Expert Nuclear Medicine Research Articles

BEACOPP Chemotherapy Is Able to Induce Durable Complete Remission in Poor-Prognosis Hodgkin's Lymphoma Patients with a Positive Interim PET after 2 ABVD Cycles

Background: Early interim-PET (PET-2) is the most powerful factor able to predict treatment outcome in advanced-stage Hodgkin Lymphoma (HL) patients treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). The 2-y PFS of PET-2 positive patients is only 12%, but the optimal treatment for this patient subset is still unknown. For this reason in January 2006 a treatment policy was designed by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) to early intensify chemotherapy with BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for HL patients with a PET-2 positive after 2 ABVD cycles.Patients and methods: 136 HL patients with advanced-stage or intermediate-stage with adverse prognostic factors (more than 3 nodal sites, ESR > 50 mm, sub diaphragmatic presentation, bulky lesion), consecutively admitted to nine GITIL Italian centers were treated with two ABVD courses and re-evaluated with interim-PET. Twenty-one of these 136 patients proved to be PET-2 positive, and 19/21 are the object of this analysis. The mean age was 31.7 years (16–64), 10 patients were in stage II, 9 in stage III–IV. Bulky disease was present in 11, and B-symptoms in 16. Fourteen patients showed an IPS score 0–2, 5 patients a score 3–7. The median interval between the end of second ABVD course and PET-2 was 11 days (5–14). BEACOPP (4 escalated and 4 standard cycles) was followed by consolidation radiotherapy in 3 patients for bulky mediastinal tumor. PET scan were centrally reviewed by two well-experienced nuclear medicine experts, using the blood pool mediastinal structures (BPMS) as reference for the residual uptake, as elsewhere published (Gallamini, JCO 2007).Results. Upon central review, 2 interim-PET scan were classified as minimally positive in 2 patients, with a single MRU (Minimal Residual Uptake) lesion showing a SUV (Standardized Uptake Value) lower than BPMS, and therefore only 19 cases were suitable for the BEACOPP salvage treatment. After a mean follow-up of 14.3 months (7.0–30.2), 15 patients remain in continuous CR and 4 had a treatment failure because of disease relapse (1) or progression (3). For the responding patients the mean duration of CR was 13.0 months (6.5–30.2). The IPS score for progressing patients was 2, 3, and 4; for the relapsing-one, 0. At time of this analysis, l8 patients are still alive and 1 died during BEACOPP treatment for disease progression. The 1-year second treatment failure-free survival (1-y 2TFFS) was 94.7 % (95% C.I. 84.7–100). The 1 y OS survival was 93.3 (95%C.I. 80.7–100). In univariate analysis the only clinical factor related to treatment failure was the presence of extra-nodal disease. (Log-rank=6.8 p=0.009).Conclusions. BEACOPP-escalated regimen was able to induce durable CR in most (15/19) HL patients with a positive interim-PET. These results, although requiring a longer follow-up and a higher number of patients, seem to suggest thatthe very-poor prognosis of PET-2 positive, ABVD-treated HL patients can be substantially improved by early chemotherapy intensification;escalated-BEACOPP is likely to represent a good treatment choice for this very poor prognosis patient subset.

Interim Positron Emission Tomography (PET) in Diffuse Large B-Cell Lymphoma: Independent Expert Nuclear Medicine Evaluation of ECOG 3404

