Positive FDG-PET Scan Research Articles

Abstract 15001: Correlating Site of Origin in Ventricular Arrhythmias With Site of Inflammation in Patients With Underlying Myocardial Inflammation via FDG-PET Scan

Introduction: Patients with underlying myocardial inflammation often present with otherwise unexplained ventricular arrhythmias. We seek to further elucidate if these arrhythmias originate from the areas of inflammatory FDG uptake, suggesting a direct arrhythmogenic substrate. Hypothesis: To determine if sites of inflammation on Fluorodeoxyglucose (FDG)-PET scan correlate with the site of origin on electroanatomic mapping for PVC/VT ablation in underlying myocardial inflammation. Methods: We retrospectively reviewed patients presenting with frequent ventricular arrhythmias (PVC/VT) with positive FDG-PET scans indicative of underlying myocardial inflammation, and included patients who had persisting, symptomatic, burdensome arrhythmias despite multiple cycles of immunosuppressive therapy or resolution of inflammation that eventually required catheter ablation for PVC/VT. Patients were then reviewed to see if their site of origin (SOO) of PVCs or VT correlated with the site of inflammation (SOI) seen on FDG-PET scan. Results: We studied 42 patients with documented PVCs or VT, a positive FDG-PET scan and eventual PVC/VT ablation. Mean age was 58.9 years + 14.5. Mean EF was 42.6 + 8.6%. Average PET SUV Max was 3.8 + 1.2, with an average involvement of 2.7 + 2.1 segments. Nearly all patients had multiple sites of FDG uptake (95.2%), with 69.% localized vs 31.0% diffuse distributions. The 42 patients had SOO in the following distribution: RVOT (30.1%), Inferoseptal (26.2%), RCC area, (19.0%), LVOT: (14.3%), Anteroseptal: (14.3%), Basal (11.9%), LV Summit (9.5%), and anterolateral (4%). 35.7% of patients had multiple SOO. Exact correlation between SOO-SOI was seen in 23/42 (54.8%), whereas partial correlation (matching sites with additional PVC locations vs uptake distributions, or additional uptake distributions vs PVC locations) was seen in 10/42 (23.8%). No correlation was seen in 9/42 (21.4%). Of the 19 that had partial or no correlation, the most frequent distributive area of uptake without PVC correlation was anterolateral, present in 7/19 (36.8%). Conclusions: In our retrospective study, patients undergoing cardiac FDG-PET scans to confirm myocarditis, had a positive correlation of site of PVC/VT origin and site of inflammation.

End-of-Treatment CT and Serial FDG-PET Imaging to Assess Residual Disease in Primary Mediastinal B-Cell Lymphoma

