tbuckley/cabot-search huggingface dataset:
Carbonic Anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy
Authors: M. Atkins, D. McDermott, M. Regan, E. Stanbridge, M. Upton, A. Youmans, P. Febbo, M. Lechpammer, S. Signoretti
Journal: Journal of Clinical Oncology (2004)

4512 Background: RCC response to IL-2 Rx and patient (pt) survival have been correlated to histology including the presence of clear cell and alveolar and the absence of papillary and granular features (Upton et al Proc ASCO, 2003) and CAIX expression (Bui et al Clin Ca Res 2003;9:802). In an effort to confirm and expand these findings we undertook a nested case-control study within the Upton cohort. Methods: Paraffin-embedded tissue sections of RCC were immunostained with an Ab to CAIX and expression levels were correlated with pathology findings, clinical outcome and the Upton model relating them. The percentage of CAIX positive tumor cells was utilized to separate high (> 85%) vs low (≤ 85%) expressers. Results: Tissue specimens were obtained from 66 pts (51M, 15F). 27 of the selected pts (41%) had responded (10CR/17PR) to IL-2. 24 (36%), 31 (47%) and 11 (17%) were classified as good, intermediate, and poor prognosis according to the Upton model. 41 specimens (62%) had high CAIX expression. 21 of 27 (78%) responding pts had high CAIX expression compared to 20/39 (51%) non-responders (OR=3.3; p=0.04); a similar survival benefit was seen (p=0.04). Survival >5 yrs was seen only in high CAIX expressors. High CAIX staining was associated with better pathology prognosis, and when stratified by group, the ORs of CAIX expression were unequal across groups (p=0.08) . The stongest association was in the intermediate group where 9/9 responders has high CAIX expression vs.11/22 non-responders, suggesting a possible refinement of the Upton model. A resultant group with good pathology or intermediate pathology and high CAIX contained 26 of 27 (96%) responders compared to only 18/39 (46%) non-responders (OR=30; p<0.01). Survival benefit was also seen (p< 0.01). Conclusions: We conclude that CAIX expression is an important predictor of outcome in RCC pts receiving IL-2-based Rx and can enhance prognostic information obtained from pathology specimens. While this refinement to the pathology model requires validation, data suggest that IL-2 Rx might ultimately be reserved for pts with Upton model good pathology alone or intermediate pathology and high CAIX staining. No significant financial relationships to disclose.
Bone targeting agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the US.
Authors: David H. Henry, Roger Von Moos, Jean-Jacques Body, Alex Rider, Jonathan De Courcy, Grace Murray, Debajyoti Bhowmik, Francesca Gatta, Jorge Arellano, Guy Hechmati, Zach Roberts, Yi Qian
Journal: Journal of Clinical Oncology (2015)

93 Background: Bone is the most common site of distant metastasis in patients with advanced breast cancer. Bone metastases (BMs) often lead to skeletal-related events (SREs) and may result in debilitating bone pain which impacts a patient’s quality of life. Bone targeting agents (BTAs) reduce the incidence of SREs and progression of pain due to BMs. This study aims to understand real world patients’ experience of bone pain and to assess BTAs treatment patterns. Methods: Data were extracted from the Adelphi Breast Cancer Disease-Specific Programme (DSP), a cross-sectional survey of 98 US oncologists conducted from February to May 2015 in the USA. Each physician completed comprehensive record forms capturing the following information about the next 12 patients being treated for advanced breast cancer: Presence of BMs, patient’s pain state at diagnosis of BMs, current pain state, time since diagnosis of BMs, current analgesic use and reasons for prescribing BTAs. Results: Bone pain was more prevalent (p &lt; 0.001) in patients with BMs (67% of 485) than those without BM (7% of 791). Mean time for pain assessment was 6.2 months after BM diagnosis. Among breast cancer patients with BMs and bone pain (n = 323), 98% required analgesic medications to manage the pain, including 40% (n = 130) who were treated with strong opioids (e.g., morphine, oxycodone, hydromorphone, or methadone). Of these patients, 100 (77%) had moderate/severe bone pain. Of the patients with BMs, 69% (n = 337) were treated with a BTA and treatment was initiated within 3 months of BMs diagnosis in 91% (n = 306) of them. The reasons for prescribing a BTA within 3 months of BM diagnosis were “bone pain” (32%), “high risk of bone complications” (25%), “prior history of bone complications”(18%), “number of BMs” (11%) and “location of BMs” (4%). Conclusions: Advanced breast cancer patients with BMs are more likely to experience bone pain, and three-fourths of the patients treated with strong opioids experienced moderate/severe bone pain.The majority of patients with BMs receive a BTA prescription for the reduction of bone pain and risk of bone complications.
A dose-escalation, Phase I study of a depot formulation of paclitaxel administered intralesionally in end-stage cancer patients with solid malignant tumors
Authors: S. J. Vukelja, W. E. Samlowski, S. P. Anthony, J. C. Arseneau, J. J. Nemunaitis, C. C. Cunningham, B. S. Berman, K. D. Fowers, K. S. Callahan
Journal: Journal of Clinical Oncology (2004)

