tbuckley/cabot-search huggingface dataset:
Reproductive factors and risk of melanoma
Authors: N.C. Støer, E. Botteri, R. Ghiasvand, M. Busund, S. Vangen, E. Lund, M.B. Veierød, E. Weiderpass
Journal: British Journal of Dermatology (2019)

Melanoma is the most severe form of skin cancer and in 2012 it accounted for 232,000 new cancer cases and 55,000 deaths worldwide. The most important risk factors for melanoma are exposure to ultraviolet radiation from the sun, indoor tanning, fair skin complexion, the presence of many nevi (moles) and freckles, light hair and skin reaction to sun. Female sex hormones such as estrogen and progestin have also been suggested to play a role in the development of melanoma due to the fact that melanoma is more common among females than males until the age of menopause, while the opposite is true after the age of menopause. One way to study how hormones are associated with the risk of developing melanoma is to study factors related to the female reproductive history, so called reproductive factors, such as age at menarche (first occasion of menstruation), menstrual cycle length, age at menopause and time from menarche to menopause, number of children, age at first and last birth and total breastfeeding duration. In the Norwegian Women and Cancer (NOWAC) study the authors investigated how reproductive factors were associated with the risk of melanoma overall, and by location on the body and melanoma subtype. NOWAC was initiated in 1991 and includes approximately 170,000 women from all over the country who were followed‐up for diagnosis of melanoma until the end of 2015. During follow‐up 1,347 melanoma cases were identified. In this large cohort the authors did not find convincing evidence of an association between reproductive factors and risk of melanoma overall. They did however observe an increased risk of the subtype superficial spreading melanoma with longer time between menarche and menopause.
Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer
Authors: Bradon R. McDonald, Tania Contente-Cuomo, Stephen-John Sammut, Ahuva Odenheimer-Bergman, Brenda Ernst, Nieves Perdigones, Suet-Feung Chin, Maria Farooq, Rosa Mejia, Patricia A. Cronin, Karen S. Anderson, Heidi E. Kosiorek, Donald W. Northfelt, Ann E. McCullough, Bhavika K. Patel, Jeffrey N. Weitzel, Thomas P. Slavin, Carlos Caldas, Barbara A. Pockaj, Muhammed Murtaza
Journal: Science Translational Medicine (2019)

Longitudinal analysis of circulating tumor DNA (ctDNA) has shown promise for monitoring treatment response. However, most current methods lack adequate sensitivity for residual disease detection during or after completion of treatment in patients with nonmetastatic cancer. To address this gap and to improve sensitivity for minute quantities of residual tumor DNA in plasma, we have developed targeted digital sequencing (TARDIS) for multiplexed analysis of patient-specific cancer mutations. In reference samples, by simultaneously analyzing 8 to 16 known mutations, TARDIS achieved 91 and 53% sensitivity at mutant allele fractions (AFs) of 3 in 10
Deep venous thrombosis and cancer (about 68 cases)
Authors: A. Tahri, M. El Hattaoui, N. Charei, M. El Belghiti, L. Mahmal, F. Tahiri, N. Bouras
Journal: Journal of Clinical Oncology (2007)

19672 Background: The association between cancer and deep venous thrombosis (DVT) has been known for a century. The goal of this retrospective study is to evaluate the risk factors and the characteristics of patients presenting with a DVT to determine the interest of a malignancy work up. Methods: This is a monocentric retrospective study of 405 DVT’s ± pulmonary embolism reported between January 2003 and July 2006, confirmed by sonogram and spiral CT. The risk factors for the embolic events as well as the diagnosis work up done to determine the origin of the embolism were analyzed. Results: In our population the mean age was 50 years, 300 patients (74 %) presented with at least one risk factor for thrombosis event, 68 cases were found to have a malignancy (16.8%) from which 9 were occult malignancies (found among 109 cases of idiopathic DVT’s).The mean age of the patients diagnosed with cancer was significantly higher with a female predominance. These malignancies were distributed as follow: 50% gynecologic origin, 25% gastrointestinal, 10% pulmonary, 9 % urologic and 6% of hematologic origin. The risk factors identified were: Surgery (OR = 4) and Chemotherapy (OR=6). The occult malignancies were mentioned during the encounter with 6 patients. The physical exam, abdomino-pelvic sonograms were sufficient for the etiologic diagnosis in 8 cases. Other exams like (tumor markers, gastrointestinal endoscopies) were non contributive, a part of the clinical orientation they provided. Conclusions: DVT’s do occur more frequently in operated cancer patients or those who received chemotherapy. The malignancies are more frequently of gynecologic or gastrointestinal origin. It appears that an extensive diagnosis work up is not cost effective, a basic work up including: a thorough history, a complete physical exam, simple blood tests (inflammatory markers and CBC) as well as a abdomino-pelvic sonogram are sufficient for the screening of a malignancy, extensive work up should be done as a second option. No significant financial relationships to disclose.
Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial
Authors: Fernando Torres, Harrison Farber, Arsen Ristic, Vallerie McLaughlin, John Adams, Jinkun Zhang, Preston Klassen, William Shanahan, John Grundy, Ines Hoffmann, Christopher Cabell, Pilar Escribano Subías, Namita Sood, Anne Keogh, Gwyn D'Souza, Lewis Rubin
Journal: European Respiratory Journal (2019)

