tbuckley/cabot-search huggingface dataset:
Advanced gynecologic cancer patients and healthy parents: Emotional distress and information given to their children.
Authors: Anna Rodriguez-Morera, Joaquin T. Limonero, Pilar Barretina
Journal: Journal of Clinical Oncology (2013)

e20704 Background: Describe relationship between advanced gynaecologic cancer (AGC) patients and healthy parents emotional distress (ED) and information amount related to the disease they give to their children. Methods: We studied 28 children, aged between 5 and 18 years, whose mothers had AGC, 13 breast (72.2%), 2 cervix (11.1%) &amp; 3 ovarian (16.7%). Interview with numerical scale from 1 to 10 points was used to assess the amount of children's information described by parents. Hospitality Ansiety Depression Scale (HADS) was used to assess parents ED. Parents and children older than 12 years gave Informed Consent. Results: 18 mothers diagnosed of AGC were included. They added up to a total of 31minor children (M=1.7;SD=0.7) 3 of them, younger than 5 years old were excluded. Emotional distress of parents did not significantly correlate with the number of minor children they had. In the other hand, depression symptoms increased with the duration of disease, for patients and healthy parents (rho=0.5,p&lt;.01;rho=0.6,p&lt;.01) also when patient's functional capacity decreased (rho=-0.4,p&lt;.05;rho=-0.5,p&lt;.05). Mothers gave the information in 60.7% of the cases, 35.7% both parents shared this task. Anxiety among patients (M=10.21;SD=5.4) and healthy parents (n=13,M=8.8;SD=4.8) had not significant correlation with the amount of information given (n=28,rho=-0.01,p&gt;0.05;n=19,rho=-0.2,p&gt;.05). Patients (M=7.3;SD=4.2) and healthy parents (n=13,M=5.2;SD=3.1) depression grade did not correlate with the amount of information children had (n=28,rho=0.2,p&gt;.05;n=18,rho=-0.1,p&gt;.05). Information given by mothers was slightly higher (M=6.8; SD=2.3), it was the same for sons and daughters (U=93.5,p&gt;.05). Yet, fathers tended to give more information to daughters (M=6.2; SD=1.8;U=22.5,p=0.06). Information given by patients and healthy parents was concordant (rho=0.5;p&lt;.05). Conclusions: AGC patients and healthy parents ED is not related with the information amount parents give to their children. We must be aware of the need to provide support to fathers during mothers’ disease in order to ease communication with the children, taking into account that mothers are who mainly give information to their children.
Digital envirotyping: quantifying environmental determinants of health and behavior
Authors: Matthew M. Engelhard, Jason A. Oliver, F. Joseph McClernon
Journal: npj Digital Medicine (2020)

Digital phenotyping efforts have used wearable devices to connect a rich array of physiologic data to health outcomes or behaviors of interest. The environmental context surrounding these phenomena has received less attention, yet is critically needed to understand their antecedents and deliver context-appropriate interventions. The coupling of improved smart eyewear with deep learning represents a technological turning point, one that calls for more comprehensive, ambitious study of environments and health.
Metabolite Imaging at the Margin: Visualizing Metabolic Tumor Gradients Using Mass Spectrometry
Authors: Ai Wen Tan, Aalim M. Weljie
Journal: Cancer Research (2020)

Abstract Glioblastoma multiforme (GBM) tumors are highly metabolic and vascularized, yet little has been reported regarding the spatial localization of metabolic activity within these tumors. A mass spectrometry imaging (MSI) study by Randall and colleagues in this issue provides provocative observations of metabolic gradients in xenograft GBM models. The intensity of acylcarnitines is dramatically increased at tumor margins, which interface with normal tissue, but not in tumor margins at the edge of the brain. A secondary examination of drug metabolites suggests that the observed metabolic gradients are pharmacologically relevant. These findings underscore previously undescribed spatial metabolic heterogeneity in GBM biology and opportunities for MSI investigations. See related article by Randall et al., p. 1258
Phase I study of BAY 57–9352, a VEGFR-2 inhibitor, in cycles of 14 days on/7 days off in patients with advanced solid tumors
Authors: D. Strumberg, K. Mross, M. Scheulen, A. Frost, S. Hedbom, P. Rajagopalan, D. Voliotis, G. Wensing, O. Christensen
Journal: Journal of Clinical Oncology (2006)

