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At least 70–80% of the patients with Hodgkin lymphoma (HL) can be cured with first-line therapy with the improvement of staging methods and the introduction of increasingly effective chemotherapy r...

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Positron emission tomography with integrated computed tomography (PET/CT) is increasingly used for the initial staging, final or even interim (mid-treatment) response assessment in malignant lymphomas. Extensive clinical experience has been gained with Hodgkin lymphoma (HL) and aggressive B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBCL) and other subtypes, which are the subject of the present review. The use of PET/CT is now considered mandatory for baseline staging in these entities, providing more accurate information and obviating the need of bone marrow biopsy (BMB) at least in HL. PET/CT has been the long-standing “gold standard” for final response assessment. Furthermore, early interim PET evaluation provides valuable prognostic information in HL and DLBCL. In HL, it appears that treatment intensification with Bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP)-escalated can improve disease control in patients with persistent PET positivity after two cycles of ABVD. However, there is no randomized evidence of survival benefit as yet. In contrast, regimens effective in overcoming the adverse impact of persistent PET positivity have not been yet described in DLBCL. The 2014 recommendations suggest the use of PET/CT for baseline staging and final response assessment in all [18F]fluorodeoxyglucose (FDG)-avid lymphoma subtypes, including the above named ones. The use of interim evaluation is not considered fully documented yet. The exact role of PET/CT in guiding treatment decisions has to be defined by ongoing and future randomized trials and evidence-based approaches are expected to become available in the near future.

AIM To examine the real-life impact of baseline positron-emission tomography/computed tomography (PET/CT) in Hodgkin lymphoma (HL). PATIENTS AND METHODS A total of 162 consecutive patients with HL were retrospectively studied. RESULTS Disease was up-staged in 26 patients (16%) and down-staged in 9 (6%). However, treatment strategy was modified in only 10 patients (6% of total). Involved field radiotherapy was delineated according to PET/CT in 36/66 patients (59%). These treatment modifications did not significantly affect outcome. Moreover, three potent prognostic parameters were identified: the number of involved sites, maximum standardized uptake value (SUVmax), and the product of SUVmax and maximal largest lesion diameter, as a surrogate of total lesion glycolysis. All three significantly correlated with 5-year freedom from disease progression p=0.004, p=0.009 and p=0.04, respectively). CONCLUSION Baseline PET/CT findings may lead to treatment modification in

Aggressive B-cell lymphomas include diffuse large B-cell lymphomas not otherwise specified (DLBCL NOS), other subtypes of DLBCL [T-cell/histiocyte-rich LBCL, DLBCL leg type, primary DLBCL of the central nervous system (CNS), and Epstein-Barr virus (EBV+) DLBCL of the elderly], “other neoplasms of large B cells,” mainly including primary mediastinal large B-cell lymphoma (PMLBCL) and several other very uncommon entities (see Chap. 4), and cases with borderline features between DLBCL and Hodgkin lymphoma (HL) or DLBCL and Burkitt lymphoma, the so-called gray-zone lymphomas. This chapter is focused to DLBCL NOS and other subtypes of DLBCL (except of primary CNS, which is covered in Chap. 13) as well as to PMLBCL, i.e., to the most frequent entities classified in aggressive B-cell lymphomas.

This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.

PET/CT has a key role in final response assessment after chemotherapy in several types of malignant lymphomas, as well as in baseline staging and interim (mid-treatment) evaluation. Its application is widely established in Hodgkin lymphoma (HL) and aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMLBCL), and other related subtypes. Its role in follicular lymphomas, mantle cell lymphoma (MCL), “nodal” T-cell lymphomas, and Burkitt lymphoma is less well established, while it is much more controversial in other low-grade lymphomas and primary extranodal lymphomas other than DLBCL.

