tbuckley/cabot-search huggingface dataset:
A phase II study of radiosurgery and temozolomide for patients with one to four brain metastases
Authors: J. B. Fiveash, S. M. Sawrie, B. L. Guthrie, S. A. Spencer, R. F. Meredith, J. M. Markert, R. A. Nordal, R. M. Conry, L. B. Nabors
Journal: Journal of Clinical Oncology (2007)

2048 Background: To determine if temozolomide reduces the risk of distant brain failure (DBF, metachronous brain metastases) in patients with 1–4 brain metastases treated with radiosurgery without whole brain radiation therapy. Methods: Twenty-five patients with newly diagnosed brain metastases were enrolled in a single institution phase II trial of radiosurgery (15–24 Gy) and adjuvant temozolomide. Temozolomide was started within 14 days of radiosurgery and was administered 150–200 mg/m 2 p.o. q day x 5 days in 28 day cycles. Temozolomide was continued for a total of 12 cycles unless the patient developed DBF, unacceptable toxicity, or systemic progression requiring other therapy. If more than 4 metastases were identified on the MRI performed on the day of radiosurgery, then the patient could still be treated on the clinical trial if all tumors could be treated with radiosurgery. In addition to clinical and radiographic follow-up, QOL was assessed utilizing the FACT-Br questionnaire. Results: Twenty-five patients were enrolled 2002–2005; three were not evaluable for determining DBF. Of the remaining twenty-two patients, tumor types included NSCLC (n=8), melanoma (n=7), other (n=7). Extracranial disease was present in ten (45%) patients. The median number of tumors was 3 (range 1–6). The median overall survival was 31 weeks. The median radiographic follow-up for patients that did not develop DBF was 33 weeks. Six patients developed DBF. The one year actuarial risk of DBF was 37%. Patients with melanoma had a higher risk of DBF than other patients (p&lt;0.001, log-rank). Only 1/15 patients without melanoma vs. 5/7 patients with melanoma developed DBF. 15 serious adverse events (SAEs) occurred in 10 of the patients, but none of the SAEs were judged to be likely related to temozolomide. Among patients that experienced DBF, no significant differences were seen in QOL when pretreatment FACT-Br and time of distant brain failure FACT-Br scores were compared. Conclusions: Adjuvant temolozomide after radiosurgery is associated with a low risk of distant brain failure in non-melanoma patients. Larger clinical trials should examine the relative efficacy and QOL of WBRT and temozolomide in non-melanoma brain metastases patients. No significant financial relationships to disclose.
Serum folate, LINE-1 hypomethylation, and overall survival in a prospective cohort of hepatocellular carcinoma patients.
Authors: Abby B. Siegel, Abhishek Goyal, Rosa Hidalgo, Robert S Brown, Alfred I. Neugut, Elizabeth Verna, Jean Emond, Benjamin Samstein, Tomoaki Kato, Mary Gamble, Lorna Dove, Regina Santella
Journal: Journal of Clinical Oncology (2012)

4101 Background: Folate plays a central role in DNA methylation reactions, but the relationship between folate and methylation status has not been studied in HCC patients. We hypothesized that low folate levels would correlate with global hypomethylation, and worsened survival in HCC patients. Methods: 72 newly-diagnosed HCC patients were enrolled in a prospective study, beginning 10/08, and followed until 9/11. We excluded those with previous malignancy, and uncompensated Child Pugh (CP) B or C disease. We used pyrosequencing to evaluate quartiles of LINE-1 methylation in plasma as a surrogate for global tumor hypomethylation. We evaluated the relationship between folate deficiency (serum folate levels &lt; 6ng/mL), DNA hypomethylation (LINE-1 methylation &lt; 25 th percentile i.e., &lt; 69.4%), and overall survival in our cohort. Results: Median age was 60; 82% were men and 67% had hepatitis C. Mean serum folate levels were 12.1 ng/mL (SD = 5.3 ng/mL), while mean % LINE-1 methylation was 69.9 (SD = 4.6). In a univariate analysis, folate deficiency and LINE-1 hypomethylation were significant predictors of poor overall survival (HR = 3.77; 95% CI: 1.37, 10.41, and HR=3.50; 95% CI: 1.51, 8.13, respectively). These markers remained independent predictors of survival in a multivariate model including age, CP class, AJCC stage and AFP. HR for folate deficiency in this model was 3.52 (95% CI: 1.16, 10.70), and HR for LINE-1 hypomethylation was 2.74 (95% CI: 1.10, 6.85). We also found a significant association between folate deficiency and LINE-1 hypomethylation (p = 0.04). Conclusions: We provide novel data that folate deficiency is an independent predictor of worsened overall survival in patients with HCC in a multivariate model. Further, we show that global changes in DNA methylation assesed in plasma correlate with folate levels, supporting a possible mechanistic link between the two. Folate supplementation, and the use of other agents which modulate methylation, deserve further study in HCC.
