Using primary site as a predictor of survival in mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare B cell lymphoma that varies in clinical behavior with some patients experiencing aggressive disease with short survival, whereas others have indolent behavior. We examined the association between primary disease site and survival in MCL patients to identify subgroups with distinct characteristics. METHODS: We analyzed the United States Surveillance, Epidemiology and End Results Program database for MCL cases reported from 2000 through 2009. Kaplan-Meier curves and Cox proportional hazard models were used to estimate the effect of primary site on survival. RESULTS: Among 4477 cases included in our study, 19.6% of patients presented with an extranodal primary site. The most common extranodal primary sites were of the gastrointestinal (GI) tract (7.8%), the head and neck (6.2%), and the hematologic/reticuloendothelial systems (3.6%). Asians/Pacific Islanders were more likely than whites or blacks to have GI tract or head and neck disease (P < .0001 and P = .002, respectively). Advanced disease and B symptoms were less common in those with primary disease of the GI tract or head and neck than in those with primary disease of the lymph nodes (both P < .0001). In a multivariate Cox regression model, patients with primary disease of the GI tract and head and neck had superior survival compared to those with primary disease of the lymph nodes; hazard ratios 0.75 (95% CI = 0.62-0.90) and 0.68 (95% CI = 0.55-0.85), respectively. CONCLUSIONS: Primary site of disease may be an important prognostic factor for patients with MCL. Further studies elucidating a biological basis for these differences are needed.

A phase 1 dose escalation study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone for untreated follicular lymphoma and other low-grade B-cell lymphomas.

BACKGROUND: Bortezomib has demonstrated efficacy in patients with relapsed B-cell non-Hodgkin lymphoma (NHL) both alone and in combination with other agents; however, limited data exist regarding its toxicity in combination with common frontline therapies for indolent NHL. A phase 1 study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (R-CHOP) was conducted in patients with untreated follicular lymphoma (FL) and other indolent NHLs. METHODS: Nineteen patients, including 10 patients with FL, were enrolled. The median patient age was 59 years (range, 29-71 years). Seven patients had a FL International Prognostic Index score ≥3. R-CHOP with the vincristine dose capped at 1.5 mg was administered on a 21-day cycle for 6 to 8 cycles, and 1 of 3 dose levels of bortezomib (1.0 mg/m(2) [n = 1], 1.3 mg/m(2) [n = 6], or 1.6 mg/m(2) [n = 12]) was administered on days 1 and 8 of each cycle using a Bayesian algorithm for dose escalation. RESULTS: The maximum tolerated dose (MTD) of bortezomib with modified R-CHOP was reached at 1.6 mg/m(2). Dose-limiting toxicity was observed in 5 patients (1 patient at a bortezomib dose of 1.0 mg/m(2), 1 patient at a bortezomib dose of 1.3 mg/m(2), and 3 patients at a bortezomib dose of 1.6 mg/m(2)). Neuropathy occurred in 16 patients (84%), including 2 patients (11%) who experienced grade 3 sensory neuropathy. Grade 4 hematologic toxicity occurred in 4 patients. Of 19 evaluable patients, 100% responded, and the complete response rate was 68%. At a median follow-up of 32 months, the 3-year progression-free survival rate was 89.5%. CONCLUSIONS: Bortezomib combined with modified R-CHOP produced high response rates without substantial increases in toxicity. A phase 2 study of R-CHOP and bortezomib given at this established MTD is currently ongoing.

