tbuckley/cabot-search huggingface dataset:
Depressive Symptoms in Patients Scheduled for Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery: Prospective Associations With Morbidity and Mortality
Authors: Carissa A. Low, Dana H. Bovbjerg, Steven Ahrendt, Sara Alhelo, Haroon Choudry, Matthew Holtzman, Heather L. Jones, James F. Pingpank, Lekshmi Ramalingam, Herbert J. Zeh, Amer H. Zureikat, David L. Bartlett
Journal: Journal of Clinical Oncology (2016)

Purpose The current study examined prospective relationships between preoperative depressive symptoms and short-term (30-day morbidity and readmission) and long-term (overall survival) outcomes after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS). Methods Ninety-eight patients scheduled for HIPEC + CS completed the Center for Epidemiologic Studies–Depression (CES-D) scale before surgery. Demographic and disease-specific factors and information about morbidity and readmission within 30 days after discharge were gathered from medical records. Survival was measured from date of surgery to death. Results Twenty-eight percent of patients had CES-D scores indicative of clinically significant depressive symptoms. Thirty-day morbidity occurred in 31.9% of patients and readmission in 22.2%. At the time of analysis (median follow-up of 49 months), 71.6% of patients were deceased, with median survival time of 11 months for those who died. After adjusting for relevant preoperative demographic and disease-specific factors, depressive symptoms were associated with greater odds of 30-day morbidity (n = 68; odds ratio, 5.50; 95% CI, 1.23 to 24.73; P = .03) and greater likelihood of 30-day readmission (n = 72; odds ratio, 5.92; 95% CI, 1.27 to 27.64; P = .02). Depressive symptoms were associated with shorter survival after adjustment for preoperative demographic and disease-specific factors (n = 87; hazard ratio, 1.88; 95% CI, 1.07 to 3.31; P = .03). This association was no longer significant when intraoperative/postoperative prognostic variables were added to the statistical model (n = 87; hazard ratio, 1.31; 95% CI, 0.72 to 2.37; P = .37). Conclusion Patients with clinically significant levels of preoperative depressive symptoms are at risk for poor clinical outcomes after HIPEC + CS, including greater risk of 30-day morbidity and readmission. Further research is warranted to determine biobehavioral mechanisms and examine whether effective interventions targeting preoperative depressive symptoms can reduce postoperative risk in this patient population.
Docetaxel and anthracycline-based neoadjuvant chemotherapy in breast cancer
Authors: D. G. Tiezzi, J. M. Andrade, A. H. Macchetti, W. S. Clagnan, H. R. Marana, F. E. Zola, F. M. Peria
Journal: Journal of Clinical Oncology (2008)

11590 Background: Reducing the primary tumor volume and increasing the breast conserving surgery (BCS) rate are the main roles of neoadjuvant chemotherapy (NAT) in breast cancer. The aim of this study was to evaluate the benefit in adding docetaxel to anthracycline neoadjuvant therapy for breast cancer. Methods: Retrospective cohort study comparing the efficacy of NAT for breast cancer in patients subjected to docetaxel (75mg/m2) and epirubicin (60mg/m2) or 5-fluorouracil (600mg/m2), epirubicin (60mg/m2) and cyclophosphamide (600mg/m2) combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was three (2 to 6) in both groups (p= 0.8). Forty-six patients in the FEC group and 90 patients in the DE group were clinical stage II. Stage III was observed in 95 and in 68 patients in the FEC and the DE groups, respectively. The primary endpoint was the clinical and pathologic response to primary chemotherapy. The BCS rate was compared. Results: In stage II patients, the objective clinical response (OR) rate was 70% in the FEC group and 81% in the DE group, and the complete clinical response was in 11% and 29% in the FEC and DE groups, respectively (p= 0.01). The complete pathologic response (pCR) rate was 2% in the FEC group and 14% in the DE group (p= 0.01). In stage III patients, the objective clinical response rate was 49.5% in the FEC group and 80% in the DE group with complete clinical response rate of 9.5% and 13% in FEC and DE groups, respectively (p= 0.0001). The complete pathologic response (pCR) rate was 3.3% and 7.7% in FEC and DE groups, respectively (p= 0.1). BCS rate was higher in patients treated with DE scheme (67.5% versus 53% in stage II patients; p= 0.002, and 43.5% versus 29.5% in stage III patients; p= 0.0003). Conclusions: The NAT with DE combination is more effective in terms of clinical and pathologic response propitiating higher BCS rate than the FEC combination in stage II and III breast cancer. No significant financial relationships to disclose.
Locoregional control significantly reduces the risk of subsequent distant metastases in patients with locally advanced breast cancer managed with radiotherapy as the primary locoregional treatment
Authors: W. Rogowski, A. Badzio, R. Dziadziuszko, J. Madrzak, M. Welnicka-Jaskiewicz, J. Jassem, P. Barrett-Lee
Journal: Journal of Clinical Oncology (2007)

