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Purpose To assess whether 11C-methionine positron emission tomography (11C-MET PET) has a clinical significance in the management of glioma patients. Patients and methods Fifty-three patients with histologically proven primary gliomas (16 grade II, 15 grade III, and 22 grade IV) were investigated repeatedly with 11C-MET PET. A total of 249 PET scans were performed, with a median of 4 scans for each patient. Functional imaging with PET was compared with concurrent MRI or CT. Results We registered high sensibility and specificity in the management of glioma patients. The mean 11C-MET uptake index results significantly correlated with histological grade. The overall survival (OS) of GBM patients who underwent 11C-MET PET serial controls and parallel CT or MRI scans resulted to be 29.24 months, significantly higher compared to OS of GBM who underwent CT or MRI alone during follow up. Conclusion 11C-MET PET allowed the detection of malignant progression in low grade glioma patients and the assessment of post-surgery status in both low and anaplastic gliomas with high sensibility and specificity. Thus, 11C-MET PET expresses its maximum potential in earlier disclosing recurrence during the long-term follow-up of GBM patients, with a relevant impact on therapeutic course and survival of these patients. Disclosure All authors have declared no conflicts of interest.

e21006 Background: Induction with novel biological agents has significantly improved progression free survival (PFS) of MM pts. However, role and timing of ASCT is unclear and there remains a need for a practical means to predict post-ASCT outcome. Our goal was to determine the prognostic value of FDG PET/CT (PET) after induction therapy (IT) in comparison with other prognostic factors and International Myeloma Working Group (IMWG) response criteria. Methods: Prospective, multicenter study of 113 newly diagnosed MM pts undergoing IT+ASCT. IT was not controlled and consisted of 2 or 3 novel agent combinations. The tested variables to predict PFS are shown in table. Two PET scoring systems were used: Score1, positive>marrow uptake; Score2, positive>liver uptake. ROC analysis determined the SUV cut-off. Results: With a median follow-up of 29.5 mo 56 (49.6%) pts relapsed (median PFS: 24.3 mo). Results are displayed in table. Post-IT, when a "+" PET (Score2) was associated with less than a VGPR response, relapses occurred in 83% of pts vs. in only 30% when PET was "-" and pts were in CR or VGPR. Multivariate analysis revealed only ISS to be an independent predictor of PFS (p=0.014). Conclusions: Post-IT a "-" PET associated with CR+VGPR suggests a durable response. Qualitative PET evaluation using a more liberal threshold (liver) to define positivity can be used to accurately assess response in MM. These data failed to prove the post-IT IMWG and PET response to be independent prognosticators while ISS was a superior predictor. This may be attributed to inadequate sample size, nonuniform pre- and post-ASCT treatments, varying follow-up times. Further analyses with stratifying various prognostic indicators and therapy schemes in a larger population are underway to determine a definitive role for PET as a predictor of post-ASCT outcome. [Table: see text]

Objectives Genital tract infection of female mice with Chlamydia muridarum closely mimics C trachomatis acute genital tract infection in women. Aim of this study was to assess the predictivity of 11C-Choline Small Animal PET for the identification of reactive animals and their follow-up at several times after vaginal challenge. Methods Chlamydiae were grown in LLC-MK2 cells, cultivated in Eagle9s MEM and elementary bodies were purified from cells by sucrose-gradients density centrifugation. Animals used in this study were 10 female Balb/c mice, 6–8 weeks old. All the animals received 2.5 mg of medroxyprogesterone acetate intramuscular nine and 2 days prior the infection. Nine mice were infected by placing 106 IFUs of C muridarum into the vaginal vault. Infection was induced under Ketamine anaesthesia. As control, one animal was challenged with SPG. At 5, 10 and 20 days after challenge mice underwent a 11C-Choline PET, as follows: each animal was anaesthetised with Sevofluorane 3–5% oxygen 1 l/min and was injected with approximately 20 MBq of 11C-Choline, via the tail vein. The residual dose was measured to verify the effective dose injected. The animal was subsequently placed on the scanner bed in the prone position, after an uptake time of 5 min. Images were acquired with a small animal PET tomograph (GE, eXplore Vista DR) for a total acquisition time of 20 min. As the axial field of view was 4 cm, one bed position was sufficient to cover the whole body. Images were reconstructed iteratively (OSEM 2D) and read in three planes (axial, sagittal and coronal). The scan was considered positive if areas of increased Choline uptake were present at sites consistent with the site of inflammation. The standard uptake value (SUV) was calculated by measuring the concentration of the labelled tracer in the region of interest and correcting it for mice body weight and injected dose. Infection was monitored by culturing cervical-vaginal secretions 6, 11 and 21 days after infection. Results At 5 days, the mean vaginal SUV (±SD) of the cases was 0.83±0.39, whereas the control showed a value of 0.278. At 10 and 20 days, SUVs of the cases were 0.94±0.25 and 1.17±0.21, respectively, whereas SUV of the control was 0.299 and 0.302, respectively. C muridarum was isolated from all the infected animals during the study period. Conclusions These preliminary data indicate that 11C-Choline PET could be a promising technique to in vivo evaluate inflammatory response to Chlamydia infection.

