tbuckley/cabot-search huggingface dataset:
Effect of laboratory parameters on prognostic value in patients with newly diagnosed brain metastases: Analysis of 1,207 cases.
Authors: Romina Koller, Anna Sophie Berghoff, Georg Widhalm, Karin Dieckmann, Christoph Zielinski, Peter Birner, Rupert Bartsch, Matthias Preusser
Journal: Journal of Clinical Oncology (2015)

e13034 Background: We investigated the prognostic value of laboratory parameters in a large cohort of brain metastasis (BM) patients. Methods: 1207 Patients treated for newly diagnosed BM from extracranial solid cancers (472/1207 (39.1%) lung cancer; 270/1207 (22.4%) breast cancer; 164/1207 (13.6%) melanoma; 121/1207 (10.0%) renal cell carcinoma; 101/1207 (8.4%) colorectal cancer; 79/1207 (6.5%) other primary tumor) were included in the analysis. Clinical characteristics including survival times and laboratory parameters at diagnosis of BM were retrieved by chart review. Laboratory parameters with significant impact on overall survival from diagnosis of BM in univariate analysis were entered in multivariate analysis together with known prognostic factors including primary tumor type, graded prognostic assessment (GPA) class and treatment modality for BM. Results: At univariate survival analysis, hemoglobin level < lower limit of normal (LLN), platelet count < LLN, leukocyte count < LLN, serum albumin level < LLN, serum c-reactive protein (CRP) concentration > upper limit of normal (ULN), serum creatinine concentration > ULN and serum lactate dehydrogenase level (LDH) > ULN correlated with unfavourable overall survival (p < 0.05, log-rank test). At multivariate analysis, hemoglobin (HR 0.7; p = 0.004), albumin (HR 0.8; p = 0.010), CRP (HR 1.6; p < 0.001) and LDH (HR 1.3; p = 0.001) concentrations retained their statistically significant impact on overall survival. Conclusions: Blood hemoglobin level, serum albumin concentration, serum CRP concentration, and serum LDH concentration have a strong and independent prognostic impact in patients with newly diagnosed BM and should be incorporated in prognostic scores.
Amatuximab, a chimeric monoclonal antibody to mesothelin, in combination with pemetrexed and cisplatin in patients with unresectable pleural mesothelioma: Results of a multicenter phase II clinical trial.
Authors: Raffit Hassan, Thierry Marie Jahan, Hedy Lee Kindler, Lyudmila Bazhenova, Martin Reck, Ira Pastan, Alison Ellis, Penny Marie Fatato, John Heyburn, Charles Schweizer, Jeff Parno, Bruce Wallin
Journal: Journal of Clinical Oncology (2012)

7030 Background: Amatuximab (MORAb-009) is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in many cancers including malignant mesothelioma (MM). Based on safety of amatuximab in phase I clinical trial and pre-clinical studies showing synergy in combination with chemotherapy, a single arm phase II study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in pts. with MM. Methods: Eligibility criteria included pts. with unresectable epithelial or biphasic pleural MM, no prior chemotherapy and KPS &gt; 70%. Pts. received amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m 2 and C 75 mg/m 2 (PC) given on day 1, of each 21 day cycle for 6 cycles. Pts. with objective response or stable disease received amatuximab monotherapy until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), objective response rate and safety of amatuximab with PC. Results: From 2/2009 to 10/2010, 89 pts. were enrolled at 26 sites. Pt. characteristics: median age 67 yrs. (range 46-80), 78% male, 70% with KPS &gt;90%, 89% epithelial MM, 11% biphasic MM and 88% had stage III/IV disease. Median number of PC plus amatuximab cycles was 5 (range 1-6) and 56 (63%) pts. received single agent amatuximab. In addition to the expected toxicity from PC, hypersensitivity reactions (12.4%; Grade 3/4=4.5%) from amatuximab were noted. By independent radiological review 30 (39%) pts. had partial response and 39 (51%) had stable disease. PFS at 6 months was 52% (95% CI: 39.5-63.5) with a median PFS of 6.1 months (95% CI: 5.4-6.5). As of 1/10/12 the median OS was 14.5 months (95% CI: 12.4-18.5) with 31 pts. still alive and 7 pts. receiving maintenance amatuximab. Conclusions: Amatuximab in combination with PC was generally well-tolerated in this study with 90% of pts. having an objective tumor response or stable disease by independent radiological review. Although PFS is not significantly different from historical results of PC alone, the median OS is 14.5 months with 35% of pts. still alive. Updated OS and biomarker data will be presented at the meeting.
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction—Executive Summary
Authors: Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. Antman, Charles R. Bridges, Robert M. Califf, Donald E. Casey, William E. Chavey, Francis M. Fesmire, Judith S. Hochman, Thomas N. Levin, A. Michael Lincoff, Eric D. Peterson, Pierre Theroux, Nanette Kass Wenger, R. Scott Wright, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Jeffrey L. Anderson, Elliot M. Antman, Jonathan L. Halperin, Sharon A. Hunt, Harlan M. Krumholz, Frederick G. Kushner, Bruce W. Lytle, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel
Journal: Journal of the American College of Cardiology (2007)
Combined use of indocyanine green fluorescence and methylene blue dye versus methylene blue dye alone for sentinel lymph node biopsy in breast cancer patients.
Authors: Shu Wang, Jiajia Guo, Deqi Yang, Yingming Cao, Fuzhong Tong, Bo Zhou, Peng Liu, Hongjun Liu, Lin Cheng, Miao Liu, Houpu Yang, Fei Xie, Siyuan Wang
Journal: Journal of Clinical Oncology (2013)

