1,721,010 research outputs found
Combination of OX40 Co-Stimulation, Radiotherapy, and PD-1 Inhibition in a Syngeneic Murine Triple-Negative Breast Cancer Model
No full textSIMPLE SUMMARY: This experimental study was designed in order to investigate the efficacy of the triple combination of radiation (SBRT), PD-1 blockade, and OX40 co-stimulation in a syngeneic murine model using ‘immunologically cold’ triple-negative breast cancer cells. SBRT can induce immunogenic tumor cell deaths and act as an in situ vaccine while OX40 signaling has been shown to improve anticancer immunity combined with PD-1 inhibition via multiple preclinical studies. In our study, triple combination therapy significantly improved primary/abscopal tumor control and reduced lung metastases compared to single or dual therapies. This was found to be through an increased ratio of CD8+ T cells to regulatory T cells and a reduced proportion of exhausted T cells in the tumor microenvironment. ABSTRACT: Immune checkpoint inhibitors have been successful in a wide range of tumor types but still have limited efficacy in immunologically cold tumors, such as breast cancers. We hypothesized that the combination of agonistic anti-OX40 (α-OX40) co-stimulation, PD-1 blockade, and radiotherapy would improve the therapeutic efficacy of the immune checkpoint blockade in a syngeneic murine triple-negative breast cancer model. Murine triple-negative breast cancer cells (4T1) were grown in immune-competent BALB/c mice, and tumors were irradiated with 24 Gy in three fractions. PD-1 blockade and α-OX40 were administered five times every other day. Flow cytometric analyses and immunohistochemistry were used to monitor subsequent changes in the immune cell repertoire. The combination of α-OX40, radiotherapy, and PD-1 blockade significantly improved primary tumor control, abscopal effects, and long-term survival beyond 2 months (60%). In the tumor microenvironment, the ratio of CD8+ T cells to CD4 + FOXP3+ regulatory T cells was significantly elevated and exhausted CD8+ T cells (PD-1+, CTLA-4+, TIM-3+, or LAG-3+ cells) were significantly reduced in the triple combination group. Systemically, α-OX40 co-stimulation and radiation significantly increased the CD103+ dendritic cell response in the spleen and plasma IFN-γ, respectively. Together, our results suggest that the combination of α-OX40 co-stimulation and radiation is a viable approach to overcome therapeutic resistance to PD-1 blockade in immunologically cold tumors, such as triple-negative breast cancer
Effects of trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-overexpressing breast cancer patients treated with chemotherapy and radiotherapy
No full textPurposeIn the present study, the ability of adjuvant trastuzumab to reduce locoregional recurrence in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer receiving adjuvant chemotherapy and radiotherapy (RT) was investigated.Materials and methodsWe retrospectively included 520 patients with HER2-overexpressing breast cancer who received surgery followed by adjuvant RT and cytotoxic chemotherapy from 2003 to 2011. Adjuvant trastuzumab was administered to 286 patients. Propensity score matching was conducted to compare trastuzumab-treated and non-treated cohorts.ResultsMedian follow-up duration was 7.1years (range 1.1-14.1years). Propensity score matching yielded 171 matched pairs of patients with no significantly different clinical factors. An improved 7-year locoregional control (LRC) rate was observed in the trastuzumab-treated cohort compared with the non-treated cohort (95.6% vs. 89.9%, p=0.014). Based on multivariate analysis, hormone receptor negativity (hazard ratio [HR]=5.348, p=0.007), positive lymph node ratio>0.25 (HR=2.549, p=0.040), and lack of adjuvant trastuzumab (HR=3.401, p=0.017) were identified as significant risk factors for poor LRC. Adjuvant trastuzumab significantly reduced the locoregional recurrence rate in patients with one or two risk factors (7-year LRC=95.0% vs. 84.2%, p=0.007); however, the benefit of adjuvant trastuzumab was non-significant in patients with no risk factors (7-year LRC=95.8% vs. 97.9%, p=0.75).ConclusionsAdjuvant trastuzumab improved LRC in patients with HER2-overexpressing breast cancer receiving adjuvant RT and cytotoxic chemotherapy, especially in hormone receptor-negative, HER2-enriched subtype, and high positive lymph node ratio breast cancer.N
Analysis of survival outcomes based on molecular subtypes in breast cancer brain metastases: A single institutional cohort
