tbuckley/cabot-search huggingface dataset:
Ambulatory serial drainage of ascitis or pleural effusion by a multiperforated catheter port system.
Authors: Emmanuel Mohandas Polycarpe, Katy Luce Meunier
Journal: Journal of Clinical Oncology (2012)

e19500 Background: Symptomatic pleural effusion or recurrent ascitis effusions are frequent in end-stage malignancies, induce serial drainage and impair quality of live. Methods: We report our experience with a multiperforated 10 Fr silicone catheter totally implanted in pleural or peritoneal cavities, by Seldinger access, connected to a subcutaneous port system surgically implanted, with local anaesthesia. To avoid tumour seeding along the catheter , it is used a purse string technique to water-tight the entry point of catheter. Patient on demand serial drainage of serosal effusion by percutaneous access to the port can be performed in outpatient department. To reduce risk of device obstruction, we rinse with saline serum under pressure to generate a turbulent outflow to flush any deposit after drainage. Results: Between January 2008 and April 2010, 28 patients underwent implants of 12 peritoneal and 18 pleural (2 bilateral) implantable multiperforated catheter port systems with a prospective follow up. There were 10 men and 18 women with a mean age of 64 years (range: 39-84 years). Primary malignancies were breast (9), pancreas (4), ovarian (4), stomach (2), endometrial (2), kidney (2), skin melanoma (2), prostate (1), peritoneum (1), and lymphoma with cardiac insufficiency (1). Twenty-seven patients obtained partial or complete relief of their symptoms. The number of aspirations performed was between 2 and 25 over a period of 8 to 454 days for 2,560 days of catheter implantation. Eight patients died within 3 weeks after placement of the system and 6 survived more than 6 months. One case of pneumothorax has been diagnosed after early symptoms recurrence and successfully aspirated throw the port. One case of infection of pleural fluid had been detected by systematic bacteriological sampling without clinical manifestation. One case of port infection was du to a previous asymptomatic infection of ascitis with multiple fluid collections and requires port removal. No case of tumour seeding or port system obstruction was observed. Conclusions: This outpatient management palliative technique is an easy option with high rate of efficacy, safety and comfort to control symptoms induced by pleural or ascitis recurrent effusion.
Efficacy of rituximab plus FAB group C chemotherapy without CNS radiation in CNS-positive pediatric Burkitt lymphoma/leukemia: A report from the Children’s Oncology Group.
Authors: J. Kimble Frazer, Stanton Goldman, Lynette Smith, Lauren Harrison, Sherrie L Perkins, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2012)

