tbuckley/cabot-search huggingface dataset:
Osteopontin (OPN), TIMP-1, and interleukin (IL)-6 as prognostic (prog) for overall survival (OS) and independent from clinical criteria in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Amado J. Zurita, Yuan Liu, Robert C. Gagnon, Anthony D'Amelio, Hai T. Tran, Arundathy N. Bartlett-Pandite, John Heymach
Journal: Journal of Clinical Oncology (2014)

4582 Background: No biomarker has been incorporated into clinically based prog algorithms for mRCC. In previous work in pts with ECOG PS ≤1 treated in a randomized placebo-controlled phase III trial of pazopanib (paz, veg105192), we identified for progression-free survival (PFS), IL-6 as predictive (pred) of paz benefit (Tran, Lancet 2012) and OPN and IL-6 as prog, independent of established criteria (Zurita, ESMO 2012). Here, we evaluate cytokines and angiogenic factors (CAFs) relative to clinical prog variables (varbs) for OS. Methods: Seven baseline plasma CAFs (IL-6, IL-8, OPN, VEGF, HGF, TIMP1, E-Selectin) were measured (Searchlight, Aushon), and 10 prognosis varbs (ECOG PS, time from diagnosis to treatment [TDT], hemoglobin, calcium, neutrophils, platelets, LDH, sum of the longest diameters [SLD], bone metastasis (meta), and number of meta sites) were correlated with OS (n=343: n=225 paz/n=118 placebo [plb]; n=310 including TDT: n=202 paz/n=108 plb) using uni- and multivariable Cox (multiCox) proportional hazard and stepwise models (stm) based on the randomization assignment. Results: Median OS for all pts was 22.7 months (mo) (95% CI 20.2-25.5), 22.9 mo (95% CI 20.2-25.4) for those treated with paz and 20.9 mo (95% CI 15.6-28.8) for plb. Neutrophilia (NEUT), anemia, high LDH, PS 1 (v 0) and SLD (plus TDT instead of LDH in n=310) were significantly associated with poor prognosis in multiCox regression and stm that only considered clinical criteria (and treatment as a variable). When the 7 CAFs were incorporated into the stm, OPN, TIMP-1 and IL-6 were identified as independently prog [Table, n=343, minus IL-6 and treatment in n=310]. Conclusions: Circulating OPN, TIMP-1 and IL-6 are prog for OS independent of established clinical criteria in mRCC pts with good PS. These CAFs should be incorporated into prog and pred models for validation in mRCC trials. Variable (n=343) HR P value TRT (paz v plb) 0.7 0.032 IL6 1.6 0.016 TIMP1 1.5 0.007 OPN 1.5 0.007 SLD 1.2 0.001 NEUT 1.7 0.001 LDH 1.7 0.014 PS 1.4 0.032 Abbreviations: HR, hazard ratio.
The effects of sodium thiosulfate (STS) on cisplatin-induced hearing loss: A report from the Children’s Oncology Group.
Authors: David Robert Freyer
Journal: Journal of Clinical Oncology (2014)

10017 Background: Cisplatin frequently causes irreversible hearing loss in children treated for cancer. STS is a thiol reducing agent shown in preclinical studies to protect hearing but not the tumor with its timed administration post-cisplatin. Methods: The primary aim of ACCL0431 was to evaluate the efficacy of STS, compared with observation (Obs), for preventing cisplatin-induced hearing loss. Eligible subjects were 1–18 years old with normal audiometry and planned cisplatin infusions of ≤ 6 hours with cumulative dose ≥ 200 mg/m2. Subjects were randomized either to Obs or treatment with STS 16 grams/m2 IV over 15 minutes 6 hours after each cisplatin dose. Hearing was measured using standard audiometry for age; data were reviewed centrally using American Speech-Language-Hearing Association criteria. The proportion of subjects with hearing loss (χ2 test) assessed at 4 weeks post the final cisplatin dose (primary endpoint) and EFS/OS (log-rank test, 2-year cumulative estimates and Cox proportional hazards model) were compared between the two groups. Results: 126 eligible subjects were enrolled with germ cell tumor (32), osteosarcoma (30), neuroblastoma (26), medulloblastoma (26), hepatoblastoma (7) or other (5). 105 subjects (64 male, 30 <5 years old) were evaluable for the primary aim. The proportion of hearing loss for STS vs. Obs was 28.6% vs. 55.4%, respectively (p=0.006). Including all 126 subjects at median post-diagnosis follow-up of 2.1 years, EFS for STS vs. Obs was 60.1% vs. 70.0% (p=0.53); OS was 74.5% vs. 88.8% (p=0.050). Subset analysis by extent of disease (determined post hoc) was performed. For subjects with localized disease, EFS was 72.5% vs. 67.1% (p=0.61); HR (hazard ratio) 0.81 (p=0.61); OS was 89.7% vs. 89.2% (p=0.73); HR 1.26 (p=0.73). For those with disseminated disease, EFS was 35.8% vs. 75.0% (p=0.047); HR 2.51 (p=0.055); OS was 49.0% vs. 88.3% (p=0.010); HR 4.03 (p=0.017). Conclusions: STS protects against cisplatin-induced hearing loss in children. However, the potentially lower survival seen in those with disseminated disease receiving STS raises the concern of a tumor protective effect when the drug is administered on this dose and schedule. Clinical trial information: NCT00716976.
Thymidylate synthase genotype specific dosing of capecitabine: Proof of concept phase I study.
Authors: Ross A. Soo, Soo-Chin Lee, Wen-Lee Tan, Ling-Zhi Wang, Xn-Yii Lim, Marie Loh, Sing-Huang Tan, Ying Kiat Zee, Andrea LA Wong, Benjamin Chuah, Daniel Boon Yeow Chan, Siew Eng Lim, Boon C. Goh, Richie Chuan Teck Soong, Wei-Peng Yong
Journal: Journal of Clinical Oncology (2012)