11076 Background: The treatment results of patients with locally advanced breast cancer still remain far from satisfactory. Both lack of locoregional control and distant metastases remain the most common pattern of failuire. The aim of this study was to evaluate whether achieving locoregional control decreases the subsequent risk of distant metastases a large series of consecutive locally advanced breast cancer patients managed with radiotherapy as the primary locoregional treatment. Methods: The records of 261 primarily inoperable locally advanced breast cancer patients treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All patients received megavoltage radiotherapy to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. In 241 patients radiotherapy constituted the only local treatment and the remaining 20 patients were subsequently subjected to mastectomy. Most patients received chemotherapy and/or endocrine therapy prior or after radiation therapy. Results: Follow-up ranged from 6 to 133 months (median 37 months). Five- year overall survival was 36% (95%CI: 28–43%) and 5-year loco-regional relapse-free survival was 48% (95%CI: 40–57%). Recurrence occurred in 167 patients (67%), including local recurence in 30 patients (12%), distant metastases - in 72 patients (27%) and both distant and local recurrence - in 65 patients (26%). Median time to distant metastases was significantly shorter among a subgroup of patients who presented locoregional failuire - 33 months as compared to patients who were free of locoregional recurrence or progression before presenting distant metastases-43 months (p&lt;0.05) Conclusions: This study demonstrated that treatment results in patients with locally advanced breast cancer are still far from satisfactory. However it confirmed the importance of putting much effort in achieving locoregional control in that group of patients as it significantly reduces the risk of subsequent distant metastases. No significant financial relationships to disclose.
Biodegradable, Elastomeric, and Intrinsically Photoluminescent Poly(Silicon‐Citrates) with high Photostability and Biocompatibility for Tissue Regeneration and Bioimaging
Authors: Yuzhang Du, Yumeng Xue, Peter X. Ma, Xiaofeng Chen, Bo Lei
Journal: Advanced Healthcare Materials (2015)

Biodegradable polymer biomaterials with intrinsical photoluminescent properties have attracted much interest, due to their potential advantages for tissue regeneration and noninvasive bioimaging. However, few of current biodegradable polymers possess tunable intrinsically fluorescent properties, such as high photostability, fluorescent lifetime, and quantum field, and strong mechanical properties for meeting the requirements of biomedical applications. Here, by a facile one‐step thermal polymerization, elastomeric poly(silicone‐citrate) (PSC) hybrid polymers are developed with controlled biodegradability and mechanical properties, tunable inherent fluorescent emission (up to 600 nm), high photostability (beyond 180 min for UV and six months for natural light), fluorescent lifetime (near 10 ns) and quantum yield (16%–35%), high cellular biocompatibility, and minimal inflammatory response in vivo, which provide advantages over conventional fluorescent dyes, quantum dots, and current fluorescent polymers. The promising applications of PSC hybrids for cell and implants imaging in vitro and in vivo are successfully demonstrated. The development of elastomeric PSC polymer may provide a new strategy in synthesizing new inorganic–organic hybrid photo­luminescent materials for tissue regeneration and bioimaging applications.
Dasatinib (BMS-354825) pharmacokinetics correlate with pSRC pharmacodynamics in phase I studies of patients with cancer (CA180002, CA180003)
Authors: F. R. Luo, F. R. Luo, Y. Barrett, P. Ji, P. Holly, E. McCann, P. Rhyne, E. Clarke, K. He, E. Bleichardt, M. Blackwood-Chirchir
Journal: Journal of Clinical Oncology (2006)

