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1.  Disparities in the early adoption of chemo-immunotherapy for diffuse large B-cell lymphoma in the United States 
Background
Since the 1970s, CHOP chemotherapy has been the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). In 2002, randomized trials changed this standard by demonstrating that adding rituximab immunotherapy to CHOP improved survival. However, how these results influenced chemo-immunotherapy adoption in clinical practice remains unclear.
Methods
Using the National Cancer Database to compare chemo-immunotherapy use with chemotherapy alone, we collected data on demographics, stage, health insurance, area-level socio-economic status (SES), facility characteristics, and type of treatment for DLBCL patients diagnosed in the United States 2001-2004. Multivariable log binomial models examined associations between race, insurance, and treatment allocation, adjusting for covariates.
Results
Among 38,002 patients with DLBCL, 27% received chemo-immunotherapy and 50% chemotherapy alone. Patients who had localized disease, were diagnosed in 2001, black, uninsured/Medicaid insured, or lower SES were less likely to receive any form of chemotherapy (all p<0.0001). Patients who were diagnosed 2001, black [relative risk (RR) 0.83, 95% Confidence Interval (CI) 0.78-0.89], >60 years (RR 0.94, 95% CI 0.90-0.98), or had localized disease (RR 0.89, 95% CI 0.86-0.92) were less likely to receive chemo-immunotherapy. Receiving treatment at high DLBCL volume teaching/research facilities was associated with the greatest likelihood of chemo-immunotherapy (RR 1.69, 95% CI 1.52-1.89).
Conclusions
Black DLBCL patients were less likely to receive chemotherapy or chemo-immunotherapy during this period.
Impact
This large national cohort study demonstrates disparities in the diffusion of chemo-immunotherapy for DLBCL. Improving DLBCL outcomes will require efforts to extend access to proven advances in therapy to all segments of the population.
doi:10.1158/1055-9965.EPI-12-0466
PMCID: PMC4155492  PMID: 22771484
Diffuse large B-cell lymphoma; Non-Hodgkin Lymphoma; Lymphoma; Healthcare Disparities; Immunotherapy; Rituximab; Chemo-immunotherapy
2.  Examining Racial Differences in Diffuse Large B-Cell Lymphoma Presentation and Survival 
Leukemia & lymphoma  2013;54(2):268-276.
We performed a retrospective cohort analysis of 701 (533 White and 144 Black) patients with DLBCL treated at two referral centers in southern United States between 1981-2010. Median age of diagnosis for Blacks was 50 years vs. 57 years for Whites (p<0.001). A greater percentage of Blacks presented with elevated lactate dehydrogenase levels, B-symptoms, and performance status≥2. More Whites (8%) than Blacks (3%) had positive family history of lymphoma (p=0.048). There were no racial differences in the use of R-CHOP (52% Black vs. 47% White, p=0.73). While black race predicted worse survival among patients treated with CHOP (Hazard ratio [HR] 1.8, p<0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p=0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome.
doi:10.3109/10428194.2012.708751
PMCID: PMC4151307  PMID: 22800091
Diffuse large B-cell lymphoma; Race; Disparities; Outcomes; CHOP regimen; R-CHOP regimen
3.  Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma 
Cancer  2013;119(18):3309-3317.
Background
Increased risk of Non Hodgkin Lymphoma (NHL) has been observed in persons occupationally exposed to benzene, but the risk among persons living near benzene release sites has not been well described.
Methods
To investigate the spatial patterns of NHL incidence and the association between NHL incidence and distance to benzene release sites, we linked and geocoded data on benzene release sites in Georgia 1988–1998 from the Environmental Protection Agency's (EPA) Toxics Release Inventory (TRI), census tract level population statistics, and NHL incidence from the Georgia Comprehensive Cancer Registry (GCCR) 1999–2008. We mapped standardized incidence ratios by census tract and performed Poisson regression on NHL and NHL subtype incidence data, using the mean distance between the tract centroids and release sites as a marker of exposure. Cluster analyses were conducted at the global, local, and focal levels.
