tbuckley/cabot-search huggingface dataset:
Number of tumor-infiltrating lymphocytes in breast cancer brain metastases compared to matched breast primaries.
Authors: Jessie Narloch, Catherine Luedke, Gloria Broadwater, Nolan Priedigkeit, Allison Hall, Terry Hyslop, Sarah LeNoir Sammons, Shannon Leigh Huggins-Puhalla, Jose Pablo Leone, Juanita Ramirez, John P Kirkpatrick, Matt G Ewend, Peter E Fecci, Adam Brufsky, Adrian V. Lee, Carey K. Anders, Kimberly L. Blackwell
Journal: Journal of Clinical Oncology (2017)

2049 Background: Breast cancer brain metastasis (BCBM) is frequent in advanced disease, has limited therapies, and is associated with poor prognosis. Increased stromal tumor infiltrating lymphocytes (sTILs) are prognostic in triple-negative breast cancer (TNBC) and predictive of therapeutic response in early breast cancer (BC). However, little is known about sTILs in the metastatic setting. We compared %sTILs between the largest known cohort of matched primary tumors and BCBM and correlated the results with clinical endpoints. Methods: We retrospectively investigated 37 matched primary tumors and BCBM tissue from three institutions. In addition, we identified 29 primary tumors from patients later diagnosed with BCBM. H&amp;E-stained sections were manually measured for %sTILs using standard criteria. Wilcoxon signed rank tests assessed for changes in %sTILs between primary and metastatic lesions. A Cox proportional hazards model was used to determine if %sTILs in the breast tissue predicts time from primary tumor biopsy to diagnosis of brain metastasis (TTDBM) while adjusting for clinicopathologic features. Results: Average age at time of BCBM diagnosis was 53.6 (SD 12.3). 52% (34/66) of primary tumors were hormone receptor (HR) positive. Of 60 patients with known HER2 status, 28% (17) were HER2 positive and 40% (24) TNBC. Median %sTILS was significantly different between all primary tumors (15, IQR 5-20) and brain metastases (10, IQR 5-10), p = 0.001. The TNBC subtype (n = 11) showed the largest decrease in %sTILs between primary tumors (20, IQR 10-20) and brain metastases (5, IQR 5-10), p = 0.022. Comparing primary tumors and brain metastases, there was a 5% decrease in %sTILs in HR-/HER2+ (n = 5, p = 0.13) and HR+/HER2- (n = 7, p = 0.13), and a 5% increase in %sTILs in the HR+/Her2+ subtype (n = 9, p = 0.69). Percent sTILs in the primary tumors was not a significant predictor of TTDBM, when adjusting for race, age, HR status, and HER2 status, p = 0.87. Conclusions: BCBM have a significantly decreased %sTILs compared to their primary tumors, most prominent in TNBC. These results suggest altered tumor immunogenicity in the metastatic setting which has broad implications for the development of immunotherapy.
Letter: Potential dilemma: the method of meeting automotive exhaust emission standards of the Clean Air Act of 1970.
Authors: J E Faggan
Journal: Environmental Health Perspectives (1975)

On page 177, I stated that BaP concentration in the exhaust emissions was a function of the lead deposits on the engine cylinder wall.The implication being that BaP concentration in exhaust emission was a function of gasoline lead content.These conclusions were drawn from the work of G. P. Gross.(The effect of fuel and vehicle variables on polynuclear aromatic hydrocarbon and phenol emissions.Paper No. 720210 presented at SAE Automotive En- gineering Congress, Detroit, Michigan, January [10][11][12][13][14] 1972).In a subsequent report, (CRC-APRAC Project No. CAPE-6-68.Fourth Annual (Final) Report on Gasoline Composition and Vehicle Exhaust Gas Polynuclear Aromatic Content, October 31, 1973) this error was rectified.Lead and phosphorus deposits on cylinder walls did not appear to influence BaP concentrations in exhaust emissions.The major variable affecting BaP concentration in exhaust emission was the fuel content of BaP.BaP concentration in exhaust emissions was also strongly influenced by the rate of oil consumption during engine operation.
Abstract 74: Worse Hemodynamics and Greater Oxidative Stress Response in Obese Rats Compared to Normal Rats Following Resuscitation From Cardiac Arrest
Authors: Giuseppe Ristagno, Francesca Fumagalli, Giovanni Li Volti, Claudia Di Giacomo, Ilaria Russo, Antonino Gullo, Roberto Latini
Journal: Circulation (2010)