Background: Positive interim PET scans have been associated with inferior outcomes in DLBCL treated with chemotherapy, alone or with rituximab. In the ECOG 3404 study for bulky and advanced DLBCL, PET scans at baseline and after 3 R-CHOP are centrally reviewed by a single reader; those with positive scans cross-over to R-ICE after 4 R-CHOP, whereas those with negative scans continue on R-CHOP. The primary endpoint of E3404 is progression-free survival. To determine the reproducibility of interim PET scan interpretation, we convened an expert panel.Methods: Three external nuclear medicine physicians visually scored baseline and interim PET scans independently and blinded to other clinical information or outcome. ECOG study criteria were binary (0,1) based on residual disease in initially involved sites with uptake greater than the liver. London criteria were on a scale of 0–5, where 4–5 was positive, based on increased uptake relative to the liver. Overall scores and agreement among experts were evaluated for both criteria, with application of the kappa statistic to correct for chance.Results: Using the ECOG criteria, external reviewers were in complete agreement in 68% of 38 interim scans and completely agreed with the central review in the same 68% cases. Agreement among the experts was 71% employing the London criteria in these cases. The range of PET+ interim scans by reviewer was 16.8% to 34.2% (p=NS) by both ECOG and London criteria. The kappa statistic for overall pairwise correlation between readers was 0.445 (0.396–0.533) using ECOG and 0.502 (0.396–0.630) using London criteria – indicating moderate consistency. Areas of disagreement often, but not exclusively, related to bone disease, the shape and focality of residual uptake, splenic disease, and rare scans without CT-fusion.Conclusions: These data show that visual criteria, either ECOG or London in this series, for interim PET results are moderately reproducible among individual nuclear medicine experts. Our finding of variability among experts indicates the need for caution in interpreting interim PET results in studies and in practice. Review of all E3404 cases is planned after accrual is completed (projected 12/08). Other ongoing studies evaluating interim PET after 1–3 cycles of therapy, the application of quantitative criteria, and consensus panels may provide further valuable information.

Use of neural networks to improve quality control of interpretations in myocardial perfusion imaging

The aim of this study was to explore the feasibility of using a technique based on artificial neural networks for quality assurance of image reporting. The networks were used to identify potentially suboptimal or erroneous interpretations of myocardial perfusion scintigrams (MPS). Reversible perfusion defects (ischaemia) in each of five myocardial regions, as interpreted by one experienced nuclear medicine physician during his daily routine of clinical reporting, were assessed by artificial neural networks in 316 consecutive patients undergoing stress/rest 99mTc-sestamibi myocardial perfusion scintigraphy. After a training process, the networks were used to select the 20 cases in each region that were more likely to have a false clinical interpretation. These cases, together with 20 control cases in which the networks detected no likelihood of false clinical interpretation, were presented in random order to a group of three experienced physicians for a consensus re-interpretation; no information regarding clinical or neural network interpretations was provided to the re-evaluation panel. The clinical interpretation and the re-evaluation differed in 53 of the 200 cases. Forty-six of the 53 cases (87%) came from the group selected by the neural networks, and only seven (13%) were control cases (P < 0.001). The disagreements between clinical routine interpretation by an experienced nuclear medicine expert and artificial networks were related to small and mild perfusion defects and localization of defects. The results demonstrate that artificial neural networks can identify those myocardial perfusion scintigrams that may have suboptimal image interpretations. This is a potentially highly cost-effective technique, which could be of great value, both in daily practice as a clinical decision support tool and as a tool in quality assurance.

Recommendations for Radioembolization of Hepatic Malignancies Using Yttrium-90 Microsphere Brachytherapy: A Consensus Panel Report from the Radioembolization Brachytherapy Oncology Consortium

To standardize the indications, techniques, multimodality treatment approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic brachytherapy. Members of the Radioembolization Brachytherapy Oncology Consortium met as an independent group of experts in interventional radiology, radiation oncology, nuclear medicine, medical oncology, and surgical oncology to identify areas of consensus and controversy and to issue clinical guidelines for Y90 microsphere brachytherapy. A total of 14 recommendations are made with category 2A consensus. Key findings include the following. Sufficient evidence exists to support the safety and effectiveness of Y90 microsphere therapy. A meticulous angiographic technique is required to prevent complications. Resin microsphere prescribed activity is best estimated by the body surface area method. By virtue of their training, certification, and contribution to Y90 microsphere treatment programs, the disciplines of radiation oncology, nuclear medicine, and interventional radiology are all qualified to use Y90 microspheres. The panel strongly advocates the creation of a treatment registry with uniform reporting criteria. Initiation of clinical trials is essential to further define the safety and role of Y90 microspheres in the context of currently available therapies. Yttrium-90 microsphere therapy is a complex procedure that requires multidisciplinary management for safety and success. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies.

