ORCID Profile
0000-0002-9614-6586
Current Organisation
Medizinische Hochschule Brandenburg - Theodor Fontane
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-07-2022
DOI: 10.1200/JCO.21.01536
Abstract: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young ( 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population–based registry. Patients were age 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs ( 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. sTILs were scored for 441 patients. High sTILs (≥ 75% 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs ( 30% 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ 2 = 46.7, P .001). Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2017
DOI: 10.1245/S10434-017-5803-9
Abstract: Data on isolated limb perfusion (ILP) in elderly melanoma patients are scarce. We aimed to evaluate the efficacy and safety of ILP in our institutional cohort of melanoma patients. We performed retrospective analysis of stage IIIB/C melanoma patients who underwent ILP for melanoma in-transit metastases (ITMs) in our institution between 2000 and 2016. Normothermic ILP was performed with either melphalan or melphalan and tumor necrosis factor. Baseline and treatment characteristics, locoregional progression-free survival (LPFS) and melanoma-specific survival (MSS) were assessed and prognostic factors for response, recurrence, and survival were analyzed using univariable and multivariable analysis. Overall, 91 patients were included in this study. Based on the median age of 70 years, we split patients into younger and elderly groups. No differences in response rates were observed between age groups, with an overall response rate of 81% and complete response (CR) rate of 47%. LPFS did not differ between age groups, and median LPFS was 16 months for patients with a CR. Median MSS was 38 months and differed between younger (45 months) and elderly patients (18 months). Toxicity was generally mild and did not differ between age groups. Two patients (2.2%) suffered Wieberdink IV toxicity, while no patients required utation because of severe toxicity. CR was prognostic for improved LPFS and MSS, while patients >70 years of age and patients with stage IIIC disease had a higher risk of melanoma-specific death. Because of its safety profile and high CR rates, ILP is a viable option for patients with bulky or multiple melanoma ITMs, including elderly (>70 years of age) patients.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2016
DOI: 10.1245/S10434-016-5396-8
Abstract: Locoregional treatment is often insufficient to guarantee long-term disease-free survival (DFS) in American Joint Committee on Cancer stage IIIB melanoma, and, in order to improve survival, effective neoadjuvant and adjuvant strategies are needed . Selecting patients for these strategies requires risk stratification, for which clinical and molecular biomarkers can be used. We aimed to detect clinical biomarkers to identify high-risk stage IIIB melanoma patients. We performed retrospective analysis of stage IIIB melanoma patients who underwent lymph node dissection (LND) in our institution between 2000 and 2015. Sentinel node-positive patients with ulcerated primary tumors, as well as patients with clinically detectable nodal metastasis with non-ulcerated tumors, were included. Baseline characteristics, melanoma-specific survival (MSS), and DFS were assessed, and prognostic factors for recurrence and survival were analyzed, using univariate and multivariate analysis. Overall, 250 patients were included. Median follow-up was 52 months (interquartile range 29-108 months), median MSS was 141 months, and median DFS was 36 months. Five- and 10-year MSS was 59 and 52 %, respectively, and 5- and 10-year DFS was 47 and 41 %, respectively. Age >50 years, Breslow thickness >2 versus ≤2 mm, and N2 versus N1 disease all carried an increased risk of death by melanoma. Age >50 years and extracapsular extension carried an increased risk of disease recurrence after LND. Age >50 years, Breslow thickness >2 mm and N2 versus N1 disease are prognostic factors for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and to help select the appropriate population for adjuvant therapy (trials).
Publisher: Oxford University Press (OUP)
Date: 05-07-2016
DOI: 10.1093/JNCI/DJW148
Abstract: Although BRCA1-deficient tumors are extremely sensitive to DNA-damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance to therapy remains a serious clinical problem. To study the underlying mechanisms, we induced therapy resistance in patient-derived xenograft (PDX) models of BRCA1-mutated and BRCA1-methylated triple-negative breast cancer. A cohort of 75 mice carrying BRCA1-deficient breast PDX tumors was treated with cisplatin, melphalan, nimustine, or olaparib, and treatment sensitivity was determined. In tumors that acquired therapy resistance, BRCA1 expression was investigated using quantitative real-time polymerase chain reaction and immunoblotting. Next-generation sequencing, methylation-specific multiplex ligation-dependent probe lification (MLPA) and Target Locus Amplification (TLA)-based sequencing were used to determine mechanisms of BRCA1 re-expression in therapy-resistant tumors. BRCA1 protein was not detected in therapy-sensitive tumors but was found in 31 out of 42 resistant cases. Apart from previously described mechanisms involving BRCA1-intragenic deletions and loss of BRCA1 promoter hypermethylation, a novel resistance mechanism was identified in four out of seven BRCA1-methylated PDX tumors that re-expressed BRCA1 but retained BRCA1 promoter hypermethylation. In these tumors, we found de novo gene fusions that placed BRCA1 under the transcriptional control of a heterologous promoter, resulting in re-expression of BRCA1 and acquisition of therapy resistance. In addition to previously described clinically relevant resistance mechanisms in BRCA1-deficient tumors, we describe a novel resistance mechanism in BRCA1-methylated PDX tumors involving de novo rearrangements at the BRCA1 locus, demonstrating that BRCA1-methylated breast cancers may acquire therapy resistance via both epigenetic and genetic mechanisms.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Wiley
Date: 15-04-2017
DOI: 10.1002/JSO.24635
Abstract: Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients. Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis. A total of 205 patients were included. Median follow-up was 20 months (interquartile range 11-43 months), median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and 5-year DFS was 23%. N3 (≥4 involved lymph nodes) and extracapsular extension (ECE) carried an increased risk of disease recurrence after LND and death by melanoma. Patients with both N3 and ECE had virtually no long-term survival. Although survival for patients with stage IIIC is poor in general, patients with both N3 disease and ECE constitute the group with the worst prognosis and should be considered for adjuvant therapy with ipilimumab or any other future effective adjuvant therapy (study).
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1038/S41591-022-01851-X
Abstract: Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg
Location: Netherlands
Location: Germany
No related grants have been discovered for Katarzyna Jóźwiak.