Role of FDG-PET/CT Surveillance for Patients with Classical Hodgkin's Disease in First Complete Response: The Stanford University Experience.

In Hodgkin's Disease (HD) the role of FDG-PET/CT is well established in staging and assessment of treatment response, however, there is a paucity of data regarding its role in surveillance after first complete response (CR) has been achieved and treatment is completed. The purpose of this study was to evaluate reports of FDG-PET/CT scans performed in follow-up (fu) of patients (pts) in first CR and correlate results with freedom from progression (FFP) and overall survival (OS). We also sought to determine the proportion of surveillance scans that identified relapses in pts prior to development of clinical signs or symptoms.

Patients and methods: We retrospectively identified pts with classical HD from the Stanford Hodgkin's Disease database who met the following predefined criteria; CR to primary treatment with all therapy and fu care at Stanford, FDG-PET/CT scans performed for the purpose of surveillance 0.3 to 5 years (y) after completion of therapy. Reports of surveillance scans were reviewed and scored as positive, if reported as suspicious for recurrence; indeterminate, if reported as likely consistent with a non-specific etiology; or negative, if there were no FDG-avid sites. Patient characteristics, therapy details, symptoms at fu visits and outcome were reviewed and clinical attributes correlated with FFP and OS.

Between 3/2002 and 1/2009, 113 pts were identified who met the predefined criteria. Surveillance scans were performed as part of a study protocol in 33 pts and at physician discretion in remainder. The median age was 31y (range 18 to 71). 10 pts had stage I, 72 stage II, 12 stage III and 19 stage IV disease. Of the pts with stage I/II disease 52 were considered to have unfavorable risk factors based on either bulky mediastinal disease and/or additional criteria per European cooperative groups (ESR > 50, >2 AA sites, any extranodal [EN] sites). For the 31 pts with stage III/IV disease, International Prognostic Scores (IPS) were 1-2 (n=9), 3 (n=9) and ≥4 (n=13). Therapy consisted of Stanford V chemotherapy (SV) for 8 weeks (w) followed by involved field radiotherapy (RT) 20 Gy (n=31) or 30 Gy (n=10), SV for 12 w and 36 Gy RT to sites > 5cm and macroscopic splenic disease (n=57), BEACOPP (n=6), ABVD (n=7) and ‘other’ (n=2). Overall 326 scans were performed; y1 (n=123), y2 (n=103), y3 (n=68), y4 (n=26) and y5 (n=6). 30 pts had one or more reports consistent with a positive scan, 26 had indeterminate or negative, and 57 had only negative scans. At a median fu of 3.2y, the overall FFP was 87% and OS 100%.

Only 14/30 pts (47%) with a positive scan relapsed; 9/82 (11%) of stage I/II pts and 5/31(16%) of stage III/IV pts. None of the pts with indeterminate or negative scans relapsed. The median time to relapse was 236 days (range 58 to 835). 12/14 (85.7%) relapses occurred within the first year and were not associated with clinical symptoms/signs in 9/12 (75%) pts. Two pts relapsed > 1y post CR (13 mo and 2.3 y) and symptoms prompted imaging with FDG-PET/CT in both. All pts were salvaged successfully with high dose chemotherapy and stem cell support.

Our retrospective data are consistent with other reports suggesting a high negative predictive value (100%) and low positive predictive value (47%) for FDG-PET/CT scans for surveillance in HD. In our data set most relapses identified by surveillance FDG-PET/CT imaging occurred within 1 yr of completion of therapy and were asymptomatic in 75% of pts. These relapses would have likely been missed in the absence of routine imaging. Whether early detection of asymptomatic relapse impacts outcome or not needs further testing. In our series, asymptomatic relapse beyond 1y was rare and our data do not support the practice of routine surveillance for all pts. Our data have important implications related to the interpretation of “positive scans” during surveillance, potential effects of radiation exposure from repeated FDG-PET/CT scanning as well as escalating health care costs. At this time the routine use of FDG-PET/CT surveillance requires further study and should be limited to prospective clinical trials.

No relevant conflicts of interest to declare.