FDG-PET as a biomarker for early response in diffuse large B-cell lymphoma as well as in Hodgkin lymphoma? Ready for implementation in clinical practice?

Abstract

A short historyMajor changes have taken place in the staging and response assessment of malignant lymphoma in the last two decades. With the introduction of fluorodeoxyglucose-positron emission tomography (FDG-PET) and positron emission tomography-computed tomography (PET-CT), the criteria for staging and monitoring response have changed dramatically. In the revised Cheson criteria published in 2007, 1 staging with FDG-PET was still optional, and end-of treatment assessment using FDG-PET and CT was obligatory for Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). In the Lugano criteria published in 2014, 2 PET-CT is recommended for staging as well as response assessment following therapy, as it is the most accurate imaging modality. However, one of the characteristics of (molecular) metabolic imaging is to be able to assess metabolic changes early in treatment. The question arises whether 'interim' FDG-PET-CT (iPET) can be used as a biomarker to differentiate good and poor responders during treatment, in order to modify therapy and to improve outcome. Recent clinical trials have addressed these questions, and we discuss the results and the implications for clinical practice. Assessment of interim-PET scansInternational guidelines recommend the use of a 5-point scale [also called the Deauville score (DS)] for grading FDG-uptake in lymphoma, compared to physiological uptake in the mediastinum and liver, for response assessment in daily practice and clinical trials. [2][3][4] No FDG uptake is graded as DS 1; uptake less than or equal in intensity to the mediastinum as DS 2; lesions with FDG uptake between mediastinum and liver are assessed as DS 3; uptake more intense than liver is scored as DS 4; and markedly increased uptake or new lymphoma-related lesions as DS 5 (Figure 1). This categorization has a high interobserver agreement in HL and DLBCL. 5,6 However, FDG-PET is also a quantitative imaging technique, allowing semi-quantitative imaging interpretation, using standardized uptake values (SUV). Reporting change of FDG uptake (usually expressed as a relative change) can also be used for interim response assessment. The reliability of the results depends on having comparable procedures for patient preparation and injection, and scanning and image reconstruction protocols, as well as comparable data analysis. Quality control and quality assurance procedures are also required to maintain the accuracy and precision of quantification.Recently, the European Association of Nuclear Medicine (EANM) guidelines for FDG-PET in tumor imaging for trials and clinical practice have been up-dated, 7 and an accreditation system is available (EARL; http://earl.eanm.org). Within clinical studies, these changes in SUV are being compared with visual assessment. Besides SUV, metabolically active tumor volume defined with FDG-PET is being investigated. Interim-PET in Hodgkin lymphomaHodgkin lymphoma is a lymphoma entity with cure rates of up to 90%. iPET predicts response early during treatment and PET-guided therapy is ...

2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management

“…The study reported that iPET scan assessed by deltaSUV but not Deauville score accurately predicted better 2‐year PFS (79.4% vs. 36.7%, p < .0001) and 2‐year OS (88.2%vs 59% p < .0001) in those patients with negative scans across all lymphoma types. However, escalation of treatment based on positive iPET did not translate into improved outcomes, similarly to several earlier trials, demonstrating the limitations of interim PET CT in guiding therapy in DLBCL 18 …”

FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas

“…A response-adapted design has failed to improve patient outcomes in several recent prospective trials in patients with aggressive NHL [ 94 ] with the exception of one study presented by the Australian Leukemia and Lymphoma Group [ 95 ]. This study enrolled 162 patients with poor prognosis DLBCL.…”

Interobserver Agreement of Interim and End-of-Treatment 18F-FDG PET/CT in Diffuse Large B-Cell Lymphoma: Impact on Clinical Practice and Trials

“…Application of 18 F-FDG PET during therapy (interim-PET, or I-PET) allows PET-guided patient management, with success in Hodgkin lymphoma (5)(6)(7)(8). In DLBCL, the value of I-PET is less clear (9): most I-PET-adapted trials in DLBCL did not demonstrate a strategy that overcomes treatment resistance (10), except for a phase II study with intensification after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at a 14-d cycle (R-CHOP14) in I-PET-positive patients to R-ICE and Z-BEAM autologous stem cell transplantation (11). Therefore, I-PET is currently not used in clinical practice.…”