9501 Background: Historically, CNS-positive (CNS+ ) mature B-NHL in children and adolescents has been associated with a dismal outcome (Miles/Cairo, Br J Haematol, 2012). Adding CNS radiation and high-dose MTX and cytarabine to group C therapy for children with CNS+ B-NHL yielded a 77% 5-yr EFS in LMB89 (Patte et al., Blood, 2001). An ensuing FAB/LMB96 trial replaced cranial radiation with further HD-MTX and intrathecal therapy with similar results (75% 4-yr EFS) (Cairo et al., Blood, 2007). Here, patients with marrow and CNS+ disease fared worse than isolated CNS + (61% vs. 83% 4-yr EFS, p&lt;0.001), with &gt;50% of CNS+ patients who progressed or recurred having systemic, but not CNS, relapse. Rituximab, a chimeric anti-CD20 antibody, improved EFS, PFS, and OS when added to chemotherapy for adults with DLBCL (Coiffier et al., N Engl J Med, 2002; Pfreundschuh et al., Lancet Oncol, 2006). We tested whether adding rituximab to FAB group C chemotherapy in pediatric patients with CNS + B-NHL was safe and efficacious. Methods: Children and adolescents (&lt;21 yrs.) with CNS+ B-NHL received FAB group C1 therapy (Cairo et al., Blood, 2007). Rituximab (375 mg/m 2 /dose) was given twice in COPADM courses 1 &amp; 2 and once in CYVE courses (Cairo et al., ASCO, 2010). CSF blasts (&gt;1), cranial nerve palsy (CNP), intra-cerebral mass (ICM), and/or parameningeal extension (PME) defined cases as CNS+. Results: Of 40 eligible Group C patients,15 (38%) were CNS+; all 15 had Burkitt morphology. Eight CNS+ patients were CSF+ [WBC median 35 (range 1-1104)] with 6 cases CNP+, 4 PME+, and 1 ICM+. No adverse events were attributed to rituximab. Fourteen of 15 CNS+ patients (93%) are alive and disease-free. Of 7 BM - /CNS+ patients, 100% are NED. In BM+/CNS+ cases, 7/8 (88%) are NED, with one patient progressing with systemic and CNS disease. Conclusions: Addition of rituximab to group C FAB therapy was well tolerated. Outcomes in this small cohort of 15 children and adolescents with CNS+ BL (93%) suggest that adding rituximab to FAB group C therapy without CNS radiation may reduce systemic relapse. Large randomized studies are warranted to test this hypothesis in this previously high-risk clinical subgroup.
Conduction Abnormalities and Long-Term Mortality Following Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Hao Cui, Hartzell V. Schaff, Rick A. Nishimura, Jeffrey B. Geske, Joseph A. Dearani, Brian D. Lahr, Steve R. Ommen
Journal: Journal of the American College of Cardiology (2019)
TNF-α–induced protein 3 is a key player in childhood asthma development and environment-mediated protection
Authors: Johanna Krusche, Monika Twardziok, Katharina Rehbach, Andreas Böck, Miranda S. Tsang, Paul C. Schröder, Jörg Kumbrink, Thomas Kirchner, Yuhan Xing, Josef Riedler, Jean-Charles Dalphin, Juha Pekkanen, Roger Lauener, Marjut Roponen, Jing Li, Chun K. Wong, Gary W.K. Wong, Bianca Schaub, Markus Ege, Martin Depner, Sabina Illi, Georg J. Loss, Harald Renz, Petra I. Pfefferle, Michael Kabesch, Jon Genuneit, Anne M. Karvonen, Anne Hyvärinen, Pirkka V. Kirjavainen, Sami Remes, Charlotte Braun-Fahrländer, Caroline Roduit, Remo Frei, Vincent Kaulek, Marie-Laure Dalphin, Amandine Divaret-Chauveau, Gert Doekes
Journal: Journal of Allergy and Clinical Immunology (2019)
Longitudinal trends in costs for palliative radiation for metastatic prostate cancer.
Authors: Timothy J Robinson, Michaela A Dinan, Yanhong Li, Robert Lee, Shelby D. Reed
Journal: Journal of Clinical Oncology (2013)

6554 Background: Prostate cancer is a leading contributor to cancer health care costs, with end of life care composing a substantial portion of overall costs. In recent years, palliative treatment of metastases has been characterized by the use of more complex radiation planning and delivery systems. However, little is known about how costs of palliative radiation treatment in patients with metastatic prostate cancer have changed over this period. Methods: Retrospective analysis of SEER-Medicare data of men aged 66 and older who died from metastatic prostate cancer between 2000 and 2007. Inclusion criteria included all fee-for-service beneficiaries treated with radiation therapy for bony metastases in the last year of life. Direct costs were obtained by summing Medicare carrier and outpatient facility payments for all radiation treatment claims following an initial radiation treatment claim for bony metastases and adjusted to 2008 dollars using Consumer Price Indexes for medical care. Results: A total of 1,705 men met study inclusion criteria. Median age at diagnosis was 74, median time from diagnosis to death was 47 months, and 37% of men had distant metastatic disease at the time of diagnosis. Total Medicare payments for radiation therapy for bony metastases increased from an average of $2,763 to $3,989 for men who died from prostate cancer in 2000 vs. 2007. Outpatient facility claims for radiation therapy increased relative to carrier claims, composing 48% ($1,316) and 57% ($2,276) of all radiation treatment Medicare payments in 2000 vs. 2007 (All P &lt; 0.001). Conclusions: Between 2000 and 2007, average Medicare payments for palliative radiation therapy for bony prostate cancer metastases increased by roughly a third. The majority of increased costs were observed within outpatient facility claims, suggesting a shift in the administration of palliative radiation therapy from free-standing clinics to hospital-based outpatient facilities. Changes in end of life palliative radiation therapy for men with prostate cancer may impact future increases in Medicare health care expenditures.
Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: A retrospective analysis.
Authors: Patrick Schoffski, Iris Timmermans, Daphne Hompes, Marguerite Stas, Veerle Boecxstaens, Paul De Leyn, Willy Coosemans, Dirk Van Raemdonck, Esther Hauben, Raf Sciot, Paul M. Clement, Oliver Edgar Bechter, Benoit Beuselinck, Feng Jung Sherida Harriette Woei-A-Jin, Herlinde Dumez, Tim Wessels
Journal: Journal of Clinical Oncology (2019)

