tbuckley/cabot-search huggingface dataset:
Potential for surgical salvage of recurrent rectal cancer is governed by patterns of recurrence and ability to achieve an R0 resection
Authors: G. Begossi, M. Disiena, D. Wrobleski, M. Vezeridis, H. Allen, H. J. Wanebo
Journal: Journal of Clinical Oncology (2004)

3759 Background: Recurrence after initial resection of rectal cancer often presents with local regional disease and distant metastases. Aggressive monitoring and surgical intervention is controversial. A recent intergroup adjuvant therapy study (0114) reported single site recurrence (potentially resectable) in 73% of 715 patients, of whom 34% had re-resection with 27% survival (Tepper, JCO 2003;21:3623). We reviewed our multidisciplinary program of aggressive monitoring and resection of rectal cancer recurrence to determine patient selection parameters augering for optimal resection and survival. Methods: 123 patients were referred with recurrent rectal cancer. Median age 61, M/F 58%/42%, Primary Stage I/II 48%, III/IV 49%. Primary surgery included anterior resection (AR) – 67 pts (59%), abdominal perineal resection (APR)-44 pts (36%), and exenteration - 3pts, plus resection other organ -6pts and liver resection - 3pts. Adjuvant chemo/radiation was given to 76 pts (62%). Median recurrence time: 22 mo. The pattern of recurrence was: local -65 pts (53%), distant mets - 40 pts. (33%), local and distant 18 pts. (15%), Recurrence site: singular in 96 pts (78%) and multiple in 27 (22%). Location: anastamotic or bowel wall - 13 pts. (11%), pelvic 52 pts. (42%), extra pelvic (regional nodes) - 10 (8%) and distant = liver - 33 pts (27%), lung 25 pts. (20%), brain 3 pts (2.9%) bone 2 pts. (16%). Curative resections: 59 pts. (79%) with pelvic/extrapelvic recurrence and 15 (37%) of pts with distant metastases. Adjuvant/neoadjuvant chemoradiation was given in 67% of patients. Results: See table. Conclusions: The optimum pattern of single site of recurrence or metastases with long free interval permitted curative R0 resection in 60% (74pts) with long-term survival in 28% of patients. Survival was similar following resection of local/pelvic recurrence or distant metastases. No significant financial relationships to disclose.
Trends in metastatic sites and survival for patients (pts) with stage IV lung cancer
Authors: K. Kubota, T. Mizuno, K. Yoh, S. Niho, K. Goto, H. Ohmatsu, Y. Nishiwaki, N. Saijo
Journal: Journal of Clinical Oncology (2008)

19029 Background: Combination chemotherapy is the mainstay in the management of stage IV lung cancer. More patients with lung cancer were diagnosed as stage IV disease in part because of brain MRI and PET scan. Optimal management of stage IV lung cancer might be different with metastatic sites and number. Methods: The National Cancer Center Hospital East Database was searched for all pts with stage IV lung cancer. Data was recorded for histology, age, sex, smoking history, metastatic sites and number and performance status (PS). Pts were divided into two groups; group A: newly registered pts from July 1992 to December 2000, group B: from January 2001 to December 2006. Survival curves were evaluated using the Kaplan-Meier methods, and statistical significance was estimated by the log-rank test. Results: 1,879 pts (932 pts group A vs. 947 pts group B) were identified. Pts demographics of each group (% group A/B) were as follows; male; 75/74, non- smoker; 16/22, PS 0–2; 87/93, small cell lung cancer (SCLC); 19/16. Median age was 63 years old in group A and 64 in group B. Metastatic sites included bone (38%), ipsilateral lung (34%), contralateral lung (29%), brain (28%), liver (17%), adrenal (11%), neck lymphnode (3%), skin (2%) and others (16%). Bone/brain metastases were diagnosed in 37/27% in group A and 40/31% in group B. Median survival (MS), 1-year survival rate (1ys), 2ys and 3ys were 6 months (M), 23%, 7% and 4% in group A non-SCLC, 9M, 39%, 18% and 8% in group B non-SCLC, respectively (P<.001). In pts with SCLC, MS, 1ys, 2ys, 3ys were 10M, 33%, 9%, 5% in group A and 10M, 40%, 11%, 5% in group B (P=.21). Multivariate analyses revealed that diagnostic period, age, smoking history, histology (NSCLC vs. SCLC), number of metastases (one vs. >=2) and PS were significant prognostic factors. Conclusions: Bone is the most frequent metastatic site in lung cancer. Although there was no improvement in survival in SCLC, significantly chronological improvement was observed in NSCLC. Metastatic sites and number should be considered in the management of stage IV lung cancer. No significant financial relationships to disclose.
The effects of sorafenib and sunitinib on bone turnover markers in patients with bone metastases from renal cell carcinoma
Authors: C. Sahi, J. J. Knox, V. Hinder, S. Deva, D. Cole, M. Clemons, R. J. Broom
Journal: Journal of Clinical Oncology (2009)

