Jessica N. Williams

Evaluating cell-of-origin subtype methods for predicting diffuse large B-Cell lymphoma survival: A meta-analysis of gene expression profiling and immunohistochemistry algorithms

BACKGROUND Patients with DLBCL exhibit widely divergent outcomes despite harboring histologically identical tumors. Currently, GEP and IHC algorithms assign patients to 1 of 2 main subtypes: germinal center B cell-like (GCB), or activated B cell-like (ABC), the latter of which historically carries a less favorable prognosis. However, it remains controversial as to whether these prognostic groupings remain valid in the era of rituximab therapy. MATERIALS AND METHODS A systematic literature review identified 24 articles from which meta-analyses were conducted, comparing survival outcomes for patients assigned to either GCB or ABC/non-GCB subtype using GEP and/or Hans, Choi, or Muris IHC algorithms. RESULTS Patients designated as GCB DLBCL using GEP fared significantly better in terms of overall survival than those with ABC DLBCL (hazard ratio, 1.85; P < .0001). In contrast, the Hans and Choi algorithms failed to identify significant differences in overall survival (P = .07 and P = .76, respectively) between GCB and non-GCB groups. CONCLUSIONS Our study illustrates a lack of evidence supporting the use of the Hans and Choi algorithms for stratifying patients into distinct prognostic groups. Rather, GEP remains the preferred method for predicting the course of a patients disease and informing decisions regarding treatment options.

Disease characteristics, patterns of care, and survival in very elderly patients with diffuse large B-cell lymphoma

Although the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) is considered standard therapy for diffuse large B‐cell lymphoma (DLBCL), patterns of use and the impact of R‐CHOP on survival in patients aged >80 years are less clear.

New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.

Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining the risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology; therefore, until recently, little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining the risk factors for NHL subtypes. We outline the heterogeneity and commonality among the risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis.

To Each Its Own: Linking the Biology and Epidemiology of NHL Subtypes

Non-Hodgkin lymphoma (NHL) constitutes a diverse group of more than 40 subtypes, each characterized by distinct biologic and clinical features. Until recently, pinpointing genetic and epidemiologic risk factors for individual subtypes has been limited by the relative rarity of each. However, several large pooled case-control studies have provided sufficient statistical power for detecting etiologic differences and commonalities between subtypes and thus yield new insight into their unique epidemiologic backgrounds. Here, we review the subtype-specific medical, lifestyle, and biologic components identified in these studies, which suggest that a complex interplay between host genetics, autoimmune disorders, modifiable risk factors, and occupation contributes to lymphomagenesis.

Patterns of use and survival outcomes of positron emission tomography for initial staging in elderly follicular lymphoma patients

Abstract The role of positron emission tomography (PET) in the initial assessment of follicular lymphoma (FL) has been a topic of debate. We examined the patterns of utilization of PET staging in FL and assessed the association of PET with survival. Using the SEER-Medicare database, we identified 5712 patients diagnosed with first primary FL between 2000 and 2009. Older age, African–American race, poor performance status, B-symptoms and history of anemia were negatively associated with PET staging. Receipt of PET staging was positively associated with treatment at institutions affiliated with research networks and with residence in areas with higher concentrations of nuclear medicine specialists. PET was associated with improved lymphoma-related (HR 0.69, 95% CI: 0.58–0.82) and overall (HR 0.75, 95% CI: 0.68–0.83) survival. Our findings substantiate the use of PET as the standard of care for imaging in FL patients. Further investigation is warranted to identify mechanisms underlying the apparent survival advantage associated with PET staging in FL.

Age-related differences in quality of life among patients with diffuse large B-cell lymphoma.

Department of Research Netherlands Comprehensive Cancer Organisation (IKNL) Eindhoven, The Netherlands Center of Research on Psychology in Somatic Diseases (CoRPS) Tilburg University Tilburg, The Netherlands Marten R. Nijziel, MD, PhD Department of Internal Medicine/Hemato-Oncology Maxima Medical Center Eindhoven/Veldhoven, The Netherlands Lonneke V. van de Poll-Franse, PhD Department of Research Netherlands Comprehensive Cancer Organisation (IKNL) Eindhoven, The Netherlands Center of Research on Psychology in Somatic Diseases (CoRPS) Tilburg University Tilburg, The Netherlands

Reply to Treatment decisions and outcome in very elderly patients with diffuse large B-cell lymphoma.

We appreciate the insightful letter by Fabbri et al regarding our article. Because patients aged>80 years have the highest incidence of diffuse large B-cell lymphoma (DLBCL) yet are rarely included in studies, we sought to characterize treatment and survival patterns in this population. We found that in patients with DLBCL who were aged >80 years (1156 patients), treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was associated with the longest survival, even after controlling for potential confounders such as performance status and comorbidity. Although the data from our study suggested that age alone should not be a contraindication to effective treatment, we agree with Fabbri et al that anthracycline toxicity is a major concern in very elderly patients given their decreased functional and physiologic reserve. Indeed, a recent study found that approximately one-third of elderly patients with DLBCL who received anthracycline-based therapy experienced toxicity requiring treatment modification. As alternatives, Fabbri et al have thoughtfully suggested reduced doses of R-CHOP, non-anthracycline-based regimens, and nonpegylated liposomal doxorubicin in this population. In addition to the aforementioned treatment modifications, radiotherapy also may be beneficial for elderly patients with DLBCL. A recent study revealed that elderly patients with limited-stage DLBCL who were treated with abbreviated R-CHOP and radiotherapy (359 patients) had a decreased risk of second-line therapy and febrile neutropenia compared with patients treated with fullcourse R-CHOP alone (515 patients); overall survival was similar between the 2 groups. These results suggest that abbreviated R-CHOP with radiotherapy may be better tolerated in elderly patients with limited-stage DLBCL, and future studies should further investigate this treatment regimen. In conclusion, we agree with the points raised by Fabbri et al and advocate for further studies examining alternative DLBCL treatment regimens for elderly patients who cannot tolerate standard therapy with R-CHOP.