tbuckley/cabot-search huggingface dataset:
Circulating tumor cells (CTCs) in metastatic breast cancer: Ethnicity and disease subtypes.
Authors: Tiffany P. Avery, Laura Austin, Jocelyn Andrel-Sendecki, Tamer Mahmoud Fouad, Antonio Giordano, James M. Reuben, Rebecca J. Jaslow, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2014)

e22027 Background: Circulating Tumor Cells (CTCs) are an independent prognostic indicator of progression free survival (PFS) and overall survival (OS) in metastatic breast cancer (MBC), and are used as a means of assessing response to treatment. The prognostic value of CTCs for clinical and pathologic MBC is known, but the detection rate and value in diverse ethnic groups has not been evaluated. Methods: This is a retrospective analysis of 516 patients with MBC from UT MD Anderson Cancer Center who had CTCs enumerated as part of their evaluation and monitoring. The baseline CTCs enumeration was evaluated for PFS and OS and associations with ethnicity, inflammatory breast cancer (IBC) vs. non-IBC, ER, PR, Her2 status, and cancer subtypes. Associations with CTCs were calculated in two ways: CTCs as a continuous variable and CTCs categorized as < 5 or ≥ 5. Results: Patients' average age was 50 years; three-quarters were White. Ethnicity was not significantly associated with CTC enumeration; however, Hispanic women had the lowest levels of CTCs (not statistically significant). Additionally, patients with IBC had significantly lower levels of CTCs than those with non-IBC (both when calculated as a continuous and categorical variable). Also of note is that HER2 negative patients had higher CTCs than the HER2 positive patients when evaluated by the continuous CTCs method (P-value= 0.006). Patients with CTCs ≥ 5 had a lower median survival time than those with < 5 CTCs (17.8 vs. 30.5 months, p < 0.001) and twice the hazard of death (HR = 2). There was no difference in PFS or OS by ethnicity. By cancer subtype, triple negative patients had the poorest overall and progression-free survival. Conclusions: CTCs enumeration is a strong independent prognostic factor whose value is not affected by ethnicity. The trend towards lower CTCs values in Hispanic women should be prospectively evaluated in a larger cohort of patients with MBC. Moreover, IBC patients demonstrated that they were less likely to have elevated CTCs than their non-IBC cohorts despite the aggressive nature of the disease which underscores its complex biology. This study further illustrates the nuances of CTCs, which will continue to evolve as they are used and evaluated in clinical practice.
Early survival outcomes in stage I-III operated colon cancer patients from a low prevalence, lower-middle income country: The Indian experience.
Authors: Rushabh Kiran Kothari, Vikas S. Ostwal, Anant Ramaswamy, Tara Chand Gupta, Sandeep Kumar Bairwa, Akhil Kapoor, Amit Kumar, Pradeep Ventrapati, Mukta Ramadvar, Supreeta Arya, Suman Kumar, Prachi Patil, Ashwin DeSouza, Avanish Saklani
Journal: Journal of Clinical Oncology (2018)

857 Background: Data regarding survival and outcomes in operated colon cancer patients from a lower-middle income and low prevalence nation like India is scarce. Methods: Patients who underwent curative resection for non-metastatic, non-rectal colon cancer from January 2013 to December 2016 were retrospectively analyzed from a prospectively maintained database for baseline demographics, disease characteristics, adjuvant chemotherapy, recurrence free survival (RFS) and overall survival (OS). RFS and OS were calculated by Kaplan Meier method. Results: 505 patients underwent resection in the pre-defined time-period. Median age of the patients was 53 years (range: 17 – 87) and 339 patients (67.3%) were male. Patients with stage I, stage II and stage III disease were 43(8.6%), 233(46.1%) and 217(42.9%), respectively, while 12 patients(2.4%) were not adequately staged, though non-metastatic. Right sided colon cancers were more prevalent as compared to left sided (56% vs. 44%) and 41 patients (8%) had signet ring adenocarcinoma on cytomorphology. Median number of nodes retrieved during surgery was 22 nodes(range:1-96 ). Adjuvant chemotherapy was planned for 406 patients (80.4%), with the common regimens used being capecitabine-oxaliplatin, capecitabine , 5-fluorouracil – oxaliplatin and 5-fluorouracil in 280 (55.2%), 80 (16%), 34 (7%) and 6 patients (1.2%), respectively. Planned adjuvant chemotherapy was completed in 334 patients(82.3%; n = 406) with 27 patients (6%) required dose reduction. 35 patients (7%) required permanent cessation of adjuvant treatment due to chemotherapy related toxicity. With a median follow up of 21.8 months (range: 0-56),estimated 3 year RFS for the entire cohort was 86.2% and estimated median OS was 95.2%. Estimated RFS in stage I, Stage II, stage III patients were 90.3%, 89.5% and 78% respectively (p-0.006). Conclusions: Early survival outcomes with Stage I-III colon cancers in a low prevalence country like India appears to be comparable or potentially superior to outcomes published from high prevalence countries. Adjuvant chemotherapy in Stage II and Stage III colon cancers in a real world scenario in India appears to be well tolerated.
Mutational landscape of metastatic colorectal cancer: Aggregate insights from a molecular tumor board.
Authors: Mark Andrew Lewis, Derrick S. Haslem, Ramya Thota, Terence Duane Rhodes, Tyler Barker, Bryce Moulton, Tyler Abraham, Gail Fulde, Robin Romero, Bryce Christensen, Lincoln Nadauld
Journal: Journal of Clinical Oncology (2018)

