The aim of this initiative was to provide consensus recommendations from a consortium of academic and industry experts in the field of lymphoma and imaging for the consistent application of imaging assessment with the Lugano classification. Methods: Consensus was obtained through a series of meetings from July 2019 to October 2021 sponsored by the PINTaD (Pharma Imaging Network for Therapeutics and Diagnostics) as part of the ProLoG (PINTaD RespOnse criteria in Lymphoma wOrking Group) consensus initiative. Results: Consensus recommendations encompass all technical imaging aspects of the Lugano classification. Some technical considerations for PET/CT and diagnostic CT are clarified with regards to required imaging series and scan visits, as well as acquisition and reconstruction of PET images and influence of lesion size and background activity. Recommendations are given on the role of imaging and clinical reviewers as well as on training and monitoring. Finally, an example template of an imaging case report form is provided to support efficient collection of data with Lugano Classification. Conclusion: Consensus recommendations are made to comprehensively address technical and imaging areas of inconsistency and ambiguity in the classification encountered by end users. Such guidance should be used to support standardized acquisition and evaluation with the Lugano 2014.

Our objective was to provide consensus recommendations from a consortium of academic and industry experts in the field of lymphoma and imaging for consistent application of the Lugano classification. Methods: Consensus was obtained through a series of meetings from July 2019 until September 2021 sponsored by the Pharma Imaging Network for Therapeutics and Diagnostics (PINTaD) as part of the PINTaD Response Criteria in Lymphoma Working Group (PRoLoG) consensus initiative. Results: Consensus recommendations clarified technical considerations for PET/CT and diagnostic CT from the Lugano classification, including updating the FDG avidity of different lymphoma entities, clarifying the response nomenclature, and refining lesion classification and scoring, especially with regard to scores 4 and 5 and the X category of the 5-point scale. Combination of metabolic and anatomic responses is clarified, as well as response assessment in cases of discordant or missing evaluations. Use of clinical data in the classification, especially the requirement for bone marrow assessment, is further updated on the basis of lymphoma entities. Clarification is provided with regard to spleen and liver measurements and evaluation, as well as nodal response. Conclusion: Consensus recommendations are made to comprehensively address areas of inconsistency and ambiguity in the classification encountered during response evaluation by end users, and such guidance should be used as a companion to the 2014 Lugano classification.

The accurate assessment of initial disease status and therapeutic responses is critical to the optimal management of patients with lymphoma. Currently, staging and treatment response evaluation for lymphoma has been standardized into the Lugano classification. Lugano classification incorporates positron emission tomography (PET) into the existing response criteria, and response assessment using FDG-PET/CT has been proven to predict the prognosis in various lymphoma subtypes effectively. We will briefly review the current staging and response evaluation system and explore the role of functional imaging in the field of lymphoma.

18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is now an integral part of lymphoma staging and management. Because of its greater accuracy compared with CT alone, PET/CT is currently routinely performed for staging and for response assessment at the end of treatment in the vast majority of FDG-avid lymphomas and is the cornerstone of response classification for these lymphomas according to the Lugano classification. Interim PET/CT, typically performed after 2 to 4 of 6 to 8 chemotherapy/chemoimmunotherapy cycles with or without radiation, is commonly performed for prognostication and potential treatment escalation or de-escalation early in the course of therapy, a concept known as response-adapted or risk-adapted treatment. Quantitative PET is an area of growing interest. Metrics, such as the standardized uptake value, changes (Δ) in the standardized uptake value, metabolic tumor volume, and total lesion glycolysis, are being investigated as more reproducible and potentially more accurate predictors of response and prognosis. Despite the progress made in standardizing the use of PET/CT in lymphoma, challenges remain, particularly with respect to its limited positive predictive value, emphasizing the need for more specific molecular probes. This review highlights the most relevant applications of PET/CT in Hodgkin and B-cell non-Hodgkin lymphoma, its strengths and limitations, as well as recent efforts at implementing PET/CT-based metrics as promising tools for precision medicine.