Results
Poisson regression indicated that for every mile the average distance to benzene release sites increased, there was an expected 0.31% decrease in the risk of NHL. Similar results were observed for all NHL subtypes analyzed. Clusters of NHL were spatially associated with benzene release sites located in metropolitan areas, but not with release sites in other areas of the state.
Conclusions
NHL incidence is significantly higher in census tracts which are closer, on average, to benzene release sites. Additional studies are needed to examine spatial patterns of NHL incidence in other geographic regions and interactions between benzene and other exposures.
doi:10.1002/cncr.28083
PMCID: PMC4151314  PMID: 23896932
Lymphoma; Non-Hodgkin; Geographic Information Systems; Benzene; Surveillance
4.  PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma 
The New England journal of medicine  2014;370(11):1008-1018.
Background
Phosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas.
Methods
In this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety.
Results
The median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%).
Conclusions
In this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424.)
doi:10.1056/NEJMoa1314583
PMCID: PMC4039496  PMID: 24450858
5.  Communicating Safe Outpatient Management of Fever and Neutropenia 
Journal of Oncology Practice  2013;9(4):207-210.
doi:10.1200/JOP.2012.000815
PMCID: PMC3710171  PMID: 23942923
6.  Exploring Risk Factors for Follicular Lymphoma 
Advances in Hematology  2012;2012:626035.
Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair gene XRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment.
doi:10.1155/2012/626035
PMCID: PMC3458409  PMID: 23028387
7.  American Cancer Society Lung Cancer Screening Guidelines 
Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation.
doi:10.3322/caac.21172
PMCID: PMC3632634  PMID: 23315954
humans; lung neoplasms; mortality; radiography; radiation dosage; randomized controlled trials as topic; risk; risk reduction behavior; x-ray; computed tomography; adverse effects; lung cancer screening
8.  Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma 
Journal of Clinical Oncology  2011;29(20):2787-2794.
Purpose
Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.
Patients and Methods
Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.
Results
Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.
Conclusion
Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
doi:10.1200/JCO.2010.33.3005
PMCID: PMC3139394  PMID: 21632504
9.  Receiver operating characteristic curve analysis of circulating blood dendritic cell precursors and T cells predicts response to extracorporeal photopheresis in patients with chronic graft-versus-host disease 
Transfusion  2010;50(11):2424-2431.
BACKGROUND
One proposed mechanism of extracorporeal photopheresis (ECP) in reducing chronic graft-versus-host disease (cGVHD) is alteration in numbers of circulating dendritic cells (DCs). This hypothesis was tested by correlating numbers of DC precursors and T cells in the blood before and during ECP therapy with response of cGVHD.
STUDY DESIGN AND METHODS
Twenty-five patients with cGVHD were treated with ECP. Data were collected with emphasis on blood cellular markers, clinical response to ECP, and overall survival.
RESULTS
Fourteen patients (56%) responded and had better 2-year survival than nonresponders (88% vs. 18%, p = 0.003). Responders had higher baseline circulating myeloid DC (mDC) and plasmacytoid DC precursors and CD4+ and CD8+ T cells compared with nonresponders. Receiver operating characteristic curve analyses showed that the best baseline cutoff values to predict response to ECP were mDC counts of 3.7 cells/µL (79% sensitivity, 82% specificity) and CD4+ T-cell counts of 104 cells/µL (71% sensitivity, 82% specificity). CD4+ T cells declined in responders over time, but not in nonresponders, and no significant changes were seen in CD8 T-cell or DC numbers over a 12-month period in responder or nonresponder groups.
CONCLUSIONS
Higher baseline numbers of circulating DCs and T cells may predict clinical response to ECP in patients with cGVHD.
doi:10.1111/j.1537-2995.2010.02712.x
PMCID: PMC3926317  PMID: 20529004
10.  Racial differences in chronic lymphocytic leukemia: Digging deeper 
Cancer  2013;119(20):3593-3595.
