Aldo N. Serafini

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION 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.

FDG PET/CT of Extranodal Involvement in Non-Hodgkin Lymphoma and Hodgkin Disease

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.

Review of tests for monitoring doxorubicin-induced cardiomyopathy.

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 patients 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-111-antimyosin). Because cardiac failure has been associated with adrenergic neuron injury, it has been proposed that radioactive methyliodobenzylguanine 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.

High incidence of false-positive PET scans in patients with aggressive non-Hodgkin's lymphoma treated with rituximab-containing regimens

BACKGROUND Positron emission tomography (PET) is a powerful predictor of relapse and survival in non-Hodgkins lymphomas (NHLs) based on studies carried out in the prerituximab era. Little is known about the predictive power of PET in rituximab-treated patients. PATIENTS AND METHODS Patients with aggressive B-cell NHL with baseline and follow-up PET studies were included. Clinical characteristics, PET and computed tomography scans, biopsy results, and outcomes were reviewed. PET was defined as positive if higher than mediastinal or background activity was observed. RESULTS In all, 51 patients (diffuse large B cell-38; mantle cell lymphoma-13) treated with rituximab-containing regimens were included. For 13 of 40 patients (32.5%), mid-therapy PET studies were positive and 9 of 48 patients (18.7%) had positive posttherapy PET. The positive predictive value (PPV), negative predictive value (NPV), sensitivity (Se), and specificity (Sp) of the mid-therapy PET for predicting relapse were 33% [95% confidence interval (CI) 19% to 49%], 68% (95% CI 51% to 81%), 33% (95% CI 6% to 76%), and 68% (95% CI 49% to 82%), respectively. For posttherapy PET, the relapse PPV, NPV, Se and Sp were 19% (95% CI 9% to 33%), 81% (95% CI 67% to 91%), 13% (95% CI 0.6% to 53%), and 80%(95% CI 64% to 90%), respectively. CONCLUSIONS 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.

Osteomyelitis of the base of the skull

Infection in the marrow of the temporal, occipital, and sphenoid bones is an uncommon, but increasing occurrence. It is usually secondary to infections beginning in the external auditory canal and is caused almost uniformly by the gram negative Pseudomonas aeruginosa bacteria. Technetium and gallium scintigraphy help in the early detection of such infections while CT scans demonstrate dissolution of bone in well‐developed cases. Headache is the predominant symptom. Dysphagia, hoarseness, and aspiration herald the inevitable march of cranial nerves. We have diagnosed and treated 17 cases of osteomyelitis of the skull base. Although the total mortality rate is 53%, it is now a curable disease. Six of our last 8 patients remain alive, although 1 is still under treatment. Treatment is medical and requires the long‐term concomitant intravenous administration of an aminoglycoside and a broad spectrum semisynthetic penicillin effective against the causative organism.

Usefulness of 123I-MIBG Scintigraphy in the Evaluation of Patients with Known or Suspected Primary or Metastatic Pheochromocytoma or Paraganglioma: Results from a Prospective Multicenter Trial

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.

Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial

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.

CURRENT STATUS OF SYSTEMIC INTRAVENOUS RADIOPHARMACEUTICALS FOR THE TREATMENT OF PAINFUL METASTATIC BONE DISEASE

PURPOSE Intractable bone pain secondary to bone metastasis from prostate, lung, breast, and other malignancies is a major problem in the management of the oncological patient. Because a number of factors are implicated in the pathophysiology of bone pain, a multidisciplinary approach in its assessment and treatment is often required. Treatment often includes the use of analgesic drug therapy; however, radiation therapy, hormonal therapy, chemotherapy, and surgery may also be needed. METHODS AND MATERIALS The use of systemic radionuclide therapy may often be helpful to relieve bone pain and improve the quality of life. In the setting of diffuse bone metastasis, intractable to conventional therapy, various radioisotopes have been advocated. These include phosphorous-32, iodine-131, strontium-89, yttrium-90, samarium-153, and rhenium-186, often as either the anionic phosphate or as a ligand (HEDP, EDTMP). RESULTS When these agents are used, pain relief often occurs in approximately 2-4 weeks and lasts several weeks to months with responses seen in 60-80% of patients, depending on the extent of disease and stage the patient is treated. Retreatment has been possible in certain cases with further palliation being offered and improvement in the various quality of life parameters being noted. CONCLUSION Myelotoxicity has been a limiting factor with certain isotopes and has led to the development of less toxic bone seeking agents. Although these each have unique physical and biokinetic properties requiring different doses and protocols for administration, they all appear to localize in osteoblastic metastatic sites in sufficient amounts to provide bone pain palliation.

Octreotide scintigraphy for the detection of paragangliomas

Paragangliomas are neuroendocrine tumors located primarily in the head and neck region, but they can also occur at other sites. Confirming the preoperative diagnosis and detecting synchronous tumors may be difficult in some patients. Octreotide is a somatostatin analog that, when coupled to a radioisotope, produces a scintigraphic image of tumors expressing somatostatin type 2 receptors. Paragangliomas, like many neuroendocrine tumors, have been found to have a high density of somatostatin type 2 receptors on the cell surface. This study compared the results of preoperative octreotide scintigraphy with the histopathology in 21 patients who underwent surgery for presumed head and neck paragangliomas. Octreotide scan findings were positive in 16 patients with paragangliomas and negative in 3 patients with other pathology. One false-positive and 1 false-negative result were obtained. Thus, this test had an accuracy of 90%, a sensitivity of 94%, and a specificity of 75%. Previously unidentified synchronous tumors were identified in 5 patients. On the basis of this series of patients, octreotide scintigraphy appears to be a reliable test to detect paragangliomas and may be quite helpful in preoperative planning.

123I-mIBG scintigraphy in patients with known or suspected neuroblastoma: Results from a prospective multicenter trial

A prospective trial was conducted to confirm the diagnostic performance of 123I‐mIBG scintigraphy in patients with known or suspected neuroblastoma.