Patterns of Failure in Advanced Stage Diffuse Large B-Cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

Shi, Zhicai; Das, Satya; Okwan-Duodu, Derick; Esiashvili, Natia; Flowers, Christopher R.; Chen, Zhengjia; Wang, Xiaojing; Jiang, Kun; Nastoupil, Loretta J.; Khan, Mohammad K.

doi:10.1016/j.ijrobp.2013.02.007

Cited by 79 publications

(71 citation statements)

References 17 publications

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“…Several retrospective analyses have suggested a benefit for radiation therapy following R-CHOP, with improved local control and possible overall outcome. [90][91][92] In a recent comparison of patients sequentially treated on the RICOVER-60 trial, the addition of consolidative radiation to sites of initial bulk appeared to improve event-free survival (EFS), with a trend to improved OS. 93 Importantly, restaging 18-fluorodeoxyglucose positron emission tomography (PET) scanning was not routinely performed in these studies.…”

Section: Consolidative Radiation Therapy and Role Of Pet Scanningmentioning

confidence: 99%

Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity

Sehn

Gascoyne

2015

Blood

469

358

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Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), patients who fail R-CHOP have a dismal outcome. Thus, optimization of front-line therapy, as well as the development of more effective salvage strategies, remains an important objective. Advances in molecular genetics have vastly improved our understanding of the biological diversity of DLBCL and have led to the discovery of key oncogenic pathways. In addition to the major molecular designations of germinal center B-cell and activated B-cell subtypes, next-generation sequencing technologies have unveiled the remarkable complexity of DLBCL and identified unique molecular targets that may be differentially exploited for therapeutic benefit. These findings have translated into a growing list of promising novel agents. Moving forward, it is of paramount importance to recognize the heterogeneity of DLBCL and to investigate these targeted agents within patient populations who are most likely to benefit. It will be necessary to prioritize drugs that affect key driver pathways and to combine them rationally to optimize their benefit. Improved prognostication and the availability of predictive biomarkers will be crucial to allow for the possibility of individualized risk-adapted therapy.

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Section: Consolidative Radiation Therapy and Role Of Pet Scanningmentioning

confidence: 99%

Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity

Sehn

Gascoyne

2015

Blood

469

358

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“…27 However, it remains unclear whether early identification of relapse through routine imaging surveillance in asymptomatic patients improves long-term outcomes compared with symptom-driven investigation in NHL. Recently, the ASH Choosing Wisely campaign identified routine surveillance scans as an area for improvement in the clinical management of patients, suggesting that routine imaging surveillance for asymptomatic patients with aggressive NHL who achieve a CR should be limited and that scans more than 2 years after achieving a CR should be avoided entirely.…”