e12006 Background: Methylene blue (MB) dye is widely used in China for sentinel lymph node biopsy (SLNB). Recently indocyanine green (ICG) was reported to be an innovative fluorescent tracer that could be visualized by near-infrared camera. In this study we compared the efficacy of combined use of ICG fluorescence and methylene blue eye versus methylene blue alone for SLNB in breast cancer patients. Methods: Two hundred and sixteen consecutive early breast cancer patients in our hospital underwent SLNB from December 2010 to May 2012, 107 patients received combined use of ICG and MB as the lymphatic mapping tracer and 109 patients received MB alone. In combination group, sentinel lymph nodes were identified by ICG fluorescence using a near-infrared camera and/or blue dye, while in blue dye alone group sentinel lymph nodes were identified as blue nodes along the blue lymphatic vessel. Intra-operative frozen section analysis was performed, followed by conventional histopathologic examination. Results: In combination group, subcutaneous lymphatic channels were successfully visualized in all the patients, 325 sentinel lymph nodes were identified in 105 patients. While in blue dye alone group, 242 SLNs were found in 100 patients. The detection rate was 98.1% vs. 91.7 %(p=0.033), the average number of SLNs was 3.1 versus 2.4(p&lt;0.001). 29 metastatic SLNs were found in 19 patients by combination method vs. 21 metastatic SLNs in 17 patients by MB alone. No axillary recurrence was observed in either group during 16 months of median follow-up. Conclusions: The combined use of ICG fluorescence and MB enables visualized and more sensitive SLN detection than MB alone.
Community and health system partnership.
Authors: Madeline G. Harris, Rebecca M. Di Piazza, Alia Tunagur, Susan E. Sellers, Kristen G. Noles, John T. Carpenter
Journal: Journal of Clinical Oncology (2017)

