An Artificial Intelligence Approach to Tumor Volume Delineation

Postponed access: the file will be accessible after 2023-11-14Masteroppgave for radiograf/bioingeniørRABD395MAMD-HELS

Feasibility of deep learning-based tumor segmentation for target delineation and response assessment in grade-4 glioma using multi-parametric MRI

Background Tumor burden assessment is essential for radiation therapy (RT), treatment response evaluation, and clinical decision-making. However, manual tumor delineation remains laborious and challenging due to radiological complexity. The objective of this study was to investigate the feasibility of the HD-GLIO tool, an ensemble of pre-trained deep learning models based on the nnUNet-algorithm, for tumor segmentation, response prediction, and its potential for clinical deployment. Methods We analyzed the predicted contrast-enhanced (CE) and non-enhancing (NE) HD-GLIO output in 49 multi-parametric MRI examinations from 23 grade-4 glioma patients. The volumes were retrospectively compared to corresponding manual delineations by 2 independent operators, before prospectively testing the feasibility of clinical deployment of HD-GLIO-output to a RT setting. Results For CE, median Dice scores were 0.81 (95% CI 0.71–0.83) and 0.82 (95% CI 0.74–0.84) for operator-1 and operator-2, respectively. For NE, median Dice scores were 0.65 (95% CI 0.56–0,69) and 0.63 (95% CI 0.57–0.67), respectively. Comparing volume sizes, we found excellent intra-class correlation coefficients of 0.90 (P .01) for non-responders, and 0.80 (P = .05) for intermediate/mixed responders. Conclusions HD-GLIO was feasible for RT target delineation and MRI tumor volume assessment. CE/NE tumor-compartment growth correlation showed potential to predict clinical response to treatment.publishedVersio

Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study

Background Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes. Methods Ten patients received intravenous BTZ 1.3 mg/m2 on days 1, 4, and 7 during each 4th weekly TMZ‐chemotherapy starting on day 3 and escalated from 150 mg/m2 per oral 5 days/wk via 175 to 200 mg/m2 in cycles 1, 2, and 3, respectively. Adverse events and quality of life were evaluated by CTCAE and EQ‐5D‐5L questionnaire, and immunological biomarkers evaluated by flow cytometry and Luminex enzyme‐linked immunosorbent assay. Results Sequential BTZ + TMZ therapy was safe and well tolerated. Pain and performance of daily activities had greatest impact on patients' self‐reported quality of life and were inversely correlated with Karnofsky performance status. Patients segregated a priori into three groups, where group 1 displayed stable clinical symptoms and/or slower magnetic resonance imaging radiological progression, expanded CD4+ effector T‐cells that attenuated cytotoxic T‐lymphocyte associated protein‐4 and PD‐1 expression and secreted interferon γ and tumor necrosis factor α in situ and ex vivo upon stimulation with PMA/ionomycin. In contrast, rapidly progressing group 2 patients exhibited tolerised T‐cell phenotypes characterized by fourfold to sixfold higher interleukin 4 (IL‐4) and IL‐10 Th‐2 cytokines after BTZ + TMZ treatment, where group 3 patients exhibited intermediate clinical/radiological responses. Conclusion Sequential BTZ + TMZ treatment is safe and promotes Th1‐driven immunological responses in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)).publishedVersio

Clinical characteristics of patients seeking treatment for common mental disorders presenting with workplace bullying experiences

Background: Targets of workplace bullying tend to develop severe mental health complaints, having increased risk of sick leave and expulsion from the workplace. Hence, these individuals are likely to be overrepresented among patients seeking treatment for common mental disorders (CMD). This study investigated the prevalence of exposure to workplace bullying in a patient group seeking treatment for CMD. Further we explored if exposed and non-exposed patients differed on clinical and work-related characteristics. Methods: The sample comprised of 675 patients from an outpatient clinic in Norway and consisted of 70% women and had a mean age of 39 (SD = 10.5) years. The study had a cross-sectional design and differences between the patient groups were analysed using chi-square, Mann–Whitney U-tests and independent sample t-tests. Results: The prevalence of exposure to bullying was 25.8%. The patients exposed to bullying reported significantly more major depressive disorders (MDDs) measured with the MINI psychiatric interview, higher levels of depressive symptoms, anxiety symptoms, subjective health complaints, alcohol use, and lower resilience as measured with questionnaires. Twice as many were on full-time sick leave, reported lower work ability, lower return to work self-efficacy, and lower job satisfaction. A majority preferred another job than the one they have today over returning to their current employment. Conclusion: Victims of workplace bullying are a vulnerable group at risk of expulsion from working life, being overrepresented among patients seeking mental health treatment for CMD. One in four patients represented with such experience have higher levels of psychological symptoms and are more often diagnosed with depression as compared to other patients. Thus, this is a problem that should be addressed in clinical settings. If not addressed there is an increased risk of sick leave and permanent exclusion from working life.publishedVersio