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Both total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients from three prospective trials: 2 Lymphoma Study Association (LYSA) studies and 1 Fondazione Italiana Linfomi (FIL) trial. Median follow up was 64 months. High TMTV (>510 cm3) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into 3 risk groups: patients with no risk factors (n = 102; 64%) had a 5-year progression-free survival (PFS) of 67% vs 33% (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.8-4.9) for patients with 1 risk factor (n = 44; 27%) and only 23% (HR, 4.6; 95% CI, 2.3-9.2) for patients with both risk factors (n = 13; 8%). 2-year PFS was respectively 90% vs 61% (HR, 4.8; 95% CI, 2.2-10.4) and 46% (HR, 8.1; 95%CI, 3.1-21.3). This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.

Both total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients from three prospective trials: 2 Lymphoma Study Association (LYSA) studies and 1 Fondazione Italiana Linfomi (FIL) trial. Median follow up was 64 months. High TMTV (>510 cm3) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into 3 risk groups: patients with no risk factors (n = 102; 64%) had a 5-year progression-free survival (PFS) of 67% vs 33% (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.8-4.9) for patients with 1 risk factor (n = 44; 27%) and only 23% (HR, 4.6; 95% CI, 2.3-9.2) for patients with both risk factors (n = 13; 8%). 2-year PFS was respectively 90% vs 61% (HR, 4.8; 95% CI, 2.2-10.4) and 46% (HR, 8.1; 95%CI, 3.1-21.3). This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.

Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P = .0475); F-PET 83% versus 64% (P < .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P = .015 vs 1.27, P = 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P = .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.

Role of interim-PET (I-PET) in diffuse large B-cell Lymphoma (DLBCL) is controversial. To determine predictive value of I-PET on progression-free survival (PFS), we enrolled 88 first-line DLBCL patients treated with 6-8 R-CHOP courses regardless of I-PET. PET/CT were performed at diagnosis, after 2 to 4 courses and at the end of therapy with central reviewing according to visual dichotomous criteria. Results are as follows: I-PET, 72% negative, 28% positive; final-PET (F-PET), 88% negative, 12% positive; clinical complete response 90%. Concordance between clinical response and F-PET negativity was 97% because of 2 false positive. With a median follow-up of 26.2 months, 2-year overall survival and PFS were 91% and 77%, respectively. Two-year PFS for I-PET and F-PET negative versus positive were as follows: I-PET 85% versus 72% (P= .0475); F-PET 83% versus 64% (P< .001). Because of a small number of events, 2 independent bivariate Cox models were tested for PFS. In model 1, F-PET contradicted I-PET (hazard ratio [HR] = 5.03, P= .015 vs 1.27, P= 691); in model 2, F-PET (HR = 4.54) and International propnostic Index score (HR = 5.36, P= .001) remained independent prognostic factors. In conclusion, positive I-PET is not predictive of a worse outcome in DLBCL; larger prospective studies and harmonization of I-PET reading criteria are needed.

Two uremic patients undergoing hemodialysis developed ophthalmic herpes zoster (OHZ), rapidly complicated by external ocular motor palsies. A total third nerve palsy was present in one case, a third with pupil sparing and fourth nerve palsy in the other. The palsies fully recovered within eight and nine weeks, respectively. Relative lymphopenia and absence of vascular brain lesions suggest a viral origin in these immunosup-pressed cases.

No relevant conflicts of interest to declare.

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder whose risk of progression to symptomatic MM (MM) is highly variable. Therefore, the identification of predictors of progression into MM is a relevant end point. Several markers (serum M protein, percentage of bone marrow plasma cells, free light chain, FLC, ratio, immunophenotyping of aberrant plasma cells and focal lesions, FLs at MRI) have already been established to identify sub-groups of SMM patients (pts) with a highest risk of progression into MM. Among imaging methods, FDG-PET/CT is a reliable technique for assessing early skeletal involvement and for predicting outcomes at the onset of MM. However, no data are available regarding the impact of PET/CT FLs in SMM on time to progression (TTP) into symptomatic disease.