To describe the role of FDG-PET in the work up and follow up of Sarcoidosis

Abstract 369 F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) has been reported to be a careful technique for a widespread screening of myelomatous lesions, both medullary and extramedullary, at the onset of multiple myeloma (MM). By the opposite, the role of FDG-PET/CT in assessing and monitoring response to therapy and the prognostic value of this imaging technique is less explored. Aim of the present study was to prospectively evaluate the prognostic significance of FDG-PET/CT at diagnosis and after therapy in an homogeneous population of patients with newly diagnosed MM who received up-front single or double autologous stem cell transplantation (ASCT). By study design, all patients were studied with FDG-PET/CT at baseline, 3 months after ASCT, every year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FL), as well as their size and associated standardized uptake values (SUV) were recorded. Extramedullary disease, if present, was described by location, size, number of lesions and SUV. A total of 146 patients who actually received the planned treatment program and were followed for a median of 39 months were analyzed. Their median age was 58 years. ISS stage was as follows: 48% stage I, 31% stage II, 14% stage III. Six per cent of the patients had renal failure, related to the presence of hypercalcemia at diagnosis. Del (13q), t(4;14) and del(17p), detected by FISH, were present in 47%, 25% and 10% of the patients, respectively. Induction treatment prior to ASCT included an IMiD in 55% of the patients, bortezomib in 34% and chemotherapy in 11% of the cases. The best overall response rate, including CR and at least VGPR, was 56% and 82%, respectively. Median PFS of the entire population was 55 months and the 5-year projected OS rate was 85%. At baseline, 22% of the patients had a negative PET/CT, 27% presented less than 3 FL and 51% 3 or more FL or a diffuse bone marrow uptake of FDG. In 44% of the cases the SUV was low (< 3.9) while in 56% was 4 or more. In 6% of the patients extramedullary disease was present. No significant differences between patients with positive or negative PET/CT were found regarding baseline characteristics and response to therapy. The entity of PET/CT involvement at baseline influenced clinical outcomes. In particular, patients with more than 3 FL and/or SUV > 3.9 had a significantly shorter OS in comparison with patients with FL < 3 and/or SUV < 3.9 (5-year projected OS: 92% vs 75%, respectively, P=0.04). After 3 months from ASCT, PET/CT was negative in 65% of the patients and remained positive, either unchanged or with a reduction in the SUV, in 35% of them. A correlation between PET/CT findings and response to ASCT was evident; in particular, among patients with negative PET/CT the rate of CR and VGPR was significantly higher than among patients with positive PET/CT (CR: 68% vs 38%; P= 0.001) (VGPR: 90% vs 76%; P= 0.008). Complete FDG suppression at PET/CT after ASCT conferred superior PFS and OS than persistence of FL (PFS: median 58 vs 45 months, respectively, P=0.05; 5-year projected OS: 92% vs 79%, respectively, P=0.004). In conclusion, involvement of PET/CT at diagnosis in terms of number of FL and intensity of tumour metabolism (SUV) predicted survival outcome. Complete FDG suppression after ASCT was strictly related with achievement of high-quality response and was prognostically relevant for durable disease control and longer OS. Disclosures: Cavo: Jansen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no.