2131 Background: To determine the systemic plasma levels, safety and maximum tolerated dose (MTD) of a depot formulation of paclitaxel, OncoGel (paclitaxel/ReGel). This is a cremophor-free formulation which is liquid at administration temperature and rapidly forms a gel depot upon injection. The depot slowly degrades over several weeks allowing controlled release of paclitaxel within the tumor. Methods: A Phase I, dose-escalation study was conducted in 16 end-stage cancer patients with 18 superficially accessible solid malignant lesions at 6 investigative sites. Four paclitaxel dosages based on tumor volume were administered with 3 patients receiving 0.06 mg/cm3, 3 patients at 0.24 mg/cm3, 6 patients with 8 tumors at 0.48 mg/cm3, and 4 patients at 1.92 mg/cm3. There were 7 females and 9 males, ages 41 to 89, with treated tumors ranging from 0.7 cm3 to 19.0 cm3. The primary diagnoses included lymphoma, melanoma, lung, head and neck, laryngeal, thyroid, and breast cancer. Results: Blood samples were collected at predose, at 3, 6, 24 and 72 hours post-dose and then at weekly intervals for up to 9 weeks after injection in 13 subjects. Nine patients had no detectable paclitaxel and four patients had minimal, <2 ng/mL, levels in 5 of 153 plasma samples analyzed. Of the 103 reported adverse events (AEs), 12 mild or moderate AEs in eight patients were considered related to the drug. 9 of these AEs were pain or erythema at the injection site with the 3 others being bruising, drainage, and muscle spasm. No drug-related serious adverse events were reported in any patient. Although not a primary endpoint, analysis of tumor response showed size regression or stable disease in approximately 50% of the injected tumors. Conclusions: The Phase I study demonstrated the drug was well tolerated, maintained paclitaxel at the injection site, and suggested efficacy in stabilizing or reducing tumor growth. No MTD was reached. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MacroMed, Inc. MacroMed, Inc.
The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer
Authors: Peter Goldstraw, Kari Chansky, John Crowley, Ramon Rami-Porta, Hisao Asamura, Wilfried E.E. Eberhardt, Andrew G. Nicholson, Patti Groome, Alan Mitchell, Vanessa Bolejack, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David G. Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A.I. Blanco Orozco, M.A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M.T. González Budiño, G. González Casaurrán, J.A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J.M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J.C. Peñalver Cuesta, J.S. Park, H. Pass, M.J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, K. Yokoi
Journal: Journal of Thoracic Oncology (2016)
Metabolic insufficiency underlies intratumoral cytotoxic T cell dysfunction
Authors: Tushar Gupta, Nicole E Scharping, Rebecca S Moreci, Greg M Delgoffe
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts T cells have the remarkable ability to recognize and remove abnormal cells with precision, a feature that is very desirable for the treatment of cancer. However, while T cells specific for tumor antigens are primed and can infiltrate tumors, they are quickly rendered dysfunctional
Rethinking Attention-Deficit/Hyperactivity Disorder
Authors: Dimitri A. Christakis
Journal: JAMA Pediatrics (2016)

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Abstract 13607: Differential Response of Local Coagulation after Implantation of New Generation Drug-Eluting Stents Compared with Sirolimus-Eluting Stent
Authors: Koji Yamaguchi, Tetsuzo Wakatsuki, Akira Takashima, Mika Bando, Sachiko Bando, Tomomi Matsuura, Takayuki Ise, Jyunko Hotchi, Takeshi Tobiume, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata
Journal: Circulation (2014)