Whilst positron emission tomography has a clear role in the evaluation of the final response to therapy in DLBCL, its predictive value at an interim time-point in this setting is controversial. Criteria of interpretation of Interim PET are yet to be standardized and the visual analysis of PET results by dichotomous evaluation is difficult to apply. Aim of the study was to determine the predictive value of interim (I-PET) and final PET (F-PET) on Progression Free Survival (PFS) in a cohort of DLBCL patients treated with R-CHOP.From April 2004 to October 2009, 88 DLBCL patients at diagnosis, at five Hematology Departments were included. All patients were treated with standard chemo-immunotherapy R-CHOP for 6 or 8 courses; therapy was performed as planned and never modified by I-PET results. Thirty-one patients received R-CHOP21, 57 R-CHOP14. Involved Field radiotherapy (IF-RT) for areas of bulky disease was delivered to 14 patients regardless of PET results. G-CSF was given to 21/31 R-CHOP21 patients and in all 57 R-CHOP14. PET scan was performed in all patients at diagnosis, during and at the end of therapy: all results were centrally reviewed and defined as positive or negative by visual dichotomous response criteria according to the First Consensus Conference (Deauville 2009). PFS and overall survival (OS) were analyzed by the Cox proportional hazards model, comparing the two arms by the Wald test with 95% CI. Due to small number of events, the Cox proportional hazards model was used in two independent bivariate analyses to assess the effect of different prognostic factors on PFS.Clinical features were: median age 55 years (18-80); males/females 41/47; stages I-II/III-IV 29/59; Low/Low Intermediate International Prognostic Index score (IPI 0–2) 53 and Intermediate/Intermediate High/High IPI score (IPI 3–5) 35. I-PET was performed after two R-CHOP in 58 patients, after 3 or 4 in 30. At the end of therapy, 79 patients (90%) achieved a complete response (CR) and nine (10%) were non responders. Sixty-three patients (72%) were negative and 25 (28%) positive at I-PET; 77 patients (88%) were negative and 11 (12%) positive at F-PET; 15/25 (60%) I-PET positive patients converted at F-PET, while only 1/63 (2%) I-PET negative case had a positive F-PET (Table 1). The concordance between clinical CR and F-PET negativity was 97%: two patients, whilst in CR, had false positive final scans due to parotid and colorectal carcinoma (histologically confirmed) respectively. We evaluated the prognostic impact of PET results on the outcome. With a median follow-up of 26.2 months, 2-year OS and 2-year PFS were 91% and 77% respectively. There was a weak correlation between PFS and I-PET results: rates were 85% in negative and 72% in positive patients (p.05) (Figure 1A). Conversely F-PET strongly predicted PFS (p <.001): 83% in negative and 64% in positive patients. (Figure 1B). In univariate analysis for PFS, elevated LDH value, ≥ 2 extranodal sites, bone marrow involvement, 3–5 IPI score, I-PET and F-PET positivity were predictors of lower PFS rates. Use of G-CSF or number of R-CHOP courses before I-PET did not influence PFS rates. Two independent bivariate analyses by Cox models were performed to properly evaluate the prognostic role of I-PET and F-PET results. In model 1, only F-PET retained its prognostic value compared to I-PET with an adjusted HR of 5.03 (95% CI 1.37–18.43, p=.015) vs 1.27 (95% CI 0.40–4.03, p=.691). In model 2, both Final-PET (HR 4.54, 95% CI 1.68–12.31) and IPI score (HR 5.36, 95% CI 1.91–15.05, p=.001) remained independent prognostic factors for PFS. (Table 2).Our results indicate that in DLBCL patients treated with first-line R-CHOP, a positive I-PET does not predict a worse outcome: indeed the majority of I-PET positive patients achieved CR at the end of therapy. Conversely, F-PET results strongly correlate with PFS. Larger prospective studies and standardization of criteria for interim PET evaluation are needed to better assess the prognostic value of interim PET in DLBCL patients.No relevant conflicts of interest to declare.

Abstract 2819

Introduction. The PET scan has a definite role to assess the response at the end of treatment of DLBCL. The evaluation of response by PET after few courses of chemotherapy might be useful to predict chemosensitivity and possibly the outcome in this subset of patients. So far, the predictive value of interim PET in DLBCL pts is still contradictory. The visual analysis of PET results by dichotomous evaluation as positive or negative is often difficult to apply and standardized criteria of interpretation of interim PET have not been established yet. Moreover, published data are often based on retrospective studies, including miscellanea of subtypes and therapies. Our study was aimed to determine the predictive value of interim and final PET on PSF in DLBCL patients. Patients and Methods. From April 2004 to December 2008, 82 newly diagnosed DLBCL patients treated in 5 Hematology Department were included. Clinical features were as follows: median age 56 years (range 19-81); 42 males and 40 females, 29 patients stage I-II and 53 stage III-IV; according to IPI score 47 at low/low-intermediate risk and 35 at intermediate/intermediate-high. All patients were treated according to planned therapy, not modified by PET-2 results, with 6-8 R-CHOP. All patients had PET scan performed at the diagnosis, during treatment (PET-2) and at the end of therapy (PET-3). All PET results were defined as positive or negative by visual dichotomous consensus response criteria. Results. All patients were evaluable for response. PET-2 was performed after 2 R-CHOP in 46 pts, after 3 in 13 and after 4 in 23. At the end of therapy 73 pts (89%) achieved a CR and 9 (11%) were non responders. Fifty-five patients (67%) were negative and 27 (33%) positive at the PET-2 and 69 pts (84%) were negative and 13 (16%) positive at the PET-3. The concordance between clinical CR and PET-3 negativity was 99%: one CR pt was false PET-3 positive due to parothid carcinoma . Correlation between PET results and outcome was evaluated. There was correlation between PET-2 results and CR rate: CR 96% in PET-2 negative pts vs 74% in PET-2 positive (p .004). With a median FU of 18 months, PFS was 78%. PET-2 did not correlate with PFS (p .198): 46/55 (84%) PET-2 negative patients were in CCR and 20/27 (74%) PET-2 positive patients did not progres (Figure 1A). Conversely PET-3 strongly predicted PFS (p .015): 58/69 (84%) were in CCR and 8/13 (61%) did not progressed. (Figure 1B). A further analysis for progression event was performed to adjust the effect of PET-2 analysis for other known risk factors (age up to/over 60, stage, Performance status, LDH, number of extranodal sites, IPI, bulky, Bone Marrow involvement): only LDH (p .005)and IPI 0-2 vs 3-5 (p .001 ) were confirmed as independent predictors of progression event. Conclusions. Our results indicate that in this omogeneous group of DLBCL patients treated with R-CHOP interim PET failed to predict outcome. However, a longer follow up is necessary to validate our data. Conversely PET results at the end of treatment strongly correlate with PFS. Prospective larger studies will be needed to establish the real role of interim PET to predict the outcome in this subset of patients.Ladetto: CELGENE: Honoraria; JANSSEN-CILAG: Research Funding. Vitolo:Roche: lecture fees.

Abstract 99