tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis of a randomized study with stereotactic radiosurgery (SRS) alone versus SRS plus whole brain radiation therapy (WBRT) for patients with brain metastasis
Authors: L. S. Lal, E. L. Chang, L. Franzini, R. B. Arbuckle, L. Miller, L. G. Reasonda, C. Feng, J. M. Swint
Journal: Journal of Clinical Oncology (2009)

6624 Background: This paper illustrates the incremental cost-effectiveness ratio (ICER) and cost-utility comparison of SRS alone versus SRS plus WBRT for brain metastasis. Methods: A decision analysis model, including subsequent treatment for recurrences, was developed and populated with data from patients randomized to either SRS alone (SA) versus SRS plus WBRT (SW), using costs from the healthcare institution perspective and outcomes based on actual life years saved (LYS) and quality-adjusted-life-years (QALYs). Utilities were captured through a time-trade -off methodology, utilizing three time horizons: 10 years, 5 years, and 1 year. Tornado diagrams and one-way sensitivity analyses were conducted to determine robustness of the model. Results: Fifty-eight patients were included in the final analysis, with 31 patients in the SA arm and 27 patients in the SW arm. The average cost of the SA arm is $119,000 versus $74,000 for the SW arm. The average effectiveness for the SA arm was 1.64 LYS versus 0.60 LYS for the SW arm. The ICER for total costs per LYS and QALYs were: $43,986 per LYS; $42,136 per QALY (10year); $43, 719 per QALY (5year); $44,686 (1year) for the SA arm. The surgical cost per LYS was $7,131 for the SA arm, and the radiation cost per LYS analysis was dominated. Tornado diagrams revealed that the following variables had the highest impact on the ICER: probability of being alive with SA in recursive partitioning analysis (RPA) class 2 and no recurrence; probability of no recurrence in RPA class 2 with SA; probability of being alive with SA in RPA class 2 and being treated for recurrence; probability of no recurrence in RPA class 1 with SA; and probability of being alive with no recurrence in RPA class 1 with SA. One-way sensitivity analysis exhibited a wide range variation for the first three of the above mentioned probabilities, with the final two having less variation. Conclusions: Compared to other interventions in the $50,000 to $100,000 per QALY cost-effectiveness range from an economic perspective, the application of SA, with subsequent surgical management of recurrences, is shown to be a reasonable treatment modality for brain metastasis. No significant financial relationships to disclose.
Comparison of FRAX score to bone mineral density for estimating fracture risk in patients with CRPC on androgen-deprivation therapy (ADT).
Authors: Marc Nicolas Bienz, Herbert James, Ilija Aleksic, Christopher Michael Pieczonka, David Albala, Peter Iannotta, Modar Alom, Neil Mariados, Vladimir Mouraviev, Fred Saad
Journal: Journal of Clinical Oncology (2014)

101 Background: A FRAX algorithm has been elaborated to estimate the ten-year hip fracture risk associated with this under-diagnosed condition. We aim to evaluate the fracture risk of patients who would otherwise be left untreated by the conventional T-score. Methods: Clinical data from 613 PCa patients undergoing ADT was collected from our AMP large urology group. Fracture risk was assessed using the country specific (USA) Fracture Risk Assessment Tool (FRAX). Also, a subset of patients (n=94) had received Dual-energy X-ray Absorptiometry (DXA). We compared the proportion of patients suitable for treatment according to the threshold of the FRAX fracture risk calculated with the BMD (&gt;3%) and the T-score (&lt;-2.5). Results: According to the FRAX algorithm (without BMD), 61.6% of our cohort require treatment. The FRAX score (with BMD) identified 46.8% of patients who had DXA suitable for treatment, in contrast to 19.1% by the T-score alone. Correlations were calculated between the various methods (Table). Conclusions: Our results demonstrate that many patients unidentified for treatment by the conventional T-score are at significant risk for fracture according to the FRAX algorithm with BMD. When calculated without the BMD, an even greater proportion of patients is found to be at risk and suitable for treatment. [Table: see text]
Detection of actionable oncogene drivers alterations in <i>HER2</i>-amplified gastric cancer by next generation sequencing.
Authors: Carlos Gomez-Martin, Roberto A. Pazo Cid, Antonieta Salud, Paula J. Fonseca, Ana Leon, MaCarmen Galan, Laura Visa, Fernando Rivera, Maria Alsina, Carlos Plaza, Barbara Angulo, Susana Hernandez Prieto, Carolina Dominguez, Margarita Rodriguez Garcia, Elena Del Valle, Soledad Fernandez, Federico Rojo, Miriam Cuatrecasas, Fernando Lopez-Rios
Journal: Journal of Clinical Oncology (2015)

