Adam J. Olszewski

Survival of Patients With Marginal Zone Lymphoma Analysis of the Surveillance, Epidemiology, and End Results Database

Prognostic factors and outcomes in patients with marginal zone lymphoma (MZL) have been studied in small cohort studies, which may not reflect the population at large.

Treatment Selection and Outcomes in Early-Stage Classical Hodgkin Lymphoma: Analysis of the National Cancer Data Base

PURPOSE The choice between combined-modality therapy (CMT) and chemotherapy alone for early-stage Hodgkin lymphoma (HL) remains controversial. Our objective was to define factors affecting treatment selection and resulting survival outcomes in the United States. PATIENTS AND METHODS We identified 20,600 patients treated with CMT or chemotherapy between 2003 and 2011 from the National Cancer Data Base. Factors affecting treatment selection were studied in a mixed-effects logistic model. Survival outcomes were compared using a propensity score analysis to account for indication bias. RESULTS Only 49.5% of patients received CMT, and this proportion steadily declined between 2003 (59.4%) and 2011 (45.2%), particularly in younger patients. Apart from classical prognostic factors (age, stage, tumor location, histology, comorbidities), treatment selection was significantly influenced by sex, black race, distance to facility, and type of insurance. Uninsured patients had the lowest odds of receiving CMT. A significant random effect related to facility-specific treatment preference was also evident. Estimated 5-year overall survival (OS) was 89.6%, and relative survival (RS) was 94.3%. After adjustment for guarantee-time and indication biases, CMT was associated with better OS (hazard ratio [HR], 0.61; 95% CI, 0.53 to 0.70) and RS (excess HR, 0.42; 95% CI, 0.33 to 0.54) than chemotherapy alone. This effect was without significant heterogeneity in subset analysis and was not sensitive to unobserved confounding. CONCLUSION Socioeconomic factors affect selection of curative treatments in HL. Widespread abandonment of CMT beyond circumstances sanctioned by guidelines may affect survival. Further research should focus on developing strategies that minimize toxicity and access disparities without compromising survival.

Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the Surveillance, Epidemiology and End Results database

Waldenström macroglobulinaemia (WM) is a rare and incurable lymphoma. Given that the survival of WM patients can be prolonged, our objective was to describe trends in overall survival (OS) and analyse competing risks of death in patients with WM. The analysis included 5784 patients diagnosed with WM between 1991 and 2010 from the Surveillance, Epidemiology and End Results (SEER) database. Multivariate hazard models for OS and cumulative incidence of death were fitted according to epoch of diagnosis (1991–2000 vs. 2001–10) while adjusting for age, sex, race, histology, site of involvement and registry. Median OS for the 1991–2000 and the 2001–10 cohorts was 6 and 8 years, respectively (P < 0·001). In the multivariate analysis, better OS [hazard ratio (HR) 0·73, 95% confidence interval (CI) 0·67–0·79; P < 0·001] was seen in the 2001–10 cohort. Survival benefits were identified, for the 2001–10 cohort, in almost every stratum analysed, with the exception of patients aged <50 years and blacks. In the multivariate competing‐risk analysis, the 2001–10 cohort experienced lower rates of WM‐related (HR 0·57, 95% CI 0·49–0·66; P < 0·001) and non‐WM‐related deaths (HR 0·72, 95% CI 0·66–0·79; P < 0·001). In conclusion, there have been significant improvements in OS, WM‐related and non‐WM‐related mortality in patients with WM diagnosed in the last decade.

Epidemiology and survival outcomes of ocular and mucosal melanomas: A population‐based analysis

Extracutaneous melanomas are poorly characterized tumors that include ocular (OM), mucosal (MM) and leptomeningeal melanomas, often lacking standardized staging and treatment guidelines. We analyzed cases of cutaneous melanoma (CM, N = 219,890), OM (N = 7,069) and MM (N = 2,755) of different anatomical origins, diagnosed between 1988 and 2010, recorded in the Surveillance Epidemiology and End Results (SEER) database. Relative survival was studied in patients grouped by summary stage classification (localized, regional or distant disease) and in multivariate models adjusting for varying distribution of baseline factors. Unlike in CM, the incidence rate in MM increased exponentially with age. Five‐year relative survival was significantly worse for OM (78%) and for most mucosal sites (aggregate 34%, range 3–69%) compared with CM (89%). The differences between primary sites were particularly pronounced in localized disease, with a hazard ratio of 5.7 for OM, 4.3–9.0 for external genital or oral cavity MM and 19.8–90.4 for other mucosal locations. Melanomas of the pharynx, gastrointestinal, urinary tract and vagina had poor outcomes regardless of clinical stage. In contrast to CM, there was no evidence of improved survival in OM and MM during the study period. A substantial proportion of patients with operable OM or MM underwent radical organ resections (13–88% depending on site and stage) or perioperative radiotherapy (0–66%). In conclusion, extracutaneous melanomas have a markedly worse survival than CM and aggressive locoregional management appears to be insufficient for their control. Because of poor outcomes in MM, studies of systemic therapy are warranted regardless of the extent of disease at presentation.

