1,721,145 research outputs found
Real-world survival outcomes in patients with locally advanced or metastatic NTRK fusion-positive solid tumors receiving standard-of-care therapies other than targeted TRK inhibitors
No full textThe clinical profiles and outcomes of patients with neurotrophic tropomyosin receptor kinase fusion-positive (NTRK(+)) solid tumors receiving standard of care other than tropomyosin receptor kinase inhibitor (TRKi) targeted therapy have not been well documented. Here, we describe the clinical characteristics of patients with NTRK(+) tumors treated in clinical practice using information from a United States electronic health record-derived clinicogenomic database. We also compared survival outcomes in NTRK(+) patients and matched NTRK fusion-negative (NTRK(–)) patients and investigated the clinical prognostic value of NTRK fusions. NTRK positivity was defined by the presence of a fusion or rearrangement involving NTRK1/2/3, determined using NGS (Foundation Medicine, Inc.). NTRK(+) patients (n = 28) were diagnosed with locally advanced/metastatic solid tumors between January 1, 2011 and December 31, 2019 and had received no TRKis (e.g., entrectinib or larotrectinib) during their patient journey. The unselected NTRK(−)population comprised 24,903 patients, and the matched NTRK(−)cohort included 280 patients. NTRK(+) patients tended to be younger, were more commonly not smokers, and had a shorter time from advanced diagnosis to first NGS report, compared with unselected NTRK(−)patients; however, these differences were not significant. Median overall survival (OS) from advanced/metastatic diagnosis was 10.2 months (95% CI, 7.2–14.1) for the NTRK(+) cohort versus 10.4 months (95% CI, 6.7–14.3) for the matched NTRK(−)cohort; hazard ratio for death in NTRK(+) versus matched NTRK(−)patients was 1.6 (95% CI, 1.0–2.5; P = 0.05). Genomic co-alterations were rare in the NTRK(+) cohort (only two of 28 patients had a co-alteration). Overall, while hazard ratios suggest NTRK fusions may be a negative prognostic factor of survival, there are no significant indications of any favorable impact of NTRK fusions on patient outcomes. TRKis, with their high response rate and good tolerability, are likely to improve outcomes for patients compared with existing standard-of-care treatments
Letter to editor/comment : Metaplastic carcinoma of the breast: Prognosis and response to systemic treatment in metastatic disease
No full textI read with a great interest a recently published clinical study of Takala et al 1 on metaplastic carcinoma of the breast. The authors explored 78 patients with the diagnosis of metaplastic carcinoma in the period 2002-2016. In line with previous studies, the authors confirmed predominantly triple-negative phenotype of metaplastic carcinomas (85%) exhibiting a poor therapeutic response with an aggressive clinical course and poor outcome.
Two things are worthy of further discussion: First, 12% of the patients were estrogen receptor (ER)-positive, eight of which received adjuvant endocrine therapy. I would appreciate more information from the authors regarding the percentage of ER positivity in these metaplastic carcinomas and a potential response to endocrine treatment. It is well known that most metaplastic carcinomas are ER-negative and if ER-positive, the percentage of positive cancer cells is usually low (range, 1%-10%). This fact may substantially affect the response to endocrine therapy, as the patients with lower ER positivity in their breast cancers are less responsive to anti-ER treatment modalities
Letter to Editor: Apocrine carcinoma is the fact. Comment on the recent paper entitled "Invasive apocrine carcinoma of the breast: Myth or fact?" by Gurrado et al (Breast J. 2019 Sep 8. doi: 10.1111/tbj.13569. [Epub ahead of print].
No full textThe most recent WHO classification of breast cancer also recognizes the concept of “pure apocrine carcinoma” (called carcinoma with apocrine differentiation) with cancers having >90% of apocrine morphology (an essential criterion) and ER‐negative, AR‐positive immunoprofile as a desirable criterion
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
Microsatellite instability status predicts response to anti-PD-1/PD-L1 therapy regardless the histotype: A comment on recent advances
Full text linkIt is well-known that somatic mutations resulting in increased number of neoantigens (“immunogenic antigens”) may enhance anti-tumor immune cell reaction. Also, high tumor mutation burden (load) [TML] is associated with improved response, durable clinical benefits and better outcome if a cancer is treated with immune check point inhibitors [anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) drugs] [1]. A subset of colorectal carcinomas (CRC) and other cancers characterized by mismatch repair deficiency (MMR) and/or microsatellite instability high (MSI-H) profiles may be particularly sensitive to the PD-1/PD-L1 blockade with immune check point inhibitors due to the common PD-L1/PD-L1 expression [2-9]. Several therapeutic antibodies inhibiting either PD-1 (nivolumab, pembrolizumab) or PD-L1 (MPDL3280A, Medi4736, BMS-936559) have been developed and approved for the treatment of various malignancies including malignant melanoma, non-small cell lung carcinoma, renal cell carcinoma, bladder carcinoma, Merkel cell carcinoma, and classical Hodgkin lymphoma [10].
A pivotal phase 2 study by Le et al. [11] highlighted the importance of mismatch-repair status in prediction of the clinical benefit of immune checkpoint blockade with pembrolizumab (anti-PD-1 drug) [11]. The study included 41 patients with progressive cancers of both CRC and non-colorectal origins and known MSI status. For CRC patients, the objective response rate and progression-free survival rate were 40% and 78%, respectively for mismatch repair-deficient tumors and 0% and 11% for mismatch repair-proficient CRCs.
A novel study by Le et al. [12] (ClinicalTrials.gov number, NCT01876511) represents an extended analysis on the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers. The study included 86 patients with 12 different histologic cancer subtypes and proved mismatch repair-deficiency status assessed by either polymerase chain reaction (PCR) or immunohistochemistry. The data presented in this study indicate objective radiographic responses in 53% of patients while complete responses were achieved in 21% of patients. Based on this and previous data, on May 23, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to anti-PD-L1 drug pembrolizumab (KEYTRUDA®, Merck & Co.) for adult and pediatric patients with unresectable/metastatic MSI-H/MMR deficient solid tumors (regardless the histotype) that have progressed following prior treatment and without satisfactory alternative treatment modalities. The approval also covered MSI-H CRC patients who progressed following treatment with a classic cytotoxic therapy (fluoropyrimidine, oxaliplatin, and irinotecan).
Taken together, these results revolutionize the cancer treatment paradigm as for the first time the cancer treatment was based solely on the molecular characteristics of cancer (in this case microsatellite instability/MSI/ status) regardless the tumor morphology (histotype). This appears to be “the FDA’s first tissue/site-agnostic approval”.
Certainly, there are still ongoing but unresolved issues regarding these treatments including other merging predictive biomarkers (optimization of PD-L1 and PD-1 evaluation, e.g. tumor versus immune cell expression; cutoffs for positivity; selection of detection antibodies), tumor mutational load and the tumor neoantigen heterogeneity/specificity [13-15]. Further studies should also elucidate the mechanisms of recently described resistance to immune checkpoint inhibitors [16-18].</jats:p
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers
Full text linkAntibody-drug conjugates represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently its overexpression has been demonstrated in various solid malignan-cies. Sacituzumab govitecan (SG), a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with regard to SG, emphasizing the predictive biomarker analysis.Scopu
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