Section: Baseline Risks Of Relapse For Various Nhl Subtypesmentioning

confidence: 99%

Optimal disease surveillance strategies in non-Hodgkin lymphoma

Cohen

Flowers

2014

Hematology

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Given the paucity of randomized controlled trial data, defining the ideal strategy for surveillance imaging in patients with non-Hodgkin lymphoma (NHL) has become increasingly challenging. The routine use of frequent surveillance scans has been a common component of patient care. Emerging data from prospective and retrospective observational studies and modeling approaches have highlighted the performance characteristics of imaging modalities and the challenges with this form of secondary screening. The majority of patients with relapsed lymphoma have clinical signs or symptoms that prompt further evaluation, and only a small proportion of patients experience relapse detected on a routine scan while being otherwise asymptomatic. Surveillance imaging is costly, may expose patients to minimal risks of mortality due to radiation-related secondary malignancies, and can lead to false-positive findings, leading to unnecessary biopsies. In addition, no prospective study has demonstrated a significant improvement in overall survival for those patients whose disease is discovered on a routine scan versus those who present with clinical symptoms. In this chapter, we examine the baseline risks of relapse for various NHL subtypes that provide the context for surveillance, review the data on imaging modalities, and establish a framework for discussing optimal surveillance strategies with individual patients. Patients should be counseled on the risks and benefits of routine surveillance imaging and decisions regarding surveillance should be made on an individual basis using patient-specific risk factors, response to induction therapy, and patient preferences with a bias toward using surveillance imaging in the 2 years after treatment only in those NHL patients with the greatest likelihood of benefit. Learning Objectives• To review recent literature regarding the use of routine imaging surveillance for patients with NHL achieving a CR to induction therapy • To develop an approach for counseling patients regarding the risks and benefits of surveillance imaging Baseline risks of relapse for various NHL subtypesThe completion of induction therapy and achievement of a complete response (CR) is a significant milestone for patients with lymphoma, but the optimal follow-up for these patients remains a subject of intense debate, especially with regard to the appropriate use of routine surveillance imaging. Unfortunately, a significant portion of patients with non-Hodgkin lymphoma (NHL) who achieve a CR will relapse and require additional treatment. In diffuse large B-cell lymphoma (DLBCL), for example, the CR rate for current standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is 75%-86%, but up to 1/3 of these patients will ultimately relapse. 1,2 The International Prognostic Index (IPI) can assist with risk stratification for newly diagnosed patients. Patients with a high-risk IPI who achieve a CR have an estimated 5-year relapse-free survival of 40% compared with 70% for patients wit...

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“…After reviewing the remaining 8 studies, we excluded another which did not have a no-RT group, 2 which did not provide data on patients with RT and 1 which did not include patients treated with rituximab. Finally, 4 relevant studies, comprising a total of 633 patients, were included [16,17,18,19]. The flowchart of the reviews showed the detailed process of selection (fig.…”

Section: Resultsmentioning

confidence: 99%

“…Four studies comprising 633 patients with stage I-IV DLBCL were analyzed for OS [16,17,18,19]. The addition of RT showed an improvement in OS in all patients (RT vs. no-RT: HR = 0.33, 95% CI 0.14-0.77, p = 0.01; fig.…”

Section: Resultsmentioning

confidence: 99%

The Role of Consolidative Radiotherapy after a Complete Response to Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma in the Rituximab Era: Results from a Systematic Review with a Meta-Analysis

Hu¹,

Deng²,

Zou³

et al. 2015

Acta Haematol

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Background: The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). The role of radiotherapy (RT) after complete response (CR) to RCHOP in patients with DLBCL remains unclear. This systematic review with a meta-analysis is an attempt to evaluate this role. Methods: Studies that evaluated RT versus no-RT after CR to RCHOP for DLBCL patients were searched in databases. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were calculated using a random-effects model. Results: A total of 4 qualified retrospective studies (633 patients) were included in this review. The results suggested that RT improved overall survival (OS; HR 0.33, 95% CI 0.14-0.77) and progression-free/event-free survival (PFS/EFS; HR 0.24, 95% CI 0.11-0.50) in all patients compared with no-RT. In a subgroup analysis of patients with stage III-IV DLBCL, RT improved PFS/EFS (HR 0.19, 95% CI 0.07-0.51) and local control (HR 0.12, 95% CI 0.03-0.44), with a trend of improving OS (HR 0.35, 95% CI 0.12-1.05). Conclusion: Consolidation RT could significantly improve outcomes of DLBCL patients who achieved a CR to RCHOP. However, the significance of these results was limited by these retrospective data. Further investigation of the role of consolidation RT in the rituximab era is needed.

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Patterns of Failure in Advanced Stage Diffuse Large B-Cell Lymphoma Patients After Complete Response to R-CHOP Immunochemotherapy and the Emerging Role of Consolidative Radiation Therapy

Cited by 79 publications

References 17 publications

Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity

Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity

Optimal disease surveillance strategies in non-Hodgkin lymphoma

The Role of Consolidative Radiotherapy after a Complete Response to Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma in the Rituximab Era: Results from a Systematic Review with a Meta-Analysis

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