Background: Primary mediastinal B-cell lymphoma (PMBCL) is biologically related to classic nodular-sclerosis Hodgkin lymphoma. R-CHOP alone appears to be inadequate for many pts with retrospective studies indicating a benefit for consolidation XRT or use of intensive therapy regimens. End-of-therapy (EOT) FDG-PET is used to assess residual disease, but cannot accurately distinguish lymphoma from inflammation. We previously showed DA-EPOCH-R is effective in PMBCL, obviating the need for XRT in most pts, and showed that a positive EOT FDG-PET was typically not associated with treatment failure (Dunleavy et al. NEJM. 2013;368(15):1408-1416). We assessed the role of serial FDG-PET imaging to more accurately distinguish active disease from inflammation following DA-EPOCH-R for PMBCL.Methods: Ninety-three untreated PMBCL pts received DA-EPOCH-R without XRT. EOT FDG-PET was performed in 83 (89%) pts within 1 week of completing treatment and retrospectively scored per Deauville criteria in a blinded manner. Twenty-five (44%) of 57 pts with a negative (Deauville 1-3) EOT scan underwent follow-up FDG-PET imaging, mostly due to Deauville 3, which is no longer considered to indicate a positive FDG-PET scan. Twenty-three (88%) of 26 pts with a positive (Deauville 4-5) EOT scan underwent serial FDG-PET imaging approximately every 6 weeks. Three Deauville 4 pts (all non-progressors) did not have follow-up scans per protocol. If progressive SUV changes were noted on follow-up PET and/or size increase on concurrent CT, biopsy was attempted to confirm disease prior to implementing salvage therapy.Results: Characteristics were similar between the 83 pts with and 10 pts without evaluable EOT FDG-PET scans, aside from greater bulky tumor >/= 10 cm in the former group (63% vs. 20%, P = 0.014) (Table 1). All 93 pts were evaluable for response by CT with an ORR of 99% (88% CR, 11% PR). All 89 pts with complete tumor measurements had a reduction in the bi-dimensional product of the largest mediastinal tumor mass by CT. There was no relationship between EOT tumor reduction and EOT FDG-PET Deauville score (Figure 1). Furthermore, there was no difference in tumor reduction between pts with (6) and without (83) treatment failure (red arrows); median reduction 92% (range, 65-99) vs. 93% (range, 62-100), respectively (Figure 1).EOT FDG-PET scan was negative (Deauville 1-3) in 57 (69%) and positive (Deauville 4-5) in 26 (31%) pts. Disease progression occurred among 1/57 (2%) Deauville 1-3 pts, 1/18 (6%) Deauville 4 pts and 4/8 (50%) Deauville 5 pts. Two pts (both Deauville 5) died of progressive disease and 2 pts (Deauville 2 and 4, respectively) died without disease.In the 83 pts with EOT FDG-PET scans, 113 follow-up scans in 48 pts were performed (median, 1; range, 0-6). Pts with a negative EOT FDG-PET scan underwent a median of 0 (range, 0-4) scans compared to a median of 2 (range, 0-6) scans in pts with a positive EOT scan. Among pts who did not relapse/progress, the SUVmax remained relatively stable over time in the 21 pts with positive (Figure 2, upper) and 56 pts with negative EOT FDG-PET scans (data not shown). Five of 6 pts with treatment failure had a progressive increase in SUVmax on serial imaging (Figure 2, lower). Four of these pts (#2, 3, 5, and 6) had normalization of SUVmax following intervention (indicated by gray diagonal bars) with 1 pt (#1) having continued progression despite multiple salvage therapies. One patient (#4) with an elevated SUVmax at EOT had normalization of uptake following XRT.Conclusions: The degree of EOT tumor reduction by CT scan was unrelated to FDG-PET Deauville score or risk of disease recurrence. Negative EOT FDG-PET scans are highly predictive of cure following DA-EPOCH-R and further FDG-PET scanning should not be performed. Positive EOT FDG-PET scans were only indicative of residual disease in a minority of pts and should not be used alone to identify pts with residual disease. However, serial scans can identify pts with residual disease who require treatment. In conclusion, serial imaging should be performed in pts with positive EOT FDG-PET scans to accurately identify pts with disease. [Display omitted] DisclosuresAdvani:Merck: Research Funding; Agensys: Research Funding; Pharmacyclics: Research Funding; Nanostring: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Research Funding; Juno Therapeutics: Consultancy; Sutro: Consultancy; Infinity: Research Funding; FortySeven: Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy; Bayer Healthcare Pharmaceuticals: Research Funding; Cell Medica: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Kura: Research Funding; Gilead: Consultancy; Genentech: Research Funding; Spectrum: Consultancy; Millennium: Research Funding. Miljkovic:Pfizer Oncology: Research Funding.

P183 Assessing the safety of treatment cessation in Takayasu arteritis

Abstract Background Takayasu arteritis (TA) is a chronic granulomatous large vessel vasculitis. Patients typically receive immunosuppressive therapies, often continued indefinitely. Despite recent publication of recommendations for treatment initiation in TA, there is limited data on whether immunosuppressive treatments can ever be safely withdrawn. Our aim was to investigate the characteristics and outcomes of patients in long-term remission in whom immunosuppressive treatment had been stopped. Methods Clinical and radiographic data from a cohort of 160 TA patients followed-up over 20 years in a single tertiary specialist centre were analysed cross-sectionally, identifying those in whom immunosuppressive treatment was fully withdrawn. Baseline demographic data was collected and compared to those remaining on treatment. Outcomes assessed included status of follow-up imaging, change in inflammatory markers (CRP and ESR) and National Institute of Health (NIH) scores where data was available. A Mann Whitney U test was used for statistical analysis. Results Of the 160 patients analysed, 134 required treatment of whom 22 (16%) (all female, median age 47 years) had treatment fully withdrawn, after receiving immunosuppression for >6 months. Median age at diagnosis was 30 years and median number of arteries involved was 3. In those remaining on treatment, 89% were female (median age 47 years). All those withdrawn from treatment had received prednisolone, 15 methotrexate, 8 azathioprine, 2 mycophenolate and 2 cyclophosphamides. Median duration of treatment was 106 months (IQR 104 months). Median time from treatment cessation to analysis was 26 months (IQR 67 months). All 22 patients remained alive at the time of analysis, 17 (77%) had follow-up imaging post-treatment withdrawal (5 currently awaited). Only one patient suffered a disease flare after immunosuppression was stopped. This occurred 4 months post-withdrawal, confirmed by imaging with a positive FDG-PET scan, concurrent increases in inflammatory markers and NIH score consistent with new active disease. In the 21 cases in whom treatment was successfully withdrawn, CRP and ESR results pre- and post-treatment cessation were not significantly different (p = 0.944 and p = 0.322 respectively). Likewise, NIH scores compared pre- and post-treatment withdrawal revealed a median change 0 (range -1 to + 3). Conclusion Little data exists on the cessation of immunosuppression in complex rheumatic disease. Of 160 TA patients, 21/22 patients off treatment had stable outcomes. The baseline characteristics of this sub-group did not differ significantly from the whole cohort, however none of them had ever received biological therapy, suggesting a less refractory course. Although these data demonstrate that immunosuppression can be safely withdrawn, the median duration of treatment was 106 months, raising the question of whether withdrawal should be attempted earlier. Biomarkers are required to help identify those in whom treatment can be withdrawn. We aim to develop protocols to facilitate safe treatment cessation in order to minimise treatment-related side-effects and with potential economic impact. Disclosures C. Dahanayake None. R. Maughan None. T. Youngstein None. J.C. Mason Other; Professor Mason has participated in medical board meetings with Roche/Chugai.

