Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt?

Abstract

Despite improvements in survival rates, relapses after first-line therapy can occur in 20-50% of patients with advanced-stage Hodgkin's lymphoma (HL) or diffuse large-B-cell lymphoma (DLBCL).1,2 In both diseases, treatment failures are usually observed within 3 years of completion of treatment with the majority of relapses occurring in the first 12 months for HL 3,4 and 18 months for DLBCL. 4 However, no consensus exists on an optimal surveillance strategy to determine a preclinical relapse after first remission, although routine [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging has become a standard practice in many centers. The benefits of monitoring for recurrence depend on the probability of relapse in the population being tested as well as the sensitivity, specificity and the frequency of the test. 5 The prevalence of relapse in both HL and DLBCL is rare, with reportedly only one relapse per 68 visits in HL 6 and per 40-45 visits for patients with aggressive non-Hodgkin's lymphoma (NHL) 5 based on routine CT scans. While PET/CT has not been closely investigated in a surveillance setting, it has become clear that its accuracy is superior to that of CT imaging. According to results from a meta-analysis, FDG-PET predicts disease relapse with a sensitivity and specificity of 50-100% and 67-100%, respectively, for HL and 33-77% and 82-100%, respectively, for NHL, irrespective of the association of a residual mass on CT.7 Even with its relatively high sensitivity, the risks and benefits of routine surveillance PET/CT imaging remain controversial, mainly, because of its cost, radiation burden and the high rate of false-positive results (30-80%) 3,[8][9][10][11][12] with potential consequences of overtreatment. In this issue of the Journal, El-Galaly et al. report the value of surveillance PET/CT in a retrospective cohort of 161 HL patients who achieved a complete or partial remission after first-line treatment.12 During a median follow-up of 34 months 14% of patients experienced a relapse. With an average of 1.9 PET/CT per patient, the positive predictive value (PPV) of routine PET/CT and clinically indicated PET/CT was 22% and 37%, respectively (P=0.02). However, in a subset of high-risk patients (with extranodal disease, a positive PET result at interim or therapy completion) the PPV increased to 36% while in those without risk factors the PPV was only 5%. Consequently, the authors concluded that the routine use of surveillance PET in HL patients entering complete remission after first-line treatment should be reserved for high-risk patients. These results were in line with those of Petrausch et al. who suggested that monitoring may be worthwhile in high-risk DLBCL populations. 11The weaknesses of the existing surveillance PET studies include retrospective design, the paucity of prospective data in distinct risk categories, non-standardized interpretation of PET/CT, and the lack of randomized multicenter setting, while the strength is that all data were obtained afte...

Baseline and ongoing PET-derived factors predict detrimental effect or potential utility of 18F-FDG PET/CT (FDG-PET/CT) performed for surveillance in asymptomatic lymphoma patients in first remission

“…In particular, in both HL and DLBCL, FDG-PET/CT evaluation after two chemotherapy cycles has been proposed as a surrogate test for chemosensitivity, proving to be a powerful independent prognostic indicator for treatment outcome [5,15,21]. Accordingly, PET2 proved to be the only variable of our series able to predict the presence of relapse on PETsv, thus increasing its PPV throughout the follow-up, even 36 month after first remission.…”

“…In fact, several lines of evidence fall against the use of surveillance FDG-PET/CT for relapse detection in lymphoma patients. In particular, although FDG-PET/CT offers the advantage of detecting metabolic changes, which usually occur earlier than morphological alteration, most disease relapses are actually heralded by clinical signs or by relapse of B-symptoms [5,6]. Moreover, FDG-PET/CT follow up exams are burdened by a significant rate of false positive results [6][7][8][9][10].…”

Optimal disease surveillance strategies in non-Hodgkin lymphoma

“…Gallamini and Kostakoglu provided reasonable recommendations of factors to consider in assessing the benefit of surveillance imaging, including: absence of clinical symptoms at diagnosis, pretreatment risk for recurrence, early response profile, cost-benefit ratio, potential survival benefit, possible site of relapse, and persistence of a residual mass at the end of treatment. 55 We agree with this approach, but recognize that these variables are not always known for each patient. Nevertheless, patients presenting with high-risk disease who are slow to respond to induction therapy and have concerning residual lesions at the conclusion of therapy likely merit closer follow-up than patients with lower-risk disease who achieve a metabolic remission after 2 cycles of induction therapy and remain in remission after a full course of therapy.…”

Diffuse large B‐cell lymphoma and mantle cell lymphoma of the ocular adnexal region, and lymphoma of the lacrimal gland: An investigation of clinical and histopathological features

“…Therefore, the incidence and frequency of recurrences could conceivable be higher than reported in the present study. Nevertheless, evidence suggests that in patients with aggressive lymphoma (including highrisk DLBCL, MCL and Hodgkin lymphoma) a relapse is detected by the patient or the physician prior to routine surveillance imaging in approximately 80% of cases (Liedtke et al 2006;Cheson et al 2007;Bestawros et al 2013;Gallamini & Kostakoglu 2012). Patient-reported symptoms include lymphoadenopathy, pain and B-symptoms (Liedtke et al 2006).…”