Marrow involvement in staging FDG PET CT in Hodgkin’s disease, does it translate into poorer survival ?

Introduction: Bone marrow involvement in Hodgkin’s disease (HD) is poor prognostic marker. Bone marrow biopsy (BMB) is used to define bone marrow involvement not the FDG PET CT (PET) in various prognostic indices. We aimed to study whether staging PET CT bone marrow uptake patterns can be used as prognostic indicator.

Objectives: To study the different patterns of marrow uptake in staging PET and its correlation with progression free survival (PFS) and overall survival (OS).

Methods: This was a single center retrospective study.PET scans of 388 biopsy proven newly diagnosed cases of HD were retrospectively reviewed. All patients had undergone staging PET in the institute between Jan 2011 to Dec 2013. The prognostic factors used for univariate analysis were age >45, gender, hemoglobin <11gm/dl, WBC count <11500 /ul, lymphopenia <8% or 600/ul, ESR >30mm/hr, LDH, hypoalbuminemia (<4 gm/dl), spleen involvement, BMB, bulky disease, bone marrow involvement on PET (positive vs negative), focal pattern of marrow involvement on PET, stage of disease (early vs advanced). Pattern of marrow uptake on PET was reported as focal, heterogeneous patchy, uniform diffuse, and no uptake. Focal and heterogeneous patchy uptakes were considered positive while uniform diffuse and no uptake were considered negative for marrow involvement. Kaplan-Meir survival analysis was used to calculate PFS and OS. Cox regression analysis was used to examine the prognostic significance of various clinicopathological features and PET CT marrow disease. Covariates with p value < 0.05 were included in the cox regression analysis.

Results: Patient cohort consisted of 292 males and 96 females. Median age was 21 years (1-69 years). Median follow-up was 41 months (6-66months).Marrow involvement on PET was seen in 78 patients out of which 66 had focal pattern. 48 patients had events in the follow up period, 42 relapsed and 6 had progressive disease. 15 patients died in the follow up period. In univariate analysis, the prognostic indicators which were statistically significant for OS were age > 45, lymphopenia, hypoalbuminemia, PET marrow involvement, focal marrow involvement and disease stage. However in multivariate analysis by Cox method only age >45 was an independent prognostic factor for OS. For PFS, prognostic indicators which were statistically significant in univariate analysis were age > 45, lymphopenia, hypoalbuminemia, LDH,ESR, spleen involvement, PET marrow involvement, focal marrow involvement disease stage. In multivariate analysis by Cox method, age >45, ESR, marrow involvement on PET and focal pattern of marrow involvement were independent prognostic indicators. The PFS for patients with marrow involvement on PET was 47 months compared to 61 months for those with no involvement (p value 0.000). The PFS for patients with focal marrow involvement was 43 months compared to 61 months in rest of the cohort (p value 0.000).The OS for patients with marrow involvement on PET was 57 .5 months compared to 65.1 months for those with no involvement (p value 0.03).The OS for patients with focal marrow involvement was 56.8 months compared to 65.2 months in rest of the cohort (p value 0.009).

Conclusion: In HD, marrow involvement on PET indicates inferior PFS and OS. Focal pattern of marrow involvement in staging PET is an independent prognostic factor for progression free survival.