality indicators for the schools, which means that schools that compete for their students tend to be more lenient, hence inflating the grades. The second paper investigates grade averages over a six-year period, starting with the first cohort who graduated from upper secondary school with a GPA based on criterion-referenced grades. The results show that grades have increased every year since the new grading system was introduced, which cannot be explained by improved performances, selection effects or strategic course choices. The conclusion is that the increasing pressure for high grading has led to grade inflation over time. The third paper investigates if grading practices are related to school size. The study is based on a similar model as paper I, but with data from graduates over a six-year period, and with school size as the main focus. The results show small but significant size effects, suggesting that the smallest schools (<300 students) are higher grading than other schools, and that the largest schools (>1000 students) are lower grading than other schools. This is assumed to be an effect of varying assessment practices, in combination with external and internal pressure for high grading. The fourth and final paper investigates if grading practices differ among upper secondary programmes, and how the course compositions in the programmes affect how students are ranked in the process of selection to higher education. The results show that students in vocationally oriented programmes are higher graded than other students, and also favoured by their programmes’ course compositions, which have a positive effect on their competitive strength in the selection to higher education. In the introductory part of the thesis, these results are discussed from the perspective of a theoretical framework, with special attention to validity issues in a broad perspective. The conclusion is that the criterion-referenced grades, both in terms of being used for educational evaluation, and as an instrument for selection to higher education, are wanting both in reliability and in validity. This is related to the conflicting purposes of the instruments, in combination with few control mechanisms, which affects how grades are interpreted and used, hence leading to consequences for students, schools and society in general.
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| 283. |
- Willén, Linda, 1979-
(author)
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Factors influencing management and outcome in non-small cell lung cancer : the role of socioeconomic status, age, geographic region of origin and aspects of quality of life
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Yearly, 4,200 individuals in Sweden are diagnosed with lung cancer, of which 85 % are non-small cell lung cancer (NSCLC). The aims of this thesis were to investigate aspects of equality of care and outcomes in patients with NSCLC and to examine indicators of quality of life. All studies used data in Lung Cancer Database Sweden (LCBaSe), a research database generated by record linkages between the National Lung Cancer Register and other population-based registers. We identified 40,000 patients with NSCLC diagnosed between 2002 and 2016.Paper I examined influence of socioeconomic status. Patients with a high educational level were more often offered PET-CT, assessed in a multidisciplinary team setting, treated with stereotactic body radiotherapy and had better survival in early-, but not in late-stage disease.Paper II investigated elderly NSCLC patients. No difference in stage was seen in patients ≤ 84 years, nor in diagnostic intensity <80 years. Treatment intensity was adapted according to age. Survival differed across age groups in early-, but not late-stage disease.Paper III examined immigrants. We found evidence of a “healthy migrant effect”. There were only small differences in management and outcome. If anything, non-Nordic immigrants had better survival in early-stage disease. Paper IV assessed psychological impact following a NSCLC diagnosis. Higher rates of depression, anxiety, intoxication and suicide were seen in NSCLC patients compared to lung cancer free individuals. The risk of depression, anxiety and suicide decreased over time but the increased risk of intoxication remained throughout the follow-up period.In summary, we found equal access of care and only minor differences in patterns of management and outcomes according to socioeconomic status, age and geographic region of origin. New diagnostics and treatment modalities need to be quickly introduced to enable equal access across socioeconomic groups. A careful assessment of older patients is important to avoid age-biased clinical decision-making. A diagnosis of NSCLC impacts psychological aspects of quality of life and active measures to identify and treat depression and anxiety as well as to identify patients at risk of intoxication and suicide is necessary.
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| 284. |
- Wode, Kathrin, et al.