e16145 Background: Bone metastases (BM) from renal cell carcinoma (RCC) are common and associated with poor outcomes. While the multi-tyrosine kinase inhibitors (TKI's) sunitinib and sorafenib have advanced the treatment of metastatic RCC, their efficacy on BM is unknown. Urinary N-telopeptide (uNTX) is a marker of bone turnover measured in nmol/mmol creatinine. Elevated uNTX levels correlate with an increased risk of skeletal related events and mortality in patients receiving bisphosphonates for BM from a range of primaries. In this pilot biomarker study we sought to prospectively evaluate the effects on BM of these multi-TKI's in RCC patients. Methods: Eligible patients had advanced RCC, at least one BM evident on imaging and no bisphosphonate exposure within 4 weeks. UNTX levels (OsteoMark) were measured at; baseline and weeks-1, 4, 8 and 12 after commencing either sunitinib or sorafenib. The primary endpoint was the percentage change (Ch) in uNTX levels from baseline. Serum samples were also collected for KIT and VEGFR-2 (Quantikine). Patients also completed pain (including bone pain) and quality of life questionnaires. Results: The uNTX results on the first 9 patients are presented in the table below (7 received sunitinib and 2 sorafenib). In this group, sVEGFR-2 and sKIT levels fell by week-1 and 4 respectively and at week-12 the mean % changes (95% CI) were -34% (-0.53,-0.14) and -38% (-0.58,-0.18). Conclusions: In patients with BM from RCC and at least moderately elevated uNTX levels at baseline, these multi-TKI's show a significant trend to decrease uNTX levels, but perhaps not as effectively as bone-specific therapies (e.g. bisphosphonates) do in other malignancies. SVEGFR-2 and sKIT levels also fell across the patient group over the same period. This pilot data raises questions about the activity of the multi-TKI's in BM from RCC and further research is needed. [Table: see text] [Table: see text]
Validation of quantitative fluorescence imaging analysis (QFIA) of β-catenin in archived prostate tissues for cancer biomarker discovery
Authors: G. P. Hemstreet, G. P. Casale, D. Huang, J. Tian, M. A. Simpson, Z. Kaleem, L. M. Smith, J. E. Elkahwaji, S. L. Johansson
Journal: Journal of Clinical Oncology (2007)