3046 Background: Dasatinib - an inhibitor of several oncologenic kinases including BCR-ABL and SRC - has demonstrated efficacy in CML and Ph+ ALL, and is being evaluated in patients with solid tumors. Studies CA180–002, and CA180–003 were multiple ascending dose studies of dasatinib in patients with refractory Ph+ leukemia, and solid tumors, respectively. We have analyzed the preliminary results of pharmacokinetics (PK) and pharmacodynamic (PD) biomarker phospho-SRC (pSRC) combined across the CA180002 and CA180003 studies. Methods: Dasatinib was administered orally at doses of 15 - 180 mg QD or 25 - 160 mg BID. Dasatinib PK was determined by LC MS/MS. The level of phospho-SRC in peripheral blood mononuclear cells (PBMCs) was determined by an ELISA and was used as a surrogate biomarker of the level of kinase activity of the SRC family members. PK-PD modeling was performed using a two-compartment PK model with first-order absorption kinetics and an indirect inhibitory E max model as the PD model. Results: On the BID regimen, pSRC inhibition was approximately dose-dependent across the dosing range. Inhibition also appeared to be directly correlated with dasatinib plasma concentration, with maximal inhibition achieved at ∼2.5 hr. Based on PK-PD modeling, the estimated EC 50 (the plasma concentration required to achieve 50% inhibition of pSRC) is 14.4 ng/mL. Conclusions: SRC family kinase activity is substantially inhibited at the exposures of dasatinib achieved to date. The optimal regimens of dasatinib to achieve both target inhibition and solid tumors efficacy will be determined based on biomarkers, clinical responses, and toxicity profiles. [Table: see text]
Multi-Institutional Study of the Angiogenesis Inhibitor TNP-470 in Metastatic Renal Carcinoma
Authors: Walter M. Stadler, Timothy Kuzel, Charles Shapiro, Jeffery Sosman, Joseph Clark, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Renal cell carcinoma is resistant to most chemotherapy, and only a minority of patients respond to immunotherapy. Its highly vascular nature suggests that antiangiogenesis therapy might be useful. We thus performed a phase II study of the fumigillin analog TNP-470 in previously treated patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Metastatic renal cell carcinoma patients with good organ function were entered onto the study through five separate institutions. There were no exclusion criteria for prior therapy. All patients were treated at a dose of 60 mg/m 2 of TNP-470 infused over 1 hour three times per week. RESULTS: Thirty-three patients were enrolled. Therapy was generally well tolerated, but asthenia, fatigue, vertigo, dizziness, sense of imbalance, and loss of concentration were common and severe enough to lead to therapy discontinuation in five patients. There was only one partial response of short duration (response rate, 3%, 95% confidence interval, 0% to 16%), but six patients (18%) remained on study for 6 or more months without toxicity or disease progression. CONCLUSION: Long-term therapy with TNP-470 has manageable toxicities and is feasible in patients with metastatic renal cell carcinoma but does not lead to any significant objective responses. Further studies in this population using TNP-470 schedules that produce more prolonged drug levels and clinical trial end points other than objective tumor regression may be indicated.
Phase Ib/Ii Study of Lee011 (Cdk4/6 Inhibitor) and Lgx818 (Braf Inhibitor) in Braf-Mutant Melanoma
Authors: M. Taylor, J. Sosman, R. Gonzalez, M.S. Carlino, M. Kittaneh, M.P. Lolkema, W. Miller, A. Marino, V. Zhang, S.G. Bhansali, S. Parasuraman, M.A. Postow
Journal: Annals of Oncology (2014)
In abstinent adults with type 2 diabetes, a daily glass of wine (vs mineral water) improved cardiometabolic factors
Authors: Meera Jain, Richard Wernick
Journal: Annals of Internal Medicine (2016)

Source Citation Gepner Y, Golan R, Harman-Boehm I, et al. Effects of initiating moderate alcohol intake on cardiometabolic risk in adults with type 2 diabetes: a 2-year randomized, controlled trial. Ann Intern Med. 2015;163:569-79. 26458258
ECOG 5805: A phase II study of eribulin mesylate (E7389) in patients (pts) with metastatic castration-resistant prostate cancer (CRPC).
Authors: M. N. Stein, Y. Chen, G. R. Hudes, M. A. Carducci, W. Tan, R. S. DiPaola
Journal: Journal of Clinical Oncology (2010)

