The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study

Alzahrani, Musa; El‐Galaly, Tarec Christoffer; Hutchings, Martin; Hansen, Jakob Werner; Loft, Annika; Johnsen, Hans Erik; Iyer, Victor Vishwanath; Wilson, Don; Sehn, Laurie H.; Savage, Kerry J.; Connors, Jacqueline; Gascoyne, Randy D.; Johansen, Preben; Clasen‐Linde, Erik; Brown, Peter N.; Villa, Diego

doi:10.1093/annonc/mdw137

Cited by 46 publications

(58 citation statements)

References 24 publications

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“…One consistent criticism regarding previous works addressing only diagnostic performance, including ours, was that independently of accuracy, PET/CT did not impact survival [3,5,19]. However, in our view, this criticism was based on conflicting data as a number of papers have shown that lack of prognostic value [6,7], whereas others did find it [8,9]. Interestingly, the largest series study in the setting of DLBCL so far sustains the abandon of the routine use of BMB based on the impact of PET/ CT on both OS and PFS, and the unlikelihood of BMB upstaging or driving clinically significant changes [9].…”

Section: Discussionmentioning

confidence: 54%

“…However, in our view, this criticism was based on conflicting data as a number of papers have shown that lack of prognostic value [6,7], whereas others did find it [8,9]. Interestingly, the largest series study in the setting of DLBCL so far sustains the abandon of the routine use of BMB based on the impact of PET/ CT on both OS and PFS, and the unlikelihood of BMB upstaging or driving clinically significant changes [9]. The inconsistency of data in the current literature can be explained by some methodological issues.…”

Section: Discussionmentioning

confidence: 88%

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Bone marrow biopsy superiority over PET/CT in predicting progression‐free survival in a homogeneously‐treated cohort of diffuse large B‐cell lymphoma

Chen-Liang¹,

Martín‐Santos

Jerez³

et al. 2017

Cancer Medicine

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Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B‐cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R‐CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow‐up of 25 months the estimated 3‐year progression‐free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB‐BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2‐microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first‐line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 88%

Bone marrow biopsy superiority over PET/CT in predicting progression‐free survival in a homogeneously‐treated cohort of diffuse large B‐cell lymphoma

Chen-Liang¹,

Martín‐Santos

Jerez³

et al. 2017

Cancer Medicine

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“…In diffuse large B-cell lymphoma, diffuse uptake is more likely to indicate reactive change than lymphomatous involvement in the bone marrow compartment. However, when diffuse uptake is due to bone marrow involvement, the uptake usually reflects diffuse low-volume, and sometimes discordant, cellular infiltration (35)(36)(37), which probably has less of an impact on prognosis (38,39) than areas of tumor bulk. In follicular lymphoma, diffuse cellular infiltration of the bone marrow is commonly missed by 18 F-FDG PET (40).…”

Section: What Should Be Included In the Assessment Of Mtv?mentioning

confidence: 99%

Time to Prepare for Risk Adaptation in Lymphoma by Standardizing Measurement of Metabolic Tumor Burden

2019

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See an invited perspective on this article on page 1094. Increased tumor burden is associated with inferior outcomes in many lymphoma subtypes. Surrogates of tumor burden that are easy to measure, such as the maximum tumor dimension of the bulkiest lesion on CT, have been used as prognostic indices for many years. Recently, total metabolic tumor volume (MTV) and tumor lesion glycolysis have emerged as promising and robust biomarkers of outcome in various lymphomas. The median MTV and the optimal cutoffs to separate patients into risk groups in a study population are, however, highly dependent on the population characteristics and the delineation method used to outline tumor on the PET image. This issue has precluded the use of MTV for risk stratification in trials and clinical practice. Standardization of the methodology is timely to allow the potential for risk adaptation to be explored in addition to response adaptation using PET. Meetings between representatives from research groups active in the field were held under the auspices of the PET International Lymphoma and Myeloma Workshop. A summary of those discussions, which included a review of the literature and a practical assessment of methods used for outlining, including various software options, is presented. Finally, a proposal is made to perform a technical validation of MTV measurement enabling benchmark reference ranges to be derived for published delineation approaches used for outlining with various software. This process would require collation of representative imaging data sets of the most common lymphoma subtypes; agreement on pragmatic criteria for the selection of lesions; generation of a range of MTVs, with consensus to be reached on final contours in a training set; and development of automated software solutions with a set of minimum functionalities to reduce measurement variability. Methods developed in the above training exercise could then be applied to another data set, with a final set of contours and values generated. This final data set would provide a benchmark against which end-users could test their ability to measure MTVs that are consistent with expected values. The data set and automated software solutions could be shared with manufacturers with the aim of including these in standard workflows to allow standardization of MTV measurement across the world.