3089 Background: BAY 57–9352 (BAY) inhibits the VEGFR-2 and VEGFR-3 tyrosine kinases, in addition to PDGFR-β and c-kit. BAY showed anti-tumor activity in colon, breast, pancreatic, and NSCLC preclinical models. Methods: This study investigated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of oral BAY in 14 days on/7 days off treatment cycles until discontinuation due to toxicity or progression. PK was assessed on days 1 and 14 of cycle 1. Dynamic contrast-enhanced MRI (DCE-MRI) was performed at baseline and in cycles 1–3. Plasma biomarkers (VEGF, sVEGFR-2) were assessed at each cycle. Results: 77 patients (pts) were enrolled at doses from 20 mg once daily to 1500 mg twice daily (bid). Common tumor types were CRC (31%) and RCC (16%). Frequent drug-related adverse events (≥5% pts) were hypertension (all grades, 11 pts [14%]; grade 3, 10 [13%]), hoarseness (10 [13%], only grade 1/2), anorexia (7 [9%], only grade 1/2), myalgia (6 [8%], only grade 1/2), fatigue (5 [6%], only grade 1/2), and diarrhea (all grades, 4 [5%]; grade 3, 1 [1%]). Hypertension in cycle 1 caused a dose reduction/interruption in 3 pts. One pt had diarrhea in cycle 7 requiring a dose reduction. One pt discontinued due to fatigue in cycle 8. BAY AUC increased dose-proportionally up to 900 mg bid. As measured by DCE-MRI, pts with CRC showed the greatest decrease in iAUC60 of Gd-DTPA, a parameter related to tumor blood flow and permeability. One pt with RCC achieved a partial response (PR); another had significant tumor shrinkage not reaching formal criteria (RECIST) for PR. PD responses (VEGF and sVEGFR-2 levels) increased in a dose-dependent manner up to 900 mg bid. Conclusions: The MTD was not reached for BAY up to 1500 mg bid in a 14 days on/7 days off schedule. BAY had a favorable safety profile. Tumor efficacy was shown in individual patients. The PD effect of BAY was demonstrated by DCE-MRI and plasma biomarkers. The recommended dose for Phase II evaluations is 900 mg bid. [Table: see text]
Triiodothyronine [T3]-induced hypothyroxinemia: Response and survival in a compassionate care cancer patient population.
Authors: Aleck A Hercbergs, David H. Garfield, Osnat Ashur-Fabian
Journal: Journal of Clinical Oncology (2012)

e19573 Background: Increased survival under chemically induced hypothyroidism has been reported in cancer patients with poor prognosis, but the associated morbidity can deter patient compliance. Acting via a receptor site upon the plasma membrane avβ3 integrin, L-thyroxine (T4) in physiological concentrations non-genomically activates mitogenesis and neo-angiogenesis of cancer cells and proliferating vascular endothelium. Occlusion of the receptor by tetraiodothyroacetic acid (tetrac), a T4 derivative, induces apoptosis, inhibits angiogenesis and enhances chemotherapy and radiation. 3, 5, 3’-Triiodo-L-thyronine (T3) in physiological concentrations is significantly less mitogenic than T4 and inhibits pituitary release of thyrotropin (TSH). Absence of TSH, but with T3 support, depletes circulating T4 without resultant hypothyroidism. Methods: 21 cancer patients at dispersed clinical sites with stage 4 solid tumors and projected limited survival received T3 [n=10] only or with methimazole (MT) [n=9]. Serum TSH, free T4 (FT4) and T3 concentrations were obtained initially, then monthly. FT4 levels below lower normal range were achieved in all patients within 3 to 12 weeks. Results: See Table. Conclusions: T3 treatment with resultant hypothyroxinemia in poor prognosis cancer patients was associated with favorable response rates in 17/19 subjects. Two others with aggressive tumors had extended survival on long-term T3. [Table: see text] [Table: see text] [Table: see text]
Liposome-encapsulated doxorubicin plus cyclophosphamide as first-line therapy in metastatic breast cancer: A phase II study
Authors: F. Giotta, V. Lorusso, G. Monticelli, P. Calabrese, G. Filippelli, M. Valerio, E. Maiello, M. Quaranta, G. Colucci
Journal: Journal of Clinical Oncology (2006)