e22522 Background: Solitary fibrous tumor (SFT), a rare variant of soft tissue sarcoma (STS), is characterized by the presence of a NAB2-STAT6 fusion. Given the orphan character of SFT we performed a retrospective analysis. Methods: We retrospectively reviewed all patients (pts) with SFT treated in our institution between 12/1990 - 09/2017. Results: We identified 94 SFT pts (incl. hemangiopericytoma) with a med. follow-up for 4.7 yrs. Common anatomic sites were chest (33%), abdomen (21.3%), brain (12.8%) and extremities (9.6%). The symptomatology at diagnosis was variable. Only 6.4% presented with synchronous metastasis. Hypoglycemia (Doege-Potter syndrome) was seen in 2.1% of cases. A resection of the primary SFT was done in 86 pts (91.5%), their disease-free survival was 35.5 mo and 43% stayed SFT-free during follow-up. Local recurrence occurred in 26.7% of cases, associated with a med. overall survival (OS) of 45.1 mo. Metachronous metastasis was seen in 30.2% of pts, occurring after a med. follow-up of 36 mo. Med. OS after diagnosis of metastasis was 19.0 mo. Systemic therapy was given to 92.9% of pts with inoperable/metastatic disease. The most common 1 st line therapy was doxorubicin single agent (57.7% of pts), achieving responses in 13.3% of pts. 2 nd line therapies included ifosfamide and pazopanib (31.3% of pts each), 3 rd line treatment was very heterogeneous. Conclusions: SFT is an orphan malignancy with a variable clinical course, low incidence of distant spread at first diagnosis but considerable risk of local failure and metachronous metastasis. Surgery is the only curative option at diagnosis, time of relapse and in case of resectable metastasis. Palliative systemic therapy is considered in pts with inoperable/metastatic disease but achieves low response rates. The natural course and survival outcomes of SFT cases treated with palliative intent tend to be better than in non-selected STS pts.
Abstract 4928: Relationship between protein biomarkers of potential chemotherapy response and microsatellite status, tumor mutational burden, and PD-L1 expression in patients with cancer
Authors: Mina Nikanjam, David Arguello, Zoran Gatalica, Donald A. Barkauskas, Razelle Kurzrock
Journal: Cancer Research (2019)

Abstract Introduction: Chemotherapy and checkpoint inhibitor immunotherapies are increasingly used in combinations. We determined associations between the presence of anti-PD-1/PD-L1 therapeutic biomarkers and protein markers of potential chemotherapy response. Methods: Data was extracted from a clinical-grade testing database (Caris Life Sciences; Feb 2015 - Nov2017): immunotherapy response markers (microsatellite instability high (MSI-H) and tumor mutation burden-high (TMB-H) (by next generation sequencing (NGS)) and PD-L1 protein expression (immunohistochemistry); and protein chemotherapy response markers (ERCC1, TOPO1, TOP2A, TS, TUBB3, RRM1, and MGMT; immunohistochemistry). Relationships were determined by the Mantel-Haenszel chi-squared test or Fischer’s exact tests. Results: Overall, 28,034 patients (40 tumor types) were assessed. MSI-H was found in 3.3% of patients, TMB-H, 8.4%, and PD-L1 expression in 11.0% of patients. Based on concurrent biomarker expression, combinations of immunotherapy with platinum (ERCC1 negativity) or with doxorubicin, epirubicin, or etoposide (TOP2A positivity), have a higher probability of response while combinations with irinotecan or topotecan (TOPO1 positivity), with gemcitabine (RRM1 negativity), and fluorouracil, pemetrexed, or capecitabine (TS negativity) may be of less benefit. The potential for immunotherapy and taxane (TUBB3 negativity) combinations is present for MSI-H but not TMB-H or PD-L1-expressing tumors; for temozolomide and dacarbazine (MGMT negative), PD-L1 is frequently co-expressed, but MSI-H and TMB-H are not associated. Conclusion: Protein markers of potential chemotherapy response along with NGS for immunotherapy response markers can help support rational combinations as part of a precision oncology approach. Citation Format: Mina Nikanjam, David Arguello, Zoran Gatalica, Donald A. Barkauskas, Razelle Kurzrock. Relationship between protein biomarkers of potential chemotherapy response and microsatellite status, tumor mutational burden, and PD-L1 expression in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4928.
Abstract 2177: Streptavidin-pHast: A readily conjugatable, pH-sensitive dye to screen for internalization
Authors: Patrick A. Shramm, Leonardo Ancheta
Journal: Cancer Research (2019)