Racial differences in the presentation and outcomes of diffuse large B-cell lymphoma in the United States.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is often cured with standard chemoimmunotherapy, but there is great heterogeneity in presentation and outcomes. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) data from 13 registries across the United States, the authors examined differences in incidence and survival for DLBCL by race. International Classification of Diseases for Oncology, third edition histology codes 9678, 9679, 9680, and 9684 were used to identify cases. RESULTS: From 1992 to 2007, 38,522 cases of DLBCL were recorded in SEER. Sixty-five percent of black patients compared with 37% of white patients presented at age ≤ 60 years, 52% of blacks compared with 44% of whites presented with stage III/IV disease, and 31% of black versus 24% of white patients presented with B symptoms (all P < .001). Although survival improved by era of diagnosis for all races (log rank P < .001), 2-year relative survival rates were better for women than men (61% vs 58%, P < .001) and white than black patients (60% vs 50%, P < .001). Black race, male sex, age at diagnosis >60, advanced stage, and B symptoms at diagnosis were predictors of worse survival (P < .001). CONCLUSIONS: Black patients with DLBCL in the United States present at younger age, more advanced stage, and have inferior survival. Epidemiological studies that examine the biological variants of DLBCL in concert with race are needed to elucidate the etiology of these disparities.

Idiotype vaccine strategies for treatment of follicular lymphoma.

Follicular lymphoma is an indolent lymphoma associated with a relapsing course. Immunization with tumor B cell idiotype (Id; a unique variable region of surface B cell immunoglobulin) may induce humoral and cellular immune response against the tumor. Based on promising results from early phase clinical trials with Id vaccine, three Phase III trials were initiated, which, despite failing to meet their primary end points, still provided a glimmer of optimism. This article describes the clinical development of the Id vaccine against follicular lymphoma, outlines the outcomes of clinical trials and delineates the future prospects for the integration of the idiotype vaccine into follicular lymphoma treatment.

Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population.

BACKGROUND: Breast magnetic resonance imaging (MRI) is a sensitive method of breast imaging virtually uninfluenced by breast density. Because of the improved sensitivity, breast MRI is increasingly being used for detection of breast cancer among high risk young women. However, the specificity of breast MRI is variable and costs are high. The purpose of this study was to determine if breast MRI is a cost-effective approach for the detection of breast cancer among young women at high risk. METHODS: A Markov model was created to compare annual breast cancer screening over 25 years with either breast MRI or mammography among young women at high risk. Data from published studies provided probabilities for the model including sensitivity and specificity of each screening strategy. Costs were based on Medicare reimbursement rates for hospital and physician services while medication costs were obtained from the Federal Supply Scale. Utilities from the literature were applied to each health outcome in the model including a disutility for the temporary health state following breast biopsy for a false positive test result. All costs and benefits were discounted at 5% per year. The analysis was performed from the payer perspective with results reported in 2006 U.S. dollars. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. RESULTS: Breast MRI provided 14.1 discounted quality-adjusted life-years (QALYs) at a discounted cost of $18,167 while mammography provided 14.0 QALYs at a cost of $4,760 over 25 years of screening. The incremental cost-effectiveness ratio of breast MRI compared to mammography was $179,599/QALY. In univariate analysis, breast MRI screening became < $50,000/QALY when the cost of the MRI was < $315. In the probabilistic sensitivity analysis, MRI screening produced a net health benefit of -0.202 QALYs (95% central range: -0.767 QALYs to +0.439 QALYs) compared to mammography at a willingness-to-pay threshold of $50,000/QALY. Breast MRI screening was superior in 0%, < $50,000/QALY in 22%, > $50,000/QALY in 34%, and inferior in 44% of trials. CONCLUSION: Although breast MRI may provide health benefits when compared to mammographic screening for some high risk women, it does not appear to be cost-effective even at willingness to pay thresholds above $120,000/QALY.

Intensive chemotherapy and consolidation with high dose therapy and autologous stem cell transplant in patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) remains incurable with conventional chemotherapy without consensus on the optimal initial treatment. We examined our single center experience with frontline therapy for patients with MCL in consecutive cases diagnosed 1995-2011. Among 81 patients, median age was 59 (28% were ≥65 years of age), 95% had stage III/IV disease and 54% had a low risk MCL International Prognostic Index score. Thirty-five percent (n=28) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and 65% received R-HCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate/cytarabine; n=53). Forty-one patients were consolidated with autologous stem cell transplant (ASCT). There were no significant differences in 2-year survival for R-CHOP versus R-HCVAD (p=0.10) or for ASCT versus observation (p=0.06). After controlling for clinical factors, R-HCVAD followed by ASCT was associated with superior progression-free survival (hazard ratio 0.26, 95% confidence interval 0.09-0.75).

