Evaluation of clonal origin of malignant mesothelioma.

Background: The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated.

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.

Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy.

Effectiveness of a tailored behavioral intervention to improve hypertension control: primary outcomes of a randomized controlled trial.

Unlabelled: Blood pressure (BP) control rates are suboptimal. We evaluated the effectiveness of 2 behavioral interventions to improve BP control via a 3-arm, randomized controlled trial of 533 adults with repeated uncontrolled BP, despite antihypertensive drug treatment for ≥6 months. The interventions were a tailored stage-matched intervention (SMI) or a nontailored health education intervention (HEI) of 6 monthly calls targeting diet, exercise, and medication.

Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313.

In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT.

Comparison of the effectiveness of frontline chemoimmunotherapy regimens for follicular lymphoma used in the United States.

To compare the effectiveness of frontline rituximab-chemotherapy regimens in clinical practice, we examined outcomes for patients with low-grade, stage III/IV follicular lymphoma receiving rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), R with cyclophosphamide, vincristine and prednisone (R-CVP) or R with a fludarabine-based regimen (R-Flu) as frontline therapy. In total, 611 patients meeting these criteria were identified in the National LymphoCare Study: 47% receiving R-CHOP (n = 287), 31% receiving R-CVP (n = 187) and 22% receiving R-Flu (n = 137). Overall response rates were high (R-CVP 87%, R-CHOP 93%, R-Flu 94%; p = 0.

In vitro and in vivo interactions between the HDAC6 inhibitor ricolinostat (ACY1215) and the irreversible proteasome inhibitor carfilzomib in non-Hodgkin lymphoma cells.

Interactions between the HDAC6 inhibitor ricolinostat (ACY1215) and the irreversible proteasome inhibitor carfilzomib were examined in non-Hodgkin lymphoma (NHL) models, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and double-hit lymphoma cells. Marked in vitro synergism was observed in multiple cell types associated with activation of cellular stress pathways (e.g.

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

Background: Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.

Methods: We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph).

Medical history, lifestyle, family history, and occupational risk factors for sporadic Burkitt lymphoma/leukemia: the Interlymph Non-Hodgkin Lymphoma Subtypes Project.

Background: The etiologic role of medical history, lifestyle, family history, and occupational risk factors in sporadic Burkitt lymphoma (BL) is unknown, but epidemiologic and clinical evidence suggests that risk factors may vary by age.

Methods: We investigated risk factors for sporadic BL in 295 cases compared with 21818 controls in a pooled analysis of 18 case-control studies in the International Lymphoma Epidemiology Consortium (InterLymph). Cases were defined to include typical BL or Burkitt-like lymphoma.

PI3K/mTOR inhibition markedly potentiates HDAC inhibitor activity in NHL cells through BIM- and MCL-1-dependent mechanisms in vitro and in vivo.

Purpose: The aim of this study is to explore the efficacy and define mechanisms of action of coadministration of the PI3K/mTOR inhibitor BEZ235 and pan-HDAC inhibitor panobinostat in diffuse large B-cell lymphoma (DLBCL) cells.

Experimental Design: Various DLBCL cells were exposed to panobinostat and BEZ235 alone or together after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis. Genetic strategies defined the functional significance of such changes, and xenograft mouse models were used to assess tumor growth and animal survival.

Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study.

Background: Present first-line therapy for diffuse large B-cell lymphoma, a subtype of non-Hodgkin lymphoma, is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Ibrutinib, a novel oral Bruton's tyrosine kinase inhibitor, has shown single-drug activity in relapsed or refractory B-cell malignancies. We investigated the safety and efficacy of ibrutinib in combination with R-CHOP for patients with previously untreated CD20-positive B-cell non-Hodgkin lymphoma.

Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.

Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m(2) IV daily for 5 days in 21-day cycles.

Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.

Background: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected.

Objective: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer.

Emerging protein kinase inhibitors for the treatment of non-Hodgkin's lymphoma.

Introduction: non-Hodgkin's lymphoma (NHL) accounts for 4.3% of all new cancers in the United States. Even in its most curable subtypes, approximately 30% of patients succumb to their disease.

