tbuckley/cabot-search huggingface dataset:
P01.088 Brain resection cavity delineation for radiation target volume definition in glioblastoma patients using deep learning
Authors: E Herrmann, E Ermis, A Jungo, M Blatti-Moreno, U Knecht, D M Aebersold, P Manser, M Reyes
Journal: Neuro-Oncology (2018)

We present results of an automated segmentation method for resection cavity in Glioblastoma (GBM) patients using deep learning technologies. The approach fully segments the resection cavity and yields estimates of uncertainty. We compare the approach to a previously reported machine learning method and show the superiority in performance of the deep learning approach while yielding estimates of segmentation uncertainty, which can be used by an operator to monitor computer’s results. We included post-OP, pre- and post-contrast T1, T2 and FLAIR MRI datasets of 30 patients with newly diagnosed, surgically resected and histologically confirmed GBM. Radiation Cavity (RC) were defined as surgical cavity plus blood products. Three radiation oncologists manually delineated the RC using all four MRI sequences. For fully automatic segmentation, we developed a deep learning cavity segmentation method, which was trained on a subset of 25 cases, and utilizes all four MRI sequences to learn RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) (volumetric overlap) and estimated volume measurements using the Kruskal-Wallis test followed by a 6-fold cross-validation using the imaging data. Median DC and interquartile range (IQR) of the different pairings of expert raters (reported as tuples) were (0.85, 0.08), (0.84, 0.07), and (0.86, 0.07). The results of the automatic segmentation compared to the three different raters were (0.83, 0.14), (0.81, 0.12), and (0.81, 0.13). We did not detect a statistically significant difference regarding the distribution of the measured volumes for the different raters and methods (Kruskal-Wallis test: chi-square=1.46, p=0.69). The main sources of error consisted in over- or under-segmentation of the RC due to signal inhomogeneity (especially in T2 and FLAIR sequences) and over-segmentation due to similar intensity patterns (edema, subarachnoid space, or ventricles). Uncertainty maps generated by the deep learning approach were visually compared against the segmentation errors, and a good spatial overlap was found between uncertainty and RC delineation errors. This allow us to conclude on the reliability and good calibration properties of the deep learning approach. The proposed deep learning approach yields good results for the segmentation of the RC. However, blood products and air can affect its performance. Compared to human experts, the computer-generated results are still subpar but outperform previously presented approaches, while providing estimates of segmentation uncertainty, which can leverage the interactions between these systems and human experts.
Message to world leaders: we cannot end tuberculosis without addressing the social and economic burden of the disease
Authors: Priya B Shete, Michael Reid, Eric Goosby
Journal: The Lancet Global Health (2018)

Tuberculosis is fundamentally a disease of poverty; being poor increases the risk of falling sick with tuberculosis. Falling sick with tuberculosis also leads to impoverishment that can trigger a downward spiral of worsening health, ongoing tuberculosis transmission, crippling medical expenses, which further entrench poverty.1 Because of these realities, purely biomedical or public health solutions are not enough to end the tuberculosis epidemic; countries must implement social policy strategies that can protect tuberculosis sufferers from the financial shocks of this deadly disease.
Bridging the gap in global advanced radiation oncology training: Impact of a web-based open-access interactive three-dimensional contouring atlas on radiation oncology practice in Russia.
Authors: Natalia Dengina, Shearwood McClelland, Marina Chernich, Erin F Gillespie, Anna Likhacheva, Sergey Usychkin, Alexandr Pankratov, Ekaterina Kharitonova, Yulia Egorova, Ilya Tsimafeyeu, Sergei Tjulandin, Charles R. Thomas, Timur Mitin
Journal: Journal of Clinical Oncology (2018)

