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        Combined PET and Biopsy Evidence of Marrow Involvement Improves Prognostic Prediction in Diffuse Large B-Cell Lymphoma

        Cerci, Juliano J.,Gyö,rke, Tamá,s,Fanti, Stefano,Paez, Diana,Meneghetti, José,Clá,udio,Redondo, Francisca,Celli, Monica,Auewarakul, Chirayu,Rangarajan, Venkatesh,Gujral, Sumeet,G Society of Nuclear Medicine 2014 The Journal of nuclear medicine Vol.55 No.10

        <P>Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. <B>Methods:</B> The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. <B>Results:</B> Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (<I>n</I> = 231) were 81% (95% confidence interval [CI], 76%–86%) for event-free survival (EFS) and 88% (83%–91%) for overall survival (OS); cases identified only on PET (<I>n</I> = 61), 81% (69%–89%) for EFS and 88% (77%–94%) for OS; cases indentified only on biopsy (<I>n</I> = 10), 80% (41%–95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (<I>n</I> = 25), 45% (25%–64%) for EFS and 55% (32%–73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48–4.79) for EFS and 3.94 (1.93–8.06) for OS. <B>Conclusion:</B> This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow <SUP>18</SUP>F-FDG uptake identified on the staging PET scan. Abnormal <SUP>18</SUP>F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.</P>

      • Prospective International Cohort Study Demonstrates Inability of Interim PET to Predict Treatment Failure in Diffuse Large B-Cell Lymphoma

        Carr, Robert,Fanti, Stefano,Paez, Diana,Cerci, Juliano,Gyö,rke, Tamá,s,Redondo, Francisca,Morris, Tim P.,Meneghetti, Claudio,Auewarakul, Chirayu,Nair, Reena,Gorospe, Charity,Chung, June-Key Society of Nuclear Medicine 2014 The Journal of nuclear medicine Vol.55 No.12

        <P>The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). <B>Methods:</B> Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2–3 cycles of chemotherapy and at the end of chemotherapy scored visually. <B>Results:</B> Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%–83%) for event-free survival (EFS) and 86% (95% CI, 81%–89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET–negative, and 117 (36%) were I-PET–positive. Two-year EFS was 90% (95% CI, 85%–93%) for I-PET–negative and 58% (95% CI, 48%–66%) for I-PET–positive, with a hazard ratio of 5.31 (95% CI, 3.29–8.56). Two-year OS was 93% (95% CI, 88%–96%) for I-PET–negative and 72% (95% CI, 63%–80%) for I-PET–positive, with a hazard ratio of 3.86 (95% CI, 2.12–7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%–98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%–100%). In contrast, the 107 I-PET–positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%–93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%–48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. <B>Conclusion:</B> This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.</P>

      • Selective Referral Using CCTA Versus Direct Referral for Individuals Referred to Invasive Coronary Angiography for Suspected CAD : A Randomized, Controlled, Open-Label Trial

        Chang, Hyuk-Jae,Lin, Fay Y.,Gebow, Dan,An, Hae Young,Andreini, Daniele,Bathina, Ravi,Baggiano, Andrea,Beltrama, Virginia,Cerci, Rodrigo,Choi, Eui-Young,Choi, Jung-Hyun,Choi, So-Yeon,Chung, Namsik,Cole American College of Cardiology 2019 JACC. Cardiovascular imaging Vol.12 No.7

        <P><B>Graphical abstract</B></P><P>[Figure]</P><P><B>Abstract</B></P><P><B>Objectives</B></P><P>This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive coronary angiography (ICA) as the index procedure.</P><P><B>Background</B></P><P>Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis.</P><P><B>Methods</B></P><P>In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy. The primary endpoint was noninferiority with a multiplicative margin of 1.33 of composite major adverse cardiovascular events (blindly adjudicated death, myocardial infarction, unstable angina, stroke, urgent and/or emergent coronary revascularization or cardiac hospitalization) at a median follow-up of 1-year.</P><P><B>Results</B></P><P>At 22 sites, 823 subjects were randomized to a selective referral and 808 to a direct referral strategy. At 1 year, selective referral met the noninferiority margin of 1.33 (p = 0.026) with a similar event rate between the randomized arms of the trial (4.6% vs. 4.6%; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.47). Following CCTA, only 23% of the selective referral arm went on to ICA, which was a rate lower than that of the direct referral strategy. Coronary revascularization occurred less often in the selective referral group compared with the direct referral to ICA (13% vs. 18%; p < 0.001). Rates of normal ICA were 24.6% in the selective referral arm compared with 61.1% in the direct referral arm of the trial (p < 0.001).</P><P><B>Conclusions</B></P><P>In stable patients with suspected CAD who are eligible for ICA, the comparable 1-year major adverse cardiovascular events rates following a selective referral and direct referral strategy suggests that both diagnostic approaches are similarly effective. In the selective referral strategy, the reduced use of ICA was associated with a greater diagnostic yield, which supported the usefulness of CCTA as an efficient and accurate method to guide decisions of ICA performance. (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization [CONSERVE]; NCT01810198)</P>

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