1,721,049 research outputs found
Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
Full text linkFrancesco Facchinetti, Paola Bordi, Alessandro Leonetti, Sebastiano Buti, Marcello Tiseo Medical Oncology Unit, University Hospital of Parma, Parma, Italy Abstract: Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development of atezolizumab allowed to derive several hints regarding clinical and immunological factors predictive of its activity and efficacy, some of them exclusive among this class of drugs. This review provides an overview of atezolizumab development throughout clinical trials toward its applicability in the routine practice, with a particular focus on patient selection based on clinical and immune-related factors. Keywords: non-small cell lung cancer, NSCLC, immune checkpoint blockers, ICB, PD-1, PD-L1, atezolizumab development, biomarker
Efficacy and safety of long-term tolvaptan treatment in a patient with SCLC and SIADH
No full textHyponatremia frequently occurs in patients with cancer and is mostly due to a syndrome of inappropriate antidiuresis caused by ectopic secretion of antidiuretic hormone (SIADH). Small cell lung cancer presents with SIADH in approximately 11%-15% of cases. Recently, a new class of drugs, vasopressin V2-receptor antagonists (vaptans), emerged as a promising treatment for SIADH, but efficacy and safety data in cancer patients are lacking. We present a case of SIADH, heralding small cell lung cancer and persisting after apparent complete remission of primary tumor following chemotherapy/radiotherapy, in a patient who underwent long-term treatment with tolvaptan without any serious adverse effects
Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer
No full textEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are current treatments for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR gene mutations. Histological or cytological samples are the standard tumor materials for EGFR mutation analysis. However, the accessibility of tumor samples is not always possible and satisfactory in advanced NSCLC patients. Moreover, totality of EGFR mutated NSCLC patients will develop resistance to EGFR-TKIs. Repeat biopsies to study genetic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumor heterogeneity. Thus, exploring accurate and less invasive techniques to (I) diagnosis EGFR mutation if tissue is not available or not appropriate for molecular analysis and to (II) monitor EGFR-TKI treatment are needed. Circulating DNA fragments carrying tumor specific sequence alterations [circulating cell-free tumor DNA (cftDNA)] are found in the cell-free fraction of blood, representing a variable and generally small fraction of the total circulating DNA. cftDNA has a high degree of specificity to detect EGFR gene mutations in NSCLC. Studies have shown the feasibility of using cftDNA to diagnosis of EGFR activating gene mutations and also to monitor tumor dynamics in NSCLC patients treated with EGFR-TKIs. These evidences suggested that non-invasive techniques based on blood samples had a great potential in EGFR mutated NSCLC patients. In this review, we summarized these non-invasive approaches and relative scientific data now available, considering their possible applications in clinical practice of NSCLC treatment
Metabolic complete response with vinflunine as second-line therapy in a kidney-transplanted patient with advanced urothelial carcinoma: A case report
No full textBackground: Patients undergone kidney transplantation present higher risk of Urothelial Carcinoma (UC) development and represent a subgroup of special interest. To date, vinflunine is the only drug approved in Europe for the treatment of advanced UC after failure of platinum-based chemotherapy. However, to our knowledge, no data on the concomitant administration of vinflunine and immunosuppressive agents are available. Case presentation: The patient, a 45 years old Caucasian male, presented poorly differentiated UC of the bladder recurred after initial cystectomy with abdominal lymphadenopathies evidenced by FDG-PET/CT. Previously, at the age of 22, he had post-glomerulonephritis renal failure and underwent kidney transplantation from deceased donor. Since then, he has been in treatment with immunosuppressive therapy. At the time of UC recurrence, he was on treatment with cyclosporine. After progression to platinum-based chemotherapy, he received second-line therapy with vinflunine resulting in a complete metabolic response after two cycles. However, despite several dose reductions, the patient experienced severe hematologic toxicity. The pharmacological interaction between vinflunine and cyclosporine, both metabolized by CYP 3A4, may explain the excellent result and the concomitant severe toxicity. Conclusions: Vinflunine is active on UC developed in kidney transplanted patients. However, special attention should be paid to concomitant administration with immunosuppressive agents that could result in increased toxicity
2PD Monitoring of secondary drug resistance mutations in circulating tumor DNA of patients with advanced ALK positive NSCLC
No full textMonitoring of secondary drug resistance mutations in circulating tumor DNA of patients with advanced ALK positive NSCLC
No full textBackground
Disease progression in ALK positive NSCLC patients treated with crizotinib occurs after a median of 9–10 months of treatment. Several mechanisms of resistance were identified and include ALK gene mutations and amplification and activation of bypassing signaling pathways like EGFR, KRAS or c-KIT. Second-generation ALK-TKIs demonstrated an enhanced spectrum of activity in crizotinib-resistant patients. However, re-biopsy in NSCLC patients represents a critical issue and analysis of circulating cell-free DNA (cfDNA) has a promising role for the identification of mechanisms of resistance.
Methods
Sixteen patients progressed during ALK-TKI were enrolled. After progression, blood was collected and DNA was extracted from plasma using QIAamp circulating nucleic acid kit (Qiagen®) and tested for ALK secondary mutations and KRAS exon 12 mutations using the Digital Droplet PCR (ddPCR – BioRad®).
Results
All patients were stage IV adenocarcinoma; 11 female and 5 male. Nine were never-smokers and 7 former-smokers. Median age was 53 yrs (range 40–81). Fifteen patients received crizotinib and 1 ceritinib. ALK-TKIs was administered mainly as second-line, in 2 cases as first and in the remaining as third-line therapy. Twelve patients had partial response, 3 stable disease, one progressed. Median PFS was 8 months. In 12 cases brain was a site of progression and only 5 patients had a tumor site that could potentially undergo re-biospy. ALK secondary mutations were identified in 4 patients. One showed both p.L1196M and p.G1269A mutations which levels decreased after 2 months of therapy with second generation ALK-TKI, along with tumor response. The second and the third patient had p.L1196M and p.G1269A, respectively. The 4th patient showed p.F1174L after initiation of second generation ALK-TKI. A total of 9 patients KRAS mutations p.G12D or p.G12V appeared in cfDNA at the time of resistance to TKI, 3 of them presented both ALK and KRAS mutations.
Conclusions
ddPCR can detect resistance mutations in cfDNA of ALK+ NSCLC and is an effective alternative to re-biopsy. The assessment of mutant allele burden could be used for response monitoring during treatment. Moreover, KRAS mutations may play a role in resistance to ALK-TKIs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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