4556 Background: Eribulin mesylate (E7389), a synthetic analog of halichondrin B, is a novel tubulin-binding agent that inhibits cancer cell proliferation at low-nanomolar levels. Methods: In a multicenter ECOG trial, pts with progressive metastatic CRPC, ECOG 0-2 were treated with eribulin 1.4 mg/m2 as an IV bolus over 5 minutes on Days 1 and 8 of a 21-day cycle. This noncomparative study stratified pts to either a chemonaive (CN), prior-taxane (Tax) only, or two prior cytotoxic (TCx) chemotherapy arm. The trialwas powered to detect a 50% PSA reduction using Consensus Criteria in at least 40% vs. 20% (90% power, one-sided α=0.10) for the CN stratum and 25% vs. 10% (power 87%, one-sided α=0.10) for the Tax and TCx strata. Results: In total, 119 pts received treatment of which 116 were eligible for the primary response determination in this study. Median age 70 yrs (range 45-88); median number of treatment cycles 4 (range 1-20+); ECOG 0-1 90%. As of this analysis, only one patient is still on treatment. Among the 115 eligible patients who have discontinued treatment, 82 were off treatment due to disease progression. Among eligible pts who received treatment, 65 had dose modifications (both planned and unplanned). PSA response rate in the CN strata was 24% (versus the anticipated 40% rate). Conclusions: Eribulin demonstrated activity in metastatic CRPC with taxane-naive disease. Clinically significant myelosuppression was noted in all strata. Although single agent activity was observed, the overall response rate did not meet predetermined levels of activity sufficient to warrant further study in CRPC. Evaluable pts ChemonaiveN = 41 Prior taxaneN = 51 Two prior cytotoxicN = 24 ≥50% PSA response: % (90% CI) 24 (13.9–37.9) 10 (4.0–19.5) 4 (0.2–18.3) % Stable disease ≥9 weeks 15 20 29 % Measurable disease response* 8 3 8 Median duration PSA response: months 7.1 3.6 – Overall survival months (median) NR** 11.4 13.7 AEs: % Neutropenia G 3/4 52 50 68 Leukopenia G3/4 33 44 52 Neuropathy—sensory G3/4 14 16 4 Fatigue G1/2-G3/4 69–17 66–8 52–12 Anorexia G1/2-G3/4 33–2 32–6 24–4 Nausea G1/2- G3/4 26–2 38–2 36–0 * 26, 38, and 13 pts with measurable disease in the CN, Tax, and TCx arms, respectively. ** Not reached. No significant financial relationships to disclose.
Value of serum procalcitonin levels in the differential diagnosis of pneumonia and pulmonary embolism
Authors: Ayse Yeter, Gungor Camsari, Gulcihan Ozkan, Aygun Gur, Nur Dilek Bakan, Mehmet Bayram
Journal: European Respiratory Journal (2011)

Objective:  Procalcitonin (PCT), a precursor hormone of calcitonin is secreted from the thyroid. It was increased in blood in bacterial infections. The aim of the study was to determine the serum procalcitonin levels in differentiating community-acquired pneumonia (CAP) from pulmonary embolism (PE).   Methods and patients:  Fifty-eight patients with ≥1 of the following symptoms; fever, cough, dyspnoea, haemoptysis, sputum, chest pain and lesion on chest x ray were included to the study. Thirty patients were diagnosed as CAP and 27 patients as PE. One patient with suspected PE was excluded because of negative pulmonary CT angiography. Serum PCT values of all patients were measured and recorded before treatment was started.   Results:  Median values of PCT were in patients with PE 0.05 ng/ml, in patients with CAP 1.38 ng/ml. The area under ROC curve was 0.83. With an optimal cut-off value 0.27 ng/ml for differentiating PE and CAP, sensitivity was 76.4%, specificity 85.2%, negative predictive value 76.7%, positive predictive value 85.2%, and accuracy 80.7%.   Conclusion:  Serum PCT has a high diagnostic value in the differential diagnosis of PE and CAP. Serum PCT can be used in differentiating CAP and PE as an inflammatory marker.
A phase II study of carboplatin, etoposide and exisulind in patients with extensive stage small cell lung cancer: CALGB 30104
Authors: X. F. Wang, R. Govindan, J. E. Herndon, R. C. Barrier, D. Watson, R. Florence, E. E. Vokes, M. R. Green
Journal: Journal of Clinical Oncology (2005)