837 Background: The mutational landscape of metastatic colorectal cancer (CRC) is being elucidated by next-generation sequencing of both primary tumors and metastatic foci. In this study, we examined the results of all stage IV CRC cases submitted to our molecular tumor board (MTB). Methods: We performed a retrospective analysis of all patients who had next-generation sequencing performed between January 2015 and August 2017 on either their primary tumor and/or metastasis. Cases were presented at a MTB convened twice monthly. For the purposes of this study only pathogenic mutations were notated, not variants of unknown significance (VUS). Results: Eighty-seven unique patients had 97 specimens sequenced (28 primary tumors and 69 metastases). The primaries averaged 3 mutations per specimen (range: 1-6) whereas the metastases averaged 4 (range: 1-14, p=.25). The most common anatomic sites of submitted metastatic tissue were the liver (n=35, average mutations=4), followed by the lungs (n=10, average mutations=3) and the omentum/peritoneum (n=8, average mutations=3). Two patients had both a primary tumor and a metastasis sequenced, with a 33% rate of concordance in inter-specimen mutations. Five patients had multiple metastases sequenced, with a 53% rate of concordance in inter-specimen mutations; in every case of longitudinal sequencing, mutational burden increased in metastases over time. The most common mutation was apc (21% of all mutations), followed by p53 (16%) and then kras (13%). Candidacy for EGFR-directed therapy was found in 8 cases, and mismatch repair defects were detected in 5 cases. Conclusions: In stage IV CRC cases sent to our MTB, tissue from metastases was more commonly submitted for analysis than from the primary tumors. There is not necessarily concordance between mutations in primary tumors and metastases, nor among multiple metastases in the same patient. Sequencing at multiple time points in the disease course may allow observation of clonal evolution and dynamic adaptation of therapeutic targets.
Cytokine genes show distinct polymorphism pattern in Hymenoptera venom allergy
Authors: Betül Ayşe Sin, Hüseyin Tutkak, Esra Birben, Kenan Köse, Zeynep Mısırlıgil
Journal: Allergy (2018)

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An Integrated Genomics Analysis Identifies Recurrent Gain- and Loss-of-Function Events and in Distinct Subtypes of Multiple Myeloma
Authors: Sara Nasser, Jessica Aldrich, Daniel Penaherrera, Austin Christofferson, Christophe Legendre, Jennifer Yesil, Daniel Auclair, Winnie Liang, Sagar Lonial, Sheri Skerget, Jonathan J Keats
Journal: Blood (2018)
Updated Results of Phase 2 Study of Ruxolitinib in Combination with 5-Azacitidine in Patients with Myelofibrosis
Authors: Lucia Masarova, Srdan Verstovsek, Jorge E. Cortes, Naveen Pemmaraju, Prithviraj Bose, Maro N. Ohanian, Lingsha Zhou, Sherry A. Pierce, Romany Gergis, Gautam Borthakur, Zeev E. Estrov, Guillermo Garcia-Manero, Hagop M. Kantarjian, Naval G. Daver
Journal: Blood (2018)
Molecular profiling of low-grade gliomas (LGG) in Colombia (ONCOLGroup).
Authors: Andres F. Cardona, Jose Behaine, Enrique Jimenez, Fernando Hakim, Nicolas Useche, Sonia Bermudez, Oscar Arrieta, Juan A. Mejia, Hernan Carranza, Jorge M. Otero, Diego Benavidez, Pierre M. Edy, Carmen Balañá, July Rodriguez, Leon D. Ortiz
Journal: Journal of Clinical Oncology (2014)

