tbuckley/cabot-search huggingface dataset:
PILLAR-2: A randomized, double-blind, placebo-controlled, phase III study of adjuvant everolimus in poor-risk diffuse large B-cell lymphoma (DLBCL).
Authors: Tongyu Lin, Jun Zhu, Kamal Bouabdallah, Michinori Ogura, Masayuki Hino, Jin Seok Kim, Cassandra Wu, Claudia Corrado, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2012)

TPS8118 Background: Effective DLBCL adjuvant therapy after first-line chemotherapy is needed as high-risk DLBCL is associated with a poor 4-year overall survival (OS) rate (Sehn et al, Blood 2007;109:1857-61). In a phase II study of the oral mammalian target of rapamycin inhibitor everolimus in relapsed, aggressive non-Hodgkin lymphoma, DLBCL patients (n=47) had a 30% overall response rate (Witzig et al, Leukemia 2011;25:341-7). Methods: PILLAR-2 is an ongoing international, randomized, double-blind, phase 3 study designed to compare everolimus efficacy and safety with that of placebo in poor-risk DLBCL patients who achieved complete response (CR) with first-line rituximab-based chemotherapy (R-chemo) (ClinicalTrials.gov: NCT00790036; sponsor: Novartis Pharmaceuticals). Eligibility criteria include age ≥18 years; confirmed stage II bulky, III, or IV DLBCL and International Prognostic Index 3-5 at diagnosis; confirmed CR per revised International Workshop Response Criteria for malignant lymphoma (Cheson et al, J Clin Oncol 2007;25:579-86) after first-line R-chemo regimen completed 6-14 weeks before study drug start; Eastern Cooperative Oncology Group performance status ≤2; no ongoing or post–R-chemo radiation; and no myelosuppressive chemotherapy or biologic therapy within 3 weeks. Patients are randomized 1:1 to everolimus 10 mg once daily or matching placebo and treated for 12 months or until disease relapse, unacceptable toxicity, or death. Radiologic tumor assessment is performed at baseline, every 12 weeks during years 1 and 2, every 24 weeks during years 3 and 4, and annually thereafter until start of new anticancer therapy or 5 years after last patient randomization. The primary endpoint is disease-free survival (DFS). Secondary endpoints are OS, lymphoma-specific survival, and safety. Expected enrollment is 687 patients. Final analysis will be performed when 279 DFS events occur; survival follow-up will continue until 338 deaths occur and the last randomized patient has been followed for ≥5 years. Currently, 422 patients are enrolled. The data monitoring committee last reviewed the trial in July 2011 and recommended that it continue as planned.
Localized vagina/uterus rhabdomyosarcoma (VU RMS): Results of a pooled analysis from four international cooperative groups.
Authors: Veronique Minard-Colin, James Robert Anderson, Gianni Bisogno, Dominique Schwob, David A. Rodeberg, Michael Stevens, Andrea Ferrari, Helene Martelli, David Walterhouse, Gian Luca De Salvo, Carola A. S. Arndt, Annie Rey, Odile Oberlin, Christine Haie Meder, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2015)

10063 Background: VU RMS is rare and recognized as one of the most favorable site of RMS. In an attempt to determine optimal therapy in relation both to cure and to late effects, the experience of four international collaborative groups (Children’s Oncology Group [COG], SIOP Malignant Mesenchymal Tumor Group [MMT], Italian Cooperative Soft Tissue Sarcoma Group [ICG], and European pediatric Soft Tissue Sarcoma Group [EpSSG]) was shared at an international workshop. Methods: From 1985 to2009, a total of 237 eligible patients were identified from group files (132 from COG, 62 from MMT, 24 from ICG, and 19 from EpSSG). Results: Median patient age at diagnosis differed among tumor location (1.9 yrs [vagina = 160 pts]; 4 yrs [uterus corpus = 34 pts]; 13.5 yrs [cervix = 43 pts]). Median follow-up was 8 years. Twenty-seven percent of pts received radiation therapy (RT) as part of primary therapy (21% COG, 27% MMT, 46% ICG, 42% EpSSG), and among those, there were significant differences regarding the use of brachytherapy (BT) between the individual groups (14% in COG, 71% in MMT, 55% in ICG, and 75% in EpSSG).Ten-year event-free (EFS) and overall survival (OS) were 72% and 92%. In univariate analysis, low OS was only correlated with enlarged nodes (N1 = 11 pts). While EFS was slightly decreased in pts without initial RT (EFS, 74% vs 82% with RT; p = NS), there was no difference in OS (OS: 93% and 90% without or with initial RT). In total, taking into account total burden of treatment (primary therapy and treatment for relapse), 117 (53%) of the 221 survivors were cured with chemotherapy +/- conservative surgery. Conclusions: These analyses show that half of patients with VU RMS can be cured without systematic RT or radical surgery. When RT is indicated, BT should be encouraged to limit late sequelae.
HER3 expression in the primary tumor as marker of metastatic potential in breast cancer patients.
Authors: Anna Sophie Berghoff, Zsuzsanna Bago-Horvath, Matthias Preusser, Guenther G. Steger, Peter Birner, Christoph Zielinski, Rupert Bartsch
Journal: Journal of Clinical Oncology (2012)