Introduction: Obesity is associated with cardiovascular fatal events, including cardiac arrest. Moreover, obesity is associated with greater oxidative stress response following an ischemic insult. ...
Outcomes of single versus double hormone receptor positive breast cancer.
Authors: Josee-Lyne Ethier, Alberto Ocana, Maribel Casas, Maria Sanchez-Arago, Rosalia Caballero, Alvaro Rodriguez-Lescure, Amparo Ruiz, Emilio Alba, Lourdes Calvo, Manuel Ruiz, Ana Santaballa, Cesar Augusto Rodriguez, Carmen Crespo, Manuel Ramos Vazquez, Jose Manuel Gracia, Ana Lluch, Isabel Alvarez, Eva Maria Carrasco, Eitan Amir, Miguel Martin
Journal: Journal of Clinical Oncology (2016)

569 Background: Retrospective data suggest that compared to double hormone receptor positive (HR+) (estrogen [ER+] and progesterone receptor [PgR+] positive), single receptor-positive (ER+/PgR- or ER-/PgR+) breast cancer (BC) patients have worse outcomes. Additionally, whether the ER-/PgR+ group is a real phenomenon or an analytic artifact remains elusive. Here, we evaluate the molecular classification and clinical outcomes of single versus double receptor positive BC patients enrolled in the GEICAM/9906 trial. Methods: We analyzed data from the GEICAM/9906 trial, a prospective adjuvant randomized phase-III study comparing six cycles of FEC to four cycles of FEC followed by eight weekly cycles of paclitaxel. HR+ patients received endocrine treatment at completion of chemotherapy. HER2+ patients did not receive adjuvant trastuzumab. Archival tumors were retrieved retrospectively and classified into intrinsic subtypes using the PAM50 gene expression assay. Distant metastasis free survival (DMFS) and overall survival (OS) were explored using a cox proportional hazard analysis Results: Of the 1,246 trial participants, data on intrinsic subtypes by central determination were available for 816 patients, from them 675 were double or single receptor positive. HER2+ disease was more common in the ER+/PgR- group (19%) than in the ER-/PgR+ or ER+/PgR+ groups (each 10%). The luminal A subtype was predominant within the double receptor positive (46%) and ER-/PgR+ (53%) patients. The majority of ER+/PgR- BC were luminal B (49%) or HER2 enriched (31%). Compared to double receptor positive patients, DMFS was similar in ER-/PgR+ patients (HR 1.12, 95%CI 0.52-2.40, p = 0.77), but worse in ER+/PgR- patients (HR 1.59, 95% CI 1.09-2.34, p = 0.02). Similar results were observed for OS (HR 1.39, 95% CI 0.71-2.74, p = 0.34 and HR 1.71 95% CI 1.20-2.74, p = 0.003 respectively). Conclusions: The ER-/PgR+ subgroup resembles double receptor positive disease in terms of distribution of molecular subtypes and outcomes. The poor outcomes of the ER+/PgR- group may be explained by the higher proportion of patients with HER2-positive disease who did not receive adjuvant trastuzumab.
Ultrasound (US) elasometry in axillary lymph node (ALN) staging for breast cancer (BC) patients.
Authors: Alexander Petrovsky, Nafset Khakurinova, Sergey Berdnikov, Mona Frolova, Vladimir Sholokhov
Journal: Journal of Clinical Oncology (2016)

e12538 Background: Tissue elasticity is related to pathology and, therefore, has important medical applications.US elastometry helps to determine the stiffness of the ALN that might be the characteristic of the metastasis. The goal of the study was to determine the status of ALN with the US elastometry comparing with the results of histological examination of surgical specimens. Methods: Materials: Between 2013 and 2015 shear wave speed (SWS) and tissue elasticity measurements were performed preoperatively in 72 women with BC stage 0-IIIC using S2000 Siemens System. Median age was 57 years. 9 women received neoadjuvant chemotherapy. SWS of less than 2.1 m/s was in normal ALN. SWS of > 3 m/s was in mts ALN. SWS of 2.1-3 m/s was in suspicious ALN. A fine niddle aspiration (FNA) was performed in this case. ALN dissection was performed in all 72 patients. Results: According to elastometry ALN mts were detected in 19 (26.4%) patients. Suspicious ALN were detected in 17 (23.6%) patients, FNA was performed to thees pts, 6 pts had mts in ALN. According to the histological examination of surgical material, ALN mts were found in 36.1% (26 patients). Sensitivity of US elastometry + FNA was of 98.6%. Specificity was of 100%, accuracy was of 98.6%. Size, number of ALN, stage of the disease, intrinsic subtipe, age, BMI didn't influence the accuracy of elastometry. Conclusions: The use of preoperative US together with elastometry and FNA can reliably estimate the probability of ALN tumor involvement. Further research will possibly eliminate the need of ALN dissection in a certain group of patients.
STELLAR: A phase 3, randomized, open-label study of eflornithine with lomustine vs lomustine for patients with first recurrence of anaplastic astrocytoma after RT and adjuvant temozolomide.
Authors: Victor A. Levin, Scott Cruickshank
Journal: Journal of Clinical Oncology (2017)

