| 1. |
- Boman, Caroline, et al.
(författare)
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Discordance of PD-L1 status between primary and metastatic breast cancer : A systematic review and meta-analysis
- 2021
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Ingår i: Cancer Treatment Reviews. - : Elsevier. - 0305-7372 .- 1532-1967. ; 99
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.METHODS: Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.RESULTS: Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001).CONCLUSION: The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
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| 2. |
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| 3. |
- Digkas, Evangelos, et al.
(författare)
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Incidence and risk factors of hypothyroidism after treatment for early breast cancer : a population-based cohort study
- 2024
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Ingår i: Breast Cancer Research and Treatment. - : Kluwer Academic Publishers. - 0167-6806 .- 1573-7217. ; 204, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: An increased incidence of hypothyroidism among breast cancer survivors has been observed in earlier studies. The impact of the postoperative treatment modalities and their potential interplay on hypothyroidism development needs to be studied.METHODS: We conducted a population- and registry-based study using the Breast Cancer Data Base Sweden (BCBaSe) including females diagnosed with breast cancer between 2006 and 2012. In total, 21,268 female patients diagnosed with early breast cancer between 2006 and 2012, with no previous prescription of thyroid hormones and no malignant diagnosis during the last ten years before breast cancer diagnosis, were included in the final analysis.RESULTS: During the follow-up (median follow-up time 7.9 years), 1212 patients (5.7%) developed hypothyroidism at a median time of 3.45 years from the index date. No association of the systemic oncological treatment in terms of either chemotherapy or endocrine therapy and hypothyroidism development could be identified. A higher risk (HR 1.68;95% CI 1.42-1.99) of hypothyroidism identified among patients treated with radiation treatment of the regional lymph nodes whereas no increased risk in patients treated only with radiation therapy to the breast/chest wall was found (HR 1.01; 95% CI 0.86-1.19). The risk of hypothyroidism in the cohort treated with radiotherapy of the regional lymph nodes was present irrespective of the use of adjuvant chemotherapy treatment.CONCLUSIONS: Based on the results of our study, the implementation of hypothyroidism surveillance among the breast cancer survivors treated with radiotherapy of the regional lymph nodes can be considered as reasonable in the follow-up program.
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| 4. |
- Digkas, Evangelos, et al.
(författare)
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Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma : A Meta-analysis
- 2022
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Ingår i: Targeted oncology. - : Springer. - 1776-2596 .- 1776-260X. ; 17:5, s. 507-515
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown.OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma.PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared.RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed.CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.
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| 5. |
- Frid, Santiago, et al.
(författare)
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Mapping the Evidence on the Impact of mHealth Interventions on Patient-Reported Outcomes in Patients With Breast Cancer : A Systematic Review
- 2024
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Ingår i: JCO clinical cancer informatics. - 2473-4276. ; 8
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: To comprehensively synthesize the existing evidence concerning mHealth interventions for patients with breast cancer (BC).DESIGN: On July 30, 2023, we searched PubMed, PsycINFO, and Google Scholar for articles using the following inclusion criteria: evaluation of mHealth interventions in patients with cancer, at least 30 participants with BC, randomized control trials or prospective pre-post studies, determinants of health (patient-reported outcomes [PROs] and quality of life [QoL]) as primary outcomes, interventions lasting at least 8 weeks, publication after January 2015. Publications were excluded if they evaluated telehealth or used web-based software for desktop devices only. The quality of the included studies was analyzed with the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies.RESULTS: We included 30 studies (20 focused on BC), encompassing 5,691 patients with cancer (median 113, IQR, 135.5). Among these, 3,606 had BC (median 99, IQR, 75). All studies contained multiple interventions, including physical activity, tailored information for self-management of the disease, and symptom tracker. Interventions showed better results on self-efficacy (3/3), QoL (10/14), and physical activity (5/7). Lifestyle programs (3/3), expert consulting (4/4), and tailored information (10/11) yielded the best results. Apps with interactive support had a higher rate of positive findings, while interventions targeted to survivors showed worse results. mHealth tools were not available to the public in most of the studies (17/30).CONCLUSION: mHealth interventions yielded heterogeneous results on different outcomes. Identifying lack of evidence on clinical scenarios (eg, patients undergoing systemic therapy other than chemotherapy) could aid in refining strategic planning for forthcoming research endeavors within this field.
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| 6. |
- Ilić, Mihailo, et al.