67 Background: HER2 amplified cases are the only subset of gastric carcinoma (GC) patients with an approved targeted therapy (≈20%). In GC it is still unknown if there is a mutually exclusive pattern of mutations in major driver oncogenes. We performed a systematic search for targetable oncogenes in a cohort of HER2 amplified GC patients. Methods: 53 Formalin-fixed paraffin embedded samples from HER2 amplified GC patients (43 tumor and 10 normal samples) were selected for next generation sequencing (NGS). Before DNA extraction a macrodissection procedure was performed to guarantee at least 30% tumor in all cases. DNA samples were sequenced using the Ion Torrent Personal Genome Machine (PGM) sequencing platform (Life Technologies, Carlsbad, CA, USA). The Ion AmpliSeq Cancer Hotspot Panel v2 was used. This panel encompasses more than 2800 mutational hotspots of 50 oncogenes and tumor suppressor genes. Data were processed using the Ion Torrent platform-specific pipeline software Torrent suite v4.2. Moreover, sequencing data were analyzed with Ion Reporter software 4.2 to detect any copy number alteration of the genes included in the panel. Results: We successfully sequenced all samples. We identified 89 mutations in 12 genes (range from 1 ~ 9). The most frequent significant mutations included TP53 mutations (30), PI3KCA (3), SMAD4 (3), CDKN2A (4), CTNNB1 (3) and MET (3). Other mutations were found in KRAS, NOTCH, APC, and VHL genes. We also detected potential amplifications in the KRAS (4), EGFR (9), PI3KCA (11), AKT (6), FGFR (6), CDKN2A (4) and CDH1(8) genes. Among 43 tumor specimens, 86% of specimens harbored at least one genetic alteration, most of them linked to actionable mutations or amplifications Conclusions: Within HER2 amplified GCs, there are additional subsets with a potentially targetable oncogene. Future testing for these targets will benefit from including HER2 amplified GC patients Supported by the Spanish Ministry of Health, Fondo de Investigaciones Sanitarias grant PI11/01005 and European FEDER (PN I+D+I 2008‐20011).
Infectivity Experiments With Nucleic Acids of the Shope Rabbit Papilloma and Derived Carcinomas&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: M. E. Hodes, Catherine Gardella Palmer, L. E. Beaty, Mary K. Swenson, J. Donald Hubbard
Journal: JNCI Journal of the National Cancer Institute (1963)

Treatment of Shope papilloma tissue with a detergent and sodium p-amino-salicylate, followed by extraction with phenol, yields a material that induces papillomas in wild or domestic rabbits in the absence of deoxyribonuclease. The infective moiety, deoxyribonucleic acid, is precipitable by alcohol and can be freed of most of the residual protein and ribonucleic acid. It resists heating at 100° for 10 to 30 minutes. These results agree with those of Ito and Evans. Infectious deoxyribonucleic acid has been isolated only from tumors yielding virus. It has not been obtained from the Vx2 or Vx7 carcinomas.
Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation
Authors: D Provan, L Bartlett-Pandite, C Zwicky, D Neuberg, A Maddocks, P Corradini, R Soiffer, J Ritz, LM Nadler, JG Gribben
Journal: Blood (1996)
Pharmacokinetics (PK) and pharmacodynamics (PD) of AMG 162, a fully human monoclonal antibody to Receptor Activator of NF kappa B Ligand (RANKL), following a single subcutaneous dose to patients with cancer-related bone lesions
Authors: M. C. Peterson, S. W. Martin, B. Stouch, D. Chen, D. L. Holloway, J.-J. Body, A. Lipton, R. Coleman, P. J. Bekker
Journal: Journal of Clinical Oncology (2004)

