Non Predictive Value of An Initial Tc-99m-MIBI Scintigraphy On the Prediction of Therapeutic Outcome in Non Hodgkin and Hodgkin Lymphoma: Preliminary Results of a Prospective Study in 81 Patients.

Tc-99m-MIBI, a radioactive tracer used in routine to explore myocardial perfusion, parathyroids or in oncology for high-grade glioma, has been described as a promising agent for the functional characterization of p-glyco-protein expression and the prediction of the therapeutic outcome in patients (pts) with Hodgkin (HL) and non-Hodgkin's lymphoma (NHL)( Liang LA, 2001; Kao CH 2002). As resistance to chemotherapy is the major cause of treatment failure in NHL, the goal of treatment is to avoid an incomplete response after first line chemotherapy. This prospective study was designed to investigate the relationship between uptake by Tc-99m-MIBI scintigraphy and response to treatment in aggressive and follicular NHL, and HL.

Study protocol was a monocentric prospective study conducted between 10/2005 and 11/2008. Inclusion criteria included untreated pts with a histological diagnosis of HL or high grade NHL or follicular (FL) and managed in a hematological regional care network: HEMATOLIM, aged 18 years and more, with an initial and final assessment by a CT scan and/or TEP scan and with an informed consent. Were excluded pregnant or lactating women, pts without social security coverage or with initial corticosteroids. During the initial assessment, a Tc-99m-MIBI was performed with an injection of 20 mCi of tracer before any therapeutics. Images were obtained 10 minutes after intra-venous injection of Tc-MIBI. The rate of complete response (CR) and incomplete response (IR) at the end of first line therapy was evaluated with and compared with MIBI uptake.

The study included 81pts, sex ratio 1.61, median age 55 years (18-84)with an histological diagnosis of HL 41.9% (n=34), FL 9.9% (n=8), and aggressive NHL 48.2% (n=39) including DLBCL 38.3% (n=31), T cell NHL 4.9% (n=4), NK cell NHL 2.5% (n=2) and MCL 2.5% (n=2). Stade Ann Arbor I 6.2% (n=5), II 43.2% (n=35), III 12.3% (n=10) and IV 38.3% (n=31). Performans status were 0 for 51.85% (n=42), 1 for 35.8% (n=29), 2 for 11.11% (n=9) and 3 for 1.24% (n=1). LDH rate were increased 28.4% (n=23), normal 69.1% (n=56) and missing 2.5% (n=2). PSS for HL was favorable 41.18% (n=14), intermediate 47.06 (n=16) and unfavorable 11.76% (n=4). FLIPI score for FL was favorable 25% (n=2), intermediate for 62.5% (n=5) and non favorable for 12.5% (n=1). IPIa score was 0 for 29.03% (n=9), 1 for 32.26% (n=10), 2 for 19.35% (n=6) and 3 for 19.35% (n=6). All patients received chemotherapy in first line. For unfavorable pts a consolidation therapy has been added by radiotherapy 27.16% (n=22), or autologous stem cell transplantation for 8.54% (n=7). For 81 pts, MIBI results had positive uptake (MIBI+) 77.8% (n=63) and no uptake (MIBI-) 22.2% (n=18). For 75/81 pts eligible for final evaluation (6 deaths due to toxicity (n=3) or to NHL (n=3)), MIBI results showed 76% (n=57) MIBI+ and 24% (n=18) MIBI-. At the end of first line therapy, 82% of MIBI+ (n= 48/57) at diagnosis were in CR and 83% of MIBI – (15/18) were also in CR. There was no significant difference between the rate of MIBI+ and MIBI- for pts in CR by histological type. The distribution of disease localization were : thoracic (T) 59.3% (n=48), thoraco-abdominal (TA) 24.7% (n=20), abdominal (A) 13.6% (n=11), cranial 1.2% (n=1) and knee 1.2% (n=1). According to the results of MIBI, 83% of pts with a T localization were MIBI+ (n=40) versus 17% MIBI- (n=8), 70% of pts with a TA localization were MIBI+ (n=14) versus 30% MIBI- (n=6) and 63% of patients with a A localization were MIBI+ (n=7) versus 37% MIBI- (n=4). OS at 3 years is 90% and 3 years PFS is 79% with no significantly difference according to the response to MIBI. Sensitivity of MIBI is 80.77%, specificity 27.59%, positive predictive value is 66.67% and negative predictive value 44.44%.

This prospective study on 81 untreated pts with HL, and several varieties of aggressive NHL do not confirm the encouraging results previously reported by an asian study obtained on 25 pts considering Tc-99m as a useful predictive tool for chemoresistance.

In our study, lack of MIBI uptake does not predict a decrease in the rate of complete response to treatment. Several explanations can be advanced: heterogeneous histology and prognostic score, small population.

No relevant conflicts of interest to declare.