Purpose This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH). Methods 61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 μg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 μg (300 μg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability. Results Ralinepag significantly decreased PVR by 163.9 dyn·s·cm −5 compared to an increase of 0.7 dyn·s·cm −5 with placebo (p=0.02); the least-squares mean change from baseline PVR was −29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients. Summary Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.
Simultaneous Left and Right Ventricular Thrombi Caused by Catastrophic Antiphospholipid Syndrome
Authors: Florie Akdime, Guillaume Voiriot, Sophie Lalevée, Clarisse Blayau, Pierre Antoine Allain, Michel Djibré, Aude Gibelin, Stephane Ederhy, Muriel Fartoukh, Vincent Labbé
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
The use and reporting of airline passenger data for infectious disease modelling: a systematic review
Authors: Margaux Marie Isabelle Meslé, Ian Melvyn Hall, Robert Matthew Christley, Steve Leach, Jonathan Michael Read
Journal: Eurosurveillance (2019)

BackgroundA variety of airline passenger data sources are used for modelling the international spread of infectious diseases. Questions exist regarding the suitability and validity of these sources.AimWe conducted a systematic review to identify the sources of airline passenger data used for these purposes and to assess validation of the data and reproducibility of the methodology.MethodsArticles matching our search criteria and describing a model of the international spread of human infectious disease, parameterised with airline passenger data, were identified. Information regarding type and source of airline passenger data used was collated and the studies' reproducibility assessed.ResultsWe identified 136 articles. The majority (n = 96) sourced data primarily used by the airline industry. Governmental data sources were used in 30 studies and data published by individual airports in four studies. Validation of passenger data was conducted in only seven studies. No study was found to be fully reproducible, although eight were partially reproducible.LimitationsBy limiting the articles to international spread, articles focussed on within-country transmission even if they used relevant data sources were excluded. Authors were not contacted to clarify their methods. Searches were limited to articles in PubMed, Web of Science and Scopus.ConclusionWe recommend greater efforts to assess validity and biases of airline passenger data used for modelling studies, particularly when model outputs are to inform national and international public health policies. We also recommend improving reporting standards and more detailed studies on biases in commercial and open-access data to assess their reproducibility.
Comparison of the incidence of colorectal cancer in young adults between the USA and Europe
Authors: Ting Wei, Peng Luo, Xiaoli Zhang, Weiliang Zhu, Jian Zhang
Journal: Gut (2019)

We read with interest the article titled ‘Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years’ by Vuik et al , in which they analysed trends in colorectal cancer (CRC) among young adults (20–49 years old) and found that CRC incidence is increasing among young adults in Europe.1 We have found that the incidence of CRC in young adults in Europe is significantly different from that in the USA.2 Therefore, we analysed the incidence of CRC in young adults with data from the Surveillance, Epidemiology and End Results database (from 1990 to 2016, a total of 78 295 cases, aged from 20 to 49 years) by the Joinpoint regression method and compared it with the results from Europe.

We found that the incidence of CRC in young adults in the USA increased annually, with an annual per cent change (APC) of 4.3% in the age group of 20–29 years, 2.47% in the age group of 30–39 years and 1.8% in the age group of 40–49 years (figure 1A–C). Although the incidence rate was increasing, the mortality rate had not changed significantly, which may be related to young adults presenting with more local or regional disease.3–5 We know little about the indications for colonoscopy in young adults, but studies have shown increases in colonoscopy use that parallel the incidence of CRC in young adults, which could explain the increasing …
Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden
Authors: Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Kazuya Nishii, Takehiro Matsubara, Hiroe Kayatani, Hisao Higo, Kiichiro Ninomiya, Akiko Sato, Hiromi Watanabe, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Minoru Takata, Yoshinobu Maeda, Katsuyuki Kiura
Journal: Journal of Thoracic Oncology (2019)
Treatment outcomes in patients older than age 60 with acute myeloid leukemia (AML) in the nonclinical trial setting.
Authors: Steven Duffy, Puneet Bains, Brian Pavlovitz, Neerja Vajpayee, Nancy Newman, Ajeet Gajra
Journal: Journal of Clinical Oncology (2012)