Incidence and survival patterns of cutaneous T-cell lymphomas in the United States.

Using the United States Surveillance, Epidemiology and End Results (SEER) 17 dataset, we examined incidence and survival patterns for patients with cutaneous T-cell lymphomas (CTCLs) diagnosed following institution of the World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification. From 2005 to 2008, 2273 cases of CTCL were diagnosed. The age-adjusted incidence rate per 100,000 person-years for mycosis fungoides (MF) was 0.55 and for Sézary syndrome (SS) was 0.01. Incidence was higher among males (MF/SS male-to-female incidence rate ratio [IRR] 1.57) and black patients (MF black-to-white IRR 1.55). Black patients with CTCL were diagnosed at a younger age and black patients with MF/SS presented with advanced stage and had worse survival than white patients. In multiple-variable Cox-regression models, age > 60 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.97-7.70), black race (HR 2.09, 95% CI 1.29-3.37) and advanced stage (HR 6.06, 95% CI 3.66-10.05) predicted worse survival for patients with MF/SS. Additional research identifying reasons for these differences are necessary to better understand these diseases and for new strategies in the treatment of CTCL.

Vinorelbine, paclitaxel, etoposide, cisplatin, and cytarabine (VTEPA) is an effective second salvage therapy for relapsed/refractory Hodgkin lymphoma.

BACKGROUND: For Hodgkin lymphoma (HL) patients with refractory or relapsed (R/R) disease after primary therapy, the standard of care is a salvage regimen followed by autologous stem cell transplant (ASCT). However, patients who fail to respond to a salvage regimen have limited options. Our phase I study of cytarabine combined with fixed doses of vinorelbine, paclitaxel, etoposide, and cisplatin (VTEPA) for patients with R/R lymphoma showed an overall response rate (ORR) of 33%. PATIENTS AND METHODS: To further examine the effectiveness of VTEPA, we conducted a retrospective review of 30 cases of R/R HL who received a salvage combination of VTEPA. RESULTS: This population included 15 men (50%), 18 stage III/IV (60%), and 14 with an International Prognostic Score ≥3 (47%). The median number of previous regimens was 2 (range, 1-4), 19 patients (63%) received previous salvage therapy with ifosfamide, carboplatin, and etoposide. Twenty-seven patients were evaluable for response. The most common Grade 3/4 toxicities were pancytopenia (19 patients, 97%), nausea/vomiting (17, 57%), fatigue (14, 47%), and infection (6, 20%). Of the 27 patients evaluable for response, the ORR was 70% (7 complete response and 12 partial response). Twenty patients (66%) went on to ASCT and 1 patient underwent allogeneic transplant. With a median follow-up of 32 months, the median progression-free survival (PFS) and overall survival (OS) in patients who received transplantation after VTEPA were 28 and 38 months, respectively. CONCLUSION: Treatment with VTEPA for R/R HL is feasible with manageable side effects. With a high ORR, the PFS and OS for this group of patients suggest that VTEPA is a promising regimen for HL patients in whom previous lines of therapy have failed.

Examining racial differences in diffuse large B-cell lymphoma presentation and survival.

We performed a retrospective cohort analysis of 701 (533 white and 144 black) patients with diffuse large B-cell lymphoma (DLBCL) treated at two referral centers in southern United States between 1981 and 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 a positive family history of lymphoma (p = 0.048). There were no racial differences in the use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; 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.

A systematic literature review and meta-analysis of radioimmunotherapy consolidation for patients with untreated follicular lymphoma.

