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- Matikas, A., et al.
(författare)
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Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
- 2021
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Ingår i: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r= 0.814), but not with the diagnostic samples (r= 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P= 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj= 0.50, 95% CI 0.26-0.97, P= 0.04) and OS (HRadj= 0.46, 95% CI 0.95, P= 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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| 3. |
- Chretien, S, et al.
(författare)
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Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to the inhibition of two immune checkpoints, Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4). Consistent with the complexity of the regulation of the tumor – host interactions and their lack of reliance on a single regulatory pathway, combinatory approaches have shown improved efficacy albeit at the cost of increased toxicity. Beyond those two checkpoints though, a large number of co-stimulatory or co-inhibitory molecules play major roles on tumor evasion from immunosurveillance. These molecules likely represent future targets of immunotherapy provided that the promise shown in early data is translated into improved patient survival in randomized trials. The biological role, prognostic and predictive implications regarding breast cancer and early clinical efforts on exploiting these immune-related therapeutic targets are herein reviewed.
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| 6. |
- Hatschek, T., et al.
(författare)
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PREDIX HER2 trial : Event-free survival and pathologic complete response in clinical subgroups and stromal TILs levels
- 2020
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 31:Suppl. 2, s. S49-S49
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neoadjuvant treatment with Trastuzumab-emtansine was associated with similar rates of pathological complete remission (pCR) as standard therapy withd ocetaxel, trastuzumab and pertuzumab in the PREDIX HER2 trial. Here, results of event-free survival (EFS), and pCR rates in key clinical-pathological subgroups and biomarkers including the abundance of stromal tumor infiltrating lymphocytes (TILs) are presented.Methods: PREDIX HER2 is a randomized, multicenter, open-label, phase 2 study involving 9 Swedish sites. Patients with HER2 positive breast cancer, verified by ISH, T>20 mm and/or verified lymph node metastases were randomized to six three-weekly courses of either docetaxel, trastuzumab SC and pertuzumab (group A), or trastuzumab emtansine (T-DM1, group B). Switch of treatment to the opposite arm was allowed in case of lack of response or severe toxicity. Radiological evaluation included 18F-FDG PET/CT. Patients in both groups received adjuvant chemotherapy with epirubicin and cyclophosphamide. TILs were evaluated using standard methodology, median 10%.Results: In total 197 pts. were evaluable, 99 in group A, and 98 in group B. pCR (ypT0/is ypN0) was achieved in 90 pts, 45.7%, with no significant difference between the two treatment groups. pCR rates were lower in the group of patients with hormone receptor (HR)epositive compared with HR-negative tumors but similar in both treatment groups. pCR rates did not differ between the two treatments in subgroups defined by age, menopausal status, tumor grade, T size, node status, HR-status, HER2 status and Ki67. Progressive disease was observed in 3 pts. (3%) during treatment with T-DM1, none in group A. After a median follow-up of 2.4 years 13 EFS events occurred, with no significant differences between the treatment groups. The presence of 10% TILs predicted pCR significantly (p¼0.009), similar in both treatment groups. We also found that a decrease of SUVmax by more than 80% was highly predictive of pCR. HRQoL was significantly better in pts. receiving T-DM1.Conclusions: Our data suggest that neoadjuvant T-DM1 may be as effective as standard neoadjuvant treatment in all clinical subgroups evaluated. Both TILs and PET/CT showed potential to predict pCR.Clinical trial identification: NCT02568839.
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| 9. |
- Pellat, A., et al.
(författare)
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Comprehensive mapping review of real-world evidence publications focusing on targeted therapies in solid tumors : A collaborative work from ESMO real-world data and Digital Health Working Group
- 2023
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 34:Suppl. 2, s. S925-S925
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: A growing body of real-world evidence (RWE) aims to better reflect outcomes of cancer patients treated in real-world settings. We aimed to conduct a first comprehensive mapping review of the RWE produced over the past 3 years in terms of tumor type, treatment strategies, setting, and data sources, focusing on targeted therapies (TT) in solid tumors.Methods: We conducted a systematic review in PubMed of RWE studies published between 01/2020 and 12/2022. We identified non-interventional studies using observational data, focusing on solid tumors exposure to targeted therapies, excluding immunotherapies. Abstract and full-text screening were performed by 11 independent reviewers.Results: A total of 7,774 publications were retrieved with 1,251 considered eligible and extracted. The number of publications per year progressively increased during this period (328 in 2020; 421 in 2021; 502 in 2022). Most studies (50%) were performed in Asia, followed by Europe (25%) and North America (17%). Only 8% of studies had patients treated in more than one country. Treatment effectiveness and safety were assessed in 71% and 42% of studies respectively. Main data sources were medical records.Conclusions: RWE publications on TT for solid tumors are heterogeneous and mostly rely on retrospective data such as medical records. Population-based and international studies are rare. Collaborative efforts towards international representativeness and the use of routinely collected and/or standardized data sources must be encouraged to increase the relevance and future quality of publications and their potential impact on oncology practice.
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