Neuroendokrine Tumoren des Gastrointestinaltraktes

Neuroendocrine tumors (NET) of the gastrointestinal tract are rare and constitute 0.5-1% of all human malignancies. Based on their endocrine secretion, they are functional active or inactive. They are further classified into fore-, mid-, or hindgut tumors. The recently published WHO-classification grouped the tumors according to their tumor size, angioinvasion and Ki-67 index. NET are mainly diagnosed in an advanced tumor stadium because of the paucity of symptoms or when symptoms occur due to endocrine hypersecretion. NET are diagnosed serologically by their hormone secretion and by measuring Chromogranin A levels. They are further detected by CT, MRI or endoscopy including endoscopic ultrasound. Many NET have somatostatin receptors on their surface and can be diagnosed by somatostatin receptor scintigrafy with high sensitivity and specificity. Only by surgery NET can be cured. Because many tumors are diagnosed late, medical options are of utmost importance. Symptom control can be established by somatostatin analogues and interferon-ot. Diazoxid can further inhibit insulin secretion, proton pump inhibitors are the therapy of choice for acid hypersecretion in Zollinger-Ellison syndrome. Advanced neuroendocrine cancers can be treated with chemotherapy. Recently, radio receptor therapy with 90Y-DOTA Octreotid and 177Lu-DOTA Octreotate was established in advanced neuroendocrine cancers and is further evaluated in studies. Net of the gastrointestinal tract should be treated in a multidisciplinary approach with gastroenterologists, surgeons and experts in nuclear medicine. An overview about epidemiology, clinical features, diagnostic methods and therapy of NET of the gastrointestinal tract will is provided in this article.

Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer

Aim of this study was to compare the diagnostic accuracy of positron emission tomography and computed tomography with (11)C-Choline (Cho-PET/CT) and whole body magnetic resonance imaging (WB-MRI) for diagnostic work-up of prostate cancer. We evaluated retrospectively 42 patients with untreated prostate cancer (n = 17), or increasing levels of prostate-specific antigen (PSA) after curative therapy (n = 25) who had been investigated by both Cho-PET/CT and WB-MRI. MRI, CT, and PET images were separately analyzed by experienced radiologists or nuclear medicine experts, followed by consensus reading. Validation was established by histology, follow-up, or consensus reading. 88/103 detected lesions were considered as malignant: 44 bone metastases, 22 local tumor, 15 lymph node metastases, 3 lung, and 3 brain metastases. One further lesion was located in the adrenal gland, which was a second tumor. Overall sensitivity, specificity and accuracy for Cho-PET/CT were 96.6%, 76.5%, and 93.3%, resp., and for WB-MRI 78.4%, 94.1%, and 81.0%, resp. 3 vertebral metastases had initially been missed by Cho-PET/CT and were found retrospectively. MRI identified 2 bone metastases and 1 lymph node metastasis after being informed about the results of Cho-PET/CT. Cho-PET/CT and WB-MRI both presented high accuracy in the detection of bone and lymph node metastases. The strength of MRI is excellent image quality providing detailed anatomical information whereas the advantage of Cho-PET/CT is high image contrast of pathological foci.

Comparison of Stress Fractures of Male and Female Recruits during Basic Training in the Israeli Anti-Aircraft Forces

In military basic training, stress fractures are a common orthopedic problem. Female recruits have a significantly higher incidence of stress fractures than do male recruits. Because the Israeli Defense Forces opened traditionally male roles in combat units to female recruits, their high risk for stress fractures is of concern. To compare the prevalence of stress fractures during Israeli Defense Forces anti-aircraft basic training among otherwise healthy young male and female recruits, in terms of anatomic distribution and severity. Ten mixed gender batteries, including 375 male recruits and 138 female recruits, carried out basic training in the Israeli anti-aircraft corps between November 1999 and January 2003. Each battery was monitored prospectively for 10 weeks of a basic training course. During that time, recruits who were suspected of having an overuse injury went through a protocol that included an orthopedic specialist physical examination followed by a radionuclide technetium bone scan, which was assessed by consultant nuclear medicine experts. The assessment included the anatomic site and the severity of the fractures, labeled as either high severity or low severity. Stress fractures were significantly more common among female recruits than among male recruits. A total of 42 male (11.2%) and 33 female (23.91%) recruits had positive bone scans for stress fractures (female:male relative ratio, 2.13; p < 0.001). Pelvic, femur, and tibia fractures were significantly more common among female recruits than among male recruits (p < 0.005). Female recruits had significantly more severe fractures in the tibia (p < 0.05). However, there was no significant difference in the severity of stress fractures in the femur or metatarsals between male and female recruits, as assessed by radionuclide uptake. We recommend that different training programs be assigned according to gender, in which female recruits would have a lower level of target strain or a more moderate incline of strain in the training program throughout basic training.