BACKGROUND: Follicular lymphoma (FL) is characterized by multiple relapses and progressively shorter response durations with subsequent therapies. Despite the development of numerous treatment strategies to reduce the risk of progression, optimal therapeutic strategies for patients with FL remain undefined. Radioimmunotherapy (RIT) with an anti-CD20 antibody linked to iodine-131 or to yttrium-90 has emerged as well-tolerated treatment after induction. We conducted a systematic literature review and meta-analyses to quantify the benefits of consolidative RIT. METHODS: We searched the CENTRAL and MEDLINE libraries, and conference abstracts for reports on phase II/III clinical trials that assessed RIT consolidation for patients with untreated FL. Extracted data included pretreatment disease status, patient characteristics, treatment regimen, response rates, progression-free survival (PFS), and overall survival (OS). Pooled estimates of complete response (CR), overall response (OR), 2- and 5-year PFS and OS rates were computed by using random effects models. RESULTS: Eight studies (n = 783) were included in the meta-analyses. CR rates after RIT ranged from 69.0% to 96.5%, 2-year PFS ranged from 64.8% to 86.1%, and 5-year PFS ranged from 47.0% to 67.3%. The pooled estimates of the CR rate and OR rate were 82.7% (95% CI, 67.4%-91.7%) and 96.2% (95% CI, 90.4%-98.6%), respectively. The pooled estimates for 5-year PFS and OS were 57.6% (95% CI, 47.8%-66.9%) and 90.1% (95% CI, 83.9%-94.1%), respectively. CONCLUSIONS: We believe that these aggregated data can further the discussion on RIT as a consolidation therapy and inform decisions on future study designs Additional studies are needed to compare the benefits of RIT consolidation to maintenance therapy with rituximab.

Exploring risk factors for follicular lymphoma.

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.

Stem cell transplantation as a biological therapy for peripheral T-cell lymphomas.

IMPORTANCE OF THE FIELD: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas in which conventional chemotherapy has been characterized by poor outcomes when compared with most aggressive B-cell lymphomas. Autologous, and to a lesser extent allogeneic, hematopoietic stem-cell transplant (HSCT) have been advocated as potential means to improve and consolidate remissions in PTCL. AREAS COVERED IN THIS REVIEW: Given the absence of large-scale randomized clinical controlled trials of transplantation for PTCL, we review existing data addressing the role and timing of HSCT in PTCL. WHAT THE READER WILL GAIN: A detailed overview of the available data of overall and progression-free survival associated with HSCT in PTCL with discussion of existing studies, data on determinants of HSCT outcome in PTCL, and future directions for research. TAKE HOME MESSAGE: The optimal roles and timing of HSCT in PTCL remain unclear. Accordingly, clinicians are encouraged to register their patients in PTCL registry studies and enroll them in clinical trials investigating the role of HSCT. Risk-adapted treatment strategies utilizing identified prognostic parameters may provide future means for identifying the optimal use of HSCT for patients with PTCL, but additional studies are needed before such approaches can be routinely applied.

Hepatitis C reactivation in patients who have diffuse large B-cell lymphoma treated with rituximab: a case report and review of literature.

BACKGROUND: Whether to interrupt or to continue induction therapy for lymphoma when hepatitis C virus (HCV) reactivation occurs during therapy with rituximab and chemotherapy remains a controversial question. There is limited evidence-based literature to help guide the management of patients with lymphoma in the setting of HCV reactivation. To address this issue we report an illustrative case and review the prevalence of non-Hodgkin lymphoma (NHL) in HCV-infected patients; the role of HCV in lymphomagenesis; the role of antiviral therapy in the management of HCV-associated lymphomas; as well as comparing the outcomes for NHL patients with and without HCV infection. CASE REPORT: A patient diagnosed with diffuse large B-cell lymphoma was treated with rituximab and chemotherapy with the patient achieving a complete remission, but treatment was complicated by asymptomatic HCV reactivation. Because conflicting data exist regarding management of such cases, the criteria for discontinuing chemotherapy, in the event of escalation in HCV replication in an asymptomatic patient, remain unclear. CONCLUSION: Patients with HCV have increased prevalence of marginal zone lymphoma, diffuse large B-cell lymphoma, and lymphoplasmacytic lymphoma. Whether HCV has a role in the lymphomagenesis is still uncertain, and limited to conjecture. The question whether to treat HCV-related lymphomas with antiviral therapy is debatable and not well-supported. Without initial liver dysfunction, HCV-infected patients can experience a similar outcome compared to their HCV-negative counterparts when treated with standard chemotherapy/immunotherapy despite differences in the presentation of the disease.