15575 Background: The objective of this study was to develop a sensitive tissue proteomic assay for quantifying proteins (e.g. β- catenin) in tissues and prostate core biopsies by QFIA. A second objective was to apply the validated methodology to quantify other biomarkers for prostate cancer risk assessment, and to study oxidative stress in BPH, prostate cancer, the cancer field, and in inflammatory prostatitis in animals and human prostatitis. Methods: Biopsies from controls and cancer patients were depariffinized, the antigen retrieved, and labeled with a robotic BioGenex Stainer with a primary mouse monoclonal antibody (1/100) to β-catenin. A secondary goat anti-mouse IgG antibody (2° Ab 1/100) coupled with Alexa Fluor 568 was used as the indicator system. The Leica Fluorescence Microscope was calibrated and standardized with fluorescence beads, LNCAP cells, and BPH tissue sections. QFIA of β-catenin was validated by RPPA methacarn fixed tissues. Adjacent 4-micron tissue sections were analyzed by QFIA for total β-catenin content by RPPA. Results: Reproducibility was 10% or less for the LNCAP cells and BPH tissue controls. Adjacent tissue sections assayed by QFIA and RPPA exhibited a strong linear correlation (r=.97) as did tissues fixed in methacarn vs.10% buffered-formalin and assayed by QFIA (r=0.84). For the core biopsy specimens the average MPI (AMPI) from 40 to 200 acini was quantified. The AMPI of cancerous acini (CA) compared to nomal acini (NA) was reduced in 37 of 42 cases p&lt;.02. ROC plots revealed that β-catenin expression in NAA identified 42% (95%CI 25 - 52%) of cancer cases, with 88% (95% CI 80%-96%) specificity. The tissue QFIA method was used to quantify oxidative stress biomarkers (MnSOD, HNE, 8-OHdG) and other field disease biomarkers (Connexin42, and UDP-glucose dehydrogenase (UGDH) in BPH, prostate cancer, and in prostatitis. Conclusions: A tissue based QFIA method has been developed for the quantification of β-catenin in prostate core biopsy specimens, and the method has been validated by RPPA. Assay of β-catenin in prostate core biopsy specimens shows promise as a potential biomarker for a profile defining individuals at risk for prostate cancer and studying oxidative stress in relation to the pathogenesis of disease. No significant financial relationships to disclose.
Predictive value of serum HGF for treatment response to EGFR tyrosine kinase inhibitor in patients with lung adenocarcinoma.
Authors: K. Kasahara, T. Arao, K. Sakai, A. Sakai, T. Sone, M. Nishio, T. Ohira, N. Ikeda, T. Yamanaka, K. Nishio
Journal: Journal of Clinical Oncology (2010)

7563 Background: EGFR mutation status has emerged to be a validated predictive biomarker for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKI) treatment in non-small cell lung cancer. However, other predictive biomarkers for EGFR-TKI have not been identified. Methods: We retrospectively analyzed the serum concentration of 13 molecules in a cohort of 95 patients (pts) with lung adenocarcinoma who received EGFR-TKI treatment from 3 centers. Pretreatment serum concentrations of HGF, amphiregulin, Beta-cellulin, EGF, sEGFR, Epiregulin, FGF-basic, HB-EGF, PDGF-BB, PIGF, tenascin C, TGF-alpha and VEGF were measured using ELISA and multiplex immunoassay system. Results: Serum concentrations of HGF and VEGF differ significantly between pts with progressive-disease (PD) and those without PD (HGF, p<0.0001, VEGF, p<0.0001). HGF and VEGF were strongly associated with progression free survival (PFS) and overall survival (OS) in univariate Cox analysis (all tests for hazard ratio [HR] showed p<0.0001). In multivariate Cox analysis stratified by EGFR mutation status (mutant, n=20 /wild-type, n=23 /unknown, n=52), high concentration of HGF showed a shorter PFS and OS independently of significant clinical variables including gender and PS (Table). Conclusions: Serum HGF is closely related with clinical outcomes of EGFR-TKI treatment and it raise the possibility of further refinement for the selection of patients in combination with EGFR mutation status. Our findings warrant further investigations in a prospective study to evaluate whether HGF is a predictive/prognostic biomarker for EGFR-TKI. Multivariate analysis stratified by EGFR mutation status (n = 95); HGF and VEGF were logtransformed Progression-free survival HR 95% CI P HR 95% CI P Gender M vs. F 1.28 (0.77-2.15) 0.34 1.72 (0.96-3.10) 0.07 PS 2-4 vs. 0-1 0.64 (0.36-1.12) 0.11 1.52 (0.86-2.66) 0.15 HGF 6.28 (2.65-14.9) <0.0001 2.78 (1.28-6.01) <0.0001 VEGF 1.94 (1.11-3.39) 0.0204 1.60 (0.85-3.02) 0.15 No significant financial relationships to disclose.
Abstract 13874: The Comparison of Defibrillation Threshold and the Incidence of Refibrillation Following Long Duration Ventricular Fibrillation in Dogs with and without Pacing-Induced Heart Failure
Authors: Qi Jin, Ning Zhang, Yang Pang, Changjian Lin, Yangxun Xin, Jian Zhou, Shaohua Liu, Qiong Wu, Gang Gu, Liqun Wu
Journal: Circulation (2012)