e20502 Background: Primary and secondary drug resistance to imatinib and sunitinib in the treatment of patients with GISTs has led a progressively growing urgency to develop new strategies such as drug combinations. Most GISTs are caused by mutations in the KIT receptor, leading to upregulated KIT tyrosine kinase activity. Imatinib (I) and nilotinib (N) directly inhibit the kinase activity of KIT, RAD001(Everolimus)(E) inhibits mTOR. We report a preclinical study on combinations of drugs in xenograft model of GIST in which effects were assessed with tumor dimensions and metabolic activity using small animal PET imaging. Methods: Tumor xenografts were induced into ADKO mice by s.c injection of GIST882 cells into the right leg. After 30 days, tumors grew in all animals (volume 0,2-0,3 cm3). Animals were randomised into 7 groups of 6 animals each for different treatment regimens: * No therapy (control) * I (150 mg/kg b.i.d.) oral gavage for 6 days, then once/day because of toxicity * E (10 mg/kg/d.) oral gav...

Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is utilized in more than 90% of cancers in staging, re-staging, assessing therapy response and during the follow-up. However, not all tumors show significant increase of metabolic activity on FDG-PET imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. In this review we have considered those already used for clinical applications such as 11C- and 18F-Choline, 11C-Methionine and 18F-FET, 18F-DOPA, 68Ga-DOTA-somatostatine analogues, 11C-Acetate and 18F-FLT. Choline presents a high affinity for malignant prostate tissue, even if low grade. Choline can be labeled with either 11C or 18F, the former being the preference due to lower urinary excretion and patients exposure. The latter is more useful for possible distribution to centers lacking in on-site cyclotron. Methionine is needed for protein synthesis and tumor cells require an external supply of methionine. These tracers have primarily been used for imaging of CNS neoplasms. The most appropriate indication is when conventional imaging procedures do not distinguish between edema, fibrosis or necrosis and disease relapse. In addition, the uptake of 11C-Methionine is proportional to the tumor grade and, therefore, the maximum small unilamellar vesicles (SUV) inside the brain mass before therapy is somehow considered a prognostic value. Neuroendocrine tumors (carcinoids, pheocromocytoma, neuroblastoma, medullary thyroid cancer, microcytoma, carotid glomus tumors, and melanoma) demonstrate an increased activity of L-DOPA decarboxylase, and hence they show a high uptake of 18FDOPA. For the study of NETs, 68Ga-DOTA-TOC/DOTA-NOC has been introduced as PET tracer. This compound for PET imaging has a high affinity for sst2 and sst5 and has been used in the detection of NETs in preliminary studies; 68Ga-DOTA-NOC PET is useful before metabolic radiotherapy in order to evaluate the biodistribution of the therapeutic compound; 18F-FLT is a specific marker of cell proliferation and the most important field of application of FLT is lung cancer. Other tracers are used in PET utilized as markers of hypoxia inside big neoplastic masses include 18F-MISO, 64Cu-ATSM, 18F-EF5, which highlight the presence of hypoxic areas are useful for patients that must be treated with radiotherapy.