8106 Background: RANKL is an essential osteoclastic differentiation/activation factor. AMG 162 PK and PD were evaluated in a phase 1, single dose, randomized, double-blind, double-dummy, active control (pamidronate), dose escalation study, in patients with breast cancer (BC) or multiple myeloma (MM), with lytic or mixed lytic-blastic bone lesions. Methods: Patients (n=54; 3–9/cohort) received a subcutaneous (SC) injection of either AMG 162 (0.1, 0.3, 1.0, or 3.0 mg/kg) or placebo (3:1 ratio) and an intravenous infusion of either 90 mg of pamidronate or saline. Blood and urine samples were collected for determinations of AMG 162 serum concentrations and the bone resorption marker, N-telopeptide levels (uNTx/Cr), respectively. Results: AMG 162 serum levels reached average maximums of 448 ng/mL (0.1 mg/kg) to 19,800 ng/mL (3.0 mg/kg) 14 to 21 days post-dose, and 625 ng/mL (0.1 mg/kg) to 20,100 ng/mL (3.0 mg/kg) 7 to 14 days post-dose in BC and MM patients, respectively. Serum levels were maintained above 100 ng/mL at 0.3 mg/kg and above 3000 ng/mL for 84 days following 3.0 mg/kg in both BC and MM patients. Rapid decreases in uNTx/Cr (within 24 hours) followed AMG 162 administration in BC and MM patients. At 0.3 mg/kg and greater, AMG 162 produced marked suppression in uNTx/Cr with median maximal suppression of greater than 50% in MM and 75% in BC patients. A 1.0 mg/kg dose produced sustained median suppression (>70%) in BC and MM patients for the duration of the study (84 days), while a 3.0 mg/kg dose produced similar suppression in BC yet less suppression in MM patients (∼38%). Conclusions: The favorable PK and PD of AMG 162 potentially allows for infrequent SC dosing in the treatment of bone disorders. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc.
Phase II study of weekly irinotecan and cisplatin for refractory or recurrent non-small cell lung cancer (NSCLC)
Authors: Y. Takiguchi, Y. Asaka-Amano, T. Moriya, T. Kawashima, A. Mizoo, K. Kurosu, K. Nagao, T. Kuriyama
Journal: Journal of Clinical Oncology (2006)

