| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Mokhtary, Arezo, et al.
(författare)
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Mammographic Density Changes over Time and Breast Cancer Risk : A Systematic Review and Meta-Analysis
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:19
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Although mammographic density is strongly linked to the risk of breast cancer, research on the relationship between changes in density over time and the risk of breast cancer has shown conflicting results. We found in the present meta-analysis that increased breast density over time was associated with higher breast cancer risk whereas decreased breast density might be associated with lower breast cancer risk. The results of the meta-analysis constitute a potential opportunity for more individualized screening strategies based on the evolution of breast density during mammography screening. The aim of this meta-analysis was to evaluate the association between mammographic density changes over time and the risk of breast cancer. We performed a systematic literature review based on the PubMed and ISI Web of Knowledge databases. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for cohort studies or odds ratios (ORs) and 95% confidence interval using inverse variance method. Of the nine studies included, five were cohort studies that used HR as a measurement type for their statistical analysis and four were case-control or cohort studies that used OR as a measurement type. Increased breast density over time in cohort studies was associated with higher breast cancer risk (HR: 1.61; 95% CI: 1.33-1.96) whereas decreased breast density over time was associated with lower breast cancer risk (HR: 0.78; 95% CI: 0.71-0.87). Similarly, increased breast density over time was associated with higher breast cancer risk in studies presented ORs (pooled OR: 1.85; 95% CI: 1.29-2.65). Our findings imply that an increase in breast density over time seems to be linked to an increased risk of breast cancer, whereas a decrease in breast density over time seems to be linked to a lower risk of breast cancer.
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| 6. |
- Nikyar, Normehr, et al.
(författare)
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Adjuvant locoregional radiation therapy in breast cancer patients with pathologic complete response after neoadjuvant chemotherapy : A systematic review and meta-analysis
- 2022
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Ingår i: Clinical and translational radiation oncology. - : Elsevier. - 2405-6308. ; 33, s. 45-52
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Forskningsöversikt (refereegranskat)abstract
- Purpose: The aim of the present meta-analysis was to investigate the impact of adjuvant locoregional radiation therapy (LRRT) in breast cancer patients with clinical lymph node metastatic disease achieving ypN0 after neoadjuvant chemotherapy (NACT).Materials and methods: A systematic review of studies on PubMed was performed. A meta-analysis was conducted by computing extracted hazard ratios (HRs) and 95% confidence intervals (CIs) into a fixed-effects model.Results: Thirteen studies were included in the meta-analysis. Adjuvant LRRT significantly reduced the risk of locoregional recurrence (LRR) in patients with N+ at diagnosis and ypN0 (HR 0.59; 95% CI 0.42-0.81). However, no statistically significant difference on disease-free survival (DFS) or overall survival (OS) was found.Conclusions: LRRT significantly reduced the risk of LRR in patients with ypN0 after NACT whereas no impact on DFS or OS was observed. The low level of evidence should be considered when interpreting the results in clinical practice.
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| 7. |
- Paakkola, N.-M., et al.
(författare)
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The prognostic and predictive impact of low estrogen receptor expression in early breast cancer : a systematic review and meta-analysis
- 2021
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Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 6:6
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Traditionally, estrogen receptor (ER)-positive breast cancer has been defined as tumors with ≥1% positive for ER. The updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines recommend that tumors with ER expression of 1%-10% should be classified as ER-low-positive, recognizing the limited clinical evidence on the prognostic and predictive role of low ER expression. We aimed to investigate the predictive role of ER-low expression to neoadjuvant chemotherapy (NeoCT) and the prognostic significance of ER-low expressing breast tumors compared with ER-positive or ER-negative breast tumors.METHODS: A meta-analysis was conducted using the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines and eligible articles were identified on PubMed and ISI Web of Science databases. The primary outcome was pathologic complete response and secondary outcomes were disease-free survival (DFS) and overall survival (OS). Twelve retrospective cohort studies were included in the meta-analysis. NeoCT resulted in higher pathologic complete response among patients with ER-low expression compared with ER-positive and comparable to ER-negative. Patients with ER-low breast cancer had a statistically significant worse DFS and OS compared with patients with ER-positive breast cancer, whereas no difference in DFS or OS was observed between ER-low and ER-negative subgroups.DISCUSSION: The current evidence suggests that ER-low breast cancer has a more similar outcome to ER-negative than to ER-positive breast cancer in terms of DFS and OS. ER-low expression seems also to have a predictive role regarding NeoCT. Considering the certainty of current evidence categorized as low to moderate, our results urge the need for well-designed prospective studies investigating the molecular background and the most appropriate treatment strategy for ER-low expressing breast cancer.