4061 Background: The aim of the study was to evaluate 18FDG-PET impact in gastric or GEJ cancer patients (pts) treated with cetuximab plus chemotherapy. Methods: Pts with stomach or GEJ unresectable/metastatic adenocarcinoma, not yet treated, EGFR+, were enrolled in the FOLCETUX study. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, CPT11 180 mg/m2 iv d1, LFA 100 mg/m2 iv followed by 5FU 400 mg/m2 iv bolus and 600 mg/m2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Anti-tumor activity was assessed by CT and PET scan at baseline and then every 6 weeks. A decrease in tumor FDG-uptake (metabolic response) was evaluated according to EORTC recommendations; objective response (OR) was evaluated with CT scan according to the RECIST criteria. Results: From November 2004 to December 2005, 22 pts (16M, 6F) performed at least 2 consecutive PET scans (at baseline and after 6 weeks), with a total of 91 PET scans (median per pts 4; range 2–8). PET was positive in 20 pts (90.9%); no FDG uptake was seen in 2 pts (9.1%) with signet ring cell carcinoma. A metabolic response correctly predicted: CR/PR in 10/12 pts (83%) after 6 weeks of therapy and in 11/12 (91.7%) after 12 weeks; SD in 4/8 pts (50%) after both 6 and 12 weeks. On the whole, response to therapy was predicted by PET after 6 weeks in 14/20 pts (70%). No correlation was demonstrated between median Standardized Uptake Value (SUV) at baseline PET and OR: 10.9 (3–29) in CR/PR pts and 9.6 (6.4–29.8) in SD pts. In the PET scan after 6, 12 and 18 weeks, the median SUV value respectively decreased to 4.4, 2.6 and No significant financial relationships to disclose.

Multiple myeloma (MM) is a malignant plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. For almost four decades bone lesions have traditionally been detected by Whole Body X-Ray (WBXR) survey. Over the last years, newer methods of evaluation have been increasingly used for the detection of MM bone disease, including magnetic resonance imaging (MRI) of the spine. In comparison with WBXR, MRI has proven to be more sensitive, although its partial field of view (FOV) is a main limitation in clinical practice. 18F-FDG PET/CT is a non invasive and total body imaging method that may be usefully employed to explore bones and soft tissues in MM, to assess the degree and extent of active MM bone disease, as well as to evaluate response to therapy by distinguishing between active and inactive bone lesions. Aim of the present study was to compare WBXR survey, MRI and 18F-FDG PET/CT scanning in a series of 28 consecutive patients with newly diagnosed MM. Moreover, we compared post-treatment evaluation with MRI and 18F-FDG PET/CT with clinical response in 14/28 patients who received double autologous transplantation as up-front therapy for MM. All patients underwent WBXR, MRI and 18F-FDG PET/CT at baseline and 3 months after the second transplantation. Findings of 18 F-FDG PET/CT were compared to those of WBXR and MRI with respect to number and site of detected bone lesions. Results of comparison of 18 F-FDG PET/CT with WBXR at diagnosis were as follows: in 16/28 pts (57%) 18 F-FDG PET/CT detected more lesions, all of whom were located in the skeleton; notably, 9 of these 16 patients had a completely negative WBXR survey. In 12/28 pts (43%) both methods were superimposable. Results of comparison of 18 F-FDG PET/CT with MRI at diagnosis were as follows: in 7/28 pts (25%), 18 F-FDG PET/CT detected more lytic bone lesions which were all located out of the FOV of MRI (6 bone lesions, 1 soft tissue lesion); in 13/28 pts (46%) 18 F-FDG PET/CT and MRI detected the same number of lesions in the spine and pelvis; in 8/28 pts (29%) MRI detected an infiltrative pattern of the spine, without evidence of lytic lesions, whereas 18 F-FDG PET/CT was negative. Results of comparison of post-transplantation 18 F-FDG PET/CT and MRI with clinical response were as follows: 5 out of 12 patients with negative 18 F-FDG PET/CT were in clinical CR and the remaining 7 patients were in 3 PR. Only 7 out of 12 patients with negative 18 F-FDG PET/CT had normal MRI. In summary, in 57% of patients at diagnosis 18 F-FDG PET/CT was more sensitive than WBXR for the detection of lytic bone lesions. MRI of the spine was superior over 18 F-FDG PET/CT in 29% of patients, particularly with a diffuse bone marrow replacement. Based on these data, it can be concluded that careful evaluation of MM bone disease at diagnosis should include both MRI of the spine and 18 F- FDG PET/CT. More data are needed to understand the role of 18 F-FDG PET/CT in assessing response to treatment.

3623 Background: The aim of the study was to evaluate the predictive value of FDG-PET in patients (pts) treated with neoadjuvant chemo-radiotherapy (CRT) for rectal cancer in the Bologna Project. Methods: Pts entering the study had histologically-proven rectal adenocarcinoma and stage uT3-T4 N-/+ or uT2 N-/+ with inferior location (

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.