2076 Background: LGG are classified according to the WHO as being astrocytoma (DA), oligodendroglioma (OD) or mixed glioma (OA). TP53 mutation and 1p19q codeletion have been the main molecular abnormalities recorded to date. Although IDH1/2 mutations have been described in up to 85% of LGG, IDH negative gliomas do occur. It has recently been found that ATRX plays a significant role in glioma oncogenesis. Methods: We searched for P53 and Olig2 protein expression, MGMT methylation status (pMGMT), 1p19q codeletion and IDH/ATRX status in 63 Colombian LGG patients (pts). Overall survival (OS) rate was estimated and compared between groups and according to genotype. Results: Mean age was 40.1-yo (±12.3), 50% of the pts were male, mean lesion diameter was 41.7 mm (±17.2 mm) and histological distribution was 61.9%, 25.4% and 12.7% for AD, OD and OA, respectively. Surgical resection was total in 47.6%, subtotal in 31.7% and biopsy was performed in 20.6% of the cases. Alterations in IDH1/2 were found in 57.1%, pMGMT+ in 65.1%, overexpression of p53 and Olig2 in 30.2% and 44.4%, and 1p19q codeletion in 34.9%. The presence of alterations in ATRX was analysed in 25 patients, being positive in 16% (all IDH1+/1p19q-). Median follow-up was 15.8 months (95%CI 7.6-42.0), OS was 39.2 months (95%CI 2.5-274) and the variables positively modifying OS were pMGMT+ (p=0.004), 1p19q codeletion (p=0.015), the extension of surgical intervention (p=0.011) and the number of lobes involved (p=0.021). Multivariate analysis showed that pMGMT and 1p19q codeletion modified the OS in our population (p=0.039 and 0.047, respectively). Conclusions: This is the first study which has evaluated the molecular profile in LGG pts from Latin-America. Our findings confirmed the prognostic relevance of pMGMT and 1p19q codeletion, without finding a positive relation for IDH1/2 mutations. This finding could have been explained by sample size and selection bias. Mutations in ATRX are limited to the population of pts having AD/OA and IDH1+/1p19q-.
SP0064 Hot session: recent advances in the management of spondyloarthritis
Authors: S. Ramiro
Journal: Annals of the Rheumatic Diseases (2018)

In the last years the treatment armamentarium for spondyloarthritis (SpA) has been expanded. In addition to non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF)-inhibitors, we nowadays count in daily clinical practice with IL-17-blockers for the treatment of patients with axial SpA. This increase in treatment options has led to an update of the ASAS-EULAR management recommendations, which will be discussed in this lecture, together with the evidence supporting them. Currently, several studies on tapering to stop biologics in patients with axial SpA with inactive disease are being conducted and the first results available will be discussed. The path is being paved for a treat-to-target approach that is gaining shape in SpA. More evidence towards such an approach has been gathered throughout the last years and strategy trials are now ongoing. Inhibition of structural progression remains a hot topic in SpA. Whether or not the current interventions we have can achieve such an outcome is not yet fully clear, and the challenges related to this will be discussed in this lecture. More data has come out to help us gain more insight into this complex relationship between disease activity and structural damage and the effect of therapy on it. <h3>Disclosure of Interest</h3> S. Ramiro Grant/research support from: MSD, Consultant for: Lilly, Novartis, AbbVie
Incidence, mortality, and temporal patterns of oropharyngeal cancer in China: a population‐based study
Authors: Jie Liu, Xu‐li Yang, Si‐Wei Zhang, Li‐Ping Zhu, Wan‐Qing Chen
Journal: Cancer Communications (2018)