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| 8. |
- Smith, Daniel, et al.
(författare)
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Yield of Surveillance Imaging After Mastectomy With or Without Reconstruction for Patients With Prior Breast Cancer : A Systematic Review and Meta-analysis
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:12
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Forskningsöversikt (refereegranskat)abstract
- IMPORTANCE: A discrepancy on current guidelines and clinical practice exists regarding routine imaging surveillance after mastectomy, mainly regarding the lack of adequate evidence for imaging in this setting.OBJECTIVE: To investigate the usefulness of imaging surveillance in terms of cancer detection and interval cancer rates after mastectomy with or without reconstruction for patients with prior breast cancer.DATA SOURCES: A comprehensive literature search was conducted in 3 electronic databases-PubMed, ISI Web of Science, and Scopus-without year restriction. References from relevant reviews and eligible studies were also manually searched.STUDY SELECTION: Eligible studies were defined as those conducting surveillance imaging (mammography, ultrasonography, or magnetic resonance imaging [MRI]) of patients with prior breast cancer after mastectomy with or without reconstruction that presented adequate data to calculate cancer detection rates for each surveillance method. DATAEXTRACTION AND SYNTHESIS: Independent data extraction by 2 investigators with consensus on discrepant results was performed. A quality assessment of studies was performed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) template. The generalized linear mixed model framework with both fixed-effects and random-effects models was used to meta-analyze the proportion of cases across studies including 3 variables: surveillance method, reconstruction after mastectomy, and surveillance measure.MAIN OUTCOMES AND MEASURES: Three outcome measures were calculated for each eligible study and each surveillance imaging method within studies: overall cancer detection (defined as ipsilateral cancer, both palpable and nonpalpable) rate per 1000 examinations, clinically occult (nonpalpable) cancer detection rate per 1000 examinations, and interval cancer rate per 1000 examinations.RESULTS: In total, 16 studies were eligible for the meta-analysis. The pooled overall cancer detection rates per 1000 examinations were 1.86 (95% CI, 1.05-3.30) for mammography, 2.66 (95% CI, 1.48-4.76) for ultrasonography, and 5.17 (95% CI, 1.49-17.75) for MRI. For mastectomy without reconstruction, the rate of clinically occult (nonpalpable) cancer per 1000 examinations (2.96; 95% CI, 1.38-6.32) and the interval cancer rate per 1000 examinations (3.73; 95% CI, 0.84-3.98) were lower than the overall cancer detection rate (including both palpable and nonpalpable lesions) per 1000 examinations (6.41; 95% CI, 3.09-13.25) across all imaging modalities. The interval cancer rate per 1000 examinations for mastectomy with reconstruction (3.73; 95% CI, 0.41-2.73) was comparable to the pooled cancer detection rate per 1000 examinations (4.73; 95% CI, 2.32-9.63) across all imaging modalities. In all clinical scenarios and imaging modalities, lower rates of clinically occult cancer compared with cancer detection rates were observed.CONCLUSIONS AND RELEVANCE: Lower detection rates of clinically occult-compared with overall-cancer across all 3 imaging modalities challenge the use of imaging surveillance after mastectomy, with or without reconstruction. Findings suggest that imaging surveillance in this context is unnecessary in clinical practice, at least until further studies demonstrate otherwise. Future studies should consider using the clinically occult cancer detection rate as a more clinically relevant measure in this setting.