Tumor size and overall survival in a cohort of young (≤40 years), nodenegative, systemically untreated breast cancer patients; by the PARADIGM study group
Authors: V. De Jong, N.D. ter Hoeve, M. Opdam, W. Vreuls, E. Koop, Z. Varga, S.M. Willems, C.H.M. van Deurzen, A. Cordoba, A. Broeks, N. Stathonikos, A. Voogd, K. Jozwiak, M. Hauptmann, G.S. Sonke, E. van der Wall, S. Siesling, P.J. van Diest, S.C. Linn, G M H E Dackus
Journal: Annals of Oncology (2019)
Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1/TRK fusion-positive solid tumors (TRIDENT-1 study)
Authors: A. Drilon, B.C. Cho, D.-W. Kim, J. Lee, J.J. Lin, V. Zhu, R.D. Camidge, S. Stopatschinskaja, J.J. Cui, D.M. Hyman, S.-H. Ou, A.T. Shaw, R.C. Doebele
Journal: Annals of Oncology (2019)
Safety of tumour treating fields delivery to the torso: Meta analysis from TTFields clinical trials
Authors: F. Grosso, M. Pless, G.L. Ceresoli
Journal: Annals of Oncology (2019)

Abstract   Background  Tumor Treating Fields (TTFields) are a non-invasive, antimitotic therapy delivered to the tumor via transducer arrays applied to the skin at tumor site. The only TTFields-related adverse event (AE) reported in clinical trials was localized dermatitis beneath the arrays. The safety of TTFields has also been investigated in glioblastoma, non-small-cell lung cancer (NSCLC), mesothelioma, pancreatic and ovarian cancer. This meta-analysis reported AEs in clinical studies with TTFields torso delivery.    Methods  192 patients from 4 pilot studies were included in the analysis: EF-15 (n = 41, advanced NSCLC), PANOVA-2 (n = 40, advanced pancreatic adenocarcinoma), STELLAR (n = 80, malignant pleural mesothelioma) and INNOVATE (n = 31, recurrent ovarian carcinoma). The frequency of TTFields applied was 150 kHz in all except 200 kHz in the INNOVATE study. All patients received standard of care systemic chemotherapy for their disease in addition to TTFields. Severity and frequency, of AEs were reported using CTCAE Version 4 and CTCAE 3 in EF-15. AEs were reported as incidence by body system and MedDRA terms.    Results  The median age was 63 (range: 44-78), 73 (49-81), 67 (27-78) and 60 (45-77) for EF-15, PANOVA-2, STELLAR and INNOVATE, respectively. Patients had an ECOG score of 0-1, except for 7 patients in the EF-15 study with ECOG score of 2. Low grade gastrointestinal (GI) toxicities reported with an incidence ≥5%: constipation (16%), diarrhea (14%), nausea (27%), vomiting (13%). None of the GI toxicities was associated with TTFields, and the incidence of high-grade GI toxicities did not reach 10%. Low grade disorders such as asthenia (12%), fatigue (18%) and anorexia (2%) were common (    Conclusions  This meta-analysis detected no new safety signals in clinical studies where TTFields were applied to the torso. The incidence of TTFields-related skin toxicity was similar to that reported in glioblastoma patients. The application of TTFields to the torso is safe.    Clinical trial identification  NCT: 01971281, 02244502; 02397928; 00749346.    Legal entity responsible for the study  Novocure.    Funding  Novocure.    Disclosure  F. Grosso: Travel / Accommodation / Expenses: Novocure. G.L. Ceresoli: Travel / Accommodation / Expenses: Novocure. All other authors have declared no conflicts of interest.