Abstract Background Thus far, the incidence, mortality, and temporal trend data of oropharyngeal cancers (OPC) in China were few. We estimated the incidence, mortality, and temporal patterns of OPC in China during 2008–2012 according to the data from 135 population‐based cancer registries to better understand the epidemiological pattern of OPC and to provide more precise information for OPC control in China. Methods According to the data of diagnosed OPC reported to 135 cancer registries during 2008–2012, we calculated age‐standardized rate of incidence and mortality by 2000 Chinese standard population (ASRIC and ASRMC) and by 1985 Segi's world standard population (ASRIW and ASRMW) by age, sex, and geographic regions; annual percentage changes of OPC incidence and mortality were calculated using Joinpoint trend analysis. Results ASRIW and ASRMW were 2.22/100,000 person‐years and 0.94/100,000 person‐years, respectively. The incidence and mortality in urban areas were higher than those in rural areas. ASRIC and ASRIW of males were higher than those of females. The overall ASRIC of OPC was significantly increased by 6.2% annually between 2003 and 2006 ( P = 0.038), but remained stable between 2007 and 2012 ( P = 0.392). ASRIC and ASRMC of males and in rural areas were significantly increased in the last decade ( P &lt; 0.05), but the rates of females remained stable during the same period ( P &gt; 0.05). Conclusions Across multiple cancer registries in China, there was an obvious increase in OPC in the recent decade, especially for incidence and mortality of males and in rural areas, whereas the rates of females remained stable. A healthy lifestyle should be advocated and early diagnosis and early treatment of OPC should be enhanced.
Efficacy and Safety of 1500 mg Voxelotor in a Phase 2a Study (GBT440-007) in Adolescents with Sickle Cell Disease
Authors: Clark Brown, Carolyn Hoppe, Adlette Inati, Miguel R. Abboud, Winfred Wang, Robert Liem, Gerald Woods, Lewis L. Hsu, Victor R. Gordeuk, Connie Piccone, Richard A. Drachtman, Erica Fong, Sandra Dixon, Margaret Tonda, Carla Washington, Joshua Lehrer-Graiwer
Journal: Blood (2018)
Prognostic factors in hemangioendotheliomas (HE): Analysis based on the Surveillance, Epidemiology, and End Results (SEER) program.
Authors: Monica Reddy Muppidi, Jayanthi Vijayakumar, Adrienne Groman, Kilian Salerno, Valerie Francescutti, John Michael Kane, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2014)

10584 Background: HE are rare vascular soft tissue (ST) tumors with variable clinical biology. Prognostic factors and treatment (rx) options are poorly defined. This study aimed to describe patient (pt) and tumor features of HE and identify predictors of survival using the SEER database (1973-2010). Methods: HE and epithelioid HE (EHE) pts were identified using codes 9130/3, 9133/3. Demographics, tumor features and rx were retrieved. We sorted age cohorts based on Adolescent and Young Adult Oncology Progress Review Groups into children (0-15 yrs), young adults (16-39), adults (40-64), elderly (>65). Overall survival (OS) and disease specific survival (DSS) were compared using multivariate (MVA) proportional hazards methods controlling for age, gender, race, grade, stage, radiation (RT), surgery (S), size, year and histology. Analyses were done using SAS version 9.4. Results: 606 pts (296 EHE) were identified; median age 52 yrs (0-97), 52% female. 72% pts were > 40 yrs and most were white (85%). 443 pts had grade (G) 3 tumors. 36% cases were diagnosed from 2001-10, compared to 20% from 1973-1980. 52% had locoregional disease and 29% were metastatic. ST (38%), liver (18%) and bone (14%) were most common sites affected. 65% underwent S and 24% received RT. Tumor size data available on 406 pts revealed 27% tumors < 5cm. At a median follow-up of 70 months (m), the median OS was 35m (95% CI 27, 46); 5-yr OS was 43%. 5-yr DSS was 58%. In a univariate model on 401 pts (excluding 205 pts with missing data), age > 40, tumor grade 2/3, size > 5cm, distant disease and absence of S predicted for poorer OS. MVA for OS confirmed worse prognosis for adults (HR 3.6; 95% CI 1.3, 9.97), elderly (HR 12.85; 4.57, 36.14), G2 tumors (HR 1.74; 1.01, 3), size 5-10cm (HR 2.92; 1.69, 5.06), size > 10cm (HR 2.45; 1.29, 4.63), distant disease (HR 3.04; 1.97, 4.7) and no S (HR 1.71; 1.22, 2.42); all p-values < 0.05. Females had improved DSS (HR 0.69; 0.48, 0.98; p=0.04) but similar OS. Race, EHE histology and RT did not affect DSS or OS. Conclusions: Recognizing inherent bias using SEER data, age, tumor size and grade were predictive factors for survival in this study, the largest of its kind in HE. Surgical resection is important for improving outcome in HE.
Retrospective Analysis of the Efficacy and Safety of Modified Bortezomib-Lenalidomide-Dexamethasonelite (modified RVD-lite) Therapy for Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma
Authors: Kiyoshi Okazuka, Tadao Ishida, Junichiro Nashimoto, Takao Yogo, Kanji Miyazaki, Kota Sato, Yui Uto, Mizuki Ogura, Yumiko Yoshiki, Yu ABE, Nobuhiro Tsukada, Kenshi Suzuki
Journal: Blood (2018)
Recurrent glioblastoma: Does the timing of bevacizumab treatment impact survival?
Authors: Susmita Sakruti, Jaskirat Singh Randhawa, Sandra D. Griffith, Glen Stevens, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2014)

