The term extranodal disease refers to lymphomatous infiltration of anatomic sites other than the lymph nodes. Almost any organ can be affected by lymphoma, with the most common extranodal sites of involvement being the stomach, spleen, Waldeyer ring, central nervous system, lung, bone, and skin. The prevalence of extranodal involvement in non-Hodgkin lymphoma and Hodgkin disease has increased in the past decade. The imaging characteristics of extranodal involvement can be subtle or absent at conventional computed tomography (CT). Imaging of tumor metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) has facilitated the identification of affected extranodal sites, even when CT has demonstrated no lesions. More recently, hybrid PET/CT has become the standard imaging modality for initial staging, follow-up, and treatment response assessment in patients with lymphoma and has proved superior to CT in these settings. Certain PET/CT patterns are suggestive of extranodal disease and can help differentiate tumor from normal physiologic FDG activity, particularly in the mucosal tissues, bone marrow, and organs of the gastrointestinal tract. Familiarity with the different extranodal manifestations in various locations is critical for correct image interpretation. In addition, a knowledge of the differences in FDG avidity among the histologic subtypes of lymphoma, appropriate timing of scanning after therapeutic interventions, and use of techniques to prevent brown fat uptake are essential for providing the oncologist with accurate information.

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131 I-meta-iodobenzylguanidine (HSA 131 I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131 I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131 I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131 I-MIBG, 17 (25%; 95% confidence interval, 16%–37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9–49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131 I-MIBG. Conclusion: HSA 131 I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Compared with previous reports in prerituximab era, addition of rituximab resulted in reduced PPV and sensitivity of mid- and posttherapy PET in patients with aggressive B-cell NHL.

The objective of this review is to make physicians aware of new radionuclide methods to detect cardiac effects of chemotherapeutic drugs. This knowledge is important because of the limitations of the physical examination and the electrocardiogram for detecting early reversible cardiac damage. Presently left ventricular ejection fraction (LVEF) is routinely used to screen for cardiotoxicity. Since LVEF obtained by radionuclide angiocardiography is more accurate than the LVEF estimated by echocardiography, serial radionuclide LVEF monitoring is most commonly used to monitor cardiotoxicity. Diastolic measurements of left ventricular function (such as peak filling rate) are now being added to routine LVEF measurements to enhance standard radionuclide evaluation. This screening test should be done prior to beginning therapy and at appropriate points based on the baseline study, therapy scheme and the patient’s clinical status. At some centers, exercise LVEF methods are being used to determine if cardiac reserve is adequate for the patient to tolerate additional chemotherapy when cardiac injury may be present. Previously, endomyocardial biopsy was needed to detect and confirm early anthracycline cardiotoxicity. This invasive test may be replaced by a new noninvasive in vivo method using radioactive monoclonal antibodies against cardiac muscle (indium-lll-antimyosin). Because cardiac failure has been associated with adrenergic neuron injury, it has been proposed that radioactive methyliodo-benzylguanine may detect the adrenergic abnormality which may predict future development of congestive heart failure or sudden death months after therapy is discontinued. Advantages and disadvantages of these methods in evaluating cardiotoxicity, and an algorithm to optimally monitor antitumor therapy-induced cardiomyopathy are discussed.

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BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma.

Although 123I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of 123I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma. Methods A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of 123I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up. Results Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), 123I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity. Conclusion This prospective study demonstrated a sensitivity of 82%–88% and specificity of 82%–84% for 123I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.