(author)
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Cancer patients' use of complementary and alternative medicine in Sweden : a cross-sectional study
- 2019
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In: BMC Complementary and Alternative Medicine. - : BioMed Central (BMC). - 1472-6882. ; 19
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Journal article (peer-reviewed)abstract
- Background: Access to and advice on Complementary and Alternative Medicine (CAM) are uncommon within Swedish conventional cancer care and little is known about cancer patients' own use of CAM. The aim of this cross-sectional study was to explore Swedish cancer patients patterns of CAM use, their experiences and preferences.Methods. Questionnaires were distributed consecutively to 1297 cancer patients at a university hospital's out-patient oncology units. The response rate was 58% (n=755). Descriptive statistics were used to analyze the survey data. A logistic regression model was used to investigate the association between CAM use and gender, age and level of education. Open-ended responses were analyzed, using qualitative content analysis.Results: Lifetime CAM use was reported by 34% (n=256), and 26% (n=198) used CAM after cancer diagnosis. Being female, younger and having higher education predicted CAM use. Most commonly used methods were natural products including vitamins and mineralsand relaxation. Main reasons for CAM use were improvement of physical, general and emotional wellbeing and increasing the body's ability to fight cancer. Satisfaction with CAM usage was generally high. Reported adverse effects were few and mild; 54% of users spent <50 Euro a month on CAM. One third had discussed their CAM use with cancer care providers. More than half of all participants thought that cancer care providers should be able to discuss (58%) and to consider (54%) use of CAM modalities in cancer care.Conclusions: Despite limited access and advice within conventional cancer care, one fourth of Swedish cancer patients use CAM. The insufficient patient-provider dialogue diverges with most patients' wish for professional guidance in their decisions and integration of CAM modalities in conventional cancer care. Concurrent and multimodal CAM use implies challenges and possibilities for cancer care that need to be considered.
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| 285. |
- Wode, Kathrin, 1968-
(author)
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Complementary and alternative medicine in cancer : from utilization to a randomized controlled trial
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Complementary and alternative medicine (CAM) are non-conventional health care approaches used in parallel with or instead of conventional medicine. Little is known about Swedish patients’ patterns of complementary CAM use in the context of cancer. Patient-provider communication concerning CAM is crucial and research about communication in situations when patients decline recommended cancer treatment and consider CAM as an alternative is scarce. One commonly used CAM approach is an herbal medicinal product from mistletoe. An open-label trial on mistletoe extract for patients with advanced pancreatic cancer reported promising results on overall survival and quality of life. Due to limited treatment options for this group of patients, this approach needs to be investigated further. Aim: The overall aim of this thesis is to explore CAM use from patients’ and physicians’ perspectives and to design a placebo-controlled randomized clinical trial to assess mistletoe extract as a complement to standard treatment in patients with advanced pancreatic cancer. Methods: A cross-sectional design with quantitative and qualitative mixed methods was used in Study I including 755 patients with solid tumors. In Study II a qualitative design with face-to-face interviews with seven patients with cancer and ten physicians from cancer care was used. In Study III, a study protocol for a multicenter, parallel group, double-blind, randomized, placebo-controlled clinical trial (RCT) was developed. Mixed methods were used by two nested ancillary studies on sub-sets of participants with a translational and a qualitative design respectively. Patients with advanced pancreatic cancer (n=290) were included; mistletoe extract/placebo was added to treatment of choice for the duration of nine months. The trial is currently being conducted. Results: One of four patients with solid tumors used CAM parallel with conventional treatment. Main reasons motivations were the hope for improvement of physical, general, and emotional wellbeing and the body’s ability to fight cancer. Satisfaction with CAM usage was generally high; reported adverse effects few and mild. One third had discussed their CAM use with cancer care providers. More than half of the patients thought that cancer care providers should be able to discuss and/or consider use of CAM modalities in cancer care. Patients declining conventional cancer treatment while using CAM had a variety of reasons for their choices: many of them valued CAM for a broader perspective on health and illness in the context of mind, body and spirit. The wish to take an active stance in relation to treatment decisions and previous negative experiences from conventional care were also cited as motives. Some patients felt a lack of respect for their choices and indicated lack of knowledge and interest on their physicians’ part. Some physicians felt a need for better expertise in CAM while others did not. Patients’ choice to decline cancer treatment was an ethical dilemma to most of the interviewed physicians. Even though communication in these situations tended to push some patients and physicians to take an extreme position, both parties wished for an open dialogue with mutual trust and understanding.The study protocol of Study III was designed and published according to the Standard Protocol Items for Clinical Trials (SPIRIT) guidelines. The trial started inclusion in 2016 and has been running at nine participating oncological departments. Inclusion was completed in December 2021 and expected end-of-study is September 2022. Thirty-one interviews have been conducted within the ancillary qualitative study and 100 patients were included in the biomarker study.Conclusions: Many patients with cancer use CAM, mainly as a complement to conventional treatment to improve wellbeing. Most have realistic expectations, express high satisfaction and awareness of side effects. In rare cases, patients decline conventional cancer treatment and use CAM as an alternative for complex reasons that are worthwhile to explore in concrete situations. Patients generally wish to stay in contact with cancer care but demand interest in and respect for their choices. The majority of CAM-using patients perceive a lack of knowledge about CAM among cancer care providers and do often not reveal their CAM use; however, patients want providers to be knowledgeable and able to give advice. Shared decision-making appears extra difficult in the clinically demanding situations when patients’ and physicians’ views on treatment choices profoundly diverge. Knowledge about CAM and competency in giving nuanced advice to interested patients seem crucial for an initiated patient-provider dialogue for safety reasons, patient satisfaction and mutual trust. Both design and conduct of the RCT are an example of research filling an identified gap of knowledge and will provide cancer care with much-needed information. The design and conduct of this trial as well as its future results may serve as a model for CAM knowledge capacity building. Evidence-based medicine is the practice of integrating individual clinical expertise and patient values with the best available external clinical evidence from systematic research. This thesis pays attention to patients’ values, builds professional competency and experience within CAM and acknowledges and contributes to systematic research.