2551 Background: Thymidylate synthase (TYMS) is the target of fluoropyrimidines (FP). TYMS 3R3R is the predominant genotype in East Asian (EA) patients and is associated with increased TYMS expression, reduced FP related toxicity and relative FP resistance. Dose finding studies for FP were developed in Caucasians, a population that typically harbors TYMS 2R2R and 2R3R genotypes. We hypothesize the recommended phase II dose (RP2D) of capecitabine is higher in 3R3R and similar for 2R allele carriers compared to the FDA approved dose. Objectives 1) To determine the maximal tolerated dose (MTD) and RP2D of capecitabine in EA patients with advanced stage malignancy 2) To determine the safety and toxicity of this regimen and 3) To perform plasma pharmacokinetics (PK) of capecitabine and its metabolites. Methods: EA patients with advanced stage cancer were prospectively allocated into two cohorts: Group A (3R3R) and Group B (2R3R, 2R2R). In each cohort, dose escalation followed a standard phase I 3+3 design. Additional patients were treated at the R2P2 dose level (DL). Initial dose was 1250/m 2 bd for 14 days q3w (DL 1) with 125 mg/m 2 bd increments subsequently. Pharmacokinetics (PK) of capecitabine and its metabolites were performed using a LC-MS/MS method. Results: 23 patients (Group A=18; group B=5) received 94 cycles (median 2.5, range 1-8). Median age was 58 (range 34-74) years. Median turnaround time for TYMS genotyping was 1 day. In group A, grade 3-4 DLTs were seen in 3 patients: diarhoea, neutropenic fever, hand-foot syndrome, and mucositis. MTD was at DL 4 (1625mg/m 2 bd) and the RP2D was 1500mg/m 2 bd (DL 3). DL 3 was expanded to n=9. At DL 3, day 1 mean (± SD) capecitabine and 5FU C max was 12.3 ± 9.9 and 0.91 ± 0.73 µg/mL, respectively and AUC 0 – t was 9.84 ± 5.53 and 1.21 ± 0.54 h*µg/mL, respectively. Compared with DL1, C max for capecitabine and 5FU was 2 and 2.02 fold higher and AUC 0-t was 1.49 and 1.59 fold higher at DL3. Accrual in group B was ceased at DL2 due to lack of patient enrolment; no DLT was seen. By ROC analysis, day 1 5FU AUC 0 – t of 1.74 h*µg/mL predicted for DLT (p=0.022, sensitivity 100%, specificity 90%). Conclusions: In EA patients with TSER 3R3R, the RP2D was 1500 mg/m 2 bd. The D1 5FU AUC 0 – t at RP2D was 59% more than the FDA approved dose (DL1).
Cost-effectiveness analysis of routine use of eribulin in patients with metastatic breast cancer in France: A retrospective analysis.
Authors: Marie-Justine Paillard, Elsa Curtit, Virginie Nerich, Laurent Cals, Fernando Bazan, Laura Mansi, Nathalie Meneveau, Philippe Montcuquet, Erion Dobi, Loic Chaigneau, Hamadi Almotlak, Antoine Thiery-Vuillemin, Cristian Villanueva, Xavier B. Pivot
Journal: Journal of Clinical Oncology (2014)