7161 Background: Despite a high rate of initial response to chemotherapy, almost all patients with extensive stage small cell lung cancer (SCLC) die from progressive disease. The standard therapy for extensive stage SCLC is a combination of a platinum agent (cisplatin or carboplatin) and etoposide. Exisulind, a derivative of sulindac, induces apoptosis in lung cancer cell lines. Addition of exisulind to chemotherapy is synergistic in vitro. Methods: The Cancer and Leukemia Group B (CALGB) conducted a phase II study of carboplatin (AUC 6) on day 1 and etoposide 80 mg/m2 on days 1–3 administered intravenously every 21 days. Patients (Pts) received a maximum of 6 cycles of chemotherapy. Exisulind was administered 250 mg orally twice daily for the duration of protocol therapy. Eligibility criteria: extensive stage SCLC, no prior chemotherapy, performance status 0–2 and adequate organ function. The primary endpoint was the percentage of patients who lived longer than 12 months after initial treatment. Secondary Objectives: response rate and toxicity. This study was designed to accrue 41 pts in order to differentiate 12-months survival rates of 40% (of no interest) versus 60% (of interest) with α=0.097 and β=0.097. Pts underwent restaging computerized tomography scans every two cycles. Results: Characteristics of the 43 eligible pts enrolled from 06/02 to 8/03: male 63%; median age 61 years (range 44–82); CALGB performance status 0: 28%, 1: 51%, 2: 12%, unknown: 9%. Toxicity data documented for 43 pts: grade 4 toxicities: neutropenia 43%; anemia 2%, hypokalemia 2%.grade 3 toxicities: thrombocytopenia 38%, neutropenia 24%, febrile neutropenia 17%, anemia 14%, hyperglycemia 12%, fatigue 10%. One patient died of treatment related stroke. Preliminary response data on 38 pts: complete response: 15%, partial response: 66%, stable disease 13%, progressive disease: 3%, inevaluable: 3%. The percentage of patients who survived 12 months was 28% (95%CI: 15%–44%). Median survival was 10.5 months (95% CI: 8-6-12.0). Median failure free survival was 6.7 months (95% CI: 5.3–7.3) Conclusion: The addition of exisulind to carboplatin and etoposide does not improve survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis, Bristol-Meyers Squibb, Eli Lilly, Genentech, Merck, Pfizer AstraZeneca, Aventis, Bristol-Meyers Squibb, Cell Pathways, Eli Lilly, Ligand, Pfizer
Impact of amifostine on radiochemotherapy-induced mucositis in patients with head and neck cancer
Authors: C. Daly, D. Ameen
Journal: Journal of Clinical Oncology (2005)

5560 Background: Grade 3/4 mucositis may occur in >70% of patients (pts) treated with radiochemotherapy (RCT) or radiation therapy (RT) alone for head and neck cancer (HNC). Amifostine is an aminothiol prodrug that protects mucosal tissue from chemotherapy and RT-induced damage. The Evaluating Cytoprotection Health Outcomes Registry prospectively followed 135 pts receiving pretreatment amifostine with RT or RCT in clinical practice. This report describes the incidence of mucositis in pts with HNC who received amifostine before RT or RCT. Methods: Data were collected using clinical report forms and pt questionnaires. Primary end points included the incidence of grade 3 or higher mucositis at any time during treatment. Weight change during treatment was also recorded. Results: Of 135 pts with HNC (101 men, 34 women), 77 (57%) pts received RT only, and 55 (40.7%) received RCT. Treatment details were unavailable for 3 pts. The mean age of pts was 58 years (±12.57 y). The majority of pts (90%) received subcutaneous (SC) amifostine. Data on mucositis incidence and severity were available for 132 pts: 27.3% (36 pts) of this group experienced grade 3 mucositis, and 1.5% (2 pts) experienced grade 4 mucositis. The incidence of grade 3/4 mucositis was lower (25.7%) in pts treated with RT alone than in those receiving RCT (32.7%). Weight change data were available for 127 pts: overall median weight loss was 14.1 pounds; however, 11 (8.7%) pts gained weight during treatment. Conclusions: In this prospective study, the incidence of grade 3/4 mucositis in pts with HNC who received amifostine treatment before RT or RCT was far lower (25.7% to 32.7%) than the 70% or greater incidence previously reported. Since 90% of pts received SC amifostine, these findings also support further investigation of SC administration in pts with HNC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune Oncology