Exploring technical and cultural appeals in strategic risk communication: the Fernald radium case.

Risk disputes are often characterized by tensions between technical and cultural understandings of risk and by communication practices that reflect those differing perspectives. This study considers how participants in risk debates draw upon and combine aspects of technical and cultural rationality as broad orientations to risk in expressing their views and formulating persuasive appeals during risk debates. Rhetorical theorist Kenneth Burke's (1984) concept of frames of acceptance is used to analyze a case study involving competing priorities for radium stored at the Fernald site, a former Department of Energy nuclear weapons facility. A rhetorical analysis is conducted using the transcript from a 1995 public meeting during which local residents and a nuclear medicine expert discussed priorities of Fernald site cleanup versus providing radium stored on site for promising cancer research. Two tensions are identified that fostered disagreement among discussants: the first a tension between a local or global context for the controversy and the second a tension between competing definitions of public participation for this issue. This study analyzes the rhetorical strategies by which participants in the Fernald radium debate articulated these tensions and argues that technical and cultural rationality (Plough & Krimsky, 1987) acted as sources of rhetorical invention influencing participants' individual frames of acceptance and the ways they defined and interpreted the situation and crafted persuasive appeals.

Una propuesta para el uso racional de la PET en oncología

This study aims to develop a Clinical Practice Guide for the rational use of the Positron Emission Tomography (PET) in Oncology, that makes it possible to approach the real existence of demand in the public health care service of Andalucía, by limiting the clinical indications, using criteria based on the existence of sufficient scientific evidence on the effectiveness and clinical impact of PET. The consensus technique was used to elaborate the Guide, gathering a group of nuclear medicine experts. Prior to this a systematic research of the scientific literature was carried out, using strict criteria for the selection of the articles, such as the evaluation of the epidemiological data, work methodology, clinical and pathological diagnosis, gold standard references and statistical analysis. In each pathology group, the existence of alternative non-invasive diagnostic techniques was assessed, comparing its effectiveness and clinical impact with the PET, and the existence of useful treatments correlated with the results of the examination was also evaluated. When it was possible, we evaluated the cost-effectiveness of the PET. Finally, the cost-effectivity of the technique was assessed and the limitation of present and future resources and the economical costs arising from the PET costs and introduction were evaluated. It was considered that the PET was indicated in the following clinical conditions: 1: Assessment of Colorectal Cancer recurrence in patients with increased levels of tumor markers and negative morphological imaging techniques. Suspicion of isolated resectable recurrence. 2: Restaging in patients with high risk melanoma. 3: Differential diagnosis of solitary pulmonary nodules. 4: Staging of non-small cell bronchial carcinoma. 5: Staging and detection of recurrences of lymphomas. 6: Restaging of head and neck cancer with possibilities of curative treatment. 7: Diagnosis of recurrences in differentiated thyroid cancer in patients with increased plasma levels of thyroglobulin and negative radioiodine scintiscan. 8: Staging and follow-up of medullary thyroid carcinoma. 9: Differential diagnosis between recurrent tumor and scar or radionecrosis in brain tumors.

The role of chemotherapy in the nonsurgical management of malignant neuroendocrine tumours.