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“…In T‐cell lymphomas, FDG‐PET/CT detects additional disease sites in 50% of the patients, but the clinical relevance of additional FDG‐PET/CT findings is uncertain as many patients have advanced stage already by conventional staging . FDG‐PET/CT is less sensitive for detection of bone marrow involvement in aggressive NHL (71–86% for DLBCL and <30% for peripheral T‐cell lymphoma [PTCL]) and diffuse bone marrow FDG‐uptake is seen more often in the setting of positive trephine biopsy suggesting that its interpretation depends on histology . Discordant bone marrow involvement by indolent lymphoma is also diagnosed in ~7% of patients with DLBCL and can be relevant for survivorship care .…”

Section: Pet/ct For Stagingmentioning

confidence: 99%

“…FDG‐PET/CT is less sensitive for detection of bone marrow involvement in aggressive NHL (71–86% for DLBCL and <30% for peripheral T‐cell lymphoma [PTCL]) and diffuse bone marrow FDG‐uptake is seen more often in the setting of positive trephine biopsy suggesting that its interpretation depends on histology . Discordant bone marrow involvement by indolent lymphoma is also diagnosed in ~7% of patients with DLBCL and can be relevant for survivorship care . Upstaging from limited to advanced stage indolent lymphoma has profound impact on treatment plan, as such patients can no longer be considered for radiotherapy with curative intent .…”

Section: Pet/ct For Stagingmentioning

confidence: 99%

FDG‐PET/CT in the management of lymphomas: current status and future directions

et al. 2018

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FDG-PET/CT is the current state-of-the-art imaging in lymphoma and plays a central role in treatment decisions. At diagnosis, accurate staging is crucial for appropriate therapy selection: FDG-PET/CT can identify areas of lymphoma missed by CT alone and avoid under-treatment of patients with advanced disease stage who would have been misclassified as having limited stage disease by CT. Particularly in Hodgkin lymphoma, positive interim FDG-PET/CT scans are adversely prognostic for clinical outcomes and can inform PET-adapted treatment strategies, but such data are less consistent in diffuse large B-cell lymphoma. The use of quantitative FDG-PET/CT metrics using metabolic tumour volume, possibly in combination with other biomarkers, may better define prognostic subgroups and thus facilitate better treatment selection. After chemotherapy, FDG-PET/CT response is predictive of outcome and may identify a subgroup who benefit from consolidative radiotherapy. Novel therapies, in particular immunotherapies, exhibit different response patterns than conventional chemotherapy, which has led to modified response criteria that take into account the risk of transient pseudo-progression. In relapsed lymphoma, FDG-PET/CT after second-line therapy and prior to high-dose therapy is also strongly associated with outcome and may be used to guide intensity of salvage therapy in relapsed Hodgkin lymphoma. Currently, FDG-PET/CT has no role in the routine follow-up after complete metabolic response to therapy, but it remains a powerful tool for excluding relapse if patients develop clinical features suggestive of disease relapse. In conclusion, FDG-PET/CT plays major roles in the various phases of management of lymphoma and constitutes a step towards the pursuit of personalized treatment.

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The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study

Abstract: In patients with DLBCL, staging PET/CT can miss BM involvement with concordant DLBCL (less common) or discordant iNHL (more common). Routine BMB does not add relevant diagnostic or prognostic value over PET/CT alone in the majority of patients with DLBCL.

Cited by 46 publications

References 24 publications

Bone marrow biopsy superiority over PET/CT in predicting progression‐free survival in a homogeneously‐treated cohort of diffuse large B‐cell lymphoma

Bone marrow biopsy superiority over PET/CT in predicting progression‐free survival in a homogeneously‐treated cohort of diffuse large B‐cell lymphoma

Time to Prepare for Risk Adaptation in Lymphoma by Standardizing Measurement of Metabolic Tumor Burden

FDG‐PET/CT in the management of lymphomas: current status and future directions

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