Prevalence of 18F-fluorodeoxyglucose positron emission tomography abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disease that causes sudden cardiac death in the young. Inflammatory myocardial infiltrates have been described at autopsy and on biopsy, but there are few data on the presence of myocarditis in living patients with ARVC using non-invasive imaging techniques. FDG-PET is a validated technique for detecting myocardial inflammation in clinically suspected myocarditis. We aimed to determine the prevalence of myocardial inflammation in patients with ARVC using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and resultsWe performed a retrospective analysis of a single centre cohort of patients with ARVC referred for FDG-PET scans between 2012 and 2017 for investigation of symptoms or suspected device infection. Sixteen patients (12 male; age 42 ± 13 years) with a definite diagnosis of ARVC were identified. Seven had positive FDG-PET scans, two of whom had cardiac sarcoidosis on endomyocardial biopsy. Of the remaining five, two carried pathogenic desmoplakin mutations. FDG uptake was found in the left ventricular myocardium in all cases. One patient also had right ventricular uptake. ConclusionIn this exploratory study, we show that some patients with ARVC have evidence for myocardial inflammation on FDG-PET, suggesting that myocarditis plays a role in disease pathogenesis.

Predicting outcomes after a positive interim FDG-PET scan in advanced Hodgkin's lymphoma

Predicting outcomes after a positive interim FDG-PET scan in advanced Hodgkin's lymphoma

DA-EPOCH-R in Primary Mediastinal B-Cell Lymphoma; Analysis of End of Therapy FDG-PET and Outcome

Background: Primary mediastinal B-cell lymphoma (PMBL) is a distinct diffuse large B-cell lymphoma that occurs in adolescents and young adults. Retrospective studies suggest dose-intensive therapy is more effective than R-CHOP, and support a role for mediastinal radiation following R-CHOP. We demonstrated that DA-EPOCH-R is effective and obviates the need for mediastinal radiation, thus eliminating the risk of long-term toxicities (NEJM 2013;368:1408-16). End of therapy (EOT) FDG-PET is often performed to assess residual mass activity. The clinical value of EOT negative FDG-PET is under investigation in an international study in which FDG-PET negative patients are randomized to receive radiation or observation following immunochemotherapy (IELSG 37). All patients with an EOT positive FDG-PET receive mediastinal radiation. Herein, we investigate the predictive value of EOT FDG-PET following DA-EPOCH-R and provide updated results from the National Cancer Institute (NCI) and Stanford University Hospital publication of PMBL (NEJM 2013;368:1408-16).Methods: Ninety-two patients with newly diagnosed PMBL were treated with DA-EPOCH-R (Table 1). DA-EPOCH-R was administered for 6-8 cycles as previously described and no patients received up-front radiation. EOT FDG-PET was performed in 76 (83%) patients and scored retrospectively according to Deauville criteria with scores 4 to 5 called positive and scores 1 to 3 called negative. Patients with EOT positive FDG-PET scans were followed with serial scans to distinguish persistent disease from resolving inflammatory changes. The NCI and Stanford cohorts showed no significant differences in outcome and were therefore combined for analysis of event free survival (EFS) and overall survival (OS). Analyses of EFS and OS in patients with Deauville positive and negative EOT FDG-PET scans were also performed.Results: Patient characteristics were similar in the NCI and Stanford cohorts (Table 1). Overall, the median age was 31 years (range, 18 to 68), 59% were female, 59% had mediastinal masses > or = 10 cm and 20% of patients had stage IV disease. At a median follow-up of 5.3 years, the EFS and OS are 90% and 94%, respectively (Figure 1). Of 76 EOT FDG-PET scans performed, 25 (33%) were positive (Deauville score 4 or 5) and 51 (67%) were negative (Deauville score 1 to 3). Only 1 (2%) patient with an EOT negative FDG-PET scan relapsed (at 1 year), and 5 (20%) patients with an EOT positive FDG-PET scan had residual disease and received further therapy. EOT FDG-PET had a sensitivity and specificity of 83% and 71%, respectively, and a positive and negative predictive value of 20% and 98%. Comparison of outcome for EOT FDG-PET negative and positive patients at 5.3 years was 92% and 80% for EFS (p= 0.043), respectively, and was 94% and 91% for OS (p= 0.37) (Figure 2). Serial monitoring of false positive EOT FDG-PET scans showed reduction or occasionally stabilization of SUV, which is consistent with inflammatory causation. There were no events in the 16 patients without evaluable EOT FDG-PET scans resulting in an EFS of 100%. This EFS, however, was not significantly different than that of patients with evaluable EOT FDG-PET scans.Conclusions: DA-EPOCH-R (without radiation) is highly effective in PMBL and has an EFS of 90% with long-term follow-up. An EOT negative FDG-PET has a negative predictive value of 98%. Even among patients with an EOT positive FDG-PET, 80% are cured of disease and achieve long-term remission. These results demonstrate that EOT Deauville 4-5 FDG-PET scans following DA-EPOCH-R do not accurately identify patients with residual disease in most cases and should not be used to justify mediastinal radiation. In the absence of disease progression on CT scans, patients with EOT positive FDG-PET scans should be carefully monitored with short interval (e.g. 4-6 weeks) repeat FDG-PET scans to assess progressive SUV changes and need for biopsy before instituting further therapy. [Display omitted] [Display omitted] [Display omitted] DisclosuresAdvani:Kyowa Hakko Kirin: Consultancy, Honoraria; Infinity: Research Funding; FortySeven: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Research Funding; Sutro: Consultancy, Honoraria; Spectrum: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Stanford University: Employment; Millennium: Research Funding; Kura: Research Funding; Celgene: Research Funding; Regeneron: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Seattle Genetics: Research Funding; Agensys: Research Funding.