(författare)
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Towards optimal learning : Investigating the impact of different model updating strategies in federated learning
- 2024
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Ingår i: Expert systems with applications. - : Elsevier. - 0957-4174 .- 1873-6793. ; 249:Part A
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Tidskriftsartikel (refereegranskat)abstract
- With rising data security concerns, privacy preserving machine learning (ML) methods have become a key research topic. Federated learning (FL) is one such approach which has gained a lot of attention recently as it offers greater data security in ML tasks. Substantial research has already been done on different aggregation methods, personalized FL algorithms etc. However, insufficient work has been done to identify the effects different model update strategies (concurrent FL, incremental FL, etc.) have on federated model performance. This paper presents results of extensive FL simulations run on multiple datasets with different conditions in order to determine the efficiency of 4 different FL model update strategies: concurrent, semi -concurrent, incremental, and cyclic -incremental. We have found that incremental updating methods offer more reliable FL models in cases where data is distributed both evenly and unevenly between edge nodes, especially when the number of data samples across all edge nodes is small.
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| 7. |
- Isheden, G., et al.
(författare)
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SWEDISH NATIONWIDE REGISTER DATA AS A LOW-COST RESOURCE TO DETECT DRUG-REPURPOSING SIGNALS : A STUDY ON DE NOVO METASTATIC BREAST CANCER PATIENTS
- 2022
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Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 25:12 Suppl., s. S375-S375
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Electronic health records have recently been highlighted as a low-cost resource to accelerate cancer therapeutics by drug repurposing discovery (Wu et al., JCO Clinical Cancer Informatics 2019:3, 1-9). The aim of this study was to test this approach on Swedish nationwide register data focusing on breast cancer cases with distant metastasis at initial diagnosis (de novo mBC). To demonstrate the feasibility of this methodology we i) evaluated the nine drug candidates identified by Wu et al. on our dataset, ii) generated drug repurposing hypotheses based on prescription drugs given to patients during metastatic breast cancer diagnosis/treatment.Methods: Patients diagnosed with de novo mBC between 2010 and 2020 were identified in the Swedish Cancer Register. Data on prescription drug use was collected from the National Prescribed Drug Register and survival data was collected from the National Cause of Death Register. Based on a 6-month window from diagnosis, drug repurposing candidates were evaluated using Cox proportional hazards models.Results: A total of 2,106 de novo mBC patients were included. The nine drug candidates found by Wu et al. (Rosuvastatin, Simvastatin, Amlodipine, Tamsulosin, Metformin, Omeprazole, Warfarin, Lisinoprol and Metroprolol) were not found significant in our data. However, a total of seven other drug repurposing hy-potheses were generated, with a plausible biological rationale for at least five of them (Calcium + Vitamin D, Morphine, Furosemide, Salbutamol and Ipratropium bromide, and Fentanyl). The other two were vaginal gel and Fluoride mouthwash.Conclusions: This study shows that the Swedish National Health Data Registers may be leveraged as a low-cost data source to detect drug repurposing signals. While results need to be interpreted with caution to not confuse causal relationships, the hypotheses generated in our study show a model for discovering noncancer drug effects on overall survival.
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| 8. |
- Jafer, Fatema, et al.
(författare)
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Postmastectomy radiation therapy in breast cancer patients with micrometastatic disease in sentinel node dissection : A cohort study and meta-analysis
- 2024
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Ingår i: Clinical and translational radiation oncology. - : Elsevier. - 2405-6308. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The potential role of postmastectomy radiation therapy (PMRT) on prognosis in patients with T1-2 breast cancer and micrometastatic disease in sentinel lymph node dissection (SLND) has not yet been established. The aim of this study was to investigate the impact of PMRT on prognosis in patients with T1-2 breast cancer and micrometastatic in SLND.METHOD: A register- and population-based cohort was utilized by identifying eligible patients on the research database BcBase 3.0. Multivariate Cox regression models were applied for survival outcomes. In addition, a systematic literature review and meta-analysis including all relevant studies on this topic was performed.RESULTS: In total, 956 patients fulfilling the inclusion criteria were found through the BcBaSe 3.0 with 237 (25.0 %) receiving PMRT and 719 (75.0 %) not receiving PMRT. No statistically significant differences between the two patient groups in terms of neither breast cancer-specific (adjusted Hazard Ratio (HR): 0.49; 95 % Confidence Interval (CI): 0.14 - 1.73) nor overall survival (adjusted HR: 0.63; 95 % CI: 0.29 - 1.35) was found. In the pooled analyses after literature review, PMRT did not result in better breast cancer-specific (5 studies; pooled HR: 1.06; 95 % CI: 0.88-1.27; I2 = 1 %; low certainty of evidence) or overall survival (6 studies; pooled HR: 1.01; 95 % CI: 0.91-1.13; I2 = 10 %; low certainty of evidence).CONCLUSION: PMRT does not seem to impact survival in patients with T1 or T2 breast cancer with micrometastatic disease in SLND. Considering the low level of evidence and the relatively short follow-up of included studies, caution in interpreting the results into clinical practice is suggested.