TPS2081 Background: Eflornithine irreversibly inhibits ornithine decarboxylase an enzyme that catalyzes the biosynthesis of putrescine, one of 3 polyamines in mammalian cells. Over 390 patients with anaplastic gliomas (AG) received eflornithine alone, with a nitrosourea, or the PCV combination in past clinical trials. A phase 3 randomized study of adjuvant chemotherapy with PCV vs eflornithine-PCV in 228 patients with AG found a median overall survival (mOS) increase from 61.1 to 75.8 months in the eflornithine-PCV arm. Methods: Patients must have histologically proven diagnosis of WHO grade 3 anaplastic astrocytoma (AA) with unequivocal evidence of first AA tumor progression or recurrence ≤ 3 months prior to randomization following surgical resection or biopsy, RT and temozolomide chemotherapy. Patients must have RT ≥ 6 months prior to randomization and have a KPS of ≥ 70. Randomization of 280 patients will be 1:1 with stratification to: Age (≤ 45 yrs, &gt; 45 yrs), region (US, Ex-US), IDH1 status (wild, mutant), and prior surgeries (biopsy, 1-2 resections). Patients will receive eflornithine 2.8 g/m 2 orally every 8 h on a 2 week on, 1 week off schedule, and lomustine 110 mg/m 2 orally once every 6 weeks, or lomustine alone dosed at 110 mg/m 2 orally once every 6 weeks. Lomustine will be limited to 6 cycles or 12 months of therapy. Eflornithine can be given up to 24 months in the combination arm. The primary endpoint will be OS. Secondary objectives include PFS and objective response rate (ORR) based on MRI. The study sample size was calculated by assuming true mOS of 12 months for lomustine monotherapy and true mOS of &gt; 18 months for the eflornithine plus lomustine arm. Such an improvement represents a true hazard ratio of 0.667 (investigational arm/control arm). Inferential comparisons of OS will be performed using a stratified log-rank test with 137 patients per arm and total information of 194 deaths with 80% power to detect a 33% reduction in the OS failure hazard rate. The study is open at 55 sites in the USA, Germany and Italy with an additional 10-15 sites being evaluated in 3 additional countries. Study enrollment is expected through 2018. Clinical trial information: NCT02796261.
Courts can decide that vaccine has caused harm despite lack of evidence
Authors: Clare Dyer
Journal: BMJ (2017)

European Union law will allow the national courts of member states to decide that a vaccine has caused harm even though there is no medical evidence to back up the finding, the European Court of Justice (ECJ) has ruled.

The ruling was criticised by British scientists but welcomed by a leading UK vaccine claimant lawyer as “common sense.”

The European Court in Luxembourg is the authority on EU law and makes preliminary rulings at the request of national courts when asked how it should be applied nationally. The latest ruling is related to a 1985 directive on liability for defective products to which member states were obliged to give effect in their national laws, allowing consumers to claim compensation if they can prove a …
Clinical trials of VAL-083 in patients with chemo-resistant glioblastoma.
Authors: Jeffrey A. Bacha, Anne Steino, Richard Stephen Schwartz, John Langlands, Sarath Kanekal, Lorena Lopez, Barbara Jane O'Brien, Zhongping Chen, Marta Penas-Prado, Dennis Brown
Journal: Journal of Clinical Oncology (2017)