Purpose: The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis. Methods: Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 − SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma. Results: The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 – 17) in EWS patients and 7.9 (range 0 – 24) in OS patients (p = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 – 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 – 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients. Conclusion: FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

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. To address this issue, we prospectively studied pts with a suspected diagnosis of SMM with FDG-PET/CT. A cohort of 73 pts, with a median age of 61 years old (range 27-83) and a confirmed diagnosis of SMM, followed for a median of 2.2 years, is herein reported. By study design, all the pts were studied with PET/CT at baseline. Bone marrow involvement was described as negative, diffuse or focal. The number of FLs, as well as size and associated standardized uptake values (SUV) were recorded. For each FL, the presence of eventual underlying osteolytic lesion was investigated by the CT part of the scan; pts with osteolytic lesions were excluded from the present study, as they were considered as having symptomatic MM. Follow-up took place every 3-4 months and included clinical history, serum and urine markers and PET/CT plus axial MRI for occurrence of symptoms or an increase in M component. Progression to MM was defined by the presence of CRAB features. Skeletal progression was defined by the appearance of one or more sites of osteolytic bone destruction, pathological fractures and/or soft masses at PET/CT or MRI. The start of systemic therapy was defined as the date of event for the analysis of TTP. Baseline patient characteristics were as follows: 83% had IgG isotype, 8% IgA and 9% BJ, with a median M component of 2.5 g/dL; 70% had ISS stage I, 23% stage II and 7% stage III. Median plasma cell involvement on bone marrow (BMPC) was 30% (range 5-100%), with 16% of the pts having more than 60% BMPC. The median serum involved/uninvolved FLC ratio was 14.39 (range 1.28-2255), with 11% of the pts presenting with a ratio ≥ 100. PET/CT was negative in 64/73 pts (88%) and positive in 9/73 (12%) of them; 5 pts had 1 FLs, 1 pt 2 FLs, 2 pts more than 3 FLs and 1 pt a diffuse bone marrow involvement. Median SUV max value was 4.45 (range 2.5-5.2). No significant differences between patients with positive or negative PET/CT were found regarding the other baseline characteristics. At the time of the present analysis, 63% of the pts remained in the asymptomatic phase while 37% of them progressed to MM, in a median time of 4 years, including 21% with skeleton involvement, with/without the appearance of other CRAB symptoms, and 16% with exclusive serological signs of progression. Sixty six per cent of the pts with positive PET/CT progressed to MM in comparison to 33% of the pts with negative PET/CT (P = 0.034). The relative risk of progression of the pts with a positive PET/CT was 2.3 (95% CI 09.-5.9, P= 0.06). Moreover, the relative risk of skeletal progression was 4.0 (95% CI 1.3-12, P= 0.013), with a median TTP of 2.2 years for pts with positive PET/CT versus 7 years for those with negative PET/CT (figure 1). The probability of progression within 2 and 3 years for pts with positive PET/CT was 48% and 65%, respectively, in comparison to 32% and 42% for negative pts. In conclusion, approximately 10% of the pts with SMM have a positive PET/CT, mainly with few FLs, without underlying osteolytic lesion, with a low FDG uptake. PET/CT positivity significantly increased the risk of progression of SMM into active MM. PET/CT could become a new risk factor to define high risk SMM. A larger cohort of pts will be presented at the meeting. Further studies are warranted to find and optimal cut off point of FLs to capture the higher risk of progression at 2 year and to merge with other prognostic factors. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract 826 Incorporation of novel agents into ASCT allowed the achievement of unprecedented high rates of CR in young MM patients, a gain which translated into extended PFS and OS. As a consequence, interest in the evaluation of the depth of CR has progressively grown. More sensitive tools, such as multiparametric flow cytometry or molecular biology, led to the demonstration of a correlation between the depth of CR and prognosis, but failed to identify the persistence of residual disease outside of the bone marrow level. 