190 Background: Breast cancer survivors face physical, psychological, medical, social, cultural and spiritual challenges. Services to address these needs are frequently not available or if available unknown. We sought to determine whether formation of a community-based comprehensive breast cancer survivorship program was feasible. Methods: After months of relationship building, the Women’s Breast Health Fund of the Community Foundation of Greater Birmingham (CFGB), awarded funding to support a systematic assessment of available services in the region. Survivors, their loved ones, providers and other national models of care were surveyed and interviewed. Focus groups including a Lesbian, Bisexual, Gay, Transgender, Queer (LGBTQ) group were held. Aggregated results were presented in monthly meetings to executive level hospital administrators from all health systems in the area, the UAB School of Nursing and CFGB. Results: Survivors seek advice from other survivors more than any other source. Gaps in services exist. Breast cancer survivors were often unaware of existing services. Services were not available to some cultural/ethnic groups or loved ones; staff of some services were not culturally sensitive to the needs of survivors. Some services were available to all, while others require payment. There was no source of authoritative, evidence-based information on breast cancer survivorship except for a few providers. After 12 months the group of executives from all health systems committed to support the formation of a community-based comprehensive breast cancer survivorship program designed to assist breast cancer survivors, their loved ones and institutions by providing reliable information about services. Conclusions: Breast cancer survivors, providers, and local health systems all support the development of a comprehensive breast cancer survivorship program. We feel that it will address unmet needs of breast cancer survivors, allowing each institution to address needs for individual patients. By using the breast cancer survivorship program to assess individual needs and to provide information about services for identified needs, we expect repetitive services will be reduced and quality of life for breast cancer survivors will improve.
Correlation of microbiomic profiles with disease status and <i>MDR1</i> methylation in head and neck squamous cell carcinoma (HNSCC).
Authors: Pauline Funchain, Gurkan Bebek, Kristi L Bennett, Brian Burkey, Charis Eng
Journal: Journal of Clinical Oncology (2012)

5573 Background: Recent studies of the aerodigestive tract have uncovered the functional importance of the microbiome, the total collection of microorganisms that reside within the human host. Furthermore, specific bacterial species have been shown to be etiologic agents or show potential as a screening biomarker in cancers including gastric, colon and pancreas. Here, we hypothesize that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Methods: Matched tumor and adjacent normal fresh frozen tissue specimens were collected from 55 prospectively enrolled HNSCC patients. Microbiomic profiles were obtained using Sanger sequencing of 16S rDNA PCR products. Methylation status of four genes previously linked to HNSCC or inflammation (MDR1, IL8, RARB, TGFBR2) was assessed in 49 samples by combined bisulfite restriction analysis and by Illumina HumanMethylation27 chip. Principle component analysis and multivariate analysis of covariance (MANCOVA) were used to identify bacterial subpopulations significantly associated with HNSCC and relevant clinical variables. Results: In this cohort, median age is 62, male:female ratio is 3:2, 16% are HPV+. Specific bacterial subpopulations associate with HNSCC over normal tissue and correlate with larger tumor size and higher nodal stage (p&lt;0.05). Furthermore, microbial populations can separate tumors by tobacco (p&lt;0.005) but not alcohol (p&gt;0.7) status. Bacterial profiles are independent of HPV status. MDR1 promoter methylation is seen in tumor samples but not in normal oral mucosa (22/49 vs 0/49), and associates with specific microbiomic subpopulations in the order Enterobacteriales and phylum Tenericutes (p&lt;0.001). Additionally, MDR1 methylation correlates with regional nodal metastases. Conclusions: Specific bacterial subpopulations differ between normal and tumor tissue and show association to specific clinicopathologic features, suggesting a role for microbial profiling in HNSCC as a novel area of investigation for diagnosis, prognostication, and therapeutic targeting.
How We Evaluate Biomarker Studies
Authors: Mintu P. Turakhia, Marc S. Sabatine
Journal: JAMA Cardiology (2017)

Karin Willeit, MD; Raimund Pechlaner, MD, PhD; Peter Willeit, MD, PhD; Philipp Skroblin, PhD; Bernhard Paulweber, MD; Christiana Schernthaner, MD; Thomas Toell, MD; Georg Egger, MD; Siegfried Weger, MD; Martin Oberhollenzer, MD; Ludmilla Kedenko, MD; Bernhard Iglseder, MD; Enzo Bonora, MD, PhD; Georg Schett, MD; Manuel Mayr, MD, PhD; Johann Willeit, MD; Stefan Kiechl, MD
Phase IIa study of single-agent MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL).
Authors: Wojciech Jurczak, Pier Luigi Zinzani, Andre Goy, Mariano Provencio, Zsolt Nagy, Tadeusz Robak, Kami J. Maddocks, Christian Buske, Roman Korolkiewicz, Mark Winderlich, Kristie A. Blum
Journal: Journal of Clinical Oncology (2015)

