Early Interim Negative FDG-PET/CT Is a High Predictive Factor for Progression-Free Survival in Hodgkin Lymphoma.
Authors: Dann Eldad J. , Bar-Shalom Rachel , Tamir Ada , Haim Nissim , Avivi Irit , Gaitini Diana , Ben-Shachar Menachem , Israel Ora , Rowe Jacob M. , Epelbaum Ron 
Published: April 2020

Abstract
The treatment of patients with Hodgkin lymphoma (HL) is currently based on pretreatment risk stratification aimed at reducing late therapy-related toxicity. Functional Gallium67 scintigraphy was previously used for an interim assessment of response to therapy. Recently, an interim FDG-PET was suggested as a prognostic parameter for a failure-free survival. Reported here is the significance of an interim PET when integrated into a therapeutic protocol and used for an interim risk assessment. A cohort of 89 patients with Hodgkin lymphoma treated in a single medical center since 2001 was evaluated. Three patients had stage I disease, 48 - stage II, 15 - stage III and 23 - had stage IV. Assessment of the patients using the International Prognostic Score (IPS) showed that 20% had early disease with no score evaluable, in 18% the score was 0–2 and 62% of patients had a score of 3–6. Twenty eight patients were treated with 6 cycles of ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) and 61 patients received BEACOPP combinations (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for 6 cycles. Baseline PET/CT was performed in 87 patients while following 1st, 2nd or 3rd cycle of chemotherapy this test was repeated in 15, 70 and 4 patients, respectively. The 3-year failure-free survival (FFS) and the overall survival (OS) for patients with an interim negative study compared to those with an interim positive study were 95% versus 79% and 98% versus 89%, respectively. A subgroup of 11 patients who received escalated therapy following a positive interim PET had a 73% FFS. Three of these patients had primary progressive disease despite interim escalation of therapy. The 3-year negative predictive value of PET/CT was independent of patient risk group or chemotherapy used. Assessing the positive predictive value is difficult owing to the relatively small number of patients (19) as well as the dilemma of interpreting outcome therapy that was intensified based on the interim positive scintigraphy. Never-the-less, the data indicate that at least 27% of patients with a positive interim PET/CT will not be disease free at 3 years. The hazard ratio for a positive interim PET study is 6.2 CI (1.5–26), p=0.012. In conclusion, an interim negative PET/CT is highly predictive of prolonged FFS and OS. Prospective studies are needed to determine whether such an interim negative scan can be used to further reduce the dose intensity. An interim positive scan portends a poorer prognosis although the precise degree of predictability cannot be assessed from this study where therapy was escalated as a result of such scintigraphic findings.
Interim PET 3-yr FFS 3-yr OS Median follow up - months n % Negative study: Group A (n=70) 67/70 95.3% 98.1% 29 (5–55) Positive study: Group B: Residual uptake (n=19) 14/19 79.0% 89.2% 36 (7–66) Escalation of therapy post positive study: Group C: (n=11) 8/11 72.7% 81.8% 37 Log rank test: Groups A vs B: 0.004 Groups A vs B: 0.05 Groups A vs C: 0.007 Groups A vs C: 0.008