Introduction: Recent studies have shown that defibrillation threshold (DFT) varies during short duration ventricular fibrillation (SDVF; VF duration < 1min) and long duration ventricular fibrillati...
Topical application of acidified nitrite to the nail causes nitrosation of cysteine groups in the nail plate and renders it antifungal to Trichophyton rubrum and T-mentagrophytes
Authors: MJ Finnen, A Hennessey, S McLean, Y Bissett, [No Value] Megson, R Weller, Richard Weller
Journal: British Journal of Dermatology (2006)
Phase I dose-escalation study of ZK 304709, an oral multi-target tumor growth inhibitor (MTGI), administered for 14 days of a 28-day cycle
Authors: S. Ahmed, R. Molife, H. Shaw, W. Steward, A. Thomas, M. Barrett, K. Kowal, C. McCoy, J. De-Bono
Journal: Journal of Clinical Oncology (2006)

2076 Background: ZK 304709 is a novel oral MTGI that induces cell cycle arrest and inhibits tumour angiogenesis by selectively inhibiting Cyclin Dependent Kinases (CDKs) 1, 2, 4, 7 and 9,VEGF-R 1, 2 and 3, and PDGF-Rβ tyrosine kinases. Methods: Adult patients (pts) (WHO PS ≤2) with a histologically or cytologically confirmed solid tumor, resistant or refractory to conventional therapy, were eligible. ZK304709 was administered orally, once daily, at a 15 mg starting dose, on days 1–14 of a 28-day cycle, then escalated by 33–100% depending on incidence of drug-related toxicity ≥ grade (gr) 2 (CTC v2.0). At least 3 pts were treated at each dose level. The primary objective was to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). Secondary objectives were to determine the tolerability, pharmacokinetic (PK) profile, and preliminary efficacy. Results: Interim results were available for 24 pts (19 M/5 F; median age 56.5) at 5 dose levels (15–120 mg qd). Pts received a median of 2 cycles (range 0–10). Common drug related toxicities were nausea, vomiting, and fatigue. Two DLT were observed: dizziness and hypertension. However, the MTD has yet to be established. The PK profile for dose levels up to 90 mg demonstrated rapid absorption and a dose-dependent increase of exposure and C max . Disease stabilization for ≥4 cycles has been observed. Conclusions: ZK 304709 was rapidly absorbed and has been tolerated on this schedule at up to 120 mg qd. The MTD has not been reached and enrolment is ongoing. These preliminary data demonstrate that oral delivery on this schedule of an agent that inhibits both cell cycle and angiogenesis is feasible. [Table: see text]
OSAS patients can exhibit nocturnal IL-6 upregulation triggered by apnea related strenuous diaphragmatic contractions and oxygen desaturation. A case controlled prospective study
Authors: Georgios Prezerakos, Emmanuil Vagiakis, Maria-Helena Karatza, Roula Vasilleiou, Argyris Tzouvelekis, Efrosyni Rigopoulou, Dimitrios Parthenis, Theodoros Vasilakopoulos
Journal: European Respiratory Journal (2014)