8500 Background: MOR208 is an Fc-engineered humanized monoclonal antibody that targets the B-cell-specific antigen, CD19. There remains a high unmet medical need for new therapies for patients (pts) with relapsed or refractory (R-R) B-cell NHL. Methods: This is a non-randomized, open-label, multicenter, two-stage, phase IIa study of MOR208 in pts with R-R NHL previously treated with rituximab, who were not candidates for high-dose chemotherapy with stem cell support. Adult pts with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or other indolent NHL (iNHL), were treated with single-agent MOR208, 12 mg/kg intravenously, weekly, over two 28-day cycles. Pts with at least stable disease by the 2007 International Response Criteria were to continue MOR208 treatment for another cycle. Pts with complete or partial response (CR or PR) could then receive maintenance MOR208 every 2 or 4 weeks, depending on investigator decision, until progression. Overall response rate (ORR) was the primary endpoint. Results: By 17 November 2014, all pts (n = 89) had been enrolled (DLBCL, n = 35; FL, n = 31; MCL, n = 12; iNHL, n = 11). Thirty-five (39%) pts were female, median age 67 (range 35–90), 78 (88%) had stage III-IV disease, and the median number of prior lines of therapy was 2 (1–4). The mean number of cycles completed was 2.2 (0–3). The investigator-assessed ORR across all NHL subtypes was 22% (20/89) with clinical activity seen in the DLBCL (26% [9/35]; 2 CR, 7 PR; preliminary median duration of response [mDoR] 7.7 months), FL (23% [7/31]; 1 CR, 6 PR; preliminary mDoR 2.6 months) and iNHL (36% [4/11]; 1 CR, 3 PR) cohorts (MCL, 0/12 responses). Grade ≥ 3 non-hematologic and hematologic treatment-emergent adverse events were recorded in 30/89 (34%) and 8/89 (9%) pts, respectively. Infusion-related reactions (8 pts) were all grade 1-2 (except for one case of dyspnea, grade 4). There were no treatment-related deaths. Conclusions: MOR208 demonstrated encouraging single-agent efficacy with CRs observed in pts with R-R DLBCL, FL, and iNHL. MOR208 is well tolerated without significant infusional toxicity. Protocols are being developed to investigate MOR208 in combination with other agents. Clinical trial information: NCT01685008.
Cervical cancer screening: Twelve years experience with high-risk population of southern Mexico.
Authors: Francisco Gutierrez-Delgado, Selene Marcial-Toledo, Jose MANUEL Enriquez-Freire, Teresa Apresa-Garcia, Leonora Chavez-Mercado, Carlos Guzman-Patraca, Jorge Perez-Romero, Lorena Venegas-Hernandez, Luis FELIPE Ortega- Beltran, Juan Mendoza-Mendoza, Sebastian Terrazas-Espitia, Noel Linares
Journal: Journal of Clinical Oncology (2014)

1579 Background: Cervical cancer is still the main cause of death from cancer in indigenous population and rural communities in Mexico. We have evaluated both screen-and-treat colposcopy and oncogenic human papilloma virus (HPV)-DNA testing as potential screening programs in high-risk population. Our experience has been previously reported (2006 and 2008 ASCO Annual Meetings; Abstracts 5012 and 16519, respectively). In this study we report a follow-up of both strategies. Methods: Between 12/2002 and 11/2013, women were offered colposcopy. From 08/2006 to 11/2013, HPV-DNA testing (Hybrid Capture II (hC2) assay (Digene Corp, Gaithersburg, MD, USA) was offered to women aged 14 to 89 years. Criteria for colposcopy diagnosis, cervical cytology, therapy for HPV diagnosis, CIN2 and CIN 3, and the methodology for (Hybrid Capture II (hC2) assay has been reported elsewhere. Women were followed in their communities Results: 17,471 women (median age 39 years, range: 14–87) were underwent colposcopy. 14,487 (83%) of them were evaluated between 2002 and 2008, and 2985 (17%) from 2009 to 2013. The median follow-up was 8 years (range 5-11) and 3 years (range 0-5), respectively. Abnormal colposcopy (HPV, CIN 1, CIN 2 or CIN 3), was diagnosed in 2,528 (14%) out of 14,487 women and 45 (0.31%) had carcinoma. 411 (14%) out of 2,985) women were diagnosed as having an abnormal colposcopy and 11 (0.36%) had carcinoma. 1,110 women were evaluated with the oncogenic HPV-DNA testing. 807 (73%) women were ≥ 30 years old years and 303 (27%) were younger 30 years old. HPV-DNA testing was positive in 134 (16%) and 97 (32%) women, respectively. In women ≥ 30 years old who had a normal colposcopy (n=681), 96 (11.8%) of them had a positive HPV test and in 38 (4.7%) of those who had an abnormal colposcopy. In women younger 30 years old HPV test was positive in 45 (14.85%) women who had a normal colposcopy (n=179) and in 52 (17.16%) diagnosed as having abnormal colposcopy. No new cervical cancer cases have been reported in the follow-up. Conclusions: Screen-and-treat colposcopy and oncogenic HPV testing are feasible strategies for cervical cancer screening in selected high-risk population and an alternative to cytology-based screening programs
Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study
Authors: Anne Kuijer, Marieke Straver, Bianca den Dekker, Annelotte C.M. van Bommel, Sjoerd G. Elias, Carolien H. Smorenburg, Jelle Wesseling, Sabine C. Linn, Emiel J.Th. Rutgers, Sabine Siesling, Thijs van Dalen
Journal: Journal of Clinical Oncology (2017)

Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. Results Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. Conclusion In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.
Retrospective analysis of treatment patterns and outcomes with subcutaneous (SQ) bortezomib (BTZ) in patients (pts) with relapsed mantle cell lymphoma (MCL).
Authors: Vijayveer Bonthapally, Marie-Helene Lafeuille, Jonathan Fortier, Mei Sheng Duh, Yvette Ng, Helgi Van De Velde, Liviu Niculescu, Esprit Ma, Andre Goy
Journal: Journal of Clinical Oncology (2014)

8554 Background: Intravenous (IV) BTZ was approved in the US for the treatment of relapsed MCL in 2006 based on the phase 2 PINNACLE study (Fisher, JCO 2006). In 2012, SQ BTZ was approved based on the phase 3 MMY-3021 study (Moreau, Lancet Oncol 2011), which showed non-inferior efficacy and an improved safety profile with SQ vs IV BTZ in relapsed multiple myeloma. There are limited data on SQ BTZ in relapsed MCL. Methods: In this retrospective observational study, data on relapsed MCL pts aged ≥18 years with ≥1 SQ BTZ dose during 2010–2013, either as a single agent or in combination therapy, were collected from an oncology electronic medical records (EMR) database and patient medical charts (Altos Solutions, Inc). Analyses of treatment patterns and outcomes, including best response, PFS, OS, and AEs, were conducted. Results: Of 37,996 lymphoma pts in the database, 806 had MCL; 42 had ≥1 SQ BTZ dose, of whom 30 had ≥1 prior therapy identified. Of these 30 pts median age was 68.7 years, 70% were male, and 53% had stage IV MCL. Pts had a median of 3 lines of prior therapy (range 1–6). Median time from diagnosis to SQ BTZ was 2.5 years. 97% of pts received SQ BTZ in 2012–2013. Median treatment duration was 2.3 months (range 0.03–19.4); 13 (43%) had single-agent SQ BTZ and 17 (57%) had combination therapy (8 with rituximab [R], 6 with R+bendamustine, 1 each with R+lenalidomide, methotrexate, and dexamethasone). Overall response rate was 37% (11/30 pts; 3% CR). After a median follow-up of 8.8 months, median PFS was 10.5 months (IQR 3.8–29.3), median OS was not reached (1-year OS 72%). Common AEs included 57% fatigue, 27% neutropenia, 27% anemia, 27% neuropathy, 20% thrombocytopenia, and 20% nausea. Local redness/tenderness were seen in 10%/7%. Common grade 3/4 AEs were 10% neuropathy and 7% infection. Outcomes with single-agent SQ BTZ (n=13) were similar to overall data but with only 2 grade 3/4 AEs: 8% neuropathy, 8% diarrhea. Conclusions: SQ BTZ was active and well tolerated in relapsed MCL. These data are consistent with the non-inferior efficacy and improved safety profile of SC BTZ in multiple myeloma. As data mature, additional analyses will further evaluate treatment outcomes and safety profile.