11001 Background: Radiation oncologists (ROs) in Russia face a number of unique professional difficulties including lack of standardized training and continuing medical education. To combat this, under the auspices of the Russian Society of Clinical Oncology (RUSSCO), our group has developed a series of ongoing in-person interactive contouring workshops that are held during the major Russian oncology conferences in Moscow, Russia. Since November 2016 during each workshop, we utilized a web-based open-access interactive three-dimensional contouring atlas as part of our didactics. We sought to determine the impact of this resource on radiation oncology practice in Russia. Methods: We distributed an IRB-approved web-based survey to 172 practicing ROs in Russia. We inquired about practice demographics, RUSSCO contouring workshop attendance, and the clinical use of open-access English language interactive contouring atlas (eContour). The survey remained open for two months until November 2017. Results: Eighty ROs completed the survey with a 46.5% response rate. Mean number of years in practice was 13.7. Sixty respondents (75%) attended at least one RUSSCO contouring workshop. Of those who were aware of eContour, 76% were introduced during a RUSSCO contouring workshop, and 81% continue to use it in their daily practice. The greatest obstacles to using the program were language barrier (51%) and internet access (38%). Nearly 90% reported their contouring practices changed since they started using the program, particularly for delineation of clinical target volumes (57%) and/or organs at risk (46%). More than 97% found the clinical pearls/links to cooperative group protocols in the software helpful in their daily practice. The majority used the contouring program several times per month (43%) or several times per week (41%). Conclusions: Face-to-face contouring instruction in combination with open-access web-based interactive contouring resource had a meaningful impact on perceived quality of radiation oncology contours among Russian practitioners and has the potential to have applications worldwide.
Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications
Authors: Min Su, Yuhang Xiao, Junliang Ma, Deliang Cao, Yong Zhou, Hui Wang, Qianjin Liao, Wenxiang Wang
Journal: Journal of Hematology & Oncology (2018)

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers and effective prognostic indicators for metastasis and recurrence has resulted in the poor prognosis of EC. In addition, the underlying molecular mechanisms of EC development have yet to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a vital role in the pathological progression of EC. LncRNAs may regulate gene expression through the recruitment of histone-modifying complexes to the chromatin and through interactions with RNAs or proteins. Recent evidence has demonstrated that the dysregulation of lncRNAs plays important roles in the proliferation, metastasis, invasion, angiogenesis, apoptosis, chemoradiotherapy resistance, and stemness of EC, which suggests potential clinical implications. In this review, we highlight the emerging roles and regulatory mechanisms of lncRNAs in the context of EC and discuss their potential clinical applications as diagnostic and prognostic biomarkers.
Residents' attitudes and beliefs towards palliative care in a community teaching hospital.
Authors: Sufana Shikdar, Noel Medeiros, Erin Kelly, Nicholas Ghionni, Deborah Cassidy, Eric Green
Journal: Journal of Clinical Oncology (2018)

89 Background: Early integrated palliative care improves the quality of life in patients with cancer. Wong et al. (2016) recently demonstrated that residents and fellows in a university hospital-based large comprehensive cancer center believed palliative care services to be beneficial for patient care. However, there are substantial differences between the clinical learning environments of a university and community teaching hospital. We aim to assess residents' attitudes and beliefs towards palliative care in the oncologic population in a community teaching hospital. Methods: We surveyed all residents (n = 90) in Mercy Catholic Medical Center's internal medicine, transitional year, and general surgery residencies about their knowledge, training, attitudes and beliefs regarding palliative care using a survey modified from Wong et al. (2015). Mercy Catholic Medical Center is a conglomeration of two community teaching hospitals in greater Philadelphia. The factors associated with awareness were analyzed using chi square or fisher exact test and logistic regression. Results: A total of 57 (63%) residents participated. The differences between the knowledge of residents from other specialties were not statistically significant. The awareness was reported more among residents who are American medical graduates (p = 0.03). The majority of the residents believed palliative care was beneficial to patients and families (98%), reduce health care costs (91%), decrease overall symptom burden (86%) and symptomatic management in newly diagnosed cancer (81%). Residents who reported having palliative care training during residency had significantly higher awareness (OR = 2.99, p = 0.04). Conclusions: Our study shows that the attitude and belief of residents at community teaching hospital is similar to the trainees at university teaching hospital. The implementation of palliative care rotation for all residents from clinical specialties can be effective in improving trainee’s attitude and belief regarding increased and early referral to palliative care.
PD-L1+CD4+ T cells and soluble PD-L1 as prognostic factors to anti-PD-1 immunotherapy in advanced non small cell lung cancer patients.
Authors: EleniKyriaki Vetsika, Despoina Aggouraki, Zacharoula Lyristi, Aristeidis Koukos, Despoina Kourougkiaouri, Vassilis Georgoulias, Athanasios Kotsakis
Journal: Journal of Clinical Oncology (2018)