Introduction:Sleep apnea patients exhibit increased plasma levels of IL-6 and TNF-a and this response may be implicated in this group9s increased cardio-cerebrovascular morbidity.  Aims:We hypothesized that this response is causatively related to the intermittent strenuous diaphragmatic contractions and the episodes of arterial oxygen desaturation and oxidative stress associated with apnoeic events and can be attenuated by the administration of oxygen,n-CPAP and antioxidants  Methods:30 patients suffering with OSAS and 11 healthy individuals underwent a standard polysomnographic study. The OSAS cohort underwent 3 additional PSG studies with concurrent oxygen administration, one month of n-CPAP therapy and one month of antioxidant supplementation, respectively. Plasma was sampled at 20 minute intervals throughout the night for measurement of IL-6 and TNF-α levels.  Results:OSAS patients exhibit higher plasma IL-6 but not TNF-a levels compared to controls. The IL-6 upregulation is nocturnal. The IL-6 variation is predicted independently by the duration of the apnoeic episodes and the average oxygen saturation. The IL-6 response to OSAS exhibits individual variation, classifiable into two groups. The different response cannot be attributed to IL-6 gene promoter polymorphisms. The two groups exhibit different sleep incident patterns. Oxygen supplementation and n-CPAP therapy reduce the nocturnal IL-6 upregulation. Antioxidant administration has no effect.  Conclusions:OSAS patients can exhibit nocturnal IL-6 upregulation triggered by apnea related strenuous diaphragmatic contractions and oxygen desaturation.
Updated remission duration and survival results of single-agent clofarabine in previously untreated older adult patients with acute myelogenous leukemia (AML) unlikely to benefit from standard induction chemotherapy due to unfavorable baseline risk factor(s)
Authors: H. P. Erba, H. M. Kantarjian, D. F. Claxton, M. Arellano, R. M. Lyons, T. J. Kovacsovics, J. Gabrilove, S. Eckert, S. Faderl
Journal: Journal of Clinical Oncology (2009)

7062 Background: The CLASSIC II trial has previously reported an independently confirmed overall remission rate of 46% (38% CR and 8% CRp) and 30- and 60-day mortality rates of 9.8% and 16.1%, respectively (Blood 112: 558, 2008). We now report updated duration of remission (DOR), disease-free survival (DFS), and overall survival (OS). Methods: Single arm, multi-center, phase II, open-label, 2-stage study of patients with untreated AML, ≥60 years old, and at least one adverse prognostic factor: age ≥70 years, antecedent hematologic disorder (AHD), PS = 2, and/or intermediate/unfavorable risk karyotype. Clofarabine (CLO) administered days 1–5 at 30 mg/m 2 during induction and 20 mg/m 2 during re-induction/consolidation for maximum 6 cycles. Patients were followed for at least 6 months past remission (CR/CRp). Results: 116 patients enrolled and 112 in full analysis set. Median age 71 years. Median DOR (censored at alternative therapy) for CR/CRp was 56 weeks (95% CI, 33 weeks - not yet estimable [n/e]) and for CR 65 weeks (95% CI, 41 weeks - n/e). Median DFS (not censored at alternative therapy) for CR/CRp was 34 weeks (95% CI, 24 - 65 weeks). Median OS was 41 weeks (95% CI 28 - 53 weeks), for CR/CRp 59 weeks (95% CI, 50 weeks - n/e ), and for CR was 72 weeks (95% CI, 53 weeks - n/e) after median follow-up of 36 weeks (range, 1 - 85 weeks). Thirty-day mortality was 9.8% for all patients with 4.7% and 13% for age &lt;70 and age ≥70 years, respectively. Conclusions: These data expand on the previously reported efficacy and safety data of single agent CLO in adult AML. Complete remissions appear durable (median &gt;1 yr), and DFS and OS compare favorably to historical experience, particularly in patients with these adverse prognostic factors. These results suggest that single agent CLO is an effective and tolerable treatment option for older adult patients with untreated AML and 1 or more unfavorable baseline prognostic factor(s). [Table: see text]
Phase I study of weekly topotecan and gefitinib in patients with platinum-resistant ovarian, peritoneal, or fallopian tube cancer
Authors: B. M. Slomovitz, R. L. Coleman, C. Levenback, M. Jung, D. M. Gershenson, J. Wolf
Journal: Journal of Clinical Oncology (2006)