17002 Background: A current option for recurrent NSCLC is monotherapy with docetaxel. However, cisplatin, if tolerable, may still have power for this condition. Irinotecan is also a key drug for NSCLC. The objectives of this study were to evaluate the clinical relevance of weekly chemotherapy consisting of irinotecan and cisplatin as a 2nd-line therapy for NSCLC. Methods: Patients meeting all following criteria were eligible: proven NSCLC refractory or recurrent after previous single-regimen chemotherapy, PS (0–2), age &gt; 15 years, adequate organ functions, measurable lesions by RECIST, life expectancy exceeding 8 weeks, and written informed consent. Patients with any of the following conditions were ineligible: previous treatment with irinotecan and/or surgery, requirement of thoracic irradiation, interstitial lung disease, pleural effusion or ascites requiring treatment, pericardial effusion, symptomatic brain metastasis, concomitant malignancy or other inadequate condition. Irinotecan (60 mg/m 2 in 500 ml electrolyte soln, day 1) and cisplatin (25 mg/m 2 in 500 ml saline, day 1, without further hydration) were administered every week for at least 6 courses unless encountering defined skip criteria. Calculated minimum sample size was 43 based on Simon two-stage optimal design with p0=0.10, p1=0.25, α error=0.05 and β error=0.20; planned sample size was 48. The primary endpoint was response rate, and the secondary ones were toxicity and survival time. Results: Since February 2002, 48 patients (consisting of 29 with adeno-, 14 with squamous cell, 3 with large cell carcinoma and 2 with NSCLC not further specified) with a median age of 62-years were enrolled, with 1 death before treatment. Therefore, 47 patients were eligible for evaluation of response rate and toxicity, whereas all 48 were analyzed for survival. Chemotherapy was administered for a median 6 courses (range, 0–15). Response rate was 25.5% (95% CI: 12.9–38.1%). Toxicity of grade 3 or 4 consisted of neutropenia (29.8%), thrombocytopenia (6.4%), anemia (29.8%), diarrhea (10.6%) and nausea (21.3%). MST was 10.6 months, and 1-year survival rate was 43%. Conclusions: This 2nd-line chemotherapy for NSCLC showed promising efficacy with tolerable toxicity. No significant financial relationships to disclose.
The Mediterranean Case-Results from the Italian Progetto CUORE Populations. Abstracts From the 2009 Joint Conference-Nutrition, Physical Activity and Metabolism and 49th Cardiovascular Disease Epidemiology and Prevention.
Authors: C Fornari, C Donfrancesco, S Giampaoli, M Riva, L Palmieri, S Panico, D Vanuzzo, M Ferrario, L Pilotto, G Cesana
Journal: Circulation (2009)
Plasma cell acid phosphatase activity as prognostic factor in multiple myeloma: relationship to the thymidine-labeling index.
Authors: M Boccadoro, A Gallamini, A Fruttero, P Gavarotti, V Redoglia, F Buffa, S Ruá, A Pileri
Journal: Journal of Clinical Oncology (1985)

Plasma cell acid phosphatase (AP) activity and thymidine labeling index (LI%) were evaluated concomitantly in 52 patients with monoclonal gammopathies. AP score, percentage of AP positive plasma cells, and LI% were significantly higher in 26 patients with multiple myeloma (MM) at the time of diagnosis than in 11 monoclonal gammopathy of undetermined significance (MGUS) and eight smoldering myeloma (SM) patients. LI% had the highest statistical correlation with disease status. A 1% cutoff could clearly separate the patients with progressive MM compared to those with stable disease (SM-MGUS) (P less than .001). There was a significant overall correlation between the AP score and LI% (P less than .005). Since LI% is a recognized powerful prognostic factor, this correlation suggests that the AP score can also be a reliable test predicting patient survival duration. In addition, we identified a subgroup of IgG MM patients with very high tumor mass who had a low LI% but a high AP score. This was associated with very poor patient survival and indicated the discrete prognostic importance of AP score in this subgroup with low LI%. Thus, both the LI% and AP score can be recommended as helpful clinical tests in patients with monoclonal gammopathies.
Abstract 12673: Placement of Proximal Edge on TCFA and Calcification Correlates With Inadequate Neointimal Coverage of Struts After Drug Eluting Stent Implantation
Authors: Tomoya Ueda, Shiro Uemura, Yoko Dote, Yutaka Goryo, Yu Sugawara, Satoshi Okayama, Makoto Watanabe, Yoshihiko Saito
Journal: Circulation (2014)