While it has been well established that there are significant racial differences in lymphoid malignancies, registry-based studies have been limited by incomplete or missing data on stage, race, important clinical and laboratory prognostic factors, treatment, treatment response, and follow-up. To overcome some of these limitations, the authors conducted a retrospective cohort study of consecutive patients with a confirmed diagnosis of chronic lymphocytic leukemia (CLL) receiving care at MD Anderson Cancer Center and Duke University Medical Center. The authors identified 84 AA patients with untreated CLL who more commonly presented with poor-risk biological features such as unmutated IGHV gene, ZAP70 expression, and chromosome 17p or 11q deletion. . When compared to a group of non-black patients, the AA group had significantly shorter median event-free survival and overall survival. These results corroborate the findings of prior studies of CLL, but forward the field by providing additional clinical details to understand the nature of these racial disparities.
PMCID: PMC3834561  PMID: 24244955
12.  Considerations in the initial management of follicular lymphoma 
Community oncology  2012;9(11):S53-S60.
doi:10.1016/j.cmonc.2012.09.015
PMCID: PMC3610920  PMID: 23544009
13.  Incidence Patterns and Outcomes for Hodgkin Lymphoma Patients in the United States 
Advances in Hematology  2010;2011:725219.
Hodgkin lymphoma (HL) demonstrates heterogenous histologic findings, clinical presentation, and outcomes. Using the United States Surveillance, Epidemiology, and End Results (SEER) data we examined relationships between patient characteristics, clinical features at diagnosis, and survival in HL patients. From 2000 to 2007, 16,710 cases were recorded in 17 SEER registries. Blacks and Asians had low incidence (black/white incidence rate ratio (IRR) 0.86, P < .01; Asian/white IRR 0.43, P < .01). The bimodal pattern of incidence was less prominent for black males. Asians and Blacks presented at a mean age of 38 years compared to 42 years for Whites (P < .001). Race was a predictor for survival with HR of 1.19 (95% CI 1.11–1.28) for Blacks. Age was the most important predictor of survival (HR for patients ≥45 years 5.08, 95% CI 4.86–5.31). These current patterns for presentation and outcomes of HL help to delineate key populations in order to explore risk factors for HL and strategies to improve treatment outcomes.
doi:10.1155/2011/725219
PMCID: PMC3010617  PMID: 21197477
14.  Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma 
Advances in Hematology  2010;2011:736261.
Epidemiological studies suggest unique occurrence patterns of Hodgkin lymphoma (HL) worldwide. In most Western countries there is a clear bimodal age distribution with an early peak in young adults followed by a second peak in older adults, particularly among males. In the Middle East and Asia, HL is more common in early childhood. There also are marked racial differences in the presentations of HL and HL subtypes, and particular single nucleotide polymorphisms (SNPs) have been identified as etiological factors suggesting that gene-gene and gene-environment interactions are involved. Personal health choices such as exercise and smoking may modify an individual's chances of developing HL. Numerous studies highlight the impact that exposure to Epstein-Barr virus and other environmental factors have on HL risk. Understanding the relative importance of each of these findings and their links to HL development and survival will help clinical researchers expand curative therapies and create preventative strategies for HL.
doi:10.1155/2011/736261
PMCID: PMC2994062  PMID: 21127715
15.  Initial management strategies for follicular lymphoma 
SUMMARY
Follicular lymphoma (FL) can vary markedly in its initial presentation, and no single standard approach for its initial management has been adopted. Available options for the initial management of FL include watchful waiting, radiation, single-agent rituximab and combination of rituximab and chemotherapy with strategies segregated for patients who have low and high tumor burden disease based on established criteria. However, marked debate occurs regarding the role of watchful waiting in the modern era for low tumor burden, asymptomatic patients, the optimal timing of rituximab, the selection of chemotherapy regimen to partner with rituximab in high tumor burden patients, and strategies for the management of relapsed disease. We provide an evidence-based discussion on these and other issues regarding the management of FL, and propose a mathematical modeling approach for addressing some of these questions.
doi:10.2217/ijh.12.7
PMCID: PMC3587762  PMID: 23476737
18.  The genetic landscape of mutations in Burkitt lymphoma 
Nature genetics  2012;44(12):1321-1325.
Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
doi:10.1038/ng.2468
PMCID: PMC3674561  PMID: 23143597
19.  Development of the Lymphoma Enterprise Architecture Database: A caBIG(tm) Silver level compliant System 
Cancer Informatics  2009;8:45-64.
Lymphomas are the fifth most common cancer in United States with numerous histological subtypes. Integrating existing clinical information on lymphoma patients provides a platform for understanding biological variability in presentation and treatment response and aids development of novel therapies. We developed a cancer Biomedical Informatics Grid™ (caBIG™) Silver level compliant lymphoma database, called the Lymphoma Enterprise Architecture Data-system™ (LEAD™), which integrates the pathology, pharmacy, laboratory, cancer registry, clinical trials, and clinical data from institutional databases. We utilized the Cancer Common Ontological Representation Environment Software Development Kit (caCORE SDK) provided by National Cancer Institute’s Center for Bioinformatics to establish the LEAD™ platform for data management. The caCORE SDK generated system utilizes an n-tier architecture with open Application Programming Interfaces, controlled vocabularies, and registered metadata to achieve semantic integration across multiple cancer databases. We demonstrated that the data elements and structures within LEAD™ could be used to manage clinical research data from phase 1 clinical trials, cohort studies, and registry data from the Surveillance Epidemiology and End Results database. This work provides a clear example of how semantic technologies from caBIG™ can be applied to support a wide range of clinical and research tasks, and integrate data from disparate systems into a single architecture. This illustrates the central importance of caBIG™ to the management of clinical and biological data.
PMCID: PMC2675136  PMID: 19492074
biomedical informatics grid; non-Hodgkin’s lymphoma; large linked database; semantic integration; caCORE SDK
20.  Treatment Strategies for Patients with Diffuse Large B-Cell Lymphoma: Past, Present, and Future 
Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring lymphoma in the Western world. DLBCL is a clinically, biologically, and pathologically heterogeneous entity with biologically distinct subtypes that have different expected treatment outcomes. The addition of rituximab to combination chemotherapy has improved outcomes for all patients with DLBCL and can produce cure for many individuals. Relapsed DLBCL is generally managed with salvage chemo-immunotherapy followed by high dose therapy and autologous stem cell transplantation which can cure additional patients. However, outcomes for patients who relapse early after upfront rituximab and chemotherapy have a poorer prognosis. Novel therapies and strategies are desperately needed for these patients and several emerging treatments hold promise for improving DLBCL treatment outcomes in the future.
doi:10.2147/BLCTT.S18701
PMCID: PMC3606548  PMID: 23532092
Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Lymphoma; chemoimmunotherapy; rituximab; treatment
21.  Development of Query Strategies to Identify a Histologic Lymphoma Subtype in a Large Linked Database System 
Cancer Informatics  2007;3:149-158.
Background:
Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specificity of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specific cancer patient population.
Methods:
Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy.
Results:
Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verified and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specificity (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%).
Conclusions:
Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.
PMCID: PMC2675837  PMID: 19455241
Large linked database; cancer outcomes research; cancer epidemiology; cancer registry
23.  The use and effectiveness of rituximab maintenance in patients with follicular lymphoma diagnosed between 2004 and 2007 in the United States 
Cancer  2014;120(12):1830-1837.
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. Patients who initiated R-maintenance within 215 days of completing induction therapy were categorized as the R-maintenance group, and those who did not initiate therapy during this period were categorized as the observation group. The objective of the current study was to determine the effect of R-maintenance on progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS).