Frequency of germline mutations in women’s cancer susceptibility genes in a large cohort of Chinese breast cancer patients
Authors: N. Liao, B. Chen, G. Zhang, C. Ren, Y. Wang, L. Guo, L. Cao, L. Wen, K. Li, M. Jia, C. Li, H. Mok, X. Chen, G. Wei, J. Lin, Z. Zhang, T. Hou, X. Shi, H. HanZhang, H. Liu
Journal: Annals of Oncology (2019)
Measures of functional status in adults aged ≥70 years with advanced breast cancer (ABC) receiving palbociclib (PAL) combination therapy in POLARIS
Authors: M.S. Karuturi, J.L. Blum, J. Wallmark, S. McCune, S. Lakhanpal, B. Telivala, M. Tsai, T. Rakowski, A. Bardia, J.C. Cappelleri, E. Richardson, Y. Wang, D. Tripathy
Journal: Annals of Oncology (2019)
The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Authors: M. Tamiya, A. Tamiya, K. Hosoya, Y. Taniguchi, T. Yokoyama, Y. Fukuda, K. Hirano, H. Matsumoto, R. Kominami, H. Suzuki, T. Hirashima, J. Uchida, M. Morita, M. Kanazu, N. Sawa, S. Hara, Y. Kinoshita, T. Kumagai, D. Fujimoto
Journal: Annals of Oncology (2019)
Prediction of S-1 adjuvant chemotherapy efficacy in stage II/III gastric cancer treatment based on comprehensive gene expression analysis
Authors: M. Terashima, K. Nakamura, K. Hatakeyama, K. Furukawa, K. Fujiya, S. kamiya, M. Hikage, Y. Tanizawa, E. Bando, K. Oshima, K. Urakami, N. Machida, H. Yasui, K. Yamaguchi
Journal: Annals of Oncology (2019)
A national comparative effectiveness study to assess definitive chemoradiation regimens in proximal oesophageal squamous cell cancer
Authors: J. de Vos-Geelen, F.J.P. Hoebers, S.M.E. Geurts, A. Hoeben, B.T.A. de Greef, F.E.M. Voncken, J.A. Bogers, P.M. Braam, C.T. Muijs, M.A. de Jong, N. Kasperts, T. Rozema, P.M. Jeene, G.J. Blom, M. Hulshof, H.W.M. van Laarhoven, H.I. Grabsch, V E P P Lemmens, V.C.G. Tjan-Heijnen, G.A.P. Nieuwenhuijzen
Journal: Annals of Oncology (2019)
Role of Folate Receptor 3 in Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia
Authors: Na Shen, Xiaojian Zhu, Shu Zhou, Yong You, Zhaodong Zhong, Xiaoying Zhu, Qing Li, Ping Zou, Yicheng Zhang
Journal: Blood (2018)
GEINO 1402: A phase Ib dose-escalation study followed by an extension phase to evaluate safety and efficacy of crizotinib in combination with temozolomide (TMZ) and radiotherapy (RT) in patients with newly diagnosed glioblastoma (GB)
Authors: M. Martinez Garcia, M.J. Gil, E. Pineda, M.C. Martin Soberón, C. Mesia Barroso, P. Foro, J. Capellades, B. Sarmiento, J. Bruna, E. Verger, A. Taus Garcia, F. Alameda, A. Hernandez Lain, G. Velasco, J.M. Sepulveda Sanchez
Journal: Annals of Oncology (2019)
Association of Use of Oral Contraceptives With Depressive Symptoms Among Adolescents and Young Women
Authors: Anouk E. de Wit, Sanne H. Booij, Erik J. Giltay, Hadine Joffe, Robert A. Schoevers, Albertine J. Oldehinkel
Journal: JAMA Psychiatry (2019)

Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear.To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use.Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019.Oral contraceptive use at 16, 19, 22, and 25 years of age.Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years).Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs -0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age, -0.021; 95% CI, -0.038 to -0.005; P = .0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P < .001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P = .006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P = .009) than nonusers.Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence.