Purpose: We have previously demonstrated local persistent hypercoagulation after sirolimus-eluting stent (SES) implantation by measuring plasma prothrombin fragment F1+2(frF1+2) levels. The aim of this study is to examine local coagulation response after biolimus-eluting stent (BES) and everolimus-eluting stent (EES) implantation. Methods: Sixty-eight patients who were treated with stents about eight months earlier to the mid-segment of the left anterior descending coronary artery, with no evidence of restenosis, were studied (BES: 12pts, EES: 15pts, SES: 23pts, and BMS: 18pts). We measured plasma levels of frF1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V). The transcardiac frF1+2 gradients (ΔfrF1+2) were defined as CS level minus V level. The patients were divided into 2 groups according to total stent length [longer stent group (≥24mm) or shorter stent group (&lt;24mm)]. Results: A larger percent diameter stenosis was observed in the BMS group than in the SES, EES, and BES groups (25.1±15.6 vs 7.1±16.5, 12.5±12.8, 10.3±14.2%, p&lt;0.05, respectively). The ΔfrF1+2 was greater in the SES group than in the BMS, EES, and BES groups, and no significant differences were observed among the BMS, EES, and BES groups (23.4±21.1 vs 4.7±13.4, 3.2±11.7, 1.5±11.1 pmol/l, p&lt;0.05, respectively). The ΔfrF1+2 in longer stent group (n=11) was significantly greater than in shorter stent group (n=12) (27.4±12.1 vs 19.2±10.1 pmol/l, p&lt;0.05) only in the SES group, however, no significant differences were observed according to total stent length in other groups. Conclusions: A lower response of local coagulation after BES and EES implantation was shown, and significant correlation between local hypercoagulation and total stent length was observed only after SES implantation. These findings might be associated with lower strut thickness and unique characteristics of polymer in second-generation drug-eluting stents.
Abstract 15558: Clinical Impact of Coronary Protection During Transcatheter Aortic Valve Replacement: First Reported Series of 20 Patients
Authors: Yigal Abramowitz, Tarun Chakravarty, Hasan Jilaihawi, Mamoo Nakamura, Wen Cheng, Mohammad Kashif, Nobuyuki Takahashi, Jorge Castellanos, Abhijeet Dhoble, Niraj Doctor, Mitch Gheorghiu, Raj R Makkar
Journal: Circulation (2014)

Background:  Coronary protection with a guidewire, coronary balloon or stent positioned in the coronary artery is a pre-emptive technique to manage coronary obstruction during transcatheter aortic valve replacement (TAVR). Reported clinical experience with this technique is limited, merely in the form of case reports. We hereby describe the largest single center experience of left main (LM) coronary protection during TAVR (Table).   Methods & Results:  Of 636 consecutive patients undergoing TAVR from 9/2012 [[Unable to Display Character: –]] 1/2014, LM coronary protection was used in 20 patients deemed to be at increased risk of LM compromise. Indications for LM protection included valve-in-valve in 7 (35%) patients, low LM in 13 (65%) patients (average CT distance between LM ostium and aortic annulus: 7.9 mm; range 1.1-11.6 mm) and pre-TAVR significant LM stenosis in 4 (20%) patients. Coronary guidewire was used in all cases; angioplasty balloon was used in 3 cases and coronary stent in 8. LM compromise occurred in 5 out of 20 cases, only 1 of them was symptomatic and the others were found during selective LM injections following valve deployment. These patients underwent unplanned LM stenting to treat de-novo LM compromise noted after valve deployment. One patient underwent planned balloon inflation in a previously placed LM ostial stent and 4 patients with pre-TAVR LM stenosis underwent planned LM stenting following valve deployment; all resulting in TIMI 3 flow without any complication. Device success was 100%; there were 3 cases of in-hospital major complications without evidence of LM compromise (1 case of atrial fibrillation and hypotension few days after TAVR, 1 prolonged hospitalization secondary to pneumonia and 1 delayed extubation in a patient with COPD). There was no in-hospital mortality.   Conclusions:  The coronary protection technique can prevent the serious complication of coronary obstruction after TAVR and should be considered in all patients deemed to be at increased risk of LM compromise.
Serum vascular endothelial growth factor as a significant marker of treatment response in Hodgkin disease
Authors: M. Weyl Ben Arush, A. Ben Barak, P. Shenzer, S. Maurice, E. Livne
Journal: Journal of Clinical Oncology (2006)

9033 Background: The aim of this pilot study was to determine VEGF serum levels (S-VEGF) at diagnosis and at restaging in children diagnosed with Hodgkin’s disease, and to investigate whether this parameter provides prognostic information for remission after 2 courses of chemotherapy Methods: S-VEGF levels of 9 consecutive pediatric patients (pts) with Hodgkin’s disease were assayed at diagnosis and at restaging. Levels of VEGF were determined using a commercially available ELISA anti-human VEGF immunoassay kit. PET-CT fusion was performed for each child at diagnosis and after 2 courses of chemotherapy in order to assess response to treatment. Results: 8 children went into complete remission or very good partial response after 2 courses of chemotherapy according to the protocol, one child developed tumor progression and respond to second line chemotherapy. At diagnosis average S-VEGF level was 655.7pg/ml (range, 1078.7–29.22 pg/ml) and at restaging decreased to 237.6 pg/ml (range, 0–453 pg/ml). (p=0.0039). One child with Hodgkin’s disease who had a higher level at first restaging and developed progressive disease responded to reinduction therapy and had a significantly lower level at the second restaging. The comparison between the levels of S-VEGF at diagnosis and at restaging showed a significant difference for the pts who responded to treatment with decreased S-VEGF and the pt who developed tumor progression with increased S-VEGF. Conclusions: Changes in S-VEGF levels correlated with response to treatment for most of the children diagnosed with Hodgkin’s disease. This provides a rationale for exploring clinical interest in S-VEGF measurements of a larger group of children with Hodgkin, and using the test for clinical trials of antiangiogenic therapies. No significant financial relationships to disclose.
Acupuncture for dysphagia after chemoradiation therapy in head and neck cancer: An ongoing pilot, randomized, sham-controlled trial.
Authors: W. Lu, J. H. Lorch, T. A. Balboni, D. J. Sher, L. A. Goguen, C. M. Norris, R. B. Tishler, M. R. Posner, D. S. Rosenthal, R. I. Haddad
Journal: Journal of Clinical Oncology (2010)

