Angelika Bischof Delaloye

Early Prediction of Response to Sunitinib After Imatinib Failure by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients With Gastrointestinal Stromal Tumor

PURPOSE Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. PATIENTS AND METHODS Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes. CONCLUSION Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging.

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts.

White paper of the European Association of Nuclear Medicine (EANM) and the European Society of Radiology (ESR) on multimodality imaging.

IntroductionNew multimodality imaging systems bring together anatomical and molecular information and require the competency and accreditation of individuals from both nuclear medicine and radiology.AimThis paper sets out the positions and aspirations of the European Association of Nuclear Medicine (EANM) and the European Society of Radiology (ESR) working together on an equal and constructive basis for the future benefit of both specialties.DiscussionEANM and ESR recognise the importance of coordinating working practices for multimodality imaging systems and that undertaking the nuclear medicine and radiology components of imaging with hybrid systems requires different skills. It is important to provide adequate and appropriate training in the two disciplines in order to offer a proper service to the patient using hybrid systems. Training models are proposed with the overall objective of providing opportunities for acquisition of special competency certification in multimodality imaging. Both organisations plan to develop common procedural guidelines and recognise the importance of coordinating the purchasing and management of hybrid systems to maximise the benefits to both specialties and to ensure appropriate reimbursement of these examinations. European multimodality imaging research is operating in a highly competitive environment. The coming years will decide whether European research in this area manages to defend its leading position or whether it falls behind research in other leading economies. Since research teams in the Member States are not always sufficiently interconnected, more European input is necessary to create interdisciplinary bridges between research institutions in Europe and to stimulate excellence. EANM and ESR will work with the European Institute for Biomedical Imaging Research (EIBIR) to develop further research opportunities across Europe.RecommendationEuropean Union grant-funding bodies should allocate funds to joint research initiatives that encompass clinical research in diagnostic imaging in conjunction with research in mechanical and electronic engineering, informatics and biostatistics, and epidemiology.

EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with (90)Y-radiolabelled ibritumomab tiuxetan (Zevalin).

BackgroundIn January 2004, EMEA approved 90Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin’s lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine.PurposeThe