e11531 Background: There is a need to perform cost-effectiveness analysis for all new treatements approved for routine use based on national economical model. Eribuline, a new anti-microtubule inhibitor got approval for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after an anthracycline, a taxane and a capecitabine containing regimens. Methods: All patients treated by eribulin in the Franche Comte region were prospectively monitored to assess efficacy, safety and cost-effectiveness of this new treatment based on a cost minimization strategy. The following costs were taken into account: drug, consultation with a medical oncologist, eventual supportive treatments, hospitalizations for treatment administration or for management of serious adverse events and the healthcare travels. Results: Ninety patients were treated by eribulin between July 2006 and October 2013. The median age was 58 (ranges: 32-79). A median number of 8 cycles (ranges 1 – 48) of eribuline were administered. The median progression free survival was 3 months (ranges 2-5), and the median overall survival was 10 months (ranges 7-20). The most common grade 3-4 side effects were neutropenia (38%), asthenia (10%) and peripheral neuropathy (7%). The median cost of the treatment was 9,767 € per patient (range: 742-55,451), The median overall monthly cost was 4,316 € per patient. Conclusions: This analysis observed similar clinical survivals and adverse events than the randomized pivotal EMBRACE study. Cost-effectiveness comparisons with other drugs will be displayed to place the cost-effectiveness of routine use of eribuline in the hierarchy of available treatment options for metastatic breast cancer.
The inclusion of high-dose therapy and autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma (FL) is associated with prolonged overall survival (OS) from diagnosis
Authors: J. W. Sweetenham, L. Rybicki, B. Pohlman, R. Sobecks, M. Kalaycio, R. Dean, S. Andresen, S. Brown, B. Bolwell
Journal: Journal of Clinical Oncology (2007)

8061 Background: Recent studies have suggested that OS for patients (pts) with FL is improving compared with older reports in which median OS was typically 8 to 10 years. We analyzed outcomes for pts with FL undergoing ASCT at any time in the course of the disease to determine whether this contributes to improved OS. Unlike previously reported transplant series, we calculated OS from the date of diagnosis to determine the potential effect of ASCT on the overall course of the disease. Methods: Between 1/79 and 10/05, 188 pts with FL underwent ASCT at our center. Male/female = 103/85. Median age = 47yrs (20–73). Other pt characteristics are summarized in the table . The International Prognostic Index (IPI) was used since data for the FLIPI were only available for a minority of pts. All pts received chemotherapy-only conditioning regimens, most commonly with busulfan, cyclophosphamide and etoposide (82%). OS was calculated from the date of diagnosis, and survival comparisons were made using the logrank test. Results: 120 pts (64%) are alive at a median follow-up of 8.2 years (0.8–23.7 years). Median follow-up from date of transplant is 5.2 years (0.1–15.3 years). The median OS from the date of diagnosis is 15.2 years. IPI at diagnosis was predictive of OS (low-risk median not reached, low-intermediate = 18.3 yrs, high-intermediate = 4.9yrs) (p = &lt;0.001). Status at transplant (CR/PR1 vs CR/PR2 vs CR/PR3 vs relapsed/refractory) had no effect on OS (p = 0.36). Conclusions: The use of ASCT as part of the overall treatment strategy for pts with FL is associated with prolonged OS and may in part be responsible for the reported improvement in survival for FL reported in recent years. Further prospective evaluation of the role of ASCT in the context of treatment regimens which include monoclonal antibodies is required. No significant financial relationships to disclose. [Table: see text]
A phase II study of intratumoral application of L19IL2/L19TNF in melanoma patients in clinical stage III or stage IV M1a with presence of injectable cutaneous and/or subcutaneous lesions.
Authors: Riccardo Danielli, Roberto Patuzzo, Anna Maria Di Giacomo, Gianfranco Gallino, Annabella Di Florio, Ornella Cutaia, Andrea Lazzeri, Carolina Fazio, Leonardo Giovannoni, Pier Adelchi Ruffini, Giuliano Elia, Dario Neri, Mario Santinami, Michele Maio
Journal: Journal of Clinical Oncology (2014)