TPS2082 Background: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Current standard of care includes surgery, radiation and treatment with temozolomide (TMZ), however nearly all tumors recur and the prognosis for recurrent GBM is dismal. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for TMZ-resistance. Second-line treatment with anti-angiogenic agent bevacizumab has not improved overall survival (OS) and 5-year survival is less than 3%. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent targeting N7-Guanine and inducing interstrand DNA cross-links, double-strand breaks and cell death in GBM cell lines and GBM cancer stem cells, independent of MGMT status in vitro. VAL-083 readily crosses the blood-brain barrier and accumulates in brain tumor tissue. Our recent phase I/II clinical trial in recurrent GBM patients failing both TMZ and bevacizumab, suggested that VAL-083 offers clinically meaningful survival benefits for patients with recurrent GBM and pinpointed a new dosing regimen (40 mg/m 2 /d on days 1,2,3 of a 21-day cycle) which was well-tolerated and was selected for study in subsequent GBM trials. Methods: These trials include i) an ongoing single-arm, biomarker driven, Phase 2 study to determine if VAL-083 treatment of MGMT-unmethylated adult GBM patients at first recurrence/progression, prior to bevacizumab improves overall survival at 9 months, compared to historical control with lomustine (clinicaltrials.gov identifier: NCT02717962). ii) A pivotal Phase 3 study in recurrent GBM after failing both TMZ and bevacizumab. The control arm will consist of a limited number of salvage chemotherapies currently used in bevacizumab-failed GBM. If successful, this study will serve as the basis for a New Drug Application (NDA) submission for VAL-083. iii) A single arm, biomarker driven, Phase 2 study to confirm the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels. The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM. Clinical trial information: NCT02717962.
IGF2BP1 Protein Binding of Erythroblast Transcription Factor mRNA: A Cytoplasm-Localized Mechanism for Globin Gene Regulation
Authors: Jaira F. de Vasconcellos, Y. Terry Lee, Colleen Byrnes, Benjamin A. Clarke, Pauline C. Xu, Antoinette Rabel, Richard L. Proia, Jeffery L. Miller
Journal: Blood (2016)
Randomized phase III study of taxane versus TS-1 as first-line treatment for metastatic breast cancer (SELECT BC).
Authors: Fumikata Hara, Nobuaki Matsubara, Tsuyoshi Saito, Toshimi Takano, Youngjin Park, Tatsuya Toyama, Yasuo Hozumi, Junji Tsurutani, Shigeru Imoto, Tsutomu Takashima, Takanori Watanabe, Yoshiaki Sagara, Reiki Nishimura, Yasuo Ohashi, Hirofumi Mukai
Journal: Journal of Clinical Oncology (2014)

1012 Background: Taxanes have been standard regimen as the first-line chemotherapy for metastatic breast cancer. However side effects such as neutropenia, peripheral neuropathy, edema or alopecia are important concerns. Phase II clinical trials of TS-1, an oral 5-fluorouracil derivatives (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate), have shown good clinical efficacy and tolerability. Therefore, we conducted a phase III open-label randomized controlled trial (SELECT BC) to verify the non-inferiority of TS-1 in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer. Methods: Six hundred eighteen patients receiving first-line chemotherapy for metastatic breast cancer were randomly assigned to either taxane group (n=309) or TS-1 group (n=309). In the taxane group, patients received docetaxel 60-75mg/m2 q3w, paclitaxel 80-100mg/m2 q1w or paclitaxel 175 mg/m2 q3w at the discretion of the treating physician. In the TS-1 group, patients received TS-1 40–60 mg twice daily based on the patient’s body surface area for 28 days on, 14-day off. The primary endpoint was OS, with a non-inferiority margin of 1.333. Secondary endpoints were time to treatment failure (TTF), progression free survival, adverse events, health-related quality of life and cost-effectiveness. Results: After a median follow-up of 34.6 months, median OS was 37.2 months in the taxane group and 35.0 months in the TS-1 group (hazard ratio 1.05, 95% CI 0.86–1.27, p=0.015). Median TTF was 8.9 months in the taxane group and 8.0 months in the TS-1 group (hazard ratio 1.10, 95% CI 0.93–1.30, p=0.022). The incidences of diarrhea, mucositis and nausea were higher with TS-1, whereas the incidences of edema, peripheral neuropathy, arthralgia, allergic reaction, fatigue and alopecia were higher with taxanes. Utilities measured by EQ5D during treatment were similar (repeated measures ANOVA p=0.66) between two groups. Conclusions: SELECT BC clearly demonstrated that OS with TS-1 is not inferior to that with taxane in patients receiving first-line chemotherapy for metastatic breast cancer. TS-1 monotherapy would be one of the standard regimens for this patient population. Clinical trial information: C000000416.
Competing risks of mortality by PAM50 intrinsic subtype: BC tamoxifen-treated cohort.
Authors: Judy-Anne W. Chapman, Shuzhen Liu, Samuel Leung, Torsten O. Nielsen
Journal: Journal of Clinical Oncology (2014)