Indium-111 monoclonal antimyosin antibody imaging is a convenient method to diagnose acute myocarditis. The present study examined the natural evolution of a positive antimyosin scan in 10 patients with acute myocarditis, in relation to left ventricular ejection fraction. All patients underwent myosin-specific monoclonal antibody imaging and radionuclide ventriculography; in all patients endomyocardial biopsy was performed. Repeat assessment of left ventricular function and antimyosin uptake was performed 1, 2 and 6 months later. A heart-to-lung ratio was used to quantify antimyosin uptake. Heart-to-lung ratio in patients with myocarditis was 2.12 +/- 0.31, significantly higher than that observed in eight controls (1.35 +/- 0.08, P0.001). During follow-up 2.2 repeat scans per patient were performed. Heart-to-lung ratio normalized (1.6) within 1 month in four patients, within 2 months in one patient and within 6 months in two patients; three patients continued to have a positive antimyosin uptake at 6 months, suggesting ongoing myocardial necrosis. At the end of follow-up, ejection fraction improved by5% in four patients; normalization or persistence of tracer uptake could not predict an improvement of ejection fraction. It is concluded that antimyosin scintigraphy is useful for diagnosing myocarditis in its subacute or chronic stage during which unknown or immune mechanisms may be in operation. An improvement in left ventricular function cannot be predicted on the basis of persistence or not of tracer uptake.

The purpose of this study was to determine the significance of transient ST-segment elevation during dobutamine infusions in patients with healed Q wave myocardial infarction. Twenty-seven patients with previous Q wave myocardial infarction were studied prospectively with dobutamine-thallium-201 single-photon emission computed tomography. The presence of ST-segment elevation in leads with Q waves was related to thallium reversibility at 4-hour redistribution imaging or after reinjection, to residual flow, as well as to wall motion abnormalities in the infarcted zone. ST-segment elevation in infarct-related leads was observed in 15 patients; 11 (73%) showed viability by thallium-201 in the infarcted zone. In patients without ST-segment elevation, viability was shown less frequently (33%, P < .05). Hypokinesis in infarcted segments was present in 60% of patients with ST-segment elevation and in 25% of patients without ST-segment elevation (.05 < P < .1). Finally, infarct-related artery was patent and/or collaterals were present in 10 patients with ST-segment elevation (67%) and in 4 patients without (33%, .05 < P < .1). In conclusion, ST-segment elevation during dobutamine infusion is a marker of residual viability in infarcted segments.

The diagnostic value of antimyosin scanning in 7 patients with biopsy-proven cardiac amyloidosis was examined in this study. Antimyosin imaging was positive in all amyloid patients, with more intense uptake in patients with heart failure.

To examine the incidence of a positive indium-111 antimyosin scintigraphy in patients with unstable angina, we prospectively examined 25 patients with unstable angina and 11 patients with stable angina. All patients were injected with 2 mCi of indium-111 on admission and planar scintigraphy was performed 48 h later. Symptoms and signs of ischemia indicating severity of ischemia were monitored during the period between injection and scanning. None of the patients developed a rise in cardiac enzymes suggesting myocardial necrosis. Seven (28%) of the 25 patients with unstable angina had positive antimyosin scanning; no stable patients had positive scanning. All seven patients with unstable angina and positive scanning had signs of severe ischemia (four patients had multiple episodes of2/day, three patients had prolonged episodes of15 min, three patients had ST depression in3 EKG leads) while only one of the eighteen unstable patients with negative scannings had signs of severe ischemia (P0.001). In conclusion, (1) a significant number of unstable angina patients present positive antimyosin scanning without an elevation of cardiac enzymes and (2) these patients usually present multiple or severe episodes of ischemia indicating that during these episodes, minor myocardial necrosis, undetected by enzymes, may occur.

111In-antimyosin scintigraphy offers a valuable noninvasive method for early detection of clinically silent cardiac involvement in patients with systemic sclerosis, even in the absence of left ventricular dysfunction. In these patients with positive antimyosin study results, intense pharmacologic treatment with vasodilators may be warranted.

Three patients, 2 women and 1 man, with primary (AL) amyloidosis without congestive heart failure are described; all 3 patients presented reduced I-123 metaiodobenzylguanidine (MIBG) myocardial uptake suggesting marked cardiac sympathetic denervation. This is the first time myocardial adrenergic denervation is described in patients with AL amyloidosis without evidence of congestive heart failure; the observed denervation could be implicated in the pathogenesis of cardiac conduction disturbances which are common in this disease.