TPS9103^ Background: Preclinical studies in three different murine models of subcutaneous tumors have shown that a single intratumoral injection of a combination of two immunocytokines, L19-IL2 and L19-TNF is more effective than each immunocytokine in monotherapy and is curative in 100% of animals. Furthermore, in the clinical setting intralesional delivery of L19-IL2 elicited objective responses in >50% of Stage III melanoma patients, with a possible benefit in terms of distant metastases-free survival rates for these patients and evidence of systemic immune responses in most evaluable patients. L19-IL2 and L19-TNF are recombinant fusion proteins, consisting of the single-chain monoclonal antibody (L19) directed against extradomain B of fibronectin, a well-characterized marker of angiogenesis, fused to IL2 or TNF cytokines, respectively. Methods: A Phase II, uncontrolled, multicenter, prospective study is ongoing at two centers in Italy (EudraCT Number: 2012-001991-13). Twenty patients with unresectable Stage IIIC/IVM1a melanoma and cutaneous or subcutaneous injectable metastases will receive intratumoral injections of L19-IL2 (10 Mio IU maximum daily dose) in combination with L19TNF (312 µg) once per week for 4 consecutive weeks. Primary objective is the assessment of efficacy measured as the rate of patients with complete response (CR) of L19IL2/L19TNF-treated lesions at week 12. Secondary objectives include ORR and DCR of treated lesions at week 12, and ORR and disease control rate (DCR) at weeks 12, 24 and 36 of treated and non-treated lesions. Additional secondary endpoints include duration of OR and DCR of treated and treated-non treated lesions, median overall survival (mOS) and safety of study drugs. Tumor assessment is performed according to RECIST vs 1.1 and modified (m) mRECIST criteria at baseline and at weeks 6, 12, 24 and 36. Adverse events will be collected according to the CTCAE v. 4.02. The study is ongoing and fifteen patients have been enrolled so far. Clinical trial information: 2012-001991-13.
Impact of the presence of EGFR mutation on definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: Pattern of relapses and survival analyses in 145 patients.
Authors: Shigehiro Yagishita, Hidehito Horinouchi, Tomoko Taniyama, Shinji Nakamichi, Satoru Kitazono, Hidenori Mizugaki, Shintaro Kanda, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Minako Sumi, Kouya Shiraishi, Takashi Kohno, Koh Furuta, Koji Tsuta, Tomohide Tamura
Journal: Journal of Clinical Oncology (2013)

7540 Background: EGFR mutational status is an important biomarker in advanced NSCLC patients. However, little is known about the frequency and clinical significance of the presence of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) eligible for definitive chemoradiotherapy (CRT). Methods: Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive NSCLC patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year relapse-free rate, first relapse sites, and overall survival were investigated according to the EGFR mutational status. Results: A total of 528 patients received CRT at the National Cancer Center Hospital during the study period. Of these, 274 were diagnosed as having non-squamous NSCLC, and sufficient specimens for mutational analyses could be obtained from 145 patients. EGFR mutants (EGFR-mt) were found at a frequency of 18% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/ light smoker), the proportion of cases with smaller (T1/2) primary lesions was higher in patients with EGFR-mt than in those carrying wild-type EGFR (EGFR-wt). EGFR-mt showed a slightly better RR (85.7% vs. 72.9%), but similar median PFS (12.2 m vs. 10.6 m) and 2-year relapse free rates (23.8% vs. 29.2%) as compared to EGFR-wt. Local recurrence as first relapse occurred less frequently in EGFR-mt than in EGFR-wt (6% vs. 20%). After disease progression, a majority of EGFR-mt received EGFR-TKIs (62%), and these patients showed longer post-progression survival and a higher 5 year survival rate (60% vs. 40%) than EGFR-wt. Conclusions: Among the LA-NSCLC patients eligible for definitive CRT analyzed, 18% had EGFR- activating mutations. Although definitive CRT was similarly effective in both EGFR-mt and EGFR-wt, slightly better local control rate was noted in EGFR-mt. Treatment with EGFR-TKIs contributed to longer post-progression survival and overall survival in LA-NSCLC patients harboring EGFR mutations.
¿HEMOS DE RECOMENDAR DIETA LÍQUIDA O DIETA SIN RESIDUOS, EL DÍA ANTES DE UNA COLONOSCOPIA DE CRIBADO?. ESTUDIO CLÍNICO RANDOMIZADO CON DOS GRUPOS PARALELOS
Authors: MA Pantaleón Sánchez, D Zaffalon Espinal, G Casals Urquiza, A Fernández Clotet, M Bonilla Montón, I Ibañez Zafón, A Raga Gil, A Seoane Urgorri, X Bessa Caserras, M Dedeu Josep, F Riu Pons, L Barranco Priego, MA Alvarez Gonzalez
Journal: Endoscopy (2015)

