Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Ewing's sarcoma of the cervix: A case report of an unusual diagnosis in pregnancy treated with surgery, adjuvant VIDE and radiotherapy.

Ewing's sarcoma of the cervix is a rare entity and presents with considerable challenges in diagnosis and therapy. Herein, we report a case of a cervical Ewing's sarcoma presenting with FIGO stage Ib, diagnosed during the first trimester of the patient's pregnancy. Imaging with CT scans, MRI of her abdomen and PET-CT verified the locoregional extension of the tumor. The diagnosis was confirmed by immunohistochemistry and molecular analysis. Fluorescence in situ hybridization and RT-PCR detected the pathognomonic EWS/FLI fusion gene. Favorable prognostic factors regarding the stage, clinocopathological and molecular characteristics of the tumor are also described. Due to the rarity of the disease, at present, there is no universal consensus on the optimal therapeutic approach. The literature has been reviewed and the therapeutic schemes and available clinical data have been discussed. The patient presented in this case report was treated aggressively with tri-modality therapy and underwent radical hysterectomy followed by adjuvant chemotherapy with Vincristine-Ifosfamide-Doxorubicin-Etoposide and radiotherapy. The patient remains free of this disease 42 months following the diagnosis of her tumor.

Breakthroughs in the treatment of advanced squamous-cell NSCLC: not the neglected sibling anymore?

During the last years, translational research has contributed in many advances in the treatment of non-small cell lung cancer (NSCLC) discovering genetic alternations or recognizing the immuno-escape and neo-angiogenesis of lung cancer. Although the majority of these advances took place in the non-squamous histological subtype, therapeutic options for patients diagnosed with advanced squamous cell lung cancer (SqCLC) have been also enriched significantly with the addition of nab-paclitaxel in the conventional chemotherapy; the introduction of necitumumab, afatinib and erlotinib in the inhibition of epidermal growth factor receptor (EGFR) axis and of ramucirumab in the inhibition of VEGF-induced angiogenesis and last with the approvals of nivolumab, pembrolizumab atezolizumab and durvalumab soon in the promising field of immunotherapies. Agents targeted various other pathways including FGFR, IGF-1, PI3K, CDK4/6, MET and PARP inhibitors are under investigation in order to open new prospects in the treatment of SqCLC. In this review, we present all published data that led to recent approvals for the treatment of advanced SqCLC and all ongoing clinical trials that keep searching for new molecular targets following a more-personalized approach.

Treating ALK-positive non-small cell lung cancer.

Targeting genomic alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements, have radically changed the treatment of patients with non-small cell lung cancer (NSCLC). In the case of ALK-rearranged gene, subsequent rapid development of effective genotype-directed therapies with ALK tyrosine kinase inhibitors (TKIs) triggered major advances in the personalized molecularly based approach of NSCLC. Crizotinib was the first-in-class ALK TKI with proven superiority over standard platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged NSCLC patients. However, the acquired resistance to crizotinib and its diminished efficacy to the central nervous system (CNS) relapse led to the development of several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib. To date, four ALK TKIs, crizotinib, ceritinib, alectinib and brigatinib have received approval from the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) and even more agents are currently under investigation for the treatment of ALK-rearranged NSCLC. However, the optimal frontline approach and the exact sequence of ALK inhibitors are still under consideration. Recently announced results of phase III trials recognized higher efficacy of alectinib compared to crizotinib in first-line setting, even in patients with CNS involvement. In this review, we will discuss the current knowledge regarding the biology of the ALK-positive NSCLC, the available therapeutic inhibitors and we will focus on the raised issues from their use in clinical practise.