Racial differences in the presentation and outcomes of chronic lymphocytic leukemia and variants in the United States.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the United States, and prolymphocytic leukemia (PLL) is a related, rare chronic lymphoproliferative disorder. METHODS: Using the United States Surveillance, Epidemiology and End Results (SEER) data from 13 registries, we examined differences in incidence and survival for CLL, small lymphocytic lymphoma (SLL) and PLL by race. International Classification of Diseases for Oncology 3(rd) edition histology codes 9670, 9823, and 9632-34 were used to identify cases. RESULTS: From 1992 to 2007, 30,622 cases of CLL/SLL and 268 cases of PLL were recorded. Males had higher incidence than females (male-to-female incidence rate ratio CLL/SLL 1.89, 95% confidence interval (CI) 1.85-1.94 and PLL 2.47, 95%CI 1.90-3.20). Black patients were diagnosed at younger age compared to white patients (mean age at diagnosis for white versus black patients for CLL/SLL, 70 versus 67 years, P < .001; for PLL, 71 versus 61 years, P < .001). Greater proportion of black patients with SLL presented with B symptoms, extranodal primary site, and advanced disease compared to white patients (P = .003, P = .012, and P = .009 respectively). White patients with CLL/SLL had better survival rates than black patients (5-year relative survival rate 77.1% versus 63.9%, P < .01). In univariate Cox regression models, black race, male gender, age at diagnosis > 65 years, advanced stage, and B-symptoms were predictors of worse survival (P < .01) among CLL/SLL patients. CONCLUSIONS: Black patients with CLL/SLL and PLL present at younger age and black patients with CLL/SLL have worse survival than white patients. Epidemiological studies examining the biological variants of these diseases in concert with race are needed to elucidate the etiology of these disparities.

A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma.

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.

Prescription opioid usage and abuse relationships: an evaluation of state prescription drug monitoring program efficacy.

CONTEXT: The dramatic rise in the use of prescription opioids to treat non-cancer pain has been paralleled by increasing prescription opioid abuse. However, detailed analyses of these trends and programs to address them are lacking. OBJECTIVE: To study the association between state shipments of prescription opioids for medical use and prescription opioid abuse admissions and to assess the effects of state prescription drug monitoring programs (PDMPs) on prescription opioid abuse admissions. DESIGN AND SETTING: A RETROSPECTIVE ECOLOGICAL COHORT STUDY COMPARING STATE PRESCRIPTION OPIOID SHIPMENTS (SOURCE: Automation of Reports and Consolidated Orders Systems database) and inpatient admissions for prescription opioid abuse (source: Treatment Episode Data Set) in 14 states with PDMPs (intervention group) and 36 states without PDMPs (control group) for the period 1997-2003. RESULTS: From 1997 to 2003, oxycodone, morphine, and hydrocodone shipments increased by 479%, 100%, and 148% respectively. Increasing prescription oxycodone shipments were significantly associated with increasing prescription opioid admission rates (p < 0.001). PDMP states had significantly lower oxycodone shipments than the control group. PDMP states had less increase in prescription opioid admissions per year (p = 0.063). A patient admitted to an inpatient drug abuse rehabilitation program in a PDMP state was less likely to be admitted for prescription opioid drug abuse (Odds ratio = 0.775, 95% Confidence Interval 0.764-0.785). CONCLUSIONS: PDMPs appear to decrease the quantity of oxycodone shipments and the prescription opioid admission rate for states with these programs. Overall, opioid shipments rose significantly in PDMP states during the study period indicating a negligible "chilling effect" on physician prescribing.

