scholarly journals Sequential intra-arterial infusion of 90Y-resin microspheres and mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study

2020 ◽  
Vol 54 (1) ◽  
pp. 33-39
Author(s):  
Brigitte Maximiliana Aarts ◽  
Elisabeth Geneviève Klompenhouwer ◽  
Raphaëla Carmen Dresen ◽  
Christophe Michel Albert Louis Omer Deroose ◽  
Regina Gien Hoa Beets-Tan ◽  
...  

AbstractBackgroundThe aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 (90Y) resin microspheres in liver metastatic breast cancer (LMBC) patients.Patients and methodsThe prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of 90Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, 18F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0.ResultsSixteen patients received 90Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after 90Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed.ConclusionsSequential treatment of intra-arterial infusion of MMC after 90Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after 90Y SIRT in LMBC patients.

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1331
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Olga Savichtcheva ◽  
Kimberly A. Holden ◽  
...  

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.


Breast Care ◽  
2007 ◽  
Vol 2 (4) ◽  
pp. 227-233
Author(s):  
Michael Braun ◽  
Bettina Schlehe ◽  
Andree Faridi ◽  
Uwe Heindrichs ◽  
Christian Rudlowski

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 579-579
Author(s):  
P. Spadaro ◽  
M. Ingemi ◽  
G. Dottore ◽  
G. Toscano ◽  
R. Maisano

579 Background: Amplification or overexpression of HER-2/neu has been identified in 10–20% of invasive breast cancers and is associated with shorter overall survival times; furthermore HER-2/neu is a predictive factor with regard to monoclonal antibody therapy with Trastuzumab. The observed association between the overexpression of HER-2/neu and higher VEGF expression indicates that HER-2/neu is involved, at least partly, in the regulation of angiogenesis in human breast cancer. Recently circulating endothelial cells (CECs) have been proposed as a marker of tumor progression and/or a response to antiangiogenic therapy; thus, we have performed a phase II study to explore the correlation between CECs and treatment with Trastuzumab in metastatic breast cancer Methods: 22 women aged ≥ 18 years with histologically proven Her-2-positive, ECOG performance status 0 to 2 who were not eligible for, or who wished to delay receiving chemotherapy received a standard loading dose of Trastuzumab 4 mg/Kg followed by 2 mg/Kg weekly. The weekly maintenance dose was continued until disease progression. A panel of monoclonal antibodies including anti CD45 to exclude hematopoietic cells, anti CD31, CD34, CD36, CD105, CD106, CD133, and KDR and appropriate analysis gates were used to enumerate resting and activated circulating endothelial cells Results: The overall response rate (RC + RP) to treatment was 25% (2 RC + 3RP). In healthy controls (N° 20) mean values of resting and activated CECs were 7.6/μL (4.6 - 11.2/μL) and 1.3/μL (0.1 - 2.4 /μL) respectively. Before treatment with Trastuzuamb the mean resting and activated CECs were 41.1/μL (16.4 - 60.5/μL) and 6.9/μL (5.1 - 8.7/μL). At a first assessment (6 wks) a significant decrease in CECs (p<0.001)was found in patients responding to treatment but not in the patients who did not achieve a remission Conclusions: Our finding has shown that resting and activated CECs are increased in metastatic breast cancer patients and decline during treatment in responding patients, furthermore, these data underline the crucial role of angiogenesis in this setting and support the rationale for a combination of Bevacizumab with Trastuzumab. No significant financial relationships to disclose.


1993 ◽  
Vol 79 (4) ◽  
pp. 254-257 ◽  
Author(s):  
Francesco Perrone ◽  
Sabino De Placido ◽  
Chiara Carlomagno ◽  
Francesco Nuzzo ◽  
Angela Ruggiero ◽  
...  

Aims In February 1986 we began a study to test the activity of mitomycin C (12 mg/m2) plus vinblastine (6 mg/m2) on day 1 of a 28-day cycle (MV) as second or third-line chemotherapy for metastatic breast cancer patients. Methods As of February 1988 the study was stopped after 26 patients had been enrolled. The median age of the patients was 54 years (range 35-78); all patients were progressive from chemotherapy; 15 (57.7 %) patients were treated as second and 11 (42.3 %) as third line; 19 (73.1 %) patients had received anthracyclines as first (13 patients) or second-line (6 patients) chemotherapy; 18 (69.2 %) patients had visceral Involvement; 7 (26.9 %) had one metastatic site, 11 (42.3 %) two sites, 6 (23.1 %) three sites and 2 (7.7 %) four sites. Results Overall, 86 cycles were administered, with a median number of 3 cycles per patient. Toxicity was mild; hematologic side effects required discontinuation of treatment in 3 cases. Vomiting occurred in 3 (11.5 %) patients, nausea in 5 (19.2 %). Moderate neurologic toxicity was recorded in 6 (23 %) patients. No complete and 3 partial responses were observed. The objective response rate was 11.5 % (exact 95 % confidence interval, 2.4-30.1). Responses occurred independently of disease-free interval, dominant metastatic site, response to previous chemotherapy, previous anthracycline and line of treatment; all responses were recorded in patients under 50 years of age. Kaplan-Meier estimated median time to progression and overall survival were 13 and 40 weeks, respectively. Conclusion The MV regimen was well tolerated but showed little activity in pretreated metastatic breast cancer.


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