Abstract Quick and efficient screening of targeting agents that internalize effectively is vital for determining their suitability as potential therapeutics. Some of the most recent successes in the treatment of cancers have been from antibodies to cell surface proteins that are responsible for tumor cell proliferation. Examples are Cetuximab (target: EGFR) approved for colorectal cancer, and Trastuzumab (target: HER2) for breast cancer. These antibodies have more than one effect on the cancer cell, but one of the most important is that, upon binding to the cell surface antigen, the complex is internalized. As such, the down-regulated cell surface protein no longer plays a role in cancer cell division. Here we describe a method for determining internalization of cell surface molecules by targeting agents using a pH-dependent fluorescent reporter cross-linked to streptavidin. Streptavidin is a tetrameric protein (molecular weight 53 kDa in its recombinant form), with each subunit able to bind a single biotin molecule. The bond between streptavidin and biotin is rapid and essentially non-reversible, unaffected by most extremes of pH, organic solvents, and denaturing reagents. It is the strongest known noncovalent biological interaction (Ka = 1015 M-1) between protein and ligand. A variety of molecules, including lectins, proteins, and antibodies, can be biotinylated and reacted with streptavidin-labeled probes or other detection reagents for use in biological assays. The fluorescence from this reporter increases intensity as the pH of its surroundings becomes more acidic, as demonstrated when exposed to the environment inside a cell (thereby providing evidence of internalization). Here we describe methods that can be used to explore candidates as cancer therapeutics in a quick, reliable and reproducible manner. Citation Format: Patrick A. Shramm, Leonardo Ancheta. Streptavidin-pHast: A readily conjugatable, pH-sensitive dye to screen for internalization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2177.
A preliminary study of the anti-κ myeloma antigen monoclonal antibody KappaMab (MDX-1097) in pretreated patients with κ-restricted multiple myeloma
Authors: Andrew Spencer, Patricia Walker, Parisa Asvadi, Douglas H. Campbell, Kate Reed, Ben R. Herbert, Edmond J. Breen, Michael C. Copeman, Rosanne D. Dunn
Journal: Blood Cancer Journal (2019)
Investigation of the pharmacogenetic influences of carbonyl reductase on doxorubicin and doxorubicinol in breast cancer patients.
Authors: Allison Gaudy, Gerald J. Fetterly, Alex A. Adjei, Tracey L. O'Connor, Adolfo Quinones, Javier G. Blanco, Daniel Ferguson, Patricia D. Meholick, James Kalabus
Journal: Journal of Clinical Oncology (2013)

2594 Background: The anthracycline doxorubicin (DOX) is widely used to treat breast cancer. Doxorubicin is associated with pharmacokinetic and pharmacodynamic variability and despite its use for several years there is limited understanding behind it. Hepatic carbonyl reductases (CBR1 and CBR3) catalyze the reduction of DOX into its main circulating C-13 metabolite doxorubicinol (DOXOL). Polymorphisms in CBR1 and CBR3 influence synthesis of DOXOL, and could potentially play a role in the pharmacokinetic (PK) variability seen with doxorubicin treatment. In this study, we examined the influence of genetic polymorphisms in CBR1 and CBR3 on DOX and DOXOL PK. Methods: DOX was administered IV to 79 breast cancer patients at 60 mg/m 2 . Population PK modeling was performed on the parent concentration-time profiles with the following patient factors: [BSA (1.4-2.6 m 2 ), weight (40-140 kg), age (25-75), race (78% white), CBR1 rs9024 (78% wild-type), CBR3 V244M (47% wild-type), CBR3 C4Y (20.5% wild-type); followed by model validation. Noncompartmental analysis (NCA) was performed for both DOX and DOXOL and the metabolic ratio was calculated as AUC DOXOL0-24 :AUC DOX0-24 . Results: A two-compartment model was used to describe DOX PK. Mean predicted (%SEM) clearance (CL), plasma volume (Vp), tissue volume and distribution clearance were 28.1 L/hr (7.72), 22.5 L (3.80), 257 L (13.8) and 13.6L (21.8), respectively. Interpatient variability on CL and Vp were 22.1% and 12.6%, respectively. BSA was found to be a significant predictor of the interpatient variability on CL. No other patient factors were found to be significant on parent drug PK. The metabolic ratio, assessing the conversion of DOX to DOXOL, was stratified by different polymorphisms of CBR1 and CBR3. There were no significant differences in metabolic ratio due to CBR1 and CBR3 genotypes. Conclusions: A PK model was developed that was able to characterize DOX pharmacokinetics. CBR1 and CBR3 polymorphisms were tested as covariates but were not found to be significant contributors to the variable pharmacokinetic profiles of DOX and DOXOL.
FOXP3+/CD8+ tumor-infiltrating T-cell ratio as a marker for pathologic response to induction therapy of non-small cell lung cancer.
Authors: Hiroyuki Tao, Kazuhiko Shien, Junichi Soh, Fumiho Sano, Tatsuro Hayashi, Hiromasa Yamamoto, Toshiki Tanaka, Eisuke Matsuda, Shinichi Toyooka, Kazunori Okabe, Kazurou Sugi, Shinichiro Miyoshi
Journal: Journal of Clinical Oncology (2012)