2039 Background: Bevacizumab (Bev) is FDA approved for use in recurrent glioblastoma (rGBM). There is limited literature on outcomes in rGBM depending on the time of initiation of Bev therapy. We examined the progression-free survival (PFS) and overall survival (OS) in rGBM patients treated with Bev at our center. Methods: With IRB approval, the Cleveland Clinic Brain Tumor database was used to examine 690 rGBM patient charts (2003 to 2013). The patients were stratified into three groups: 1) patients treated with Bev at first recurrence, 2) second recurrence, and 3) ≥ 3 recurrences. OS and PFS between the three cohorts were calculated using Kaplan-Meier analysis and compared using Renyi log-rank tests. Results: One hundred and fifty patients, median age 56 years (range: 24-83), were included in this analysis. Median KPS prior to Bev treatment was 80 (range: 40-100). Twenty-eight patients had multifocal and 122 had unifocal GBM at time of starting Bev therapy. The median number of comorbidities at diagnosis were 1 (range: 0-4). Seventy five patients (50%) received Bev at first recurrence, 50 patients (33%) started Bev at second recurrence, and 25 patients (17%) were treated with Bev at third or later recurrences. Median OS from start of Bev was 12.2 months (95% CI: 10.0, 14.3) and median PFS was 8.3 months (95% CI: 6.2, 10.2). Stratified by recurrence and initiation of Bev, median PFS was 7.1 months (95% CI: 5.9, 10.1) for the first recurrence, 9.9 months (95% CI: 6.3, 25.2) for second recurrence, and 9.4 months (95% CI: 3.8, 16.8) for the third recurrence (p=0.09). Median OS was 11.7 months (95% CI: 10.3, 14.3) for first recurrence, 10.0 months (95% CI: 8.1, 39.3) for second recurrence, and 13.9 months (95% CI: 8.2, 18.4) for the third recurrence (p=0.26). Conclusions: There was no significant difference in median OS or PFS in the three rGBM groups treated with Bev. GBM N OS [months] (p=0.26) PFS [months] (p=0.09) 1st recurrence 75 11.7 7.1 2nd recurrence 50 10.0 9.9 ≥3rd recurrence 25 13.9 9.4
The different roles on metastasis of fibulin-2 gene in lung cancer.
Authors: Hulya Yazici, Mukaddes Avsar, Ozge Sukruoglu, Seda Kilic, Demet Akdeniz, Bugra Tuncer, Rumeysa Ciftci, Aysel Ahmedova, Sezai Vatansever, Makbule Tambas
Journal: Journal of Clinical Oncology (2014)

e19130 Background: The Fibulins are a recently discovered family of ECM proteins.In this study, expression levels of the fibulin-2 (FBLN2) gene in lung cancer patients and its role in the formation of different metastatic foci have been investigated. Methods: We analyzed 106 lung cancer patients with different organ metastasis and 8 paraffin-embedded tissues and 27 healthy controls which were ethnicity, age and gender matched were investigated for expression levels of FBLN2 gene. cDNAs obtained from plasma, peripheral blood lymphocytes and tumor tissues of patients were amplified with both specific primers for FBLN2 target gene and HPRT1 housekeeping gene by Quantitative Real Time PCR (qRT-PCR). Results: FBLN2 gene expression levels of peripheral blood lymphocytes were found to be decreased approximately 2 fold in all subsets of lung cancer patients. Our results indicate a significant difference between patients subgroups and healthy controls (p <0.05) statistically. However, we observed no statistically significance (p> 0.05) among subgroups of lung cancer for expression levels of FBLN2 gene. Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues of lung cancer patients compared to their peripheral blood lymphocytes. Conclusions: Despite dramatic increase of FBLN2 gene expression levels in paraffin embedded tissue, decrease of FBLN2gene expression levels in peripheral blood lymphocytes suggest that fibulin-2 molecules might induced metastatic potential through interaction with the other molecules in the microenvironment.The present work was supported by the Research Fund of Istanbul University. Project No. 25255.