The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

Abstract

Given the excellent survival rates for early-stage Hodgkin lymphoma (HL), the young age of many patients, and concerns regarding acute and late treatment-related toxicities, there is a desire to have a predictive tool that enables therapy to be tailored toward the individual patient. Early (or interim) (18)F-fluorodeoxyglucose positron emission tomography with computerized tomography (FDG-PET/CT), as a test of tumor sensitivity to ongoing/planned therapy, has been shown to be prognostic for survival in HL. Based on results of interim FDG-PET/CT, therapy may be subsequently modified through minimization or via intensification for low- and high-risk patient populations, respectively (ie, response-adapted therapy). Important data have been generated to standardize the interpretability and reproducibility of interim FDG-PET/CT (eg, the Deauville 5-point system), and observational and noncontrolled prospective studies have produced evidence supporting the hypothesis that response-adapted therapy may potentially serve as a predictive tool. Furthermore, results from noninferiority phase 3 clinical trials randomizing early-stage HL patients with negative interim FDG-PET/CT to combined modality therapy versus chemotherapy alone have been reported. The current collective findings from these randomized early-stage HL studies have shown that acute relapse rates are lower with combined modality therapy, even in patients with negative interim FDG-PET/CT. Additional randomized response-adapted studies are ongoing and novel FDG-PET/CT applications involving quantitative techniques and innovative imaging modalities are being investigated to identify more robust imaging biomarkers. Treatment of early-stage HL remains a clinical management choice for physicians and patients to make with consideration of acute and long-term outcomes.

Figure 1

The Deauville 5PS. Shown are the criteria for interpretation of interim FDG-PET/CT. A Deauville score >3 is the most optimal cutoff for interim PET with advanced-stage HL to increase PPV if intensification of therapy is planned, whereas a cutoff <3 is desirable for nonbulky early-stage HL to enhance NPV. ES indicates early-stage; and AS, advanced stage.

Figure 2

Prognostication of FDG-PET/CT in early-stage HL. Shown is the PFS according to the result of interim FDG-PET/CT (status-post 2-3 ABVD cycles) of 57 early-stage (A) and 28 advanced-stage (B) HL patients. Treatment was continued regardless of FDG-PET/CT result. (Reprinted with permission from Hutchings et al.) (C) PFS for 88 patients with early-stage nonbulky HL treated on a US Cooperative group phase 2 study using AVG frontline therapy. Incl indicates including; MRU, minimal residual uptake. (Reprinted with permission from Straus et al.)

Figure 3

Clinical trial designs of recently completed and ongoing phase 3 randomized studies of response-adapted therapy for adult early-stage HL. (A) EORTC/LYSA/FIL H10F study. *None of the following present: large mediastinal mass, age ≥50 years, high ESR, or 4 or more areas. (B) EORTC/LYSA/FIL H10U study. *Any of the following present: large mediastinal mass, age ≥50 years, high ESR, and/or 4 or more areas. (C) UK-led RAPID study; all PET-3⁺ patients received a 4th cycle of ABVD followed by 30 Gy of IFRT. (D) GHSG HD16 favorable trial. *None of the following present: large mediastinal mass, extranodal disease, high ESR, or 3 or more areas. (E) GHSG HD17 unfavorable trial. *Any of the following present: large mediastinal mass, extranodal disease, high ESR, and/or 3 or more areas. High ESR for all of above defined as: >50 mm without B symptoms or ESR <30 mm with B symptoms. esc indicates escalated; ESR, erythrocyte sedimentation rate; LYSA, Lymphoma Group and the Lymphoma Study Association; FIL, Fondazione Italiana Linfomi; and pts, patients.

Figure 4

How I treat early-stage adult HL in 2014. Shown are the treatment strategies advocated by A.M.E. based on current clinical data. Based on available data, treatment should not be modified based on results of interim FDG-PET/CT; however, continued follow-up of ongoing studies, including results from studies examining intensification based on “positive” interim FDG-PET/CT, is needed. The treatment algorithms are separated by different early-stage subgroups: favorable, unfavorable (nonbulky), bulky, and older patients.