18 F-FDG PET/CT is a careful technique to detect with high sensitivity and specificity the presence of active bone lesions and/or bone marrow involvement in newly diagnosed and previously treated MM. We prospectively analysed the prognostic significance of FDG-PET/CT at diagnosis, after induction therapy and ASCT in an homogeneous population of 192 patients with newly diagnosed MM, followed for a median of 43 months. By study design, all patients were studied with FDG-PET/CT at baseline, after induction treatment, after 3 months from ASCT (single or double), once a year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FLs), as well as size and associated standardized uptake values (SUV) were recorded. Extra-medullary disease (EMD), if present, was described by location, size, number and SUV. Twenty four percent of the patients had a negative PET/CT scan at diagnosis. Among PET/CT-positive patients, 44% showed ≥3 FLs, 46% had SUV values >4.2 and in 6% EMD could be detected. These 3 variables adversely affected 4-year estimates of PFS and OS. In particular, both EMD and severe FDG uptake were significantly associated with shorter PFS and OS. Thirty seven percent of the patients were PET/CT-negative after induction. A strong correlation between conventional response and SUV max reduction was evident, the mean SUV value of patients achieving CR being significantly lower in comparison with that of patients reaching very good partial response (VGPR) or partial response (mean: 1.4 vs 3, respectively) (Cuzick's trend test, P= 0.016). Persistence of severe FDG uptake (SUV max still >4.2) after induction predicted for shorter PFS at 4 years (P= 0.004). PET/CT negativity (PET-CR) was observed in 65% of patients after 3 months from ASCT(s). A close relationship between PET/CT negativity and response to ASCT was evident, since 95% of patients with a negative PET/CT had achieved at least a VGPR (P= 0.003). Moreover, a correlation between conventional response and SUV max reduction was evident after ASCT as well (mean: 0.8 vs 1.8, respectively) (Cuzick's trend test, P= 0.001). PET-CR after ASCT conferred superior PFS and OS in comparison with persistence of FDG uptake. In particular, the 4-year estimates of PFS and OS for PET-CR patients were 66% and 89%, respectively, as compared with 45% and 65% for positive patients (P=0.02 both for PFS and OS). Notably, 23% of patients achieving CR according to conventional criteria still had positive PET/CT scans and their 4-year estimate of PFS was 30%, as compared with 61% for negative patients (P=0.02). After ASCT, patients were followed with evaluation of M protein every 3 months and of PET/CT once a year. In 44% of those who had a conventionally-defined relapse or progression, the mean time to relapse/progression was 27.6 months for PET-negative patients as compared with 18 months for positive patients (P=0.05). In PET-positive patients, the SUV max was inversely correlated to the time to relapse (correlation coefficient −0.7, P= 0.003). In multivariate analysis, both severe PET/CT involvement at diagnosis (SUV >4.2 and/or EMD) and persistence of FDG uptake after ASCT were independent predictors of worst PFS (SUV >4.2= HR: 2.0, 95%CI: 1.13–3.72; EMD= HR: 15.0, 4.0–55.8; FDG uptake after ASCT= HR: 2.12, 1.19–3.77) and OS (EMD= HR: 6.99, 2.28–21.46; FDG uptake after ASCT= HR: 3.57, 1.03–12.39). In conclusion, PET-defined CR was linked to conventionally-defined CR and was an independent prognostic factor in MM patients receiving up-front novel agent-based induction therapy and ASCT. PET/CT contributed to a more careful definition of CR, in particular after ASCT, and could be usefully incorporated into the algorithm to evaluate the depth of response in young MM patients. Disclosures: No relevant conflicts of interest to declare.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties used for treatment of renal cell carcinoma and gastrointestinal stromal tumors at a dose of 50 mg/day consecutively for 4 weeks followed by 2 weeks off per cycle. At present, no data are available on the early prediction of sunitinib response in renal cell carcinoma. We report a clinical case of a patient with metastatic renal cell carcinoma diagnosed with 11C-acetate PET and conventional CT and treated with sunitinib. Partial and complete remission documented by CT was preceded by early functional tumor inhibition shown by 11C-acetate-PET after only 14 days of therapy. This case report highlights some interesting points related to the potential role of a novel non-FDG PET tracer, 11C-acetate, in the early prediction of the response to targeted therapies in metastatic renal cell carcinoma.