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| 9. |
- Jafer, Fatema, et al.
(författare)
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Postmastectomy radiation therapy in breast cancer patients with micrometastatic disease in sentinel node dissection : A cohort study and meta-analysis
- 2024
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier. - 2405-6308. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- AimThe potential role of postmastectomy radiation therapy (PMRT) on prognosis in patients with T1-2 breast cancer and micrometastatic disease in sentinel lymph node dissection (SLND) has not yet been established. The aim of this study was to investigate the impact of PMRT on prognosis in patients with T1-2 breast cancer and micrometastatic in SLND.MethodA register- and population-based cohort was utilized by identifying eligible patients on the research database BcBase 3.0. Multivariate Cox regression models were applied for survival outcomes. In addition, a systematic literature review and meta-analysis including all relevant studies on this topic was performed.ResultsIn total, 956 patients fulfilling the inclusion criteria were found through the BcBaSe 3.0 with 237 (25.0 %) receiving PMRT and 719 (75.0 %) not receiving PMRT. No statistically significant differences between the two patient groups in terms of neither breast cancer-specific (adjusted Hazard Ratio (HR): 0.49; 95 % Confidence Interval (CI): 0.14 – 1.73) nor overall survival (adjusted HR: 0.63; 95 % CI: 0.29 – 1.35) was found. In the pooled analyses after literature review, PMRT did not result in better breast cancer-specific (5 studies; pooled HR: 1.06; 95 % CI: 0.88–1.27; I2 = 1 %; low certainty of evidence) or overall survival (6 studies; pooled HR: 1.01; 95 % CI: 0.91–1.13; I2 = 10 %; low certainty of evidence).ConclusionPMRT does not seem to impact survival in patients with T1 or T2 breast cancer with micrometastatic disease in SLND. Considering the low level of evidence and the relatively short follow-up of included studies, caution in interpreting the results into clinical practice is suggested.
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| 10. |
- Jonsson, Gabriel, et al.
(författare)
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Upfront Radiotherapy in Patients With Asymptomatic Incurable Rectal Cancer : A Retrospective Cohort Study
- 2020
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:10, s. 5853-5860
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: The optimal treatment sequencing for asymptomatic de novo metastatic rectal cancer is unclear. The aim of this study was to investigate the role of upfront radiotherapy, with or without chemotherapy on risk for local complications, in patients with asymptomatic advanced metastatic rectal cancer treated with palliative intention.PATIENTS AND METHODS: All patients with de novo metastatic rectal cancer diagnosed between January 2008 and December 2017 in two healthcare regions in Sweden (Örebro län, Sörmland) were identified and data were extracted from electronic medical records. Patients were divided into 3 groups based on treatment sequence: upfront radiotherapy, upfront chemotherapy, and only palliative surgery.RESULTS: In total, 102 patients were included in the study cohort, 30 patients in upfront radiotherapy group, 54 in upfront chemotherapy, and 18 in only palliative surgery group. Patients with only upfront CT [odds ratio (OR)= 5.10; 95% confidence interval (CI)=1.24-20.91, p=0.024] had a higher risk to suffer from a local complication compared to those who received upfront radiotherapy. Cause-specific Cox regression analysis among patients who received oncological therapy revealed that female patients [cause-specific hazard ratio (csHR)=3.61; 95% confidence interval (CI)=1.67-7.81] and upfront chemotherapy [csHR=1.85; 95% CI=1.11-3.77] were associated with increased cumulative incidence of local complication over time, whereas primary surgery with ostomy or stent with lower risk [csHR=0.45; 95% CI=0.21-0.99].CONCLUSION: Patients who received upfront radiotherapy, with or without chemotherapy, had fewer local complications due to primary tumor compared to patients who only received chemotherapy. This could indicate that radiotherapy to the primary tumor could be discussed with the patients as a first treatment option for asymptomatic metastatic rectal cancer to prevent local complications later during the disease.
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