Arginase 1 Is a Marker of Myeloid-Mediated Immunosuppression with Prognostic Meaning in Classic Hodgkin Lymphoma

Purpose: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL.Experimental design: First, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N=40) and validation (N=78) sets.Results: s-Arg-1 was higher in patients with advanced stage (p=0.045), B-symptoms (p=0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p=0.012). Baseline levels of s-Arg-1 >200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2.Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p=0.0004 and p=0.012).Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N=63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N=46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N=9) with a 3-Y PFS of 37% (p=0.0004).Conclusions: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a potential novel potential biomarker for HL prognosis. DisclosuresVetro:MLL Munich Leukemia Laboratory: Employment. Chiarenza:Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy.

The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma.

PurposeNeutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL.Experimental designFirst, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N = 40) and validation (N = 78) sets.Resultss-Arg-1 was higher in patients with advanced stage (p = 0.045), B-symptoms (p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2.Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012).Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% (p = 0.0004).ConclusionsWe conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.

Controversies on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma.

Hodgkin lymphoma, even in advanced-stage, is a highly curable malignancy, but treatment is associated with short-term toxicity and long-term side effects. Early predictive markers are required to identify those patients who do not require the full-length standard therapy (and thus qualify for therapy de-escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of 18 F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) after a few cycles of chemotherapy (also known as 'interim FDG-PET') in predicting outcome in advanced-stage Hodgkin lymphoma. Furthermore, multiple interim FDG-PET-adapted trials, in which patients with positive interim FDG-PET scans are assigned to escalated therapies, and patients with negative interim FDG-PET scans are assigned to de-escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma in patients with positive and negative interim FDG-PET findings following continuation of standard chemotherapy or escalated/de-escalated therapy.

The Prognostic Value of the Myeloid-Mediated Immunosuppression Marker Arginase-1 in Classic Hodgkin Lymphoma