e21033 Background: Breast cancer (BC) is the most common cancer related cause of death in women. Therefore, identification of novel prognostic markers is an important field of research. Recently, HER3 expression was postulated as risk factor for metastatic spread to the brain. We aimed to analyze the predictive value of HER3 expression in patients with metastatic BC treated between 1993 and 2010 at the Medical University of Vienna. Methods: Patients of each subtype (luminal, HER2 positive, triple negative) with metastatic breast cancer were identified from a breast cancer data base. Tissue of the primary tumor was raised from a breast cancer bio-bank. Immunohistochemical staining of estrogen-receptor, progesterone-receptor, HER2 and HER3 was performed. Chi 2 test was used to correlate two factors. Overall survival (OS) and time to progression (TTP) were estimated using the Kaplan-Meier method. Results: A total of125 patients (39 luminal, 42 HER2 positive, 44 triple negative) with metastatic BC were available for this analysis. 71 patients (56.6%) had visceral metastases and 67 patients (46.4%) had brain metastases. 7.4% of specimens showed a positive, uniform, intense membranous staining of &gt; 30% of invasive tumor cells (Her3 3+). Less intense, incomplete, membranous staining was observed in a further 34.4%. HER3 expression in the primary tumor did not correlate with BC subtype (luminal 12.8%; HER2 positive 2.4%; triple negative 6.8%; n.s.; Chi 2 test). Furthermore, no correlation with the likelihood of developing brain metastases (5% vs. 9.8%; n.s.; Chi 2 test) or visceral metastases (7.3% vs. 7.7%; p:n.s.; Chi 2 test) was found. Counter intuitively, patients with HER3 overexpression in the primary tumor had a significantly longer TTP (21 vs. 47 months; p=0.03; log rank test) and a trend towards longer OS was observed as well (53 vs. 112 months; p=0.073; log rank test). Conclusions: In contrast to previous reports, we could not validate that HER3 expression predicts for metastatic potential in general and also with regard to brain metastases of BC in a population that was equally distributed between BC subtypes. Further studies are therefore needed to evaluate the prognostic value HER3 expression in BC.
A retrospective analysis on the impact of preoperative neutrophil to lymphocyte ratio in stage II colon cancer.
Authors: Deepna Jaiswal, Suparna Mantha, Lucas Wong, Luis Seija, Yolanda Munoz
Journal: Journal of Clinical Oncology (2017)

794 Background: Inflammation has a critical role in tumor genesis and progression of cancer. The neutrophil to lymphocyte ratio (NLR) is an indication of balance between the immune systems pro and defense mechanism against cancer. Elevated NLR is of interest in many cancers, including colon cancer. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant chemotherapy for stage II colon cancer has remained debatable. We proposed to study the impact of the NLR in patients with stage II colon cancer and to identify high risk patients who would benefit from adjuvant chemotherapy. Methods: Three hundred and eighty patients diagnosed with Stage II colon cancer at our institution were included in this retrospective study. Kaplan-Meir curves and multivariate Cox-regression analyses were calculated for overall survival. Results: Univariate analysis showed NLR was not statistically significant as predictor of mortality (p-value=0.0857). However, after adjusting for recurrence, chemotherapy, age, white blood cell count, the NLR was predictive for survival, with a hazard ratio of 1.05 and 95% confidence interval of (1.006 - 1.1). Recurrence and age were also significant predictors of survival (p-values of &lt;0.0001 for both), and HR of 3.1 (2.0 – 4.6) and 1.4 (1.2 – 1.5), respectively. Conclusions: The neutrophil to lymphocyte ratio might be an independent prognostic marker for overall survival in stage II colon cancer patients. Given the retrospective nature of our study, further studies are indicated to confirm our findings.
Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis
Authors: Eric C Sun, Anjali Dixit, Keith Humphreys, Beth D Darnall, Laurence C Baker, Sean Mackey
Journal: BMJ (2017)