No full textPurpose To evaluate the survival outcomes based on molecular subtypes of breast cancer in patients with brain metastasis. Materials and methods We retrospectively reviewed 106 breast cancer patients treated for brain metastases, from January 2005 to May 2016. Patients were divided into four groups based on the tumor molecular subtype: luminal A (Estrogen Receptor [ER]/Progesterone Receptor [PR] positive, human epithelial growth factor receptor-2 [HER2] negative), luminal B (ER/PR positive, HER2 Positive), HER2 (HER2 positive and ER/PR negative), and Triple negative (TNBC). Results The median follow-up time for surviving patients was 22 months (range: 11.2-51.1 months). The median survival of all patients was 14 months, with a 1-year overall survival (OS) rate of 57.5% and a 2-year OS rate of 32.1%. Thirty patients (28.3%) had a solitary brain metastasis while 62 (58.5%) patients had multiple metastases. A significant difference was observed in the survival rates of the two groups. Based on the Karnofsky performance score, the performance status of the patients at the time of brain metastasis was also found to affect survival. Patients with different molecular subtypes had different survival rates; the luminal A group showed the highest median survival (luminal A: 23.1, luminal B: 15.0, HER2: 12.5 and TNBC: 6.4 months, respectively), which was statistically significant. Conclusion In breast cancer patients with brain metastasis, survival rates were different based on the molecular subtype of the tumor, despite various local and systemic treatments. Appropriate and tailored treatment approaches should, therefore, be considered for the different molecular subtypes.OAIID:RECH_ACHV_DSTSH_NO:T201825675RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079552CITE_RATE:2.424FILENAME: Brain Mets Molecular subtypes in breast cancer brain metastases_Wan Jeon_TBJ_2017.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/1988908f-0616-4574-8ca7-76f953cc9b87/linkN
Central nervous system failure in Korean breast cancer patients with HER2-enriched subtype: Korean radiation oncology group 16-15 multicenter retrospective study
No full textPurpose: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). Methods: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). Results: The median follow-up duration was 84 (range, 8-171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076-4.746; p = 0.031). Conclusion: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.OAIID:RECH_ACHV_DSTSH_NO:T201909705RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A079552CITE_RATE:2.456DEPT_NM:의학과EMAIL:[email protected]_YN:YY
Feasibility of anomaly score detected with deep learning in irradiated breast cancer patients with reconstruction
No full textThe aim of this study is to evaluate cosmetic outcomes of the reconstructed breast in breast cancer patients, using anomaly score (AS) detected by generative adversarial network (GAN) deep learning algorithm. A total of 251 normal breast images from patients who underwent breast-conserving surgery were used for training anomaly GAN network. GAN-based anomaly detection was used to calculate abnormalities as an AS, followed by standardization by using z-score. Then, we reviewed 61 breast cancer patients who underwent mastectomy followed by reconstruction with autologous tissue or tissue expander. All patients were treated with adjuvant radiation therapy (RT) after reconstruction and computed tomography (CT) was performed at three-time points with a regular follow-up; before RT (Pre-RT), one year after RT (Post-1Y), and two years after RT (Post-2Y). Compared to Pre-RT, Post-1Y and Post-2Y demonstrated higher AS, indicating more abnormal cosmetic outcomes (Pre-RT vs. Post-1Y, P = 0.015 and Pre-RT vs. Post-2Y, P = 0.011). Pre-RT AS was higher in patients having major breast complications (P = 0.016). Patients with autologous reconstruction showed lower AS than those with tissue expander both at Pre-RT (2.00 vs. 4.19, P = 0.008) and Post-2Y (2.89 vs. 5.00, P = 0.010). Linear mixed effect model revealed that days after baseline were associated with increased AS (P = 0.007). Also, tissue expander was associated with steeper rise of AS, compared to autologous tissue (P = 0.015). Fractionation regimen was not associated with the change of AS (P = 0.389). AS detected by deep learning might be feasible in predicting cosmetic outcomes of RT-treated patients with breast reconstruction. AS should be validated in prospective studies
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
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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