| 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. |
- Colleoni, Marco, et al.
(författare)
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Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
- 2018
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Ingår i: The Lancet. Oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 19:1, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.Novartis and the International Breast Cancer Study Group.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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. - : American Society of Clinical Oncology. - 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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| 7. |
- 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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| 8. |
- 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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| 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
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- Joona, Therse Björkin, et al.
(författare)
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Influenza vaccination in breast cancer patients during subcutaneous trastuzumab in adjuvant setting
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 184:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting.Methods: A prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured.Results: Twenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%,pvalue = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination.Conclusion: Breast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.
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| 13. |
- Kamposioras, Konstantinos, et al.
(författare)
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Synthesis of Recommendations From 25 Countries and 31 Oncology Societies : How to Navigate Through Covid-19 Labyrinth
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers. - 2234-943X. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak.Methods: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies.Results: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis.Conclusions: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.
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| 14. |
- Karakatsanis, Andreas, et al.
(författare)
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Axillary evaluation in ductal cancer in situ of the breast: challenging the diagnostic accuracy of clinical practice guidelines
- 2021
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 108:9, s. 1120-1125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Staging of the axilla is not routine in ductal cancer in situ (DCIS) although invasive cancer is observed in 20-25 per cent of patients at final pathology. Upfront sentinel lymph node dissection (SLND) is advocated in clinical practice guidelines in certain situations. These include expected challenges in subsequent SLN detection and when the risk for invasion is high. Clinical practice guidelines are, however, inconsistent and lead to considerable practice variability. Methods: Clinical practice guidelines for upfront SLND in DCIS were identified and applied to patients included in the prospective SentiNot study. These patients were evaluated by six independent, blinded raters. Agreement statistics were performed to assess agreement and concordance. Receiver operating characteristic curves were constructed, to assess guideline accuracy in identifying patients with underlying invasion. Results: Eight guidelines with relevant recommendations were identified. Interobserver agreement varied greatly (kappa: 0.23-0.9) and the interpretation as to whether SLND should be performed ranged from 40-90 per cent and with varying concordance (32-88 per cent). The diagnostic accuracy was low with area under the curve ranging from 0.45 to 0.55. Fifty to 90 per cent of patients with pure DCIS would undergo unnecessary SLNB, whereas 10-50 per cent of patients with invasion were not identified as 'high risk'. Agreement across guidelines was low (kappa=0.24), meaning that different patients had a similar risk of being treated inaccurately. Conclusion: Available guidelines are inaccurate in identifying patients with DCIS who would benefit from upfront SLNB. Guideline refinement with detailed preoperative work-up and novel techniques for SLND identification could address this challenge and avoid overtreatment.
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| 15. |
- Karakatsanis, Andreas, et al.
(författare)
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Axillary Staging in the Setting of a Preoperative Diagnosis of Ductal Cancer In Situ (DCIS) : Results of an International Expert Panel and a Critical Guideline Performance Using Frequentist and Bayesian Analysis
- 2020
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 27:Suppl. 2, s. S337-S338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB.Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion.Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB in 41.3/61.4%, whereas individual rates ranged from 11 to 100%. Agreement among panelists was low (kappa=0.37). In multivariate regression analysis for the entire panel, type of surgery was the most common determinant, (simple WLE=less, OPBCS=more and Mx=constant for SLNB), followed by symptomatic diagnosis and DCIS size. Most (26) members had a clear decision-making pattern regarding SLND, based mainly on DCIS size and type of surgery. Individual decision-making performed modestly in identifying patients with underlying invasion (AUC range 0,47-0,59), resulting mainly in overtreatment in 44-77% of patients. The panel performed similarly by majority (AUC 0,5) and by consensus (AUC 0,55) but “undertreated” 60-75% of patients with invasion, failing to identify them as "high-risk." After the recognition of different decision-making patterns, panelists were divided in subgroups with similar decision-making pattern. Analysis identified subgroups with difference in SLNB rate but not with better AUC. The disagreement among panelists in the same subgroups was significant, not only regarding which patients should undergo SLNB, but also on what factors that recommendation was based on. Eight guidelines with relevant recommendations were identified [USA (ASCO/NCCN), Europe (ESMO), Sweden, Denmark, UK, Netherlands and Italy, retrieval date May 2019]. Agreement among raters for each guideline separately varied (kappa: 0.23-0.9). Interpretation as to whether SLNB should be performed ranged widely (40-90%) and with varying concordance (32-88%). No guideline demonstrated accuracy (AUC range 0.45-0.55). Overtreatment risk was high (50-90%), whereas 10-50% of patients with invasion were not identified as “high- risk.” Agreement across guidelines was low (kappa=0.24), meaning that different patients had similar risk to be treated inaccurately, regardless of which guideline was examined.Conclusions: Individualized decision-making and guideline interpretation may be highly subjective and with low accuracy in terms of prediction of invasive disease, resulting in almost random risk for over- or undertreatment of the axilla in patients with DCIS. This suggests that current views and guidelines should be challenged. More accurate preoperative workup and novel techniques to allow for delayed SLNB may be of value in this setting.
