1,721,073 research outputs found
Prognostic and predictive role of miRNAs, CTCs AND AR-V7+ CTCs expression in advanced prostate cancer treated with new hormonal agents: a feasibility study
Full text linkBackground. Circulating tumor cells (CTC) counts of 5 or more/7.5 mL predict shorter survival in men with mCRPC. Moreover, the presence of androgen receptor splice variant-7 mRNA (AR-V7) in CTCs is thought to play a relevant role in the development of primary or acquired resistance to enzalutamide or abiraterone.
MiRNAs, small endogenous mRNA, have been identified as associated to the presence and aggressiveness of prostate cancer and for instance, overexpression of some miRNAs contributes to resistance to docetaxel and cabazitaxel.
We developed a new immunofluorescence-based assay for AR-V7 expression in CTCs and tested its prognostic association with PFS and OS.
Co-primary aims are to investigate AR-V7 with a new integrated assay and to study role of miRNAs in mCRPC patients treated with abiraterone or enzalutamide, and to study the relationship between AR-V7 expression, CTCs, and miRNAs with PFS or OS.
Methods. We performed a single-centre, observational, prospective trial enrolling patients with mCRPC candidate to receive enzalutamide or abiraterone. CTC samples have been collected at baseline, after 1 month and every three months thereafter until progression or at 12 months without progression. CTCs have been enumerated with CellSearch System. We integrated the standard assay with a monoclonal antibody able to recognize the AR-V7 protein. Slides created from pts’ samples underwent automated immunofluorescent staining and AR-V7+ CTCs were enumerated. MiRNAs have been evaluated at the same time point.
Results. Since Sep 2016, 31 patients have been enrolled. We compared CTC counts between standard assay and the integrated assay and found no statistical differences in the mean total CTC number ± SD (Wilcoxon Signed Rank test, p= 0.313).
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Sixteen out of 28 evaluable patients (57%) had 1 or more CTCs at baseline, 9 pts (32%) had more than 5 CTCs/7.5 ml, and 4 pts (14.3%) were AR-V7+ before any exposure to abiraterone or enzalutamide.
After a median follow-up time of 8.1 months, 6 patients have progressed and 4 have died. No association has been found between CTCs ≥ 5/7.5 mL and survival. The presence of at least one AR-V7+ CTC at baseline did not correlate with PSA response, but had a weak association with shorter PFS (log-rank test, p = 0.055) and a statistically significant impact (p = 0.02) on OS.
MiRNA failed in this analysis to correlate with survival outcome.
Conclusion. We developed a new integrated assay for detecting AR-V7+ CTCs, based on an automated platform that permits serial sampling with low inter- and intra-test variability. The clinical utility of this test in anticipating the resistance to abiraterone or enzalutamide is under study
Prevention of Hepatitis B Virus Reactivation With Lamivudine in a Patient With Advanced Renal Cell Carcinoma Treated With Everolimus.
No full textTreatment of Estrogen Receptor-positive Breast Cancer
No full textEstrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging
Long-term response to first-line trabectedin in an elderly female patient with a metastatic leiomyosarcoma unfit for anthracycline
No full textAdjuvant and neoadjuvant chemotherapy for soft tissue sarcomas
No full textSarcomas of the soft tissue are a heterogeneous, rare and complex group of mesenchymal malignant tumors, accounting for less than 1% of all adult malignancies and about 10-15% of childhood cancer. Despite local disease control obtained with surgery and pre- or postoperative radiotherapy, roughly one half of patients with high-grade tumors experience metastatic disease. The adjunction of chemotherapy, either before or after resection, is not currently viewed as standard practice due to the lack of reproducible impact on survival. The 1997 SMAC meta-analysis based on individual data from randomized studies confirmed a significant impact of adjuvant chemotherapy on both local and metastatic relapse, without any significant benefit on survival. Further meta-analyses demonstrated a significant benefit also in overall survival. Yet, the latest adjuvant EORTC trial was disappointedly negative. To date, adjuvant chemotherapy may be recommended as a reasonable option for the high-risk individual patient who should be well informed on the possible risks and benefits of treatment. Also the indications for neoadjuvant chemotherapy remain controversial. A local benefit may be gained, facilitating surgery, but data on survival are limited and affected by a strong patient selection bias. In order to improve our knowledge on sarcomas and to offer patients the best of current standards, we strongly recommend that all patients be referred to a sarcoma multidisciplinary group, under whose supervision they could receive the correct combined-modality management as well as have access to new clinical trials appropriately stratified for risk and histological and/or molecular subtype
The Role of Radiolabeled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for the Evaluation of Renal Cancer
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First- and second-line systemic treatments for metastatic and locally advanced soft tissue sarcomas in adults
No full textThis is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of systemic therapy for the treatment of metastatic soft tissue sarcomas in a first-line metastatic setting. To assess the effects of systemic therapy for the treatment of metastatic soft tissue sarcomas in a second-line metastatic setting. To assess the effects of chemotherapy regimens adapted to specific sarcoma histologies. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
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