RESULTS
A total of 1439 patients completed R-based induction therapy, 1186 of whom met all inclusion criteria (541 patients received R-maintenance and 645 patients were observed). Characteristics that were found to be predictive of receiving R-maintenance were histology grade (1/2), Ann Arbor stage of disease (III/IV), geographic region (region other than the West), and practice setting (community practice). With a median follow-up of 5.7 years, R-maintenance was associated with superior PFS (hazards ratio [HR], 0.68; 95% confidence interval [95% CI], 0.56-0.84 [P = .0003]) and TTNT (HR, 0.66; 95% CI, 0.52-0.84 [P = .0007]). No significant difference in OS was observed (HR, 0.81; 95% CI, 0.58-1.14 [P = .23]).
CONCLUSIONS
R-maintenance in patients with FL and at least stable disease after R-based induction therapy provided significantly longer PFS and TTNT in comparison with observation, but no significant difference in OS was observed with 5-years of follow-up. This comparative effectiveness study aligns with the results of randomized trials suggesting that similar outcomes occur with R-maintenance in FL with the treatment variations observed in clinical practice. Cancer 2014;120:1830–1837. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
The authors present what, to their knowledge, is the largest published series to date of prospectively enrolled patients with previously untreated follicular lymphoma in the modern era examining the effectiveness of rituximab maintenance in clinical practice. With > 5 years of follow-up, it was found that, compared with observation, receipt of rituximab maintenance therapy was associated with significantly longer progression-free survival and time to next treatment in previously untreated patients with follicular lymphoma who achieved at least stable disease after rituximab-based induction therapy.
doi:10.1002/cncr.28659
PMCID: PMC4265986  PMID: 24668580
follicular lymphoma; rituximab maintenance; frontline therapy; outcomes; non-Hodgkin lymphoma
24.  A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma 
ISRN Hematology  2011;2011:623924.
Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.9% (95% CI 23.4–50.7%) for enteropathy-type T-cell lymphoma (ETTL) to 65.8% (95% CI 54.0–75.9%) for anaplastic large cell lymphoma (ALCL). The 5-year OS was 38.5% (95% CI 35.5–41.6%) for all PTCL patients and ranged from 20.3% (95% CI 12.5–31.2%) for ETTL to 56.5% (95% CI 42.8–69.2%) for ALCL. These data suggest that there is marked heterogeneity across PTCL subtypes in the benefits of anthracycline-based chemotherapy. While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS or ETTL. Novel agents and regimens are needed to improve outcomes for these patients.
doi:10.5402/2011/623924
PMCID: PMC3197255  PMID: 22084700
25.  Follicular Lymphoma in the United States: First Report of the National LymphoCare Study 
Journal of Clinical Oncology  2009;27(8):1202-1208.
Purpose
Optimal therapy of follicular lymphoma (FL) is not defined. We analyzed a large prospective cohort study to identify current demographics and patterns of care of FL in the United States.
Patients and Methods
The National LymphoCare Study is a multicenter, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States. Patients were enrolled between 2004 and 2007. There is no study-specific prescribed treatment regimen or intervention.
Results
Two thousand seven hundred twenty-eight subjects were enrolled at 265 sites, including the 80% of patients enrolled from nonacademic sites. Using the Follicular Lymphoma International Prognostic Index (FLIPI), three distinct groups independent of histologic grade could be defined. Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%. The choice to initiate therapy rather than observe was associated with age, FLIPI, stage, and grade (P < .01). Significant differences in treatment (P < .01) across regions of the United States were noted. Contrary to practice guidelines, treatment of stage I FL frequently omits radiation therapy.
Conclusion
Widely disparate therapeutic approaches are utilized for FL. Initial therapy is deferred in a small subset of patients. There is no single standard of care for the treatment of de novo FL, although antibody use is ubiquitous when therapy is initiated. These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse.
doi:10.1200/JCO.2008.18.1495
PMCID: PMC2738614  PMID: 19204203

Results 1-25 (28)