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| 16. |
- Karihtala, Peeter, et al.
(författare)
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Clinical trials in older patients with cancer : typical challenges, possible solutions, and a paradigm of study design in breast cancer
- 2024
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 63, s. 441-447
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND AND PURPOSE: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial.PATIENTS AND METHODS: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial. RESULTS: The recognized barriers can be roughly divided into trial design-related (e.g. the adoption of strict inclusion criteria, the lack of pre-specified age-specific analysis), patient-related (e.g. lack of knowledge, valuation of the quality-of-life instead of survival, transportation issues), or physician-related (e.g. concern for toxicity). Several strategies to mitigate barriers have been identified and should be considered when designing a clinical trial dedicated to older patients with cancer. The pragmatic, de-centralized IMPORTANT trial focusing on dose optimization of CDK4/6 -inhibitors in older breast cancer patients is a paradigm of a study design where different mitigating strategies have been adopted.INTERPRETATION: Because of the existing barriers, older adults in clinical trials are considerably healthier than the average older patients treated in clinical practice. Thus, the study results cannot be generalized to the older population seen in daily clinical practice. Broader inclusion/exclusion criteria, offering telehealth visits, and inclusion of patient-reported, instead of physician-reported outcomes may increase older patient participation in clinical trials.
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| 17. |
- Karihtala, Peeter, et al.
(författare)
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Clinical trials in older patients with cancer - typical challenges, possible solutions, and a paradigm of study design in breast cancer
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63:1, s. 441-447
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Forskningsöversikt (refereegranskat)abstract
- Background and purpose: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial.Patients and methods: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial.Results: The recognized barriers can be roughly divided into trial design -related (e.g . the adoption of strict inclusion criteria, the lack of pre-specified age-specific analysis), patient-related (e.g . lack of knowledge, valuation of the quality-of-life instead of survival, transportation issues), or physician-related (e.g . concern for toxicity). Several strategies to mitigate barriers have been identified and should be considered when designing a clinical trial dedicated to older patients with cancer. The pragmatic, de-centralized IMPORTANT trial focusing on dose optimization of CDK4/6 -inhibitors in older breast cancer patients is a paradigm of a study design where different mitigating strategies have been adopted.Interpretation: Because of the existing barriers, older adults in clinical trials are considerably healthier than the average older patients treated in clinical practice. Thus, the study results cannot be generalized to the older population seen in daily clinical practice. Broader inclusion/exclusion criteria, offering telehealth visits, and inclusion of patient -reported, instead of physician -reported outcomes may increase older patient participation in clinical trials.
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| 18. |
- Kofteridis, Diamantis P., et al.
(författare)
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Factors Influencing Non-albicans Candidemia : A Case-Case-Control Study
- 2017
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Ingår i: Mycopathologia. - : Kluwer Academic Publishers. - 0301-486X .- 1573-0832. ; 182:7-8, s. 665-672
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Tidskriftsartikel (refereegranskat)abstract
- The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.
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| 19. |
- Kofteridis, Diamantis P., et al.
(författare)
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Treatment pattern, prognostic factors, and outcome in patients with infection due to pan-drug-resistant gram-negative bacteria
- 2020
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 39:5, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.
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| 20. |
- Kornalijnslijper-Altena, Renske, et al.
(författare)
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PREDIX II HER2 : Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC)
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:15 Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy.Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007.
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| 21. |
- Lampropoulos, Konstantinos, et al.
(författare)
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ASCAPE : An open AI ecosystem to support the quality of life of cancer patients
- 2021
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Ingår i: 2021 IEEE 9th International Conference on Healthcare Informatics (ICHI). - : IEEE Computer Society. - 9781665401326 - 9781665429801 ; , s. 301-310
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Konferensbidrag (refereegranskat)abstract
- The latest cancer statistics indicate a decrease in cancer-related mortality. However, due to the growing and ageing population, the absolute number of people living with cancer is set to keep increasing. This paper presents ASCAPE, an open AI infrastructure that takes advantage of the recent advances in Artificial Intelligence (AI) and Machine Learning (ML) to support cancer patients' quality of life (QoL). With ASCAPE health stakeholders (e.g. hospitals) can locally process their private medical data and then share the produced knowledge (ML models) through the open AI infrastructure.