10646 Background: The objective of this study is to evaluate the efficacy and toxicity of the liposome- encapsulated doxorubicin (TLC D-99) plus cyclophosphamide (CTX) as first-line treatment of metastatic breast cancer in light of the potential cardioprotective effect of TLC D-99 as compared to conventional doxorubicin. Furthermore the study is aimed also to understand the role of troponin I as a sensitive marker of left ventricular dysfunction. Methods: Sixty-three patients as defined in a phase II group sequential design will be enrolled. Since september 2004, fifty-four patients with untreated metastatic breast cancer were enrolled. They received TLC D-99 at the dosage of 60 mg/m 2 plus CTX 600 mg/m 2 , with cycles repeated every three weeks. Cardiac function was assessed by ultrasonography at baseline and every three weeks, as well as troponin I dosage. Results: The principal characteristics of the 54 actually enrolled patients were as follows: median age 60 years (range 33–75), median WHO performance status 1 (range 0–2) and dominant disease site (viscera/bone/soft tissue) 36/10/8. To date 39 pts are evaluable: 8 complete responses and 18 partial responses were observed for an overall response rate of 67%; a further 9 pts had stable disease and the remaining 4 pts progressed. Median number of administered cycles was 6. Median duration of response was 10 months (range 3–15+) and median duration of survival was 12+ months (range 2+-15+). Hematological toxicity consisted in leucopenia (G1-G2) in 11 patients ed anemia (G1-G2) in 10 pts; G1 thrombocytopenia was observed only in 2 pts. Non-hematological toxicity was generally mild with G1-G2 nausea/vomiting in 14 pts e G2 mucositis in one patient. Hair-loss was registered in 12 pts and it was G2 in 6 pts. As to concer cardiac toxicity, one patient developed an asymptomatic 20% decline of left ventricular ejection fraction from the baseline value. Conclusions: The preliminary data show that the combination of TLC D-99 plus CTX is active and well tolerated, with no unexpected toxicity. The relationship between cardiac function and troponin I is underway. No significant financial relationships to disclose.
Relationship between thymidylate synthase expression and p53 levels with the treatment of cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy(CMF) versus docetaxel (TXT) in locally advanced carcinoma of the breast
Authors: M. Brandi, A. Calascibetta, D. Cabibi, A. Martorana, F. Aragona, F. Fulfaro, M. Valerio, J. Dispenza, R. Sanguedolce
Journal: Journal of Clinical Oncology (2006)