5090 Background: To determine the dose limiting toxicity and the maximum tolerated dose (MTD) of weekly topotecan in combination with standard dose gefitinib in patients with relapsed, platinum-resistant, ovarian, peritoneal or fallopian tube cancers that are EGF-R positive (&gt;/= 1+). Methods: Patients with measurable, recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gefitinib at a dose of 250 mg oral dose daily and topotecan at a dose of 2.0 mg/m 2 on days 1, 8, and 15, with cycles repeated every 28 days. Dose escalations were planned for topotecan (Dose Levels 1–3: 2, 3, 4 mg/m 2 ) until the MTD was reached. A conventional 3+3 algorithm was used. The 2mg/m 2 dose of topotecan was chosen as a starting dose because there are reported responses to this level when it has been used as a single agent on this schedule. Results: Thirteen patients received a total of 45 cycles. Twelve patients were evaluated for toxicity and 11 patients for response. Median age range was 63 years. At the time of initial diagnosis, all twelve patients underwent tumor debulking surgery. One patient had one prior chemotherapy regimen, 6 patients had 2, 4 patients had 3 and 1 patient had more than 3 prior chemotherapy regimens. There were 3 patients treated at dose level 1, 3 patients at dose level 2 and 7 patients treated at dose level 3 (1 patient was inevaluable). One of 6 evaluable patients in the dose level 3 group had a grade 4 thrombocytopenia. Therefore, dose level 3 will used for the Phase II portion of the trial. There were no treatment related deaths. Of the 11 patients evaluated for response, there were 4 patients with stable disease (mean number of cycles 6.5, range 3–12) and 7 had progressive disease. Conclusions: Gefitinib with weekly topotecan infusion is a well-tolerated regimen and suitable for study in platinum-resistant or refractory ovarian or tubal cancers. The phase II component of this study is ongoing. No significant financial relationships to disclose.
Health care practitioner prescribing patterns and perspectives on oral chemotherapy management: A survey of cancer centers in Toronto, Canada.
Authors: Mark Pasetka, Larissa Day, Maggie Ford, Angela Boudreau, Angie Giotis, Yoo-Joung Ko, Sonal Gandhi
Journal: Journal of Clinical Oncology (2013)

48 Background: With an increasing number of patients receiving oral cancer therapies, evaluation of safe prescription practices, effective patient education, and toxicity monitoring of these agents is imperative. Methods: Multi-disciplinary oncology practitioners at several cancer centres in Toronto, Canada were surveyed using a web-based platform, to evaluate their prescription practices, use of patient education and symptom management tools, as well as their views on patient adherence and toxicity reporting. Results: Of 170 respondents, 43% were nurses, 34% were pharmacists, and 23% were physicians. Seventy nine percent considered patient education, medication adherence (76%), and toxicity management (78%) as “very important” components of oral chemotherapy management. Prescription methods varied: 59% of respondents used written prescriptions, 39% computerized physician order entry (CPOE), and 0% pre-printed orders, ≥50% of the time. Clinicians felt that patients report side effects from oral agents only “some of the time” (53%), and the most problematic toxicities were nausea (61%) and diarrhea (61%). Practitioners perceived the most common reasons for patient underreporting of side effects to be “fear of treatment interruption” (62%), and that “toxicities are part of the treatment” (66%). Seventy three percent of those surveyed felt individual counseling, follow-up calls (69%), and updated medication information (57%) would improve patient adherence and safety. Conclusions: A diverse group of surveyed oncology professionals expressed the importance of utilizing educational and toxicity monitoring tools for patients on oral cancer therapies, particularly as patients are thought to under-report symptoms. Prescription practices are variable, and CPOE use should be improved. The results of this survey will also be compared to a patient survey, to help develop better tools and policies to standardize practice, and improve patient adherence and toxicity management on oral cancer agents.
Abstract 15915: Rapamycin Eluting Biodegradable Extravascular Stent Prevents Vein Graft Stenosis at Long Term in a Canine Model
Authors: Yusuke Suzuki, Shunsuke Kawamoto, Naotaka Motoyoshi, Masatoshi Akiyama, Kiichiro Kumagai, Yukihiro Hayatsu, Koki Ito, Satoshi Matsuo, Yoshikatsu Saiki, Toshimitsu Yokobori, Toshihito Ohmi, Ryohei Monma, Sachiko Watanabe, Yoichi Endo
Journal: Circulation (2012)

Background.Autologous veingraft stenosis and occlusion at long term have been a significant clinical issue. We tested the hypothesis that rapamycin (RM) eluting biodegradable poly L-lactic acid and...