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| 22. |
- Matikas, Alexios, et al.
(författare)
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PD-1 protein and gene expression as prognostic factors in early breast cancer
- 2020
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Ingår i: ESMO Open. - : BMJ Publishing Group Ltd. - 2059-7029. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study's aim was to comprehensively investigate it.Methods: The study consisted of three parts: a correlative analysis of PD-1 protein and gene expression from an original patient cohort of 564 patients with early BC; a systematic review and trial-level meta-analysis on the association between PD-1 protein expression and disease-free survival/overall survival (OS) in early BC; and a pooled gene expression analysis from publicly available transcriptomic datasets regarding PDCD1 expression.Results: In the study cohort, PD-1 protein, but not gene expression, was associated with improved OS (HRadj=0.73, 95% CI 0.55 to 0.97, p=0.027 and HRadj=0.88, 95% CI 0.68 to 1.13, p=0.312, respectively). In the trial-level meta-analysis, PD-1 protein expression was not found to be statistically significantly associated with outcomes in the overall population. Finally, in the pooled gene expression analysis, higher PDCD1 expression was associated with better OS in multivariable analysis in the entire population (HRadj=0.89, 95% CI 0.80 to 0.99, p=0.025) and in basal-like tumours.Conclusions: PD-1 protein and gene expression seem to be promising prognostic factors in early BC. Standardisation of detection and assessment methods is of utmost importance.
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| 23. |
- Matikas, Alexios, et al.
(författare)
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Prognostic implications of PD-L1 expression in breast cancer : systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data
- 2019
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 25:18, s. 5717-5726
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer.EXPERIMENTAL DESIGN: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells or both, per subtype and per antibody used; and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed.RESULTS: Of the initial 4184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI 15 - 33%) in tumor cells and 33% (95% CI 14 - 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR = 1.63; 95% CI 1.07 - 2.46, p=0.02); there was significant heterogeneity (I2 = 80%, pheterogeneity<0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR=0.82, 95% CI 0.74 - 0.90, p<0.001 for OS) and in basal-like tumors (HR=0.64, 95% CI 0.52 - 0.80, p<0.001 for OS), pinteraction 0.005.CONCLUSION: The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like BC. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.
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| 24. |
- Mauri, Davide, et al.
(författare)
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Behind the numbers and the panic of a viral pandemic : fixed restrictive oncology guidance may jeopardize patients' survival
- 2020
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Ingår i: Balkan Union of Oncology. Journal. - : Zerbinis Publications. - 1107-0625. ; 25:3, s. 1277-1280
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Tidskriftsartikel (refereegranskat)abstract
- To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of tele-health services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits.Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening,follow-up and radical surgeries increase patients' risk of developing metastatic disease.A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients' outcomes.A present international oncologists' panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.
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| 25. |
- Mauri, Davide, et al.
(författare)
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Cancer pain ... who cares? : International and national patterns of evidence-based global guide-lines recommendations for physicians on the Web (2011 vs. 2018)
- 2020
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Ingår i: Journal of B.U.ON. (JBUON). - 1107-0625 .- 2241-6293. ; 25:1, s. 62-73
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although pain is a common event during treatment of cancer, its assessment and management remains suboptimal in everyday clinical practice at global level.Methods: Considering both the important role of Internet in daily life and that clinical guidelines are important for translating evidence in clinical practice, we performed a prospective study to scrutinize the magnitude of updated evidence-based cancer-pain guideline recommendation for physicians on the web. Changes over-time at a global level were scrutinized at two time points: 2011 for baseline and 2018 at first follow-up. Both anesthesiology and oncology societies were analyzed.Results: In 2011 we scrutinized 181,00 WebPages and 370 eligible societies were identified; 364 of these were eligible for analyses both in 2011 and 2018. The magnitude of cancer pain updated and evidence-based guideline recommendations on the web for health care providers was extremely low at global level and at any time point considered 1.1% (4/364) in 2011 and 4.7% (17364) in 2018. Continental and intercontinental patterns, National's highest developmental index, oncology tradition and economic-geographic areas were not found to influence cancer pain web-guideline provision. In 2018, pain & supportive care societies provided the highest rate of updated evidence-based cancer-pain guidelines for clinicians. Only 3/25 medical oncology societies and 1/34 radiation oncology societies, provided own or e-link (to other societies) evidence-based guidelines in their websites.Conclusions: Major medical oncology and radiation oncology societies - at global level - fail to produce updated cancer pain recommendations for their physicians, with most of these providing no or inconsistent or outdated guidelines.
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