<b>Objectives</b>&nbsp;To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose. <b>Design</b>&nbsp;Retrospective analysis of claims data, 2001-13. <b>Setting</b>&nbsp;Administrative health claims database. <b>Participants</b>&nbsp;315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid. <b>Interventions</b>&nbsp;Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. <b>Main outcome measures</b>&nbsp;Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose. <b>Results</b>&nbsp;9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P&lt;0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P&lt;0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P&lt;0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16). <b>Conclusions</b>&nbsp;From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.
Contents, Vol. 38, 1982
Authors: Y. Ago, M. Sugita, H. Teshima, T. Nakagawa, Caroline B. Thomas, Joyce McDougall, M. von Rad, F. Lolas, Louise Demers-Desrosiers, Graeme Taylor, Kenneth Doody, H. Warnes, Réjean Fontaine, Denis Boisvert, A.H. Crisp, A.V. Bhat, Adolph-Ernst Meyer, R.A. Ramsay, A.J. Krakowski, Z. Rydzynski, M. Jarosz, F. Engelsmann, J. Ananth, K. Köhle, E. Gaus, C. Simons, C. Westphale, Yujiro Ikemi, Akira Ikemi, Hellmuth Freyberger, Lutz Besser, Adam J. Krakowski, J. Bastiaans, Chase Patterson Kimball, John C. Nemiah, Louis A. Gottschalk, David R. Hawkins, J. Binder, A. Dobler-Mikola, J. Angst, Giovanni A. Fava, Issy Pilowsky, Alessandra Pierfederici, Manuela Bernardi, Dorothy Pathak, G.H.B. Baker, H.B.M. Murphy, Finn Askevold, Albert J. Silverman, Michael Plaut, Stanford B. Friedman, Ronald Grossarth-Maticek, Dusan T. Kanazir, Peter Schmidt, Hermann Vetter
Journal: Psychotherapy and Psychosomatics (1982)
In Vitro Comparison of ADCC and CAR Sensitivity of Adult HER-2+ B-ALL Using the NK-92 Human Cell Line Transduced with a Human CD16 (ADCC) or an Anti-HER2 Chimeric Antigen Receptor (CAR)
Authors: Beatrice Clemenceau, Thierry Guillaume, Nelly Robillard, Regine Vivien, Pierre Peterlin, Alice Garnier, Marie-Christine Bene, Henri Vié, Patrice Chevallier
Journal: Blood (2016)
Abstract 12941: Gender Differences in Age-Related Aortic Elongation and Dilatation: Longitudinal Results From the Multiethnic Study of Atherosclerosis
Authors: Majd AlGhatrif, Yoshiaki Ohyama, Bharath Ambale-Venkatesh, Dhananjay Vaidya, Gisela Teixido-Tura, Alban Redheuil, Colin Wu, William G Hundley, David Bluemke, Edward Lakatta, Joao Lima
Journal: Circulation (2015)

Background: Major aortic remodeling processes ensue with aging. Information on the patterns of the longitudinal changes in aortic geometry is essential to understand the dramatic hemodynamic changes observed with aging. Methods: Data from 1396 MESA participants who had aortic magnetic resonance imaging in 2000-02 and 2010-12 were analyzed. Ascending aorta diastolic diameter (Add), strain (Astr), arch length (Alen) and their rates of change (Δ) were determined using the validated automated software (ARTFUN, INSERM LIB). Multivariate analysis was performed to examine the correlates of the changes of these parameters. Least square means of Add and Alen adjusted for body surface area were plotted against age for those not on anti-HTN drugs on either visit (n=590). Results: The main correlates of increased ΔAdd, and ΔAlen were male gender, smaller baseline Add, and Alen, lower PP, greater MAP and ΔMAP. Increased ΔAdd was also associated with greater baseline Astr and with not being on anti-HTN drugs, while greater ΔAlen, was associated with smaller ΔPP in women only (P&lt;0.05 for all). Figures.1 shows cross sectional Add, and Alen (upper panels) and their longitudinal changes (lower panels). In men, Add, and Alen increased with aging; ΔAlen was steady but ΔAdd increased significantly after the 7th decade. In women, although Add and Alen increased with aging, ΔAdd decreased linearly with advancing aging while ΔAlen increased after the 7th decade. Conclusion: Gender, baseline blood pressure parameters and baseline aortic geometry and elasticity are the main determinants of aortic remodeling. Aortic elongation and dilatation follow different trajectories and vary by gender. In contrast to men, aortic dilation in women was minimal beyond the 7th decade and aortic elongation was the main remodeling process and was inversely associated with changes in PP. Gender differences in aortic remodeling might explain the increased pulsatility observed in women with advancing aging.
Long-Term Disease-Free Survival of Patients with AML Relapse After T-Cell-Depleted Allogeneic Stem Cell Transplantation by Re-Induction Therapy and Subsequent Interferon-Boosted Donor Lymphocyte Infusion
Authors: M. Eefting, C.J.M. Halkes, S. Kersting, W.A.F. Marijt, P.A. von dem Borne, J.H. Veelken, J.H.F. Falkenburg
Journal: Blood (2011)
Comparison of <i>HER2</i> gene amplification (AMP) in primary esophageal and gastroesophageal junction adenocarcinomas (EAC) and their metastatic regional lymph nodes (MLNs).
Authors: Harry H. Yoon, Qian Shi, William R. Sukov, Christopher A. Sattler, Anne E. Wiktor, Robert B. Diasio, Tsung-Teh Wu, Robert B. Jenkins, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2015)