Peripheral Neuropathy Is an Under-Recognized Feature of Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study of 18,668 MGUS Patients and Their 97,641 Matched Controls
Authors: Sæmundur Rögnvaldsson, Vilhjálmur Steingrímsson, Ingemar Turesson, Magnus Björkholm, Ola Landgren, Sigurður Yngvi Kristinsson
Journal: Blood (2017)
Reaching sustainable oncology care via the National Cancer Control Program (NCCP)
Authors: B. Zakotnik, V. Zadnik, T. Žagar, M Primic Žakelj, U. Ivanuš, T. Jerman, J Maučec Zakotnik, D Novak Mlakar, T Kofol Bric, M. Kadivec, K. Jarm
Journal: Annals of Oncology (2019)
New therapy for intrahepatic cholangiocarcinoma targeted to cancer associated fibroblasts
Authors: T. Yamanaka, N. Harimoto, K. hoshino, R. Muranushi, K. Hagiwara, D. Gantumur, N. Ishii, M. Tsukagoshi, T. Igarashi, A. Watanabe, N. Kubo, K. Araki, K. Shirabe
Journal: Annals of Oncology (2019)
Incidence of tumour BRCA1/2 variants in relapsed, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer
Authors: R.D. Morgan, M. Bulman, A.R. Clamp, S. MacMohon, L. Thompson, S. Ribeiro, A. Davies, R. Best, S. Palmer-Smith, B. Frugtniet, D.G.R. Evans, G.C. Jayson, A.J. Wallace
Journal: Annals of Oncology (2019)
Additional Layer of Regulation via Convergent Gene Orientation in Yeasts
Authors: Jules Gilet, Romain Conte, Claire Torchet, Lionel Benard, Ingrid Lafontaine
Journal: Molecular Biology and Evolution (2019)

Convergent gene pairs can produce transcripts with complementary sequences. We had shown that mRNA duplexes form in vivo in Saccharomyces cerevisiae via interactions of mRNA overlapping 3'-ends and can lead to posttranscriptional regulatory events. Here we show that mRNA duplex formation is restricted to convergent genes separated by short intergenic distance, independently of their 3'-untranslated region (UTR) length. We disclose an enrichment in genes involved in biological processes related to stress among these convergent genes. They are markedly conserved in convergent orientation in budding yeasts, meaning that this mode of posttranscriptional regulation could be shared in these organisms, conferring an additional level for modulating stress response. We thus investigated the mechanistic advantages potentially conferred by 3'-UTR mRNA interactions. Analysis of genome-wide transcriptome data revealed that Pat1 and Lsm1 factors, having 3'-UTR binding preference and participating to the remodeling of messenger ribonucleoprotein particles, bind differently these messenger-interacting mRNAs forming duplexes in comparison to mRNAs that do not interact (solo mRNAs). Functionally, messenger-interacting mRNAs show limited translational repression upon stress. We thus propose that mRNA duplex formation modulates the regulation of mRNA expression by limiting their access to translational repressors. Our results thus show that posttranscriptional regulation is an additional factor that determines the order of coding genes.
Better living through peptide-conjugated chemistry: next-generation antisense oligonucleotides
Authors: Elizabeth M. McNally, Brian D. Leverson
Journal: Journal of Clinical Investigation (2019)

Two different antisense oligonucleotide–based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. This success, for Duchenne muscular dystrophy and spinal muscular atrophy, offers hope not only for additional neuromuscular diseases, but also for other disorders that could benefit from RNA-targeted therapies. A major limitation for more widespread application of ASOs relates to relatively poor tissue penetration. In this issue of the JCI, Klein et al. showed that conjugating an ASO with an arginine-rich cell-penetrating peptide, Pip6a, enhanced delivery, resulting in corrective outcome for a mouse model of myotonic dystrophy. Linking ASOs to cell-penetrating peptides, or even other moieties, is an approach currently under development with treatment potential to expand to other disorders.
Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): Results from 15 prospective advanced first-line clinical trial
Authors: M.G. McNamara, A. Lopes, H. Wasan, D. Malka, D. Goldstein, J. Shannon, T. Okusaka, J.J. Knox, A.D. Wagner, T. Andre, D. Cunningham, M. Moehler, L.H. Jensen, D. Koeberle, T. Bekaii-Saab, J.A. Bridgewater, J.W. Valle
Journal: Annals of Oncology (2019)
Deep learning radiomics distinguishes intrapulmonary disease from metastases in immunotherapy-treated melanoma patients
Authors: T.D.L. Nguyen-Kim, S. Trebeschi, J.E.E. Pouw, G. Milanese, L. Topff, Z. Bodalal, J. Mangana, T. Frauenfelder, J B A G Haanen, C.U. Blank, H J W L Aerts, R. Beets-Tan, R. Dummer
Journal: Annals of Oncology (2019)
Trastuzumab plus docetaxel in patients with advanced HER2-positive salivary duct carcinoma: Exploratory biomarker analyses
Authors: H. Takahashi, D. Kawakita, C. Fushimi, T. Nagao, H. Hirai, N. Saigusa, T. Masubuchi, T. Matsuki, T. Okada, D. Baba, K. Miura, T. Saotome, Y. Tada
Journal: Annals of Oncology (2019)
Abstract 319: Mild Hypothermia Preserves Cerebral Cortex Microcirculation After Resuscitation in a Rat Model of Cardiac Arrest
Authors: PingGong, ShenZhao, JiangangWang, JieQian, ZhengfeiYang, XiaoboWu, JenaCahoon, NeilDuggal, WanchunTang
Journal: Circulation (2014)

Introduction: Mild hypothermia is one of the effective treatments in comatose patients after cardiac arrest. However, its neuroprotective mechanism is not fully clear. In the present study, we investigated the effect of mild hypothermia on cerebral cortex microcirculation and cerebral oxygen extraction ratio (CERO2). Hypothesis: Mild hypothermia is associated with an improved cerebral cortex microcirculation and a decreased CERO2. Methods: Twenty-five male Sprague-Dawley rats were randomized into 3 groups: hypothermic (HT, n=10), normothermic (NT, n=10) or sham control group (SC, n=5). Ventricular fibrillation was electrically induced and untreated for 8 mins, followed by 8 mins of precordial compressions and mechanical ventilations. Core temperature was reduced to 33±0.5°C at 14 mins after return of spontaneous circulation (ROSC) with a combination of ice packs, an electrical fan and a cooling blanket. The temperature was maintained at 33°C for 8 hrs. Hemodynamics, jugular venous and aortic blood gas, an...
High level of activity of nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Authors: C. Tournigand, A. Flechon, S. Oudard, E. Saada-Bouzid, D. Pouessel, C Le Tourneau, P. Augereau, M. Beylot-Barry, J.J. Grob, B. Chibaudel, J.-C. Soria, C. Simon, D. Couch, N. Hoog-Labouret, C. Tiffon, S. Chevret, T. Andre, A. Marabelle
Journal: Annals of Oncology (2019)
Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: Pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001
Authors: G.D. Demetri, L. Paz-Ares, A.F. Farago, S.V. Liu, S.P. Chawla, D. Tosi, E.S. Kim, C.M. Blakely, J.C. Krauss, D. Sigal, L. Bazhenova, T. John, B. Besse, J. Wolf, T. Seto, E. Chow-Maneval, P.S. Multani, A. Johnson, B. Simmons, R.C. Doebele
Journal: Annals of Oncology (2018)
BAROCCO: A randomized phase II study of weekly paclitaxel vs cediranib-olaparib combination given with continuous or intermittent schedule in patients with recurrent platinum resistant ovarian cancer (PROC)
Authors: N. Colombo, M.O. Nicoletto, P. Benedetti Panici, G. Tognon, A. Bologna, A.A. Lissoni, A. DeCensi, F. Tomao, R. Fossati, F. Tettamanzi, E. Rulli, F. Galli, M. De Luca, M.F. Alvisi, R. Mancari, M. Ratti, A. Baldoni, V. Torri, E. Biagioli
Journal: Annals of Oncology (2019)
An Australian multi-centre experience of the use of peptide receptor radionuclide therapy for bronchial carcinoid tumours
Authors: L.E. Lim, D.L. Chan, D. Thomas, D.K. Wyld, G. Cehic, W. Macdonald, Y.T. Du, G. Tincknell, A. Kuchel, N. Pavlakis, D. Bailey, A. Davis, E. Segelov
Journal: Annals of Oncology (2019)