Introduction: Inadequate neointimal coverage of the stent struts is one of the risks for late stent thrombosis, especially in DES. Using OCT, we studied the morphological characteristics of coronary segment of both proximal and distal edges, and evaluated their influence on the neointimal coverage of the strut in chronic phase. Methods: Of 111 culprit coronary lesions in 91 patients, baseline OCT tissue characteristics were evaluated at both proximal and distal edges after DES implantation. The second OCT examination was performed on 9.1 months after implantation, and neointimal coverage of struts was assessed within 5mm inner segments from each stent edge. An uncovered strut was defined as having the signal thickness less than 30 μm from the center of strut. Results: Of 10995 apposed stent struts, uncovered struts were detected in 5.3% within distal and 6.8% within proximal edges. For further statistical analysis, edge segments were classified into two categories according to the ratio of uncovered struts, as the poorly-covered group (highest quartile with % uncovered struts), and the well-covered group (the remaining lower quartiles with % uncovered struts). As to OCT tissue characteristic, 1) fibrous plaque was significantly less observed in the poorly-covered group at both distal and proximal edges (p=0.0031 and p=0.0046, respectively). 2) Lipid pool was more frequently observed in the poorly-covered group than the well-covered group at both distal and proximal edges (p=0.0037 and p=0.0061, respectively). 3) Thin-cap fibroatheroma (TCFA) and calcification were also more frequently observed in the poorly-covered group than the well-covered group (p=0.0025 and p=0.0070, respectively) at proximal stent edge. Logistic regression analysis revealed that existence of calcification at proximal edge was an independent predictor for uncovered struts (OR: 5.48, 95%CI: 1.46-23.46, p=0.0119). TCFA at proximal edge was also an independent predictor (p=0.0044). Conclusions: TCFA and calcification at proximal edge were predictors of uncovered struts. Although mechanism should be further elucidated, placement of proximal edge on such tissue characteristics should be avoided.
Early therapeutic intervention based on blood tumor markers (TMs) in patients with primary breast cancer (PBC).
Authors: J. F. Robertson, J. Mathew, P. Prinsloo, A. Agrawal, E. Gutteridge, E. Merenah, K. Cheung
Journal: Journal of Clinical Oncology (2010)

639 Background: This study was initiated to pilot the concept of early therapeutic intervention based on sequential TM measurements in patients during follow-up for PBC. Methods: Patients with oestrogen receptor positive and moderate/poor prognostic PBC with no evidence of symptomatic metastases were invited to participate. Patients were followed up 3-monthly with clinical assessment and TM (CA15.3 and CEA) measurements. The clinical team were blinded to TM results. Patients who were asymptomatic and developed raised (based on pre-defined cut-offs) TMs were randomized to treatment change or control (no change). Patients who developed symptomatic metastases came off the study. The primary and secondary endpoints were intervals from randomization to symptomatic metastases and to last follow-up/death respectively. Results: 85 patients (median age = 54 years [30-72]) were recruited with a median follow-up of 81 months (1-124). 12 patients coming off the study because they developed symptoms without any TM rise. Sixteen patients were randomized as described. There was no difference between the treatment change and no change groups with regards to interval from randomization to symptomatic metastases: 23 (2-62) and 22 (1-63) months respectively (p = 0.9). There was also no significant difference between the two groups in terms of randomization to last follow-up/death: 36 (7-63) and 37 (10-63) months, respectively (p = 0.9). Conclusions: Despite long follow-up, this small study has thus far shown no significant difference in outcome. However, a significant proportion of patients with metastasis had asymptomatic rise in TMs prior to their diagnosis. We have confirmed the feasibility of this study design but a larger study will be required to show if there is a benefit to this approach. No significant financial relationships to disclose.
Dynamic contrast-enhanced CT (DCE-CT) as an early biomarker of response in metastatic renal cell carcinoma (mRCC) under anti-angiogenic treatment
Authors: L. Fournier, R. Thiam, C. Cuenod, J. Medioni, L. Trinquart, D. Balvay, E. Banu, J. Balcaceres, G. Frija, S. Oudard
Journal: Journal of Clinical Oncology (2007)