Several authors reported the superiority of 68Ga-DOTANOC PET/CT to conventional imaging (CI) for the assessment of neuroendocrine tumors (NET). However, the detection of a higher number of lesions is not necessarily followed by a modification of disease stage or therapeutic approach. The aim of this study was to assess the impact of 68Ga-DOTANOC PET/CT on the clinical management of NET patients. Methods: The study included 90 patients with pathologic confirmation of NET, CT performed within a month of 68Ga-DOTANOC PET/CT, and a follow-up period of at least 1 y. PET/CT results were compared with CI results. As a standard of reference to finally evaluate PET results, clinical and imaging follow-up data were used. To assess the clinical impact of PET findings, all referring physicians were contacted after PET and asked about how patients were managed. Stage or therapy modifications were independently recorded, and the overall impact was evaluated patient by patient if PET results either affected therapy or caused a change in disease stage. Results: Considering PET/CT and CI concordant cases (47/90 [52.2%]), PET findings affected the therapeutic management in 17 of 47 (36.2%) patients. Although PET did not result in modification of disease stage, 68Ga-DOTANOC detected a higher lesion number in most patients. PET/CT and CI findings were discordant in 42 of 90 (46.7%) patients: PET resulted in a modification of stage in 12 patients (28.6%) and affected the treatment plan in 32 patients (76.2%). PET and CT were both equivocal in 1 patient (1/90). Considering all cases, 68Ga-DOTANOC PET/CT affected either stage or therapy in 50 of 90 (55.5%) patients. The most frequent impact on management (27 patients) was the initiation or continuance of peptide receptor radionuclide therapy, followed by the initiation or continuance of somatostatin analog medical treatment (7 patients) and referral to surgery (6 patients). PET prevented unnecessary surgery in 6 patients and excluded from treatment with somatostatin analogs 2 patients with NET lesions that did not express somatostatin receptors. Less frequent impacts on management included the initiation of radiotherapy (1 patient), further diagnostic investigation (1 patient), and liver transplantation (1 patient). Conclusion:68Ga-DOTANOC PET/CT either affected stage or caused a therapy modification in more than half the patients, thus confirming the clinical role of PET in the management of NET.

Background: Vertebral biopsy is fundamental in determining whether a spinal lesion is of infectious or neoplastic etiology. Accurate diagnosis is critical for proper medical and/or surgical treatment and consequently for the prognosis of the patient. CT-guided percutaneous spinal biopsy (CTSB) may minimize the risk of contamination and complications. Aim: To demonstrate the importance and efficacy of CTSB and subsequent microbiologic/histological examination in the diagnosis of spinal lesions, particularly for those of an infectious nature. Materials and Methods: Two series of spinal infection patients. Prospective series of 69 patients (2009-2011), 24 of whom underwent CTSB. Retrospective series of 130 patients (1999-2008), 65 of whom underwent CTSB. All patients had microbiologic and histological testing of biopsy samples, when possible. Results: For the 2009-2011 patient series, histological examination yielded a diagnosis in 81.8% of cases, microbiologic culture and PCR for Mycobacterium tuberculosis in 45.8%. For the 1999-2008 series, histological examination yielded a diagnosis in 69% of cases, culture in 38.5%. Spinal lesions in 4 patients with previous histories of malignancy were assumed to be metastatic and treated with radiation at outside institutions. After biopsy, all were revealed to be spondylodiscitis. Conclusions: Percutaneous CT-guided needle biopsy is the mainstay of diagnosis for spine lesions of unknown etiology, thus guiding appropriate treatment. Histological diagnosis, when possible, is critical before initiation of therapy and may be helpful in cases where cultures are negative. In the case of a spinal lesion of unknown origin, even in the setting of a previous malignancy, metastasis should not be assumed; infection and new primary lesions should always be considered as part of the differential diagnosis.

Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.