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- Mattsson, Mattias
(författare)
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Chronic lymphocytic leukemia : Studies from genetics to epidemiology with focus on the impact of different treatments
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The progress in our understanding of the biology and pathophysiology of chronic lymphocytic leukemia (CLL), as well as the development of new treatments, necessitates additional research on; (i) the impact of different therapies within subgroups of CLL patients, (ii) solid epidemiological data on the prevalence of CLL and on comorbidities within the CLL population, and (iii) new means of prognostication, as the value of traditional prognostic markers is uncertain when applied to new treatments.In paper I we studied the efficacy of chemo(immuno)therapy in stereotyped subsets #1 and #2. We could demonstrate that the improvement in survival seen over time in CLL in general, was not observed in these two subgroups. This suggests that alternative treatment options should be explored in these patients, and that subset assignment can be used as a predictive tool.In paper II we could demonstrate a significant rise (56%) in the prevalence of CLL in Sweden from 2000 to 2015. We then developed a model to estimate the future prevalence of CLL. Applying this, we estimated a further increase in the absolute number of CLL patients with approximately 70% over the next 20 years, a rise with important health-economic impact.In paper III we showed that 32% of all CLL patients were diagnosed with at least one cardiovascular disease (CVD) within 10 years before diagnosis, as well as 37% before start of treatment. Of these, 81% had ≥3 concomitant CVD diagnoses. Within 5 years after start of treatment, an additional 28% of patients (without previous CVD) were diagnosed with a CVD. This is particularly important considering the known cardiovascular side-effects of BTK-inhibitors.In paper IV we studied clonal dynamics in 10 patients with high-risk CLL during treatment with ibrutinib, with a long-term clinical follow-up. Seven out of 10 displayed major clonal shifts and 5 of these experienced disease progression, which was not seen in the 3 patients without clonal shifts. We suggest further studies of clonal shifts as a new means of prognostication in patients treated with BTK-inhibitors.We conclude that; (i) CLL patients of subsets #1 and #2 do not benefit of “old” treatments and should be explored for alternatives, (ii) the prevalence in CLL is higher than previously described with an expected continuing rise, (iii) the burden of cardiovascular comorbidities in CLL is high, and (iv) the occurrence of clonal shifts during ibrutinib treatment suggests inferior outcome.
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| 2. |
- Berglund, Eva Caroline, et al.
(författare)
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A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias
- 2022
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
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| 3. |
- Cuppen, Edwin, et al.
(författare)
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Implementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care
- 2022
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Ingår i: JCO Precision Oncology. - : American Society of Clinical Oncology. - 2473-4284. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE The combination of whole-genome and transcriptome sequencing (WGTS) is expected to transformdiagnosis and treatment for patients with cancer. WGTS is a comprehensive precision diagnostic test that isstarting to replace the standard of care for oncology molecular testing in health care systems around the world;however, the implementation and widescale adoption of this best-in-class testing is lacking.METHODS Here, we address the barriers in integrating WGTS for cancer diagnostics and treatment selection andanswer questions regarding utility in different cancer types, cost-effectiveness and affordability, and otherpractical considerations for WGTS implementation.RESULTS We review the current studies implementing WGTS in health care systems and provide a synopsis of theclinical evidence and insights into practical considerations for WGTS implementation. We reflect on regulatory,costs, reimbursement, and incidental findings aspects of this test.CONCLUSION WGTS is an appropriate comprehensive clinical test for many tumor types and can replacemultiple, cascade testing approaches currently performed. Decreasing sequencing cost, increasing number ofclinically relevant aberrations and discovery of more complex biomarkers of treatment response, should pave theway for health care systems and laboratories in implementing WGTS into clinical practice, to transform diagnosisand treatment for patients with cancer.
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| 4. |
- Stenzinger, Albrecht, et al.
(författare)
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Trailblazing precision medicine in Europe : A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 84, s. 242-254
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Tidskriftsartikel (refereegranskat)abstract
- Over the last decades, rapid technological and scientific advances have led to a merge of molecular sciences and clinical medicine, resulting in a better understanding of disease mechanisms and the development of novel therapies that exploit specific molecular lesions or profiles driving disease. Precision oncology is here used as an example, illustrating the potential of precision/personalized medicine that also holds great promise in other medical fields. Real-world implementation can only be achieved by dedicated healthcare connected centers which amass and build up interdisciplinary expertise reflecting the complexity of precision medicine. Networks of such centers are ideally suited for a nation-wide outreach offering access to precision medicine to patients independent of their place of residence. Two of these multicentric initiatives, Genomic Medicine Sweden (GMS) and the Centers for Personalized Medicine (ZPM) initiative in Germany have teamed up to present and share their views on core concepts, potentials, challenges, and future developments in precision medicine. Together with other initiatives worldwide, GMS and ZPM aim at providing a robust and sustainable framework, covering all components from technology development to clinical trials, ethical and legal aspects as well as involvement of all relevant stakeholders, including patients and policymakers in the field.
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