10546 Background: Adjuvant chemotherapy is used in the treatment of breast carcinoma independently of axillar node involvement. Different drug combinations such as CMF, FAC, FEC are still used; recently new drugs such as TXT (NEJM 332:1004,1997) show activity and are used also in adjuvant chemotherapy. 5 Fluorouracil (5Fu), a drug involved in main therapeutic regimens, blocks Thymidylate Synthase (TS), an enzyme involved in the DNA synthesis. TS not only links its own mRNA, but also p53 mRNA, inhibiting post transcriptional p53 protein synthesis. TS protein overexpression (Cancer Res 55:1407,1995), and/or its absence (Cancer Res 61:1421,2001) are some of the main mechanisms of 5-Fu drug resistance; moreover TS protein could inhibit p53 protein synthesis. Many clinical studies demonstrate that tumours with mutations of p53 are resistant to anthracyclines chemotherapy, 5Fu and radiotherapy (Carcinogenesis 17:1417,1996). Other studies show that the relationship between p53 and taxanes chemosensitivity seems to be more complex, because p53 mutations are associated with better taxanes drug response (Nature Med 2:255,1996). Aim of the study is to find association between TS and p53 levels, and relation with CMF or TXT treatment. Methods: We detected TS and p53 protein levels with immunohistochemistry assay in 84 paraffin embedded tumour samples from untreated patients (pts) who underwent surgery for primary breast cancer. Stage was T2N2M0 and pts were divided into two groups depending on the drug treatment received. One group (44 pts) was treated by 6 cycles of adjuvant CMF chemotherapy, the other by 4 cycles TXT alone. Results: 30% of pts showed lower TS and higher p53 levels, and had better TXT, while worse CMF treatment response; 30% of pts showed higher TS and lower p53 levels and all had worse response to all treatments; 40% of pts showed intermediate TS and p53 levels and different response to both CMF or TXT. Conclusions: On the basis of these results we identified a sub-group of pts showing lower TS and higher p53 levels that could be treated by a first line therapeutic regimen including Taxanes, not by drug combinations including 5 FU. No significant financial relationships to disclose.
IMPORTANCE OF ISCHEMIA AMONG ASYMPTOMATIC PATIENTS WITH DIABETES MELLITUS UNDERGOING POSITRON EMISSION TOMOGRAPHY (PET) MYOCARDIAL PERFUSION IMAGING
Authors: Krishna Patel, Annapoorna Singh, Poghni Peri-Okonny, Femina S. Patel, Kevin Kennedy, Kyle Lehenbauer, John A. Spertus, Randall Thompson, Brett Sperry, Arthur McGhie, Ibrahim Saeed, Michael Nassif, Timothy Bateman
Journal: Journal of the American College of Cardiology (2020)
Adverse events with pertuzumab and trastuzumab: Evolution during treatment with and without docetaxel in CLEOPATRA.
Authors: José Baselga, Javier Cortes, Seock-Ah Im, Xavier B. Pivot, Emma Clark, Adam Knott, Graham Ross, Sandra M. Swain
Journal: Journal of Clinical Oncology (2012)

597^ Background: In CLEOPATRA, the HER2-dimerization inhibitor pertuzumab (P) was combined with trastuzumab (T) and docetaxel (D) in HER2-positive 1st-line MBC. P+T+D significantly improved efficacy compared with placebo (Pla)+T+D while having little effect on safety. Pts were recommended to receive ≥6 cycles of D but could discontinue D prior to Cycle 6 due to poor tolerability or progressive disease (PD) or continue D beyond Cycle 6 at investigators’ discretion. Once D was discontinued, pts received Pla+T or P+T until PD. To understand the full safety profile of the regimen, adverse events (AEs) occurring before and after D discontinuation were analyzed. Methods: Treatment was given q3w (Pla/P: 840 mg loading, then 420 mg; T: 8 mg/kg loading, then 6 mg/kg; D: 75 mg/m 2 , escalating to 100 mg/m 2 if tolerated; de-escalation by 25% allowed). AEs were graded according to NCI-CTCAE v3.0, monitored continuously during the treatment period, and their relationship to study drugs was assessed by investigators. Results: From 808 pts enrolled, 804 were analyzed in the safety population (pts who received ≥1 dose of study treatment). AEs that led to discontinuation of all study treatment were experienced by 5.3% (Pla+T+D) and 6.1% (P+T+D) of pts, whereas discontinuation of D alone due to AEs occurred in 23.2% (Pla+T+D) and 23.6% (P+T+D) of pts. Conclusions: Treatment in both arms was well tolerated. After discontinuation of D, there was a clear reduction in grade ≥3 AEs; however, the incidence of grade ≥3 diarrhea remained slightly elevated with P+T+D. The AE profile of P+T is consistent with that seen in previous Phase II studies (Gianni Lancet Oncol 2012; Baselga JCO 2010). These data suggest that the combination of P+T may also be well tolerated in other breast cancer settings, such as in adjuvant therapy, which is currently under phase III study (APHINITY; NCT01358877). [Table: see text]
CLO20-028: Clinical Utility of Encyclopedic Tumor Analysis to Treat Breast Cancer Patients who have Failed Standard of Care Treatments
Authors: Dadasaheb Akolkar, Darshana Patil, Anantbhushan Ranade, Revati Patil, Sachin Apurwa, Sanket Patil, Pradip Fulmali, Pradip Devhare, Navin Srivastava, Ajay Srinivasan, Rajan Datar
Journal: Journal of the National Comprehensive Cancer Network (2020)