Las guías clínicas no permiten decidir cuáles son las modificaciones dietéticas ideales en la preparación para la colonoscopia en el programa de cribado poblacional del cáncer colorectal (PCP-CCR).
Myths in the assessment of progression: How frequently should we assess patients in clinical trials?
Authors: A. M. Stone, N. Fernandes, C. Morris
Journal: Journal of Clinical Oncology (2007)

6521 Background: It is often believed that within a clinical trial a patient’s progression status should be assessed as frequently as practically possible if the primary objective is to compare progression-free survival (PFS). However, the statistical analysis of PFS data compares rates of progression rather than a specific percentile such as a median, and results in an estimate of the hazard ratio (HR)—the ratio of event rates. Methods: We provide results of simulations assessing the power and bias of an analysis of PFS in controlled trials according to visit frequency, rate of progression and analysis method. The simulations assume a true HR of 0.8 and that data are analyzed after 630 patients have an event to provide a nominal power of 80%. All simulations assume patients are assessed according a symmetric visit schedule as otherwise, if data are analyzed asymmetrically, bias will follow (Proc Am Assoc Cancer Res 2002; abst 975). Results: If patients are assessed at a time interval equal to the median divided by two, there is a negligible (=2%) loss of power for the analysis of PFS data. Data presented in the table show that in a disease with a comparator median of 4 and 8 months when 1,000 patients are randomized, there is little increase in power if patients are assessed more often than every 2 and 4 months, respectively, using a standard log- rank test. The simulations presented assume there is some variability (SD=1 week) of the actual assessment date around the protocolled date. If PFS data are analyzed by moving PFS times to the scheduled assessment time, alternative methods of analysis (grouped survival techniques) preserve power and avoid bias by appropriately handling the excessively tied PFS times. Conclusions: Within the context of a clinical trial, a fully powered analysis of PFS is possible if patients are assessed at a frequency which is one-half of the median of the disease under study, and therefore patients need not be assessed more frequently unless clinical practice outside of a clinical trial would dictate otherwise. [Table: see text] [Table: see text]
Use of WHONET-SaTScan system for simulated real-time detection of antimicrobial resistance clusters in a hospital in Italy, 2012 to 2014
Authors: Alessandra Natale, John Stelling, Marcello Meledandri, Louisa A Messenger, Fortunato D'Ancona
Journal: Eurosurveillance (2017)

Resistant pathogens infections cause in healthcare settings, higher patient mortality, longer hospitalisation times and higher costs for treatments. Strengthening and coordinating local, national and international surveillance systems is the cornerstone for the control of antimicrobial resistance (AMR). In this study, the WHONET-SaTScan software was applied in a hospital in Italy to identify potential outbreaks of AMR. Data from San Filippo Neri Hospital in Rome between 2012 and 2014 were extracted from the national surveillance system for antimicrobial resistance (AR-ISS) and analysed using the simulated prospective analysis for real-time cluster detection included in the WHONET-SaTScan software. Results were compared with the hospital infection prevention and control system. The WHONET-SaTScan identified 71 statistically significant clusters, some involving pathogens carrying multiple resistance phenotypes. Of these 71, three were also detected by the hospital system, while a further 15, detected by WHONET-SaTScan only, were considered of relevant importance and worth further investigation by the hospital infection control team. In this study, the WHONET-SaTScan system was applied for the first time to the surveillance of AMR in Italy as a tool to strengthen this surveillance to allow more timely intervention strategies both at local and national level, using data regularly collected by the Italian national surveillance system.
Hypersensitivity to bacteria in eczema.
Authors: W.E. PARISH, ESTHER WELBOURN, R.H. CHAMPION
Journal: British Journal of Dermatology (1976)

The amounts of agglutinating antibody to staphylococcal and micrococcal phenol‐extracted (probably teichoic acids) and protein antigens, prepared from Baird Parker types SI, SIV and Ml, were no greater in eczematous than in control persons. Most antibody to phenol‐extracted antigens was IgM which frequently activated complement to lyse red cells which had adsorbed the bacterial antigen. IgG antibody against phenol‐extracted staphylococcal antigen (Staph. aureus, Baird Parker type SI) was shown to be specific antibody combining by the F(ab)2 portion of the molecule. The phenol‐extracts did not contain staphylococcal Protein A that binds to the Fc portion of IgG. Furthermore, the presence of Protein A in the protein or total antigen extracts did not appear to modify the results of the tanned cell agglutination test. The occurrence of immediate or of 4 h, Arthus‐like skin test responses to staphylococcal or micrococcal antigens was unrelated to the agglutinin or complement‐lysis titre of the relevant antibody.