// Alessandra Romano 1 , Nunziatina Laura Parrinello 1 , Calogero Vetro 1 , Daniele Tibullo 1 , Cesarina Giallongo 1 , Piera La Cava 1 , Annalisa Chiarenza 1 , Giovanna Motta 1 , Anastasia L. Caruso 1 , Loredana Villari 2 , Claudio Tripodo 3 , Sebastiano Cosentino 4 , Massimo Ippolito 4 , Ugo Consoli 5 , Andrea Gallamini 6 , Stefano Pileri 7 , Francesco Di Raimondo 1 1 Division of Hematology, AOU “Policlinico - Vittorio Emanuele”, University of Catania, Catania, Italy 2 Division of Pathology, AOU “Policlinico - Vittorio Emanuele”, Catania, Italy 3 Tumor Immunology Unit, Department of Health Science, University of Palermo, Palermo, Italy 4 Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy 5 Division of Hematology, ARNAS Garibaldi, Catania, Italy 6 Research, Innovation and Statistics Department. A. Lacassagne Cancer Centre, Nice, France 7 Unita di Diagnosi Emolinfopatologica, IEO, Milano, Italy Correspondence to: Alessandra Romano, email: sandrina.romano@gmail.com Francesco Di Raimondo, email: diraimon@unict.it Keywords: Arginase-1, Hodgkin lymphoma, PET-2 Received: June 30, 2016 Accepted: September 05, 2016 Published: September 14, 2016 ABSTRACT Purpose: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. Experimental design: First, N-HL function was evaluated in vitro , showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training ( N = 40) and validation ( N = 78) sets. Results: s-Arg-1 was higher in patients with advanced stage ( p = 0.045), B-symptoms ( p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2. Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012). Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% ( p = 0.0004). Conclusions: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.

Residual FDG-PET metabolic activity in metastatic melanoma patients with prolonged response to anti-PD-1 therapy.

18-Fluorodeoxyglucose positron emission tomography (FDG-PET) scans were performed on 27 patients with unresectable stage IIIC or IV melanoma after prolonged treatment with anti-PD-1 antibodies to examine the hypothesis that patients with prolonged response to treatment may have metabolically inactive lesions by FDG-PET. Scans were performed at a median of 15.2months (range 12-29months) after starting treatment. Overall, 15 of 27 (56%) patients had a positive FDG-PET scan. Eight patients with positive scans underwent biopsy; 5 of 8 (62%) were melanoma and 3 of 8 (38%) were immune cell infiltrates. Of the 12 patients with negative FDG-PET scans, six had residual computerized tomography-visible lesions, five have ceased treatment, and none have recurred with follow-up of 6-10months. Patients with residual metastases after a prolonged period without progression on anti-PD-1 therapy may have metabolically inactive lesions. Isolated metabolically active lesions in clinically well patients may reveal immune cell infiltrates rather than melanoma.

False Positive FDG-PET Scan Caused by Uterine Leiomyoma

Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose (18F-FDG-PET) has an important role in the management of lymphoma, but it is important to keep in mind that not only lymphoma but also a number of other pathologic and non-pathologic processes can cause increased tissue FDG uptake. Our case is a rare example when a uterine fibroid caused differential diagnostic problem.

FDG PET in early stage cutaneous malignant melanoma

Fluorodeoxyglucose positron emission tomography (FDG PET) is not recommended in early stage melanoma; however, a significant number of cases are referred to our institution for FDG PET. We refer to early stage disease as American Joint Committee on Cancer (AJCC) stage I and II, which includes all cases without metastases. A retrospective review was undertaken to determine the clinical utility of FDG PET in this patient group. A retrospective study of FDG scans on all patients presenting to the WA PET Centre with early stage melanoma over a 5½ year period was undertaken. The positivity rate of the initial study for detection of malignant melanoma was determined. In patients with an initially negative FDG PET, the time from initial diagnosis to a positive surveillance study was determined. Both the initial positivity rate and time to a positive study were correlated with Breslow staging. Three hundred twenty-two patients were included in the study, of which 74 had initial positive FDG PET scans (23%). Adequate follow-up was available in 51 patients with the PET result confirmed as true positive in 37 (positive predictive value 73%). One hundred eight of 248 patients initially negative had follow-up scans during the follow-up period, of which 48 became positive. The 73% of recurrences were over 12 months post-diagnosis. No correlation with Breslow thickness was demonstrated. Despite FDG PET not being recommended for early cutaneous malignant melanoma, 27% of melanoma cases referred for FDG PET during the study period were AJCC stage I or II. Our results suggest FDG PET in early stage melanoma demonstrates occult disease in 17% of cases.

Blood Soluble PD-L1 Protein In Aggressive Diffuse Large B-Cell Lymphoma Impacts patient's Overall Survival