4059 Background: The status of HER2 AMP in primary EACs compared to their MLNs is unknown. This is clinically important since selection of patients for HER2-targeted therapy is usually based on HER2 analysis in primary tumors. Here, we report the largest HER2 evaluation of MLNs in EACs to date. Methods: Resected primary tumors and MLNs (209 patients) were tested for HER2 AMP (fluorescence in situ hybridization) and protein expression (immunohistochemistry; IHC 0, 1+, 2+, 3+). Primaries were designated AMP-positive (pos) or -negative (neg) using standard criteria (HER2/CEP17 ≥ 2 in > 5% tumor cells). HER2AMP status in primaries and MLNs were compared (Wilcoxon, Fisher’s). Results: HER2 by AMP vs IHC within individual MLNs (726 MLNs; median 3 MLNs per patient) were 92% concordant (P < .0001). HER2 AMP status was concordant in primaries vs MLNs in 89% (186/209) of patients (Table). Yet among AMP-neg primaries, 7% (10/146) had at least 1 AMP-pos MLN. Importantly, among AMP-neg primaries (n = 146), those with a small AMP subpopulation (ie, < 1% tumor cells) were more likely than uniformly AMP-neg primaries to have an AMP-pos MLN (33% vs 4%; P = .001). Among AMP-pos primaries, those with non-uniform AMP (ie, 6% - 49% tumor cells) were more likely than uniform AMP primaries (ie, ≥ 50% tumor cells) to have entirely AMP-neg MLNs. Across the whole cohort, among patients with at least 1 AMP-pos MLN, an average of 95% of MLNs (standard deviation 17%) was AMP-pos. Conclusions: HER2 status was generally concordant between primary EACs and MLNs. But the strength of concordance diminished significantly among primaries with a small HER2-amplified subpopulation, where a considerably higher rate of HER2-amplified nodal metastases was observed compared to uniformly non-amplified primaries. These novel data suggest that testing MLNs in this subgroup may identify new candidates for HER2-targeted therapy. Primary tumor MLNs All MLNs are AMP-neg Any MLN is AMP-pos P AMP-neg n = 146 Uniform neg n = 131 96% (126) 4% (5) 0.001 Small AMP subpopulation n = 15 67% (10) 33% (5) AMP-pos n = 63 Uniform pos n = 54 17% (9) 83% (45) 0.078 Non-uniform pos n = 9 44% (4) 56% (5)
Alternating non-cross-resistant multiagent chemotherapy (ANCRC) and high-dose chemotherapy followed by autologous stem cell support (HDC-ASCS) in first remission to improve outcome in patients with T-cell lymphoma.
Authors: Potjana Jitawatanarat, Richa Dawar, Kaweesak Chittawatanarat, Nicolas Batty, Myron Stefan Czuczman, Francisco J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2012)