6572 Background: Optimal treatment of older adults with AML remains challenging. While AML tends to be a disease of older adults, this population experiences greater treatment-related toxicity and worse overall survival than younger patients. Only fit older adults enter clinical trials and thus the results may not apply to the entire population. Methods: We conducted a retrospective analysis of patients &gt; 60 years with AML (APL excluded) diagnosed prior to 2008 with IRB approval. The association of clinical factors (age, sex, comorbidities, prior chemotherapy), leukemia (prior myelodysplastic syndrome or myeloproliferative neoplasm, cytogenetics, WBC count), and therapy (induction chemotherapy, palliative chemotherapy, and best supportive care) as they relate to overall survival was evaluated using bivariate and multivariate regression analyses. Results: Of 87 patients (median age 73), 45% were male, 58% had high risk cytogenetics, 38% had prior MDS/MPD, 92% were chemotherapy naive, and 21% were in the high/very high Charlson risk class. The majority (67%) received standard dose induction chemotherapy (IC), 9% received (palliative intent) low-dose chemotherapy (LDC), and 24% received best supportive care (BSC). The median overall survival (OS) of the entire cohort was 2.5 months. On bivariate analysis high WBC (&gt;50,000 at presentation) was negatively associated (1.0 vs 2.7 months p &lt;0.01) with survival. OS for IC, LDC, and BSC were 3.1, 2.8, and 0.7 months, respectively (p=0.001). On multivariable analysis, IC conferred longer survival when compared to LDC and BSC combined (OR 0.33 CI 0.2-0.6, p&lt;0.001). High WBC was associated with a decreased survival time (OR 2.96 CI 1.6-5.5, p=0.02). Mortality during induction or consolidation chemotherapy was 38%. At 5-year follow-up, only 4 patients were alive. Conclusions: In a non-clinical trial setting, OS of older adults with AML remains dismal. While IC offers a chance of longer survival, mortality with IC is unacceptably high. Further studies are required to identify and validate tools for risk stratification in older adults with AML as well as to utilize therapies with an improved toxicity profile.
VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer
Authors: G. Lurje, A. M. Schultheis, A. E. Hendifar, S. Ashouri, W. Zhang, M. A. Gordon, F. Nagashima, H. M. Chang, D. Yang, H. J. Lenz
Journal: Journal of Clinical Oncology (2007)

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.
Injection Practices and Sexual Behaviors Among Persons with Diagnosed HIV Infection Who Inject Drugs — United States, 2015–2017
Authors: Sharoda Dasgupta, Yunfeng Tie, Ansley Lemons, Kathleen Wu, Janet Burnett, R. Luke Shouse
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During 2016, 6% of persons in the United States who received a diagnosis of human immunodeficiency virus (HIV) infection had their HIV infection attributed to injection drug use (1). Injection practices and sexual behaviors among HIV-positive persons who inject drugs, such as injection equipment sharing and condomless sex, can increase HIV transmission risk; nationally representative estimates of the prevalences of these behaviors are lacking. The Medical Monitoring Project (MMP) is an annual, cross-sectional survey that reports nationally representative estimates of clinical and behavioral characteristics among U.S. adults with diagnosed HIV (2). CDC used MMP data to assess high-risk injection practices and sexual behaviors among HIV-positive persons who injected drugs during the preceding 12 months and compared their HIV transmission risk behaviors with those of HIV-positive persons who did not inject drugs. During 2015-2017, approximately 10% (weighted percentage estimate) of HIV-positive persons who injected drugs engaged in distributive injection equipment sharing (giving used equipment to another person for use); nonsterile syringe acquisition and unsafe disposal methods were common. Overall, among HIV-positive persons who injected drugs, 80% received no treatment, and 57% self-reported needing drug or alcohol treatment. Compared with HIV-positive persons who did not inject drugs, those who injected drugs were more likely to have a detectable viral load (48% versus 35%; p = 0.008) and engage in high-risk sexual behaviors (p<0.001). Focusing on interventions that reduce high-risk injection practices and sexual behaviors and increase rates of viral suppression might decrease HIV transmission risk among HIV-positive persons who inject drugs. Successful substance use treatment could also lower risk for transmission and overdose through reduced injection.
A combined evaluation strategy of FDG PET/CT and contrast-enhanced diagnostic CT (ceCT) for lymph nodes in the neck.
Authors: Neetha Gandikota, Su Ann Ng, Ryan Cotter, Yildiz Akin, Peter M. Som, Eric Genden, Sherif Heiba, Lale Kostakoglu
Journal: Journal of Clinical Oncology (2012)