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| 9. |
- Tollan, Clare Josephine, et al.
(författare)
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A Systematic Review and Meta-Analysis on the Role of Repeat Breast-Conserving Surgery for the Management of Ipsilateral Breast Cancer Recurrence
- 2022
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 29:10, s. 6440-6453
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Forskningsöversikt (refereegranskat)abstract
- Introduction: The standard surgical management of ipsilateral breast cancer recurrence (IBCR) in patients previously treated with breast-conserving surgery (BCS) and radiotherapy (RT) is mastectomy. Recent international guidelines provide conflicting recommendations. The aim of this study was to perform a systematic literature review and meta-analysis of the oncological outcomes in patients with IBCR treated with repeat BCS (rBCS).Methods: The MEDLINE and EMBASE databases were searched for relevant English-language publications, with no date restrictions. All relevant studies providing sufficient data to assess oncological outcomes (second local recurrence [LR] and overall survival [OS]) of rBCS for the management of IBCR after previous BCS and RT were included (PROSPERO registration CRD42021286123).Results: Forty-two observational studies met the criteria and were included in the analysis. The pooled second LR rate after rBCS was 15.7% (95% confidence interval [CI] 12.1-19.7), and 10.3% (95% CI 6.9-14.3) after salvage mastectomy. On meta-analysis of comparative studies (n = 17), the risk ratio (RR) for second LR following rBCS compared with mastectomy was 2.103 (95% CI 1.535-2.883; p < 0.001, I-2 = 55.1%). Repeat RT had a protective effect (coefficient: - 0.317, 95% CI - 0.596 to - 0.038; p = 0.026, I-2 = 40.4%) for second LR. Pooled 5-year OS was 86.8% (95% CI 83.4-90.0) and 79.8% (95% CI 74.7-84.5) for rBCS and salvage mastectomy, respectively. Meta-analysis of comparative studies (n = 20) showed a small OS benefit in favor of rBCS (RR 1.040, 95% CI 1.003-1.079; p = 0.032, I-2 = 70.8%). Overall evidence certainty was very low.Conclusions: This meta-analysis suggests rBCS could be considered as an option for the management of IBCR in patients previously treated with BCS and RT. Shared decision making, appropriate patient selection, and individualized approach are important for optimal outcomes.
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| 10. |
- Valachis, Antonis, 1984-, et al.
(författare)
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Discrepancy in BRAF status among patients with metastatic malignant melanoma : A meta-analysis
- 2017
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 81, s. 106-115
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Forskningsöversikt (refereegranskat)abstract
- The incidence of malignant melanoma is growing rapidly. Approximately half of the cases are BRAF mutated, making treatment with kinase inhibitors a (MEK and BRAF inhibitors) preferred choice in the advanced setting. The vast majority of these patients will benefit from the treatment. It is therefore of vital importance that the BRAF analysis is reliable and reflects the true nature of the tumour. Intraindividual tumour BRAF heterogeneity may exist, and changes of BRAF status over time might occur. We reviewed the literature by searching the PubMed database and 630 potentially relevant studies were identified. Thereafter, studies that investigated intralesional heterogeneity only, studies with ≤10 patients and studies that did not include adequate data to calculate discrepancy rates were excluded. Twenty-two studies met our inclusion criteria and were included in the meta-analysis. The pooled discrepancy rate between primary and metastatic lesions was 13.4% (95% confidence interval [CI]: 9.2-18.2%) while it was 7.3% (95% CI: 3.3-12.6) between two metastatic lesions. The number of patients whose tumoural BRAF status was changed from mutation to wild type and from wild type to mutation, respectively, was comparable. We conclude that a clinically meaningful discrepancy rate in BRAF status both between primary-metastatic and metastatic-metastatic melanoma lesions exists. Our results support the polyclonal model of melanomas in which subclones with different BRAF status co-exist in the same melanoma lesion. In addition, the results indicate a need for biopsy of a metastatic lesion for subsequent BRAF analysis when treatment with kinase inhibitors is considered.
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