e24091 Background: During the last years, immune checkpoint inhibitors (ICI) have emerged as a promising therapeutic approach for non small cell lung cancer (NSCLC). Therefore, the discovery of predictive biomarkers for ICI remains a major need in NSCLC. In this study, we evaluated the prognostic value of PD-1/PD-L1 expression on immune cells (IC), as a marker in the peripheral blood (PB) to anti-PD-1 therapy in NSCLC patients. Methods: PB was collected from 42 metastatic pre-treated NSCLC patients before anti-PD-1 therapy. Flow cytometry was performed to identify and quantify PD-1 and PD-L1 expression on circulating IC and on immunosuppressive CD4+ Treg cells. In addition, soluble PD-L1 (sPD-L1) was measured in matched plasma using ELISA. The association of the pre-treatment levels of PD-1+ and PD-L1+ IC, as well as of the sPD-L1 with overall (OS) and progression-free (PFS) survival was evaluated; Median value was used as a cut off. Results: Both PD-1 and PD-L1 expression was detected on all IC. A significantly decreased PFS was observed in the low CD4+PD-L1+ T cells group compared with the high CD4+PD-L1+group (14.3 vs 5.9 months, p = 0.03). Univariate analysis revealed that the high pre-treatment percentages of CD4+PD-L1+ T cells were an independent prognostic biomarker for ameliorated PFS in NSCLC patients treated with anti-PD-1 (HR = 3.1, p = 0.04). A possible explanation might be the enhancement of anti-tumor immunity following anti-PD-1 therapy. Indeed, after 3 cycles of therapy, the percentages of PD-L1+CD4+ T effector cells were augmented (p = 0.01), while the levels of PD-1+CD4+ Tregs were decreased (p = 0.008). In contrast, the patients with elevated pre-treatment levels of sPD-L1 had shorter PFS compared to those with low levels, however this difference was not significant (7.4 vs 11.5 months, p = 0.27). No correlation was observed between PD-1+ and PD-L1+ IC and response to anti-PD1 treatment and OS. Conclusions: These data provide evidence that the pre-treatment peripheral PD-L1+CD4+T cells are a significant predictor of better PFS in NSCLC patients and could be considered as a potential marker for the selection of patients who might benefit from PD-1/PD-L1 inhibitors.
Palbociclib versus placebo in combination with letrozole for patients with advanced or recurrent endometrial cancer: The NSGO ENGOT-EN3/PALEO trial.
Authors: Mansoor Raza Mirza, Vanda Salutari, Cesar Mendiola, Jalid Sehouli, Rene dePont Christensen, Line Bjorge, Sandro Pignata, Marta Gil-Martin, Radoslav Chekerov, Gitte-Betina Nyvang, Domenica Lorusso, Maria Pilar Barretina-Ginesta, Frederic Marme, Graziana Ronzino, M Jesus Rubio, Ingo B. Runnebaum, Trine Juhler-Nøttrup, Joan Løhndorf, Annika Auranen
Journal: Journal of Clinical Oncology (2017)