"CLO20-028: Clinical Utility of Encyclopedic Tumor Analysis to Treat Breast Cancer Patients who have Failed Standard of Care Treatments" published on 20 Mar 2020 by National Comprehensive Cancer Network.
CORONARY ANATOMY, ISCHEMIA AND ANGINA: ASSOCIATIONS AT BASELINE IN THE ISCHEMIA TRIAL
Authors: Harmony R. Reynolds, Leslee J. Shaw, James Min, Daniel Mark, John A. Spertus, Daniel S. Berman, Bernard Chaitman, Michael Picard, Raymond Y. Kwong, Courtney B. Page, Lawrence Phillips, Karen Alexander, Roxy Senior, Jiyan Chen, Hanna Szwed, Rolf Doerr, Kevin Bainey, Ruben Ramos, Peter Ong, Sripal Bangalore, William E. Boden, Sean O'Brien, David Joel Maron, Judith S. Hochman
Journal: Journal of the American College of Cardiology (2020)
Dasatinib plus SMO antagonist versus dasatinib alone for treating patients (pts) with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP): Design of CA180-363, a phase II, open-label randomized trial.
Authors: Geralyn C. Trudel, Prashni Paliwal, Ioannis Lainas
Journal: Journal of Clinical Oncology (2012)

TPS6634 Background: Dasatinib 100 mg once daily (QD) is approved as first-line therapy for pts with newly diagnosed Ph+ CML-CP and those who are resistant or intolerant to prior therapy, including imatinib, based on demonstrated efficacy and tolerability. BMS-833923 (SMO antagonist), selectively blocks hedgehog (Hh) pathway signaling by binding to and antagonizing Smoothened (SMO), preventing downstream signaling and activation of target genes. In preclinical studies, SMO loss or inhibition reduces hematopoietic stem cell renewal, induces CML stem cell depletion, and inhibits imatinib-resistant CML cell growth (Dierks, Cancer Cell 2008; Zhao, Nature 2009). In pts with CML, Hh signaling genes (Sonic hedgehog, SMO, and Gli1) are significantly upregulated compared with control pts (Long, J Exp Clin Cancer Res 2011), suggesting that drug resistance and disease recurrence may be overcome by targeting the Hh signaling pathway. Methods: CA180-363 is a phase 2 trial to assess dasatinib activity with or without SMO antagonist in pts with newly diagnosed Ph+ CML-CP. Pts receive dasatinib 100 mg QD for 12 months and are then randomized 1:1 to continuing dasatinib 100 mg QD with or without SMO antagonist up to 24 months, followed by dasatinib 100 mg QD alone until end of study (60 months). Randomization is stratified by Sokal score at diagnosis and major molecular response (MMR) at 12 months (yes/no). Eligible pts are aged ≥18 years, have an Eastern Cooperative Group (ECOG) performance status of 0-2, and previously untreated Ph+ CML-CP diagnosed within 6 months of enrollment. Primary endpoint (evaluated in pts who do not achieve MMR prior to randomization) is comparison of MMR rates for dasatinib alone vs dasatinib plus SMO antagonist. Other endpoints (evaluated in all pts) are complete molecular response, progression-free survival, event-free survival, transformation-free survival, and safety of the combination regimen. Recruitment started in September 2011 (14 pts enrolled to date); estimated primary completion date is November 2014. ClinicalTrials.gov ID: NCT01357655.
Do patients with cardiovascular diseases have earlier relapse in stage I-III non-small cell lung cancer?
Authors: Robert M. Crescentini, Richard R. Reich, Pooja Bardhan, Martine Extermann
Journal: Journal of Clinical Oncology (2013)