1993). The initial management of NET comprises surgical excision of the primary tumour (aimed at reducing as much as possible of the tumour mass); additionally, in patients who are not cured by surgery alone, medical therapy is used for the control of symptoms and humoral syndromes with agents such as somatostatin analogues and/or a-interferon. Specific therapy with radiopharmaceuticals using radio-labelled substances such as meta-iodobenzylguanidine (MIBG) or somatostatin analogues appears promising for some tumours which show diagnostic uptake, and is the first-line systemic management for sensitive cases. Hepatic artery ligation and/or chemoembolization is also used in patients with excessive hepatic tumour load and uncontrollable symptoms. The control of tumour growth with chemotherapeutic agents is currently mainly reserved for patients with recurrent and/or progressive disease and where other therapeutic modalities have failed. Chemotherapy may be particularly helpful for selected cases of advanced NET, especially pancreatic or poorly differentiated NET. This review deals with the general role of chemotherapy in the management of malignant NET, its integration with other modes of therapy, and the specific protocols which have been used. Histological classification and differentiation of NET

Ictal SPECT and interictal PET in the localization of occipital lobe epilepsy.

To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.

Multidisciplinary approach to selective sentinel lymph node mapping in breast cancer.

Although the role of axillary lymph node dissection is controversial with respect to survival benefits, its role as a staging procedure has been well established since nodal involvement is the most reliable prognostic indicator for patients with breast cancer. Selective sentinel lymph node (SLN) dissection is gaining acceptance as a useful staging procedure because it is minimally invasive and spares approximately 70-80% of the patients a more extensive axillary lymph node dissection. The evolving techniques for selective SLN dissection using blue dye and radiotracer methods are reviewed in this article. Based on the classic definition of the breast lymphatic drainage and recently published articles addressing the issue of peritumoral and intradermal injections, a possible new and simplified approach using intradermal injection may identify the axillary SLN more quickly and reliably. This article emphasizes the importance of a multidisciplinary approach in the identification of SLNs by preoperative lymphoscintigraphy performed by expert nuclear medicine physicians, the intraoperative mapping and harvesting of SLNs by well trained surgeons and the meticulous examination of SLNs by experienced pathologists. Therefore, to achieve the highest rate of accuracy regarding SLN status, it is imperative that a multidisciplinary team with close communication and cooperation be formed. The clinical significance of SLNs will be determined by results from follow-up and clinical trials.

Book reviewGeriatric nuclear medicine. Ed. by IioM. and WagnerH. N., pp. ix + 430, 1983 (Igaku-Shoin, Tokyo), $73.00. ISBN 0–89640–085–9

The editors have assembled together some thirty-odd individual authors, almost exclusively from Japan and the USA, to produce this 430-page work. The pattern in the introductory eight chapters is echoed in subsequent ‘body system’ sections with chapters by geriatricians on the pathology and physiology of aging plus contributions by nuclear medicine experts on instrumentation, radiopharmaceuticals and radiation dosimetry. As a nuclear medicine specialist, I found the contributions on aging and geriatric pathology fascinating whereas the details of nuclear medicine, its instrumentation etc. were essentially those to be seen in any text book of our subject: presumably however they would be of interest to a geriatrician who might be reading this book. Each chapter is followed by a useful bibliography, though few references are later than 1980/1981. There is also a useful index.

Treatment of hyperthyroidism.

During the past decade, our understanding of thyroid pathophysiology has expanded greatly. Recent advances include insights into the mechanisms of thyroid hormone action, the peripheral metabolism of thyroid hormones, and immunologic aspects of thyroid disease. Refinements in thyroid hor­ mone assays and the availability of thyrotropin-releasing hormone (TRH) have provided more direct and definitive approaches to the diagnosis of hyperthyroidism. Using these new laboratory aids, researchers recently demonstrated that hyperthyroidism is more common than was formerly believed, occurring in as much as 2% of the adult female population (1, 2). However, the therapeutic tools with which we approach hyperthyroid pa­ tients have changed little in the past 30 years. Each of the three principal methods, antithyroid drugs, radioiodine, and surgery, can be used effec­ tively and each has its advantages, its advocates, and its tradition in the therapy of hyperthyroid individuals. The management of a specific patient will be influenced by the nature and severity of the hyperthyroidism, the patient's age and general health, the experience of the responsible physician, the availability of expert nuclear medicine and surgical colleagues, and by the patient's own feelings regarding therapy.