TPS5612 Background: Endometrial cancer (EC) patients with advanced or recurrent disease and endometrioid histology have a short progression-free survival (PFS). These malignancies are hormone dependent and endocrine therapy with aromatase inhibitors is well established. Palbociclib is an oral and selective inhibitor of cyclin-dependent kinases CDK4 and CDK6. Studies in breast cancer have demonstrated superiority of letrozole treatment in combination with palbociclib vs. letrozole monotherapy in oestrogen receptor positive (ER+) HER2- advanced disease. The combination is generally well tolerated with an acceptable toxicity profile. This multicenter, prospective, double-blind, placebo-controlled, randomized, phase II trial is evaluating the efficacy of letrozole when combined with palbociclib against letrozole-placebo combination therapy in women with ER+ advanced or recurrent EC. Methods: The primary objective of this trial is to demonstrate superiority of palbociclib against placebo in combination with letrozole, as defined by investigator-assessed progression-free survival (PFS). Key eligibility criteria include: histologically confirmed ER+ EC of endometrioid type; stage 4 or recurrent disease; prior surgery, adjuvant chemotherapy, radiation therapy, hormonal therapy (e.g. megestrol acetate) is permitted; measurable/evaluable disease according to RECIST 1.1. 78 patients will be randomized 1:1 to receive palbociclib 125mg daily or placebo on days 1-21 and letrozole 2.5mg daily on days 1-28 in a 28 days cycle until disease progression, unacceptable toxicity, or withdrawal. Secondary endpoints include PFS in sub-populations, overall response rate, disease control rate, PFS2, time to first subsequent therapy, time to second subsequent therapy, overall survival, safety &amp; tolerability, patient reported outcomes (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24) and PFS in patients with or without retinoblastoma protein-expressing tumors. The following cooperative groups are participating: NSGO (DK, FIN, NOR), MITO (ITA), GEICO (SPA) &amp; NOGGO (GER). Clinical trial information: NCT02730429.
Personal visceral fat index (PVF index), a new predictive factor for chemotherapy efficacy in patients with advanced gastric cancer.
Authors: Xiaodong Zhu
Journal: Journal of Clinical Oncology (2018)

e16049 Background: It has been reported that skeletal muscle depletion is a poor prognostic factor for a variety of cancers. Whether the changes of visceral fat or skeletal muscle during chemotherapy are related with the efficacy of treatment is still unclear. This study aimed to investigate the relationship between clinical efficacy and the changes of visceral fat or skeletal muscle during chemotherapy. Methods: This is a retrospective analysis based on a phase II clinical trial (NCT00767377) conducted during June 2007 to July 2012 in Fudan University Shanghai Cancer Center, in which all the AGC patients received EOF (epirubicin, oxaliplatin and fluorouracil) regimen as first line therapy. The computed tomography(CT) scans at baseline and after two cycles of treatment were used, and total abdominal fat area(TFA), visceral fat area(VFA), subcutaneous fat area(SFA) and skeletal muscle area(SMA) were measured with the software of GE Healthcare-Centricity RIS CE V3.0. Results: Because our PACS CT system only retains the data after 2010, only 53 patients with available data were included in the analysis. In terms of viscera fat area, we identified a variate as personal visceral fat index (PVF index), which stands for the difference between VFA/TFA after 2 cycle chemotherapy and baseline VFA/TFA. Receiver operating characteristic (ROC) curve showed that PVF index < 0.02 offered the best overall sensitivity (72.41%) and specificity (70.83%) for prediction of longer PFS time (AUC 0.7155). So patients were classified into low( < 0.02) and high(≥0.02) PVF index group. Compared with high PVF index group, patients of low PVF index group had significantly higher response rate (59.3% vs 30.8%, p= 0.037), longer PFS time (7.1months vs 5.1months, p= 0.036) and a tendency for a longer OS time (19.0months vs 9.6months, p= 0.190). Multivariate Cox proportional hazards model showed that PVF index < 0.02 was an independent predictive factor for PFS (HR, 0.377; 95%CI 0.146-0.978; P = 0.045). In terms of skeletal muscle area, no relationship between SMA and PFS, OS or response rate was found. Conclusions: PVF index can be used to predict for both favorable PFS and response in AGC patients treated with EOF regimen.
Abstract 14425: Exome Sequencing Reveals a Low Frequency Variant in BMPER in a Pedigree With Recurrence of Left Ventricular Outflow Tract Obstruction Defects
Authors: Emmi Helle, Tiina Ojala, Markus Perola, Euan Ashley, James R Priest
Journal: Circulation (2016)

Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart defect affecting 1-2% of the population and is etiologically related to more severe left ventricular outflow tract (LVO...
The role of diffusion weighted magnetic resonance imaging for the characterisation of mediastinal lymphadenopathy.
Authors: Mandeep K Garg, Eniyavel Ramamoorthy, Paramjeet Singh, Ashutosh Nath Aggarwal, Nalini Gupta
Journal: Journal of Clinical Oncology (2017)

e23113 Background: To assess the diagnostic performance and additional value of diffusion-weighted (DW) magnetic resonance imaging (MRI) in the characterization of mediastinal lymphadenopathy. Methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. A total of 43 patients [23 males and 20 females with mean age of 49 years] with mediastinal lymphadenopathy underwent DW and T2 weighted MRI and pathological examination in the period of January 2015 to June 2016. Diffusion restriction pattern, apparent diffusion coefficient (ADC) mean value, size and T2 heterogeneous signal intensity of the nodes were evaluated. Receiver operating characteristic curve analysis was used to determine ADC mean threshold values. The best predicting combinations of these four parameters were selected by means of stepwise logistic regression analysis. Results: ADC mean value of malignant lymphadenopathy (0.873±0.109×10−3 mm2/s) was significantly different from that of benign lymphadenopathy (1.663±0.311×10−3 mm2/s) (P &lt; 0.001). When an ADC mean value of 1.0955×10 −3 mm 2 /s was used as a threshold value for differentiating malignant from benign nodes, the best results were obtained with a sensitivity of 94%, a specificity of 96% and area under the curve of 0.996. The three other predictor variables didn’t add anything statistically significant to the regression equation with ADC mean. Conclusions: ADC mean value of malignant mediastinal lymphadenopathy was significantly different from the benign lymphadenopathy. The ADC mean value was the strongest independent predictor of malignancy.
Preclinical in vitro and in vivo study of UD-017, a novel highly selective and orally available CDK7 inhibitor, in a variety of cancers.
Authors: Kazuhiro Onuma, Yasuhiro Aga, Sayaka Ogi, Takashi Matsushita, Hidetoshi Sunamoto, Ayumi Ogawa, Yasunori Tokunaga, Shigeru Ushiyama
Journal: Journal of Clinical Oncology (2017)

e14086 Background: Cyclin dependent kinase 7 (CDK7) modulates mRNA transcription and some oncogenes are reported to be sensitive to inhibition of transcription in certain cancer cells. CDK7 inhibitors have been considered as an intriguing approach to treat cancers that depend on transcriptional regulation of their oncogenes. We synthesized a novel highly selective CDK7 inhibitor, UD-017, and found that the compound showed antitumor potency in a variety of cancers in vitro and in vivo. We therefore explored underlying mechanisms especially focusing on an oncogenic driver, c-Myc. Methods: We examined CDK7 selectivity of UD-017 against the other CDKs and kinases. We evaluated an antiproliferative activity of UD-017 in over 200 multiple types of cancer cell lines including patients-derived cancer cells. We then investigated the correlation between c-Myc expression levels and an antiproliferative activity of UD-017 in cancer cells. Antitumor efficacy of UD-017 was assessed in multiple types of cancer xenograft models and patients-derived xenograft model. We determined whether an intratumoral c-Myc expression levels correlated with in vivo antitumor efficacy of UD-017 in xenograft models. Results: UD-017 inhibited CDK7 enzyme (IC 50 = 16 nM) highly selectively among the CDKs (over 300-fold) and almost mono-specifically in a panel of 313 kinases assay. In a cellular antiproliferative panel assay, UD-017 broadly inhibited the proliferation of a variety of cancer cells and c-Myc expression levels showed the good correlation with antiproliferative activity. UD-017 showed favorable PK profile and good oral absorbability and showed the potent antitumor activity in multiple types of cancer xenograft models in mice. In correlation with the PK, UD-017 reduced the intratumoral c-Myc mRNA levels time-dependently after dosing of UD-017 in the colorectal cancer xenograft model. Conclusions: We identified a highly selective and orally available CDK7 inhibitor that showed the broad in vitro and in vivo antitumor activity in a variety of cancers, modulating c-Myc as an oncogenic driver. These data support the rationale for further advancing towards clinical development.