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| 286. |
- Wode, Kathrin, et al.
(author)
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Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer : study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL)
- 2020
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In: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported.The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life.Methods: The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews.Discussion: To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer.
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| 287. |
- Wode, Kathrin, 1968-, et al.
(author)
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Mistletoe extract in patients with advanced pancreatic cancer : a double-blind, randomized, placebo-controlled trial (MISTRAL)
- 2024
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In: Deutsches Ärzteblatt International. - : Deutscher Arzte-Verlag GmbH. - 1866-0452. ; 121:11, s. 347-354
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Journal article (peer-reviewed)abstract
- Background: Patients with advanced pancreatic cancer have limited survival and few treatment options. We studied whether mistletoe extract (ME), in addition to comprehensive oncological treatment and palliative care, prolongs overall survival (OS) and improves health-related quality of life (HRQoL).Methods: The double-blind, placebo-controlled MISTRAL trial was conducted in Swedish oncology centers. The main inclusion criteria were advanced exocrine pancreatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0–2. The subjects were randomly assigned to ME (n=143) or placebo (n=147) and were stratified by study site and by eligibility (yes/no) for palliative chemotherapy (June 2016–December 2021). ME or placebo was injected subcutaneously three times a week for nine months. The primary endpoint was overall survival (OS); one of the secondary endpoints was the HRQoL dimension global health/ QoL (EORTC–QLQ–C30), as assessed at seven time points over nine months.Trial registration: EudraCT 2014–004552–64, NCT02948309Results: No statistically significant benefit of adding ME to standard treatment was seen with respect to either OS or global health/ QoL. The adjusted hazard ratio for OS was 1.13 [0.89; 1.44], with a median survival time of 7.8 and 8.3 months for ME and placebo, respectively. The figures for the HRQoL dimension “global health/QoL” were similar in the two groups (p=0.86). The number, severity, and outcome of the reported adverse events were similar as well, except for more common local skin reactions at ME injection sites (66% vs. 1%).Conclusion: ME is unlikely to have a clinically significant effect on OS or the HRQoL dimension global health/QoL when administered in patients with advanced pancreatic cancer in addition to comprehensive cancer care.
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| 288. |
- Woltmann, Andrea, et al.
(author)
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Systematic Pathway Enrichment Analysis of a Genome-Wide Association Study on Breast Cancer Survival Reveals an Influence of Genes Involved in Cell Adhesion and Calcium Signaling on the Patients' Clinical Outcome
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e98229-
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.
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| 289. |
- Wu, Wendy Yi-Ying, et al.
(author)
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The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes
- 2019
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In: Cancers. - : MDPI. - 2072-6694. ; 11:12
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Research review (peer-reviewed)abstract
- Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.
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| 290. |
- Wu, Xuping, et al.
(author)
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Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity.
- 2012
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 51:1, s. 69-76
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Journal article (peer-reviewed)abstract
- Abstract Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines. Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = -0.74), docetaxel (r = -0.69), and vinorelbine (r = -0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication.
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