5578 Background: Accurate assessment of cervical lymph nodes (LNs) for determination of metastatic involvement is of prime importance for management. Our objective was to determine the incremental value of combining metabolic and morphologic information in the differentiation between benign and malignant LNs. Methods: A total of101 pts with head and neck squamous cell (n=91) or thyroid cancer (n=6) or lymphoma (n=4) were included in the study. PET/CT and neck ceCT were acquired simultaneously or sequentially at staging (n=48) or restaging (n=53). In 131 LNs, variables evaluated includes SUVmax, size, shape (elliptical vs non-elliptical), presence of extracapsular extension (Ecext-irregular margins), necrosis, and fatty hilum. Histopathology (n=96) and 12 mo follow-up (n=35) were used for confirmation of the findings. ROC analyses determined the SUVmax cut-off. Results: Of131 LNs, malignancy wasconfirmed in 49 (37%).Results are shown in table. In the detection of malignancy, SUVmax of 4.5 yielded the best balance between the sensitivity and specificity, performing better than all CT variables alone. Combination analysis improved results only when SUVmax (4.5) was added to Ecext. However, best combination results were obtained at a SUV cut-off of 3.7. Higher SUV cut-off did not significantly improve overall performance of SUVmax alone (Table). Conclusions: In the differentiation of malignant from benign LNs, SUVmax (4.5) yields better results than CT variables alone. However combining a lower SUVmax (3.7) with Ecext produced the best results. Increasing SUVmax cut-off only produced a gain in specificity at a significant cost of sensitivity. [Table: see text]
Abstract 4018: Pan-cancer predictions of drug sensitivity based on protein-coding and non-coding RNA biomarkers
Authors: John P. Lloyd, Nathan Merrill, Eric Lachacz, Jun Z. Li, Sofia Merajver, Matthew Soellner
Journal: Cancer Research (2019)

Abstract Molecular characteristics that accurately forecast tumor response to drug therapies represent an important target for precision cancer treatment. However, it is not known whether tumor drug response can be predicted in a tissue-agnostic manner or if predictions must be established within historically-defined cancer types and subtypes. To address this question, we utilized public datasets to test whether multi-omics biomarkers in 346 tumor cell lines representing 17 cancer types can predict response to five small molecule therapies (2 MEK, 2 PI3K, and 1 FGFR inhibitors). The pool of potential biomarkers tested included 51,268 total RNA expression levels and DNA variants. We identify a panel of 45 gene expression levels capable of accurately predicting response to MEK inhibitors (AUC-ROC &amp;gt;0.90), indicating that tumor response to small molecule drugs can be predicted regardless of cancer type. We found that RNA expression levels, notably among non-coding sequences, were most important for predictions. Experimental validation of the 45-gene panel is demonstrated based on predicted and observed MEK inhibitor sensitivity in 12 cell lines from 5 cancer types without previously known drug sensitivities. Successful pan-cancer predictions of drug response in cancer cell lines represents a critical step toward truly personalized treatment in real time, based on the characteristics of individual tumors. Citation Format: John P. Lloyd, Nathan Merrill, Eric Lachacz, Jun Z. Li, Sofia Merajver, Matthew Soellner. Pan-cancer predictions of drug sensitivity based on protein-coding and non-coding RNA biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4018.
Iron-deficiency anemia and cardio-renal toxicity of doxorubicin in hypertensive rats.
Authors: Jorge E Toblli, Carlos Rivas, Gabriel Cao, Jorge Giani, Fernando Dominici
Journal: Journal of Clinical Oncology (2012)

e19569 Background: Hypertension and anemia are common in patients with neoplasm and may increase the toxicity of anti-cancer drugs. This study evaluated cardio-renaltoxicity of doxorubicin (DOX) in combination with iron deficiency anemia (IDA) in Spontaneously Hypertensive Stroke Prone (SHRSP) rats. Methods: SHRSP rats were randomized into six groups (A-F; n=8 each). IDA was induced in groups A-D by 12 weeks low iron diet; groups E and F had normal diet. After 6 weekly DOX or control treatments (0.9% saline), echocardiography was performed and blood analyzed for hemoglobin (Hb) and transferrin saturation (% TSAT). Tissue sections and homogenates from heart and kidney samples were analyzed for markers of oxidative-nitrosative stress and inflammation. Results: IDA plus DOX was associated with significantly lower cardiac performance (% FS) and kidney function (CrCl) and a higher degree of cardio-renal oxidative-nitrosative stress and inflammation (Table). Conclusions: The results show that IDA can aggravate dose dependent DOX-induced cardio-renal toxicity in hypertensive rats and confirm that IDA significantly induces oxidative-nitrosative stress and inflammation. [Table: see text]