TPS270 Background: Dysphagia is a common side effect following chemoradiation therapy (CRT) in patients with head and neck cancer (HNC). Dysphagia and other treatment-related conditions such as aspiration, xerostomia, and fibrosis can significantly impact quality of life (QOL) in HNC patients. Acupuncture could potentially impact dysphagia by improving salivary production, restoring swallowing reflex, and inhibiting the fibrosis process. Preliminary clinical studies suggest that acupuncture may improve radiation–induced xerostomia in HNC patients. However, acupuncture has not been rigorously tested for dysphagia in HNC patients in a randomized controlled trial. The purpose of the ongoing pilot, randomized, sham-controlled trial is to assess the feasibility of recruiting and retaining HNC patients, and to collect preliminary data on the efficacy and safety of acupuncture on dysphagia and health-related quality of life (QOL). Methods: Eligible participants are patients diagnosed with squamous cell carcinoma of the head and neck at stage II, III and IV, without evidence of distant metastasis, receiving chemoradiation. They are randomized to 12 sessions of either active acupuncture (n=18) or sham acupuncture (n=18). All study personnel and study participants, except the treating acupuncturist, are blinded to the treatment assignment. The active acupuncture consists of manual and electro stimulation at extremities, while sham acupuncture needles are placed at adjacent sites with a mock stimulation device. The primary endpoint of the study is to assess the feasibility of recruiting and retaining HNC patients into a randomized controlled trial of acupuncture. The study will be considered feasible for further study if at least 75% of intervention participants are compliant and at least 80% of participants in each group complete all study evaluations. Secondary end points include: The M. D. Anderson Dysphagia Inventory and other QOL questionnaires are measured periodically during the treatment and a 6 months following up period. The planned study recruitment period is from January 2008 to December 2010. Seven patients have been enrolled into the study as of January 2010. No significant financial relationships to disclose.
Bone metabolism biomarkers in men with advanced prostate cancer (PC) and bone metastases treated with denosumab versus zoledronic acid (ZA).
Authors: Matthew Raymond Smith, Janet Elizabeth Brown, Karim Fizazi, Laurence Klotz, Gavin M. Marx, Huei Wang, Douglas Warner, Allan Lipton
Journal: Journal of Clinical Oncology (2015)

267 Background: Denosumab, compared with ZA, has recently demonstrated significant benefits in preventing skeletal-related events (SREs) in a double-blind phase 3 study of men with castration-resistant PC and bone metastases (N=1901). This post hoc analysis was performed to determine if key bone metabolism biomarker levels correlated with time-to-first SRE. Methods: Time-to-Grade ≥2 increase in total serum alkaline phosphatase (ALP) was assessed for correlation with time-to-first SRE. Levels of urinary N-telopeptide (uNTX) and serum bone-specific alkaline phosphatase (BSAP) markers were measured at baseline and study week 13, and correlations with time-to-first SRE were assessed. Covariate analyses were performed using a Cox proportional hazards model, stratified by treatment group or (for baseline analyses) with treatment group as the independent variable. Results: Analysis of the relationship between time-to-Grade ≥2 increase in total ALP and time-to-first SRE demonstrated that Grade ≥2 increases in ALP of PC patients were associated with a higher risk of first SRE (hazard ratio [HR] 1.838, 95% confidence interval [CI] 1.559, 2.167; P&lt;0.0001). In dichotomized analyses (&lt; vs ≥ median), a higher level of uNTX and BSAP (at baseline or week 13) was correlated with an increased risk of first SRE (Table). In baseline covariate analyses, treatment benefit for denosumab was maintained after adjusting for either baseline uNTX (HR 0.818, 95% CI 0.703, 0.951; P=0.0091) or BSAP (HR 0.813, 95% CI 0.700, 0.943; P=0.0061). Conclusions: Higher levels of uNTX or BSAP at baseline or week 13 were associated with worse SRE outcomes in men with advanced PC and bone metastases. Denosumab was more efficacious for preventing or delaying SREs compared with ZA, regardless of bone-related biomarker levels. Relationship of covariate to time-to-first SRE Clinical trial information: NCT00321620. [Table: see text]