Survival trends in Waldenström macroglobulinemia: an analysis of the Surveillance, Epidemiology and End Results database

To the editor: Waldenstrom’s macroglobulinemia (WM) is a rare indolent B-cell lymphoma. Approximately 1000-1500 new cases of WM are diagnosed every year in the United States.[1][1] Although previous studies suggested prolonged survival in WM patients, it is unclear whether there have been

Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: An analysis of the Surveillance, Epidemiology and End Results database

Approximately a third of the patients with diffuse large B‐cell lymphoma present with extranodal involvement. Our study aims to identify primary extranodal sites of disease associated with prognosis in patients with diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. A secondary objective is to describe epidemiological and clinical characteristics of patients with extranodal DLBCL. We included adult patients from the Surveillance, Epidemiology and End Results (SEER) database (2004–2009) in whom DLBCL was the first malignancy diagnosed. Extranodal primary sites were divided into 12 groups according to the topography code reported by SEER. Multivariate overall survival (OS) analyses were performed using Cox proportional‐hazard regression models adjusted for age, sex, race, and stage. From a total of 25,992 adult DLBCL patients included in our analysis, 32% presented with extranodal primary sites. Gastrointestinal tract (34%), head/neck (H&N; 14%), and skin/soft tissue (11%) were the most common. In comparison with nodal DLBCL, patients with extranodal involvement were older (with exception of skeletal sites) and presented with earlier stages. In the multivariate analysis, sites associated with worse OS rates were gastrointestinal (Hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.15–1.33; P <0.001), pulmonary (HR 1.59, 95% CI 1.38–1.83; P <0.001), and liver/pancreas (HR 1.58, 95% CI 1.35–1.85; P <0.001), whereas H&N was associated with better survival (HR 0.79, 95% CI 0.70–0.89; P <0.001). In this population‐based study, primary extranodal sites of involvement are associated with distinct outcomes in patients with DLBCL. Gastrointestinal, pulmonary, and liver/pancreas sites had a significant worse outcome than nodal sites. Am. J. Hematol. 89:310–314, 2014.

Empowering Targeted Therapy: Lessons from Rituximab

Rituximab, a monoclonal antibody directed against the B cell–specific protein CD20, has revolutionized lymphoma treatment by providing a highly effective form of therapy with relatively mild toxic side effects. Effective as a single agent against some forms of B cell lymphoma, rituximab also has a chemosensitizing effect, enhancing the efficacy of chemotherapy against other forms of the disease. Although the mechanisms whereby rituximab achieves its effects remain incompletely understood, these seem to involve at least three distinct phenomena: (i) antibody-dependent cell-mediated cytotoxicity, (ii) complement-mediated cell lysis, and (iii) stimulation of apoptosis in target cells. The latter occurs through interaction of complexes of rituximab and CD20 in lipid rafts, with elements of a signaling pathway involving Src kinases. Effector molecules trigger various gene expression events, leading to sensitization of malignant cells to proapoptotic stimuli. Lessons learned from the research on rituximab may be applied to the rational development of antibody-based therapies against other forms of cancer.

Population‐based prognostic factors for survival in patients with Burkitt lymphoma: An analysis from the Surveillance, Epidemiology, and End Results database

Burkitt lymphoma (BL) is an aggressive but potentially curable lymphoma, previously described in small, single‐institution studies. This study evaluated prognostic factors for survival in adult patients with BL and a potential outcome improvement over the past decade in a population‐based cohort.

Survival of patients with neuroendocrine carcinoma of the colon and rectum: a population-based analysis.

BACKGROUND: High-grade neuroendocrine carcinoma is a rare colorectal pathology described in a case series. The role of surgery in this disease has been questioned. OBJECTIVE: The purpose of this work was to describe the incidence, management, and outcomes of neuroendocrine carcinoma in comparison with high-grade adenocarcinoma. DESIGN: This was a retrospective, population-based outcomes research study. SETTINGS: The Survey of Epidemiology and End Results database was used. PATIENTS: A total of 1367 patients with colorectal neuroendocrine carcinoma (distinguishing small-cell and non–small-cell subtypes) and 72,533 with high-grade adenocarcinoma diagnosed between 2000 and 2011 were included in this study. INTERVENTIONS: Resection of the primary tumor was the main intervention. MAIN OUTCOME MEASURES: Median overall and 5-year relative survival were measured. Trends were expressed as the annual percent change in incidence and relative survival. RESULTS: The incidence rate increased for neuroendocrine carcinoma (annual percent change, +2.2%; p =0.035) and decreased for high-grade adenocarcinoma (annual percent change, –3.1%; p < 0.00001) during the study period. Relative survival at 5 years in neuroendocrine carcinoma was 16.3% overall and 57.4%, 56.4%, 26.3%, and 3.0% for stages I, II, III, and IV cancer. Small-cell tumors had worse survival (10% versus 19% for non-small cell). There was no improvement in the relative survival for neuroendocrine carcinoma (annual percent change, –1.1%; p =0.06) in contrast to adenocarcinoma (annual percent change, +0.7%; p < 0.00001). Patients with localized non–small-cell neuroendocrine carcinoma had better overall survival with surgery (median, 21 months) than without (6 months; log-rank, p < 0.0001), whereas those with small-cell neuroendocrine carcinoma did not (18 versus 14 months; p = 0.95). Prognosis in resected neuroendocrine carcinoma was worse with an increasing number of metastatic lymph nodes. LIMITATIONS: Histology and grade assignments were not centrally verified. Data on chemotherapy use, patient performance status, and comorbidities were unavailable. CONCLUSIONS: Neuroendocrine carcinoma did not benefit from advances in the prevention and treatment of colorectal adenocarcinoma over the past decade. Relatively poor survival in early stage neuroendocrine carcinoma warrants studies of adjuvant systemic therapy. The differences in outcomes between small-cell and non–small-cell neuroendocrine carcinomas indicate a need for histology-specific management.

Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.