14003 Background: Evaluation of treatment response for cancer relies on application of criteria based on size such RECIST. However, changes in size are often delayed and small. An accurate and early evaluation of tumor vascular characteristics would allow selection of patients (pts) who would most likely benefit of these therapies and early detection of treatment response to tailor therapy on an individual basis. Changes in tumor vascular parameters were quantified using dynamic contrast-enhanced computed tomography (DCE-CT) as a biomarker for tumor angiogenesis. Methods: A total of 44 mRCC pts were enrolled in an imaging study corollary of two phase III trials evaluating efficacy of anti-angiogenic drugs: sorafenib (N=9) vs. placebo (N=13), or sunitinib (N=17) vs. interferon (N=5). Perfusion CT acquisitions after injection of 80 ml of iodinated contrast agent were performed on a single “functional metastatic target” before treatment and every 6 weeks for follow-up. Microvascular parameters of the functional target were calculated using a dedicated software based on compartmental models: tumor blood flow (TBF) (ml/min/100g), tumor blood volume (TBV) (%), vascular permeability (VP) (ml/min/100g) and mean transit time (MTT) (s). These parameters were correlated to the best treatment response as evaluated by the size variation of the RECIST targets. Results: Among the 26 treated pts, there was a statistically significant drop in TBF and TBV as early as the first cycle of treatment (respectively -50%, p=0.03 and -51%, p&lt;0.01) compared to pre-treatment, showing the biological effect of the drug on tumor vascularity. There was a significantly higher drop in TBF and TBV in pts who would be later classified as responders (N=16) vs. non-responders (N=10) after the first cycle of treatment (-66% vs. -6%, p=0.02; -60% vs. -26.5%, p=0.04). The changes in MTT and VP were not correlated to the best response. Conclusions: The functional imaging biomarkers TBF and TBV quantified by DCE-CT detect the biological effect of anti-angiogenic drugs on tumor vessels. TBF appears as very early predictor of mRCC response to anti-angiogenic drugs supporting the hypothesis that DCE-CT may constitute a surrogate biomarker of angiogenesis inhibition. No significant financial relationships to disclose.
Providing practitioner-specific outcomes is associated with higher patient satisfaction with information about prostate cancer treatment
Authors: S. M. Gilbert, M. G. Sanda, R. L. Dunn, T. Greenfield, L. Hembroff, E. Klein, C. Saigal, J. Michalski, H. Sandler, M. S. Litwin, J. T. Wei
Journal: Journal of Clinical Oncology (2006)

6106 Background: After being diagnosed with prostate cancer, patients must assimilate abundant cancer related information. Satisfaction with Information (SWI) is a patient’s cognitive evaluation of information sources used to understand and select therapy. We sought to describe sources of information used by prostate cancer patients and to identify factors associated with SWI. Methods: 1,072 men with newly diagnosed prostate cancer have enrolled in the prospective, multi-center PRostate cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA) study. Reports of source(s) of information were documented prior to treatment (radical prostatectomy, external radiation, brachytherapy or combination). The validated SWI domain of the Service Satisfaction Scale-Cancer (SSS-Ca) was completed by patients 2 months following treatment. Relationships between socio-economic factors, demographics, cancer severity, and types of information sources and satisfaction (SWI) were evaluated with multivariate regression. Results: Sources of information endorsed by patients varied by race ( Table ), education, and study site. The most helpful sources of information were description of treatment by a physician (32.8%), books and internet (18.3% each), family/friends (16.6%) and pamphlets/brochures (11.4%). In bivariate analysis internet use was negatively associated with SWI (p=0.025). In multivariable models patient age (p=0.005) and information provided by the physician regarding their own outcomes (p=0.01) were independently associated with SWI. Conclusions: Although a variety of informational sources were endorsed by patients, only printed results for physician’s own patients was associated with SWI. Because SWI is a function of both experiences and expectations, providing patients with a treating physician’s results may improve satisfaction by enhancing concordance of expectations and outcomes. [Table: see text] [Table: see text]