e17517 Background: Survival benefits of induction therapy followed by surgery for advanced non-small cell lung cancer (NSCLC) have been shown. Anti-cancer agents are suggested to mediate cytotoxic effect not only directly on tumor cells but also through the immune system. We investigated the relationship between the status of T-cell differentiation in tumor stroma and pathologic responses to induction therapy in patients with advanced NSCLC. Methods: A total of 69 patients with c-stage IIA to IIIB NSCLC who underwent induction therapy followed by R0 surgery between January 2002 and July 2011 were enrolled. Tumor-infiltrating T cells expressing CD8 or FOXP3 were detected by immunohistochemical staining from biopsy and surgically removed specimens using anti-CD8 antibody and anti-FOXP3 antibody. Staining-positive T cells were counted in 10 fields at 200× magnification of digital images, and then FOXP3+/CD8+ T cell ratio was determined based on the average counts. Results: The mean values of FOXP3+/CD8+ T cell ratio in operative specimens were 1.11 for the patients with pathological no change (p-NC), 0.32 for those with pathological partial response (p-PR), and 0.21 for those with pathological complete response (p-CR) (p = 0.002). There was no association of FOXP3+/CD8+ T cell ratio with gender, histologic types of tumor, or clinical stages. Patients with p-CR showed better relapse-free survival, though statistically no-significant (p = 0.323). Pre-treatment TBLB specimens were available in 12 patients (3 p-NCs, 7 p-PRs, and 2 p-CRs). FOXP3+/CD8+ T cell ratios in operative specimens after induction therapies were elevated compared with that of biopsy specimens in p-NC patients (p = 0.105), whereas the ratios were decreased in p-PR and p-CR patients (p = 0.021). Conclusions: The status of tumor-infiltrating T cell differentiation indicated by FOXP3+/CD8+ T cell ratio was correlated with pathologic response in patients treated with induction therapy followed by surgery for NSCLC. FOXP3+/CD8+ T cell ratio can be a marker for effectiveness of induction treatment.
Development of an electronic, integrated quality monitoring and needs assessment tool for palliative care.
Authors: Arif Kamal, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2012)

e16556 Background: In order to facilitate uptake of continuous quality improvement in oncology and palliative care, practical data capture and reporting solutions are needed that allow real-time collection of structured data that simultaneously contributes to quality measurement and aids clinical care. We aimed to build and test a point-of-care system for continuous quality monitoring in community palliative care. Methods: Within a four-organization, academic/community quality consortium, we first conducted a focus group to inventory characteristics of an effective system. A systematic review and prioritization of quality measures for supportive oncology and palliative care followed. These results informed development of a set of data elements and electronic platform. A usability study with think-aloud protocols was then conducted with twenty providers using two mock cases across paper, laptop, and tablet computer platforms. Results: Identified priorities for a proposed system were: 1. Use of information technology (IT); 2. Point-of-care use with patient-report and provider-entry; and 3. Immediate, provider-level reporting on quality conformance. In the systematic review, 282 quality measures (152 prioritized for clinical utility and feasibility) for supportive oncology and palliative care were identified; these measures informed the development of a 92 item dataset of validated clinical tools within National Quality Forum quality domains. Data elements were harmonized with the National Cancer Institute’s Cancer Bioinformatics Grid (CaBIG) and other metadata sets. To foster electronic, point-of-care data capture, the Quality Data Collection Tool (QDACT) was then developed. The QDACT informs 82% (125) of high-priority quality measures; a color-code reminder system provides immediate conformance feedback. The usability study demonstrated high satisfaction, less than 15 minutes for completion, and a low error rate. Conclusions: Electronic systems that can integrate point-of-care quality monitoring and clinical assessments are buildable and usable in palliative care. Feasibility testing within the context of routine outpatient and inpatient palliative care practice is ongoing.