e18538 Background: T-cell lymphomas represent a challenge for the practicing oncologist as evidence-based medicine is limited and the ORR to chemotherapy, PFS and OS rates are inferior when compared to B-cell lymphoma. CHOP offers limited activity, and there is a growing consensus that alternative regimens should be tested. We studied the impact of ANCRC or HDC-ASCS vs. CHOP in outcome of T-cell lymphoma. Methods: We retrospectively analyzed differences between the ORR, PFS and OS of T-cell lymphoma patients excluding ALCL treated with CHOP or HyperCVAD regimen alternating with HDAM in the front-line setting following by observation or HDC-ASCS. Pre-treatment demographic, clinical, and pathological characteristics were collected. Differences in outcomes were analyzed using a Cox proportional analysis. Results: ALCL, PTCL-NOS and AITL were the most common subtypes. After excluding ALCL (N=29), a total of 49 patients were included in the final analysis; 23 pts treated with CHOP; 12 pts with HyperCVAD/HDAM and 14 pts treated with other induction regimens. After induction therapy, 12 patients underwent HDC-ASCS in first remission. There were no differences in demographic and clinical characteristics between groups analyzed. There was a higher ORR and PFS among patients treated with hyperCVAD/HDAM (83.3%) vs. pts treated with CHOP (62%). However it did not improved OS when compared to CHOP. The use of HDC-ASCS in first remission was associated with improved OS. The median OS for pts observed after front-line chemotherapy was 32 months and 59 months for pts that received HDC-ASCS [Hazard ratio 0.54 (95% CI 0.16-1.83) (p=0.32)]. Conclusions: Our data suggest that hyperCVAD/HDAM results in higher ORR and PFS in T-cell lymphoma than CHOP. More importantly, the use of HDC-ASCS in first remission appears to improve the OS of non-ALCL T-cell lymphoma patients. ANCRC regimens incorporating novel agents follow by HDC-ASCS in first remission is emerging as an attractive therapeutic intervention for a selected group of T-cell lymphoma patients been evaluated in ongoing clinical trials.
A randomized, open-label, Phase II trial evaluating the clinical benefit of a maintenance treatment targeting tumor molecular alterations in patients with advanced solid tumors.
Authors: Maud Toulmonde, Christophe Le Tourneau, Antoine Italiano, Christelle Seigne, Isabelle Laure Ray-Coquard, Claire Cropet, Aude Flechon, Françoise Desseigne, Marie Alt, Christelle De La Fouchardiere, Jerome Fayette, Edith Borcoman, Pierre-Etienne Heudel, Laure Jaouen, Mathilde Bernardin, David Pérol, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2015)

TPS2622 Background: Therapeutic decision for most cancers is mainly based on primary disease site, histological type and/or tumor burden. However, genotype-driven clinical trials where treatments are adapted to the molecular alteration supposed to drive tumor progression have recently emerged with promising early results (e.g. BATTLE, SAPHIR01/02, SHIVA, ...). Methods: MOST (My Own Specific Therapy) is a multicenter, randomized, open-label, adaptive phase II trial conducted in patients (pts) with progressive solid tumors (any subtype) after at least one prior therapy in the advanced setting. This trial aims to evaluate the clinical benefit of maintenance therapy targeting molecular alterations identified in the patient’s tumor. Primary endpoint is progression-free survival. Secondary endpoints include toxicity, objective response rate (RECIST1.1) and overall survival. Based on the presence of molecular alterations detected by a previous tumor molecular profiling, pts are treated with one of the following targeted therapies: nilotinib (400 mg BID for ABL1, KIT, PDGFRA/B, DDR1/2, CSF1R mut/amp/transloc.); everolimus (10 mg QD for PIK3CA, PIK3R1, AKT1/2, mTOR mut/amp or TSC1/2 or PTEN loss); sorafenib (400 mg BID for VEGFR1-3, PDGFRB, FLT3, BRAF, CRAF, KRAS or RET mut/amp/transloc); lapatinib (1500 mg QD for HER2 mut/amp) or pazopanib (800 mg QD for VEGFR1-3, PDGFRA/B or KIT mut/amp). After 12 weeks of treatment, pts with objective response are proposed to continue the targeted therapy, while pts with stable disease are randomly assigned (1:1) to continuation (arm A) or interruption of treatment (arm B; reintroduction is allowed at disease progression). Statistical analysis will be carried out in each of the 5 treatment groups using a sequential Bayesian approach. Three interim analyses are planned after randomization of 10, 15 and 20 pts per arm. The trial will continue until the maintenance arm is shown with high posterior probability to be superior to the interruption arm according to a pre-defined stopping rule, or until the maximum sample size (i.e. 50 pts) is reached. To date, 66 of 400 planned patients have been enrolled. Clinical trial information: NCT02029001.