PurposeProgrammed death 1 (PD-1) protein is a key immune-checkpoint receptor expressed by activated T cells and it mediates immunosuppression. It has been recently shown that the blockade of PD-1 or its ligand, PD-L1, by monoclonal antibodies may lead to significant antitumor effects. In diffuse large B-cell lymphoma PD-L1 has been reported expressed by tumor cells and PD-1 by tumor-associated T cells. The dosage of soluble programmed death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed during a clinical trial. We evaluated the clinical impact of PD-L1 level measured at the time of diagnosis for newly diagnosed aggressive diffuse large B-cell lymphomas. MethodsTranslating a previous study (NEJMed2004; 350: 1287) in the rituximab era, the Groupe Ouest-Est des Leucemies et des Autres Maladies du Sang (GOELAMS) 075 study is a multicenter randomized trial in which adults 18 to 60 years old with untreated histologically proved CD20 positive diffuse large B-cell lymphoma were randomly assigned to receive 8 courses of R-CHOP or, high-dose chemotherapy associated to rituximab followed by autologous stem cell support (clinicaltrials.gov: NCT00561379). Patients were required to have an Ann Arbor stage of I or II with bulk greater or equal to 7 cm or, III or IV with 0 to 3 adverse prognostic factors as defined by the age-adjusted International Prognostic Index. The population of interest consisted of 288 of the 340 consecutively enrolled patients with available plasma collected at the time of diagnosis before any treatment. Soluble PD-L1 was measured using an ELISA assay. The median follow-up was 41.4 months. ResultssPD-L1 levels were found significantly increased in the plasma collected at diagnosis for patients compared to healthy -gender and age matched- subjects' levels (P<0.0001). The optimal cut-off point for PD-L1 measured at diagnosis was found to be equal to 1.52 ng/mL. Eighty-nine (30.9%) patients had a PD-L1 level greater than the cut-off point as compared to two (3%) controls. The high-level sPD-L1 group was significantly associated with bone marrow involvement, more than one extranodal localization and, 2-4 performance ECOG status. None of the other patients' characteristics, including the assigned arms of randomization and, the positive vs. negative FDG-PET scan response at the intermediate evaluation, was associated with high PD-L1 level. The PD-L1 immunohistochemical analysis showed that 55 out of the 73 interpretable tissue microarrays presented at least 5% of PD-L1-positive tumor cells. No association was found between sPD-L1 and tumor PD-L1 expressions (p=0.5). The 73 patients were representative of our 288 patients' cohort, with significantly decreased overall survival for patients with a high level of sPD-L1 compared to those with low sPD-L1 levels (64.6 vs. 86.7%, P=0.007). Cell-of-origin analysis using Hans's criteria on the tissue microarrays did not shown any correlation between elevated sPD-L1 and GC or non-GC origin.Patients with elevated PD-L1 experienced a poor prognosis with a three-year overall survival of 76 vs. 89 percent (P<0.001).There was no difference of overall survival rates between the two arms of treatment. Univariate analysis identified age greater than 50 years old, high-intermediate and, high age-adjusted International Prognostic Index score, bone marrow involvement, more than one extranodal localization, Ann Arbor stage after FDG-PET scan of III or IV, abnormal lymphocyte-monocyte score and, high level of sPD-L1 as factors associated with poor survival. High level of sPD-L1, bone marrow involvement and, abnormal lymphocyte-monocyte score were found after multivariate analysis to be the only factors remaining significant after adjustment with a P-value <0.05. Soluble PD-L1 was detectable in the plasma and not in the serum, found elevated in lymphoma patients at diagnosis compared to healthy subjects and its level dropped back to normal value for patients in complete remission. The intention-to-treat analysis showed that elevated PD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). [Display omitted] ConclusionSoluble PD-L1 protein expression in peripheral blood at the time of diagnosis is a potent predicting biomarker in diffuse large B-cell lymphoma and may indicate usefulness of alternative therapeutic strategies using PD1 axis inhibitors. Disclosures:Fest:Roche SA France: Research Funding.

Hexokinase 2 as oncotarget

Hexokinase 2 as oncotarget

Early Treatment Intensification in Advanced-Stage High-Risk Hodgkin Lymphoma (HL) Patients, with a Positive FDG-PET Scan After Two ABVD Courses – First Interim Analysis of the GITIL/FIL HD0607 Clinical Trial