Development of the Lymphoma Enterprise Architecture Database: a caBIG Silver level compliant system.

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.

A Markov model assessing the effectiveness and cost-effectiveness of FOLFOX compared with FOLFIRI for the initial treatment of metastatic colorectal cancer.

OBJECTIVE: To analyze the efficacy and cost-effectiveness of FOLFOX compared with FOLFIRI for patients with metastatic colorectal cancer. METHOD: We developed a Markov decision model using a hypothetical cohort of patients with metastatic colorectal cancer to compare beginning chemotherapy with FOLFOX or FOLFIRI. Probabilities of toxicities, including neutropenia, diarrhea, and neuropathy, were based on published literature for FOLFOX and FOLFIRI. Costs for physician and hospital services unadjusted for geographic location were estimated using Centers for Medicare and Medicaid services reimbursement data. Drug costs were estimated using Medicare B reimbursement and the Federal Supply Schedule. Health outcomes were measured in quality-adjusted life years (QALYs). Univariate and probabilistic sensitivity analyses were performed to address uncertainty in the model parameters. RESULTS: The FOLFOX strategy provided 1.003 QALYs at a cost of $29,865, whereas FOLFIRI provided 0.921 QALYs at a cost of $24,551. The incremental cost-effectiveness ratio for FOLFOX treatment was $65,170/QALY. In 10,000 probabilistic Monte Carlo simulations, FOLFOX was cost-effective in 48.59% of trials using a $50,000/QALY threshold. The most influential variables in univariate sensitivity analysis were the expected years of survival associated with each chemotherapy regimen. CONCLUSIONS: FOLFOX and FOLFIRI are similar in terms of costs and benefits. The slight QALY benefits associated with FOLFOX are within the range of $100,000/QALY, an accepted threshold in oncology.

Idiotype vaccine strategies for improving outcomes in follicular lymphoma.

BACKGROUND: Follicular lymphoma (FL) is a common indolent lymphoma associated with a relapsing course. Preclinical models and clinical studies demonstrate that immunizing FL patients against their own tumor idiotype induces humoral and cellular immunity and supresses tumor growth. METHODS: We review idiotype vaccine strategies that have been tested in FL patients in frontline and relapsed settings to examine the safety and efficacy of this approach. RESULTS: Several Phase II trials of recombinant or hybridoma-produced vaccines or vaccines combined with other immunotherapy demonstrate cellular and humoral anti-idiotype responses and clinical responses, indicating that idiotype vaccines provide promise for improving FL outcomes. CONCLUSION: These strategies are now being evaluated in Phase III trials but have yet to demonstrate clear advantages in progression-free survival.

Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States.

Peripheral T-cell lymphomas (PTCL) represent a small subgroup of non-Hodgkin lymphomas historically difficult to diagnose. We conducted a comprehensive assessment of 3287 PTCL cases diagnosed from 1992 to 2005 in 13 Surveillance, Epidemiology and End Results registries. Incidence trends, age-adjusted incidence rates and relative survival rates were compared across the study period, and by sex, race and age groups. From 1992 to 2005, PTCL incidence increased by 280%. Age-adjusted incidence rates were higher in males (Male/Female incidence rate ratio (IRR) 1.8) and in Blacks (Black/White IRR 1.2). Asian predominance was pronounced for extranodal NK/T-cell lymphoma, nasal type. Whites had higher 5-year survival than other racial groups for most histologic subtypes; however, the differences were not statistically significant. The variance in incidence rates and outcomes across PTCL subtypes support the pursuit of ongoing research to identify the etiology, pathophysiology, treatment patterns and differences in treatment response for PTCL subsets.