The Lugano classification was published in 2014 to form the basis for revising the recommendations regarding anatomic staging and evaluation of disease before and after therapy. This staging system was adopted by the eighth edition of the Cancer Staging Manual of the American Joint Committee on Cancer. In this review, we aimed to discuss this updated staging system for malignant lymphomas. The most important change was that fluorodeoxyglucose positron emission tomography/computed tomography became the new standard imaging technique for staging of all fluorodeoxyglucose-avid histologies. Due to the introduction of fluorodeoxyglucose positron emission tomography/computed tomography for staging, the evaluation of not only lymph node involvement but also organ involvement, including liver or spleen, has become simplified. Furthermore, it is possible to eliminate bone marrow biopsies in patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Although patients were grouped according to the absence (A) or presence (B) of disease-related symptoms based on the previous classification, only the patients with Hodgkin lymphoma need to be assigned the designations A or B in this revision. Hopefully, these revised recommendations will improve patient management and the conduct of clinical trials.

OBJECTIVE: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PETInterim) and end-of-induction therapy PET/CT (PETEOI) in patients with FL.
METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PETInterim was performed 3 or 4 cycles after chemotherapy and PETEOI after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (-), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test.
RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CT studies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5-72.7 months). On PETInterim, 23 patients were negative and 10 were positive. On PETEOI scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PETEOI(-) was associated with longer PFS. PETInterim(+) and PETEOI(+) patients had a significantly shorter PFS than PETInterim(-) patients (39.9 months, 95% confidence interval [CI] 23.0-56.9, versus 55.5 months, 95% CI 49.7-61.2, p = 0.005) and PETEOI(-) patients (14.2 months, 95% CI 8.5-19.8, versus 60.5 months, 95% CI 52.1-69.0, p < 0.001).
CONCLUSIONS: For patients with FL, PETInterim and PETEOI response is predictive of PFS, and PETEOI(+) is an independent prognostic factor for progression of FL.

OBJECTIVE: To assess 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images in primary thyroid lymphoma (PTL) patients before and after treatment.
METHODS: We conducted a retrospective review of data for ten patients (four men, six women) of mean age 65 (range 48-88) years, with histopathologically confirmed malignant thyroid lymphoma who underwent pre-treatment and post-treatment 18F-FDG PET between January 2005 and December 2014. Thyroid uptake was assessed by the 5-point scale score based on maximum intensity projection images.
RESULTS: Four of the ten patients were judged to have a complete metabolic response (scores 1-3) and four to have a partial metabolic response (PMR; scores 4-5). Three of the four PMR patients had a good outcome with a treatment-free interval and overall survival of at least 53.0 months, although two of these three patients showed residual FDG uptake in the thyroid for more than 2 years after completion of treatment. Two of the ten patients were considered to have progressive metabolic disease.
CONCLUSIONS: In patients with PTL, residual FDG uptake in the thyroid after treatment that corresponds to a PMR may not always indicate a poor outcome.

The International Extranodal Lymphoma Study Group (IELSG)-37 is a prospective randomized trial assessing the role of consolidation mediastinal radiotherapy after immunochemotherapy to patients with newly diagnosed primary mediastinal large B-cell lymphoma (PMBCL). It is a positron emission tomography (PET) response-guided study where patients obtaining a complete metabolic response on an end-of-therapy PET-computed tomography (CT) scan evaluated by a central review are randomized to receive radiotherapy or no further treatment. The aims of this study were to measure agreement between reviewers reporting PET-CT scans for this trial and to determine the effect of training upon concordance rates. The review panel comprised 6 experienced nuclear physicians who read PET-CT scans using the 5-point Deauville scale. Interobserver agreement (IOA) was measured at 4 time points: after a blinded review of a \"training set\" of 20 patients with PMBCL from the previous IELSG-26 study (phase 1); after the first 10 clinical cases enrolled in the IELSG-37 (phase 2); and after 2 further groups of 50 (phase 3) and 40 clinical cases (phase 4). After feedback from the training set and the first 10 cases, a meeting was held to discuss interpretation, and a detailed set of instructions for the review procedure was agreed and acted upon. Between 2012 and 2014, the first 100 patients were reviewed. Using Deauville score 3 as the cutoff for a complete metabolic response, the overall IOA among the reviewers was good (Krippendorff α = 0.72.) The binary concordance between pairs of reviewers (Cohen κ) ranged from 0.60 to 0.78. The IOA, initially moderate, improved progressively from phase 1 to 4 (Krippendorff α from 0.53 to 0.81; Cohen κ from 0.35-0.72 to 0.77-0.87). Our experience indicates that the agreement among \"expert\" nuclear physicians reporting PMBCL, even using standardized criteria, was only moderate when the study began. However, agreement improved using a harmonization process, which included a training exercise with discussion of points leading to disagreement and compiling practical rules to sit alongside commonly adopted interpretation criteria.