AbstractAbstract 550 Background:Interim FDG-PET performed after 2 chemotherapy courses (PET-2) is the most powerful predictor of treatment outcome in advanced-stage, ABVD-treated HL (AAHL) patients (pts). Whether early therapy intensification in PET-2 positive HL pts improves overall treatment efficacy for all AAHL pts compared to standard ABVD is still unproven. Patients and study design:In the HD 0607 clinical trial (ClinicalTRial.gov identifier 00795613), AHL (stage IIB-IVB) pts prospectively enrolled by 26 Italian and one Israelian institution are treated with 2 ABVD courses and a PET-2 performed afterwards. PET-2+ pts are randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4+4 courses) or Be+Bb (4+4) and Rituximab (R). PET-2 negative pts are treated with 4 additional ABVD and, upon CR achievement, randomized to either consolidation radiotherapy (Rxt) on the sites of initial bulky disease or no further treatment. Primary endpoint is the efficacy and feasibility of the overall therapeutic strategy. All the non-negative PET-2 (nnPET-2), defined as scans without any residual FDG uptake in any site outside the physiological areas of the tracer concentration, are uploaded in a website for blinded independent central review (BICR) by 6 nuclear medicine experts. Scans are interpreted by visual assessment according to the Deauville 5-point scale (5PS). Results:Starting from 07/2008 till 07/2012, 497 AHL pts were consecutively enrolled and 446 scanned with PET-2. 189/446 (42%) PET-2scans, judged as nnPET-2 by the local PET center, underwent review: 92 were adjudged as positive (62 score 4, 30 score 5) and 97 as negative (score 1–3). Altogether, of 446 pts scanned with a PET-2, 92 (20%) resulted positive and 354 (80%) negative. Age, sex, stage III-IV, bulky, extranodal sites or IPS class where equally distributed among PET-2 positive and negative pts.(p>.05). The median time from PET uploading in the website to review was 45.38 hours, (1–119). The BICR yielded a binary concordance rate among pair of reviewers “very good”, ranging from 0.77 to 0.83 (Cohen’s k coefficient) and a overall concordance rate of 0.77 (Krippendorf’s alpha). In 92 PET-2+ pts, 60 showed a single site of residual uptake in mediastinal (48), laterocervical (4), supraclavear (2), abdominal (3), axillary (1) nodes and in lung (2).In 32 there were ≥ 2 sites of persistent FDG uptake. In 38/40 pts with a positive PET-2 and bulky disease at baseline the residual FDG uptake (singe or multifocal) was seen within the bulky lesion. Overall response to treatment could be assessed in a cohort of 263 pts who had been fully restaged after lymphoma treatment. Forty-one (15%) had a positive and 222 (84%) a negative PET-2 scan. The relative dose intensity (RDI) for Be+Bb ± R and ABVD ± RxT treated pts. was 94.7% and 97.8%, respectively. Among 41 PET-2+ pts CR was achieved in 30 (73%), PR in 1 (2%) Progression or Relapse (Pro/Rel) in 8 (19%) and not evaluable (NE) in 2(5%). Among 222 PET-2- pts. CR was achieved in 212 (95.5%), PR in 2 (1%), Pro/Rel in 6 (3%), NE in 1 (0,5%). Treatment efficacy could be assessed in a cohort of 187 pts. with a complete treatment and a minimum follow-up of 12 months from treatment completion: 27 (15%) with a positive PET-2, treated with Be+Bb ± R and 160 (85%) with a negative PET-2, treated with ABVD ± RxT. The median follow-up from diagnosis was 845 days (101–1345). Among 27 PET-2+ pts, CCR (Continuous CR) was recorded in 22 (81%) Pro/Rel in 5 (18%). Three patients died in CR: 2 for septic shock and one for pneumonia. Among 160 PET-2- pts. CCR was recorded in 146 (91%), Pro/Rel in 9 (5%), Lost of FU (in CR) in 5 (3%). The 1-y PFS was 80.5%, 97.3% and 94.7% for PET-2+, PET-2- p, and for the entire population, respectively. Overall, treatment was well tolerated: 512 Adverse effects were reported: WHO grade 0+1: 453, grade 2: 45. Grade 3 were observed in 12 pts: anemia (2), neutropenia (6), pancytopenia (1), sepsis (1), diverticulitis (1), Vomiting (1). Grade 4 in 2 pts: pneumonia and neutropenia. Conclusions:These preliminary findings suggest that 1) an early switch from ABVD to escalated BEACOPP can be done safely in PET-2 positive pts, with CR achievement in the majority of cases; 2) a centralized online PET scan review system is feasible and allows a real time decision making process, without significant reduction in the RDI administered; 3) 5PS is a reliable interpretation criteria for interim PET scan, with a very good concordance rate among reviewers. Disclosures:No relevant conflicts of interest to declare.

Probability of Malignancy in Solitary Versus Multiple Pulmonary Nodules in Positive FDG PET Scan

PURPOSE: Determination of the performance of PET in predicting the probability of malignancy in patients with solitary versus multiple pulmonary nodules with/without hilar and mediastinal lymphadenopathy.

A pilot safety and feasibility trial of a reduced carbohydrate diet in patients with advanced cancer.