562 Background: We previously showed that baseline patient/tumour characteristics, or prior treatment affected cause of death in NCIC CTG endocrine therapy trials (MA.14, MA.17, MA.27), in particular older age was associated with non-breast cancer death. We now examine whether PAM50 intrinsic subtypes were differentially associated with cause of death in a cohort of British Columbia tamoxifen-treated patients. Methods: Patients were 718 post-menopausal women, treated with tamoxifen, without adjuvant chemotherapy who had tumours which were Luminal A, Luminal B, Basal, or HER2 intrinsic subtype and known cause of death [cancer-specific (BrCa); other cause (OC)]. We tested whether intrinsic subtype and other patient and tumour characteristics were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: Patients were followed a median of 11.7 years. In women <70 years of age, 138/425 (32% died of breast cancer) and 80/425 (19% died of other causes); 138/218 (63% of deaths were due to breast cancer). In those ≥70, 78/293 (27% died of breast cancer) and 133/293 (45% died of other causes); 78/211 (37% of deaths were due to breast cancer). Two factors were differentially associated with type of death: intrinsic subtype was associated with breast cancer death (p=0.001), while older age was associated with other causes of death (p<0.0001). Additionally, step-wise cause-specific models indicated larger tumour size (p=0.0002), higher number of positive number of lymph nodes (p<0.0001), and less PgR stain (p=0.03) were associated with worse breast cancer survival; higher number of positive lymph nodes (p=0.002) and no lymphovascular invasion (p=0.02) were associated with worse all cause mortality. Survival from breast cancer and other causes is provided by these factors at 5-, 10-, and 15-years, adjusted for the effects of other significant factors. Conclusions: Intrinsic subtype was associated with breast cancer death, and did not affect other cause mortality. Again, older age was associated with other cause mortality with the majority of women 70 or older surviving breast cancer.
Lessons Learned on Health Adaptation to Climate Variability and Change: Experiences Across Low- and Middle-Income Countries
Authors: Kristie L. Ebi, Mariam Otmani del Barrio
Journal: Environmental Health Perspectives (2017)

There is limited published evidence of the effectiveness of adaptation in managing the health risks of climate variability and change in low- and middle-income countries.To document lessons learned and good practice examples from health adaptation pilot projects in low- and middle-income countries to facilitate assessing and overcoming barriers to implementation and to scaling up.We evaluated project reports and related materials from the first five years of implementation (2008-2013) of multinational health adaptation projects in Albania, Barbados, Bhutan, China, Fiji, Jordan, Kazakhstan, Kenya, Kyrgyzstan, Philippines, Russian Federation, Tajikistan, and Uzbekistan. We also collected qualitative data through a focus group consultation and 19 key informant interviews.Our recommendations include that national health plans, policies, and budget processes need to explicitly incorporate the risks of current and projected climate variability and change. Increasing resilience is likely to be achieved through longer-term, multifaceted, and collaborative approaches, with supporting activities (and funding) for capacity building, communication, and institutionalized monitoring and evaluation. Projects should be encouraged to focus not just on shorter-term outputs to address climate variability, but also on establishing processes to address longer-term climate change challenges. Opportunities for capacity development should be created, identified, and reinforced.Our analyses highlight that, irrespective of resource constraints, ministries of health and other institutions working on climate-related health issues in low- and middle-income countries need to continue to prepare themselves to prevent additional health burdens in the context of a changing climate and socioeconomic development patterns. https://doi.org/10.1289/EHP405.
Abstract 11553: A New Method to Estimate Aortic Pulse Wave Velocity and Central Systolic Blood Pressure by Measuring Brachial Cuff Pulse Waveform
Authors: Kazuki Shiina, Hirofumi Tomiyama, Mari Odaira, Masanobu Yoshida, Akira Yamashina, Tatsuya Kobayashi, Kenji Fujii, Toshihiko Ogura
Journal: Circulation (2011)

Objectives: Measuring not only brachial blood pressure but central blood pressure has been shown to be valid in assessing the risk of a cardiovascular event and evaluating drug efficacy. We develop...