A phase I study of PRO131921, a novel anti-CD20 monoclonal antibody in patients with relapsed/refractory CD20+ indolent NHL: correlation between clinical responses and AUC pharmacokinetics.

PRO131921 is a third-generation, humanized anti-CD20 monoclonal antibody with increased antibody-dependent cytotoxicity and complement-dependent cytotoxicity compared to rituximab. In this phase I study, PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent non-Hodgkin lymphoma (NHL) who had been treated with a prior rituximab-containing regimen. The primary aim of this study was safety and tolerability of PRO131921.

Principles and reality of proton therapy treatment allocation.

Purpose: To present the principles and rationale of the Proton Priority System (PROPS), a priority points framework that assigns higher scores to patients thought to more likely benefit from proton therapy, and the distribution of PROPS scores by patient characteristics

Methods And Materials: We performed multivariable logistic regression to evaluate the association between PROPS scores and receipt of proton therapy, adjusted for insurance status, gender, race, geography, and the domains that inform the PROPS score.

Results: Among 1529 adult patients considered for proton therapy prioritization during our Center's ramp-up phase of treatment availability, PROPS scores varied by age, diagnosis, site, and other PROPS domains. In adjusted analyses, receipt of proton therapy was lower for patients with non-Medicare relative to Medicare health insurance (commercial vs Medicare: adjusted odds ratio [OR] 0.

R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0433.

Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled patients with newly diagnosed, advanced stage or bulky stage II, histologically confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then iodine-131 tositumomab radioimmunotherapy consolidation 30-60 d after completion of chemotherapy.

Comparison of referring and final pathology for patients with T-cell lymphoma in the National Comprehensive Cancer Network.

Background: T-cell lymphomas (TCLs) are uncommon in the United States. The accurate diagnosis of TCL is challenging and requires morphologic interpretation, immunophenotyping, and molecular techniques. The authors compared pathologic diagnoses at referring centers with diagnoses from expert hematopathology review to determine concordance rates and to characterize the usefulness of second-opinion pathology review for TCL.

The use and effectiveness of rituximab maintenance in patients with follicular lymphoma diagnosed between 2004 and 2007 in the United States.

Background: The authors examined the "real-world" effectiveness of rituximab (R) maintenance therapy (R-maintenance) compared with observation after R-based induction therapy in patients with previously untreated follicular lymphoma (FL) in the United States.

Methods: The National LymphoCare Study is a prospective, multicenter, observational study that enrolled > 2700 untreated patients with FL diagnosed from 2004 to 2007 at 265 sites in the United States. Among these, patients who achieved at least stable disease after R-based induction therapy were eligible for the current analysis.

Who is being reached for a telephone-delivered intervention for patients with uncontrolled hypertension?

Background: Telephone-delivered interventions to provide health counseling for complex chronic medical conditions are convenient, acceptable, and cost-effective. However, little is known about which patients are reached, their characteristics, and who benefits most from telephone-delivered counseling.

Materials And Methods: This study examined whether baseline characteristics are predictive of being easily reached for a monthly, telephone-delivered behavioral intervention to improve treatment adherence in Veterans with uncontrolled hypertension.

Hemophagocytic lymphohistiocytosis masquerading as progressive chronic lymphocytic leukemia.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome characterized by a non-malignant expansion of the macrophage population in the setting of a heightened cytokine response with subsequent widespread hemophagocytosis. It can occur as either genetic or acquired forms; the latter of which frequently occurs in the setting of infection, autoimmune disease, or malignancy. We present the second known case of HLH associated Chronic Lymphocytic Leukemia (CLL) in the absence of infectious etiology and review the current literature.

Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy.

Older adults constitute a significant proportion of the cancer population, but are underrepresented in clinical trials. We conducted a retrospective analysis of the safety and efficacy of brentuximab vedotin in adults ≥ 60 years with relapsed CD30-positive lymphomas. Baseline characteristics and safety data were compared for older (median age 66) and younger patients (< 60 years, median age 32).