e13573 Background: Most aggressive cancers share a glycolytic phenotype associated with increased uptake of 18F-2-fluoro, 2-deoxyglucose (FDG) that may be detected by positron emission tomography (PET). We hypothesized that a carbohydrate restricted (CR) diet, by inhibiting insulin secretion, enlists plausible mechanisms to limit cancer growth. Methods: Patients with advanced incurable cancer were eligible if they had a positive FDG-PET scan, an ECOG performance status of 0-2 associated with normal organ function, no diabetes or recent weight loss, and a BMI >20 kg/m2. A supervised CR diet (5% of total kCal) was monitored weekly for macronutrient intake, body weight, serum electrolytes, betahydroxybutyrate concentrations [BHB], insulin, and insulin like growth factor-1 and 2 (IGF-1and IGF 2]. A FDG-PET scan was obtained before and after the CR diet. Results: Ten subjects completed 26-28 days of the CR diet without associated adverse effects. Mean caloric intake decreased by (35 + 6)% compared to baseline predictions of caloric requirements, and weight decreased by a median of 4% (range 0.0-6.1%.). One patient had advanced but indolent disease. Patients with non-progression (n=5), representing stable disease (SD) or partial remission (PR) on the post-CR diet FDG-PET scan exhibited three-fold higher dietary ketosis (p<0.02) when compared with patients with progressive disease (PD; n=4); but non-progression was not correlated with reduced calorie intake (p=0.65) or weight loss (p=0.35). Ketosis correlated inversely with serum insulin levels (r=0.62, p<0.001). Conclusions: A carbohydrate restricted diet is feasible in selected patients with advanced cancer, resulting in reduced serum insulin concentration and ketosis. Disease stabilization is correlated with the highest degrees of ketosis, supporting further evaluation of CR as a means of insulin secretory inhibition, and as a complementary approach in conjunction with standard and endocrine therapies. Energy deficit Pt. no. PET scan Ketosis on CR diet compared with baseline levels 0.35 3* SD 2.7 ± 1.2 0.42 2 PR 23.3 ± 14.2 0.29 5 SD 13.1 ± 18.5 0.53 7 SD 14.6 ± 11.8 0.07 8 SD 8.2 ± 2.8 0.45 10 SD 23.6 ± 8.2 0.33 1 PD 2.1 ± 1.9 0.28 4 PD 2.8 ± 1.2 0.31 6 PD 4.2 ± 2.8 0.60 9 PD 11.4 ± 4.5

Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival

The aim of the present study was to investigate the prognostic role of pre- and/or early post-autologous stem cell transplantation (ASCT) (18)F-flourodeoxyglucose (FDG) positron emission tomography (PET) in patients with relapsed/refractory Hodgkin lymphoma. Forty-three consecutive patients were enrolled in this study. FDG-PET/CT was performed following salvage chemotherapy within 6 weeks of undergoing ASCT and at the first month after ASCT. FDG-PET positivity was found in 26 patients before ASCT and in 13 patients after ASCT. The patients who had negative PET scan before or after ASCT had significantly better outcomes in terms of overall survival (OS) and progression-free survival (PFS). Pre- and post-ASCT FDG-PET positivity was found to be independently associated with PFS while post-ASCT FDG-PET was an independent factor with an impact on OS in multivariate analysis. (18)F-flourodeoxyglucose positron emission tomography imaging may be useful in predicting prognosis after ASCT. Furthermore, effective treatment options including allogeneic stem cell transplantation might be considered in patients with positive FDG-PET scan after salvage chemotherapy and ASCT.

Risk-Adapted Dose-Dense Immunochemotherapy Determined by Interim FDG-PET in Advanced-Stage Diffuse Large B-Cell Lymphoma

PURPOSE In studies of diffuse large B-cell lymphoma, positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) performed after two to four cycles of chemotherapy has demonstrated prognostic significance. However, some patients treated with immunochemotherapy experience a favorable long-term outcome despite a positive interim FDG-PET scan. To clarify the significance of interim FDG-PET scans, we prospectively studied interim FDG-positive disease within a risk-adapted sequential immunochemotherapy program. PATIENTS AND METHODS From March 2002 to November 2006, 98 patients at Memorial Sloan-Kettering Cancer Center received induction therapy with four cycles of accelerated R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by an interim FDG-PET scan. If the FDG-PET scan was negative, patients received three cycles of ICE (ifosfamide, carboplatin, and etoposide) consolidation therapy. If residual FDG-positive disease was seen, patients underwent biopsy; if the biopsy was negative, they also received three cycles of ICE. Patients with a positive biopsy received ICE followed by autologous stem-cell transplantation. RESULTS At a median follow-up of 44 months, overall and progression-free survival were 90% and 79%, respectively. Ninety-seven patients underwent interim FDG-PET scans; 59 had a negative scan, 51 of whom are progression free. Thirty-eight patients with FDG-PET-positive disease underwent repeat biopsy; 33 were negative, and 26 remain progression free after ICE consolidation therapy. Progression-free survival of interim FDG-PET-positive/biopsy-negative patients was identical to that in patients with a negative interim FDG-PET scan (P = .27). CONCLUSION Interim or post-treatment FDG-PET evaluation did not predict outcome with this dose-dense, sequential immunochemotherapy program. Outside of a clinical trial, we recommend biopsy confirmation of an abnormal interim FDG-PET scan before changing therapy.