9603 Background: Diabetes mellitus (DM) has been reported to be an independent risk factor in the development of recurrence of NSCLC following treatment of early stage disease. We evaluated to see if there was a similar effect of cardiovascular disease in patients with newly diagnosed NSCLC. Methods: Using the Moffitt Cancer Center (MCC) databases, patients were identified who were treated for stage I, II and III NSCLC at MCC from 2001-2003. Charts were reviewed and descriptive data were recorded including histories of DM, coronary artery disease (CAD), hypertension, cerebrovascular disease and congestive heart failure (CHF). The use of aspirin and antihypertensive agents at the time of diagnosis were also recorded. Primary endpoint was disease free survival (DFS). Overall survival (OS) was a secondary endpoint. Kaplan Meier curves and Cox regression analyses were used for DFS and OS. Results: A total of707 patients were identified. Ninety-seven patients had DM, 158 had CAD, 396 had hypertension, 43 had cerebrovascular disease and 56 had CHF. DFS was worse in patients with DM (p&lt;0.001, OR 0.63, 95% CI 0.50-0.80), CAD (p&lt;0.001, OR 0.70, 95% CI 0.57-0.85), hypertension (p=0.016, OR 0.81, 95% CI 0.67-0.96), cerebrovascular disease (p=0.006, OR 0.62, 95% CI 0.45-0.87) and CHF (p&lt;0.001, OR 0.56, 95% CI 0.42-0.75). Bivariate analysis showed that CAD, cerebrovascular disease and CHF were associated with shorter DFS independent of DM. OS was also worse in patients with DM (p&lt;0.001, 95% CI 0.50-0.81), CAD (p&lt;0.001, OR 0.62, 95% CI 0.51-0.78), hypertension (p=0.004, OR 0.77, 95% CI 0.64-0.92), cerebrovascular disease (p=0.02, OR 0.66, 95% CI 0.47-0.94) and CHF (p&lt;0.001, OR 0.54, 95% CI 0.41-0.73). In patients with hypertension, there was an improvement in DFS (p=0.047, OR 1.35, 95% CI 1.004-1.819) for those treated with thiazide diuretics. There were no other statistically significant differences in patients based on antihypertensive regimens or aspirin use. Conclusions: DM,CAD, hypertension, cerebrovascular disease and CHF are associated with shorter DFS and worse overall prognosis in patients with non-metastatic NSCLC. CAD, cerebrovascular disease and CHF are associated with shorter DFS independent of DM.
Abstract 10406: Borderline Q-Waves in Individuals Without Overt Cardiovascular Disease: Relations With Adiposity, Subclinical Atherosclerosis and Vascular Stiffness
Authors: Theodora Elffers, Stella Trompet, Renée de Mutsert, Arie Maan, Hildo Lamb, Peter Macfarlane, Frits Rosendaal, Wouter Jukema
Journal: Circulation (2018)

Background: Characteristics and risk factors associated with electrocardiographic borderline Q-waves are not fully elucidated, especially in individuals without overt cardiovascular disease (CVD). ...
IMPACT OF HYPERTENSION ON LEFT VENTRICULAR FUNCTION IN PATIENTS WITH MALIGNANT LYMPHOMA AFTER ANTHRACYCLINE CHEMOTHERAPY
Authors: Yusuke Tanaka, Hidekazu Tanaka, Keiko Hatazawa, Kentaro Yamashita, Keiko Sumimoto, Ayu Shono, Makiko Suzuki, Nao Shibata, Shun Yokota, Makiko Suto, Jun Mukai, Hiroki Takada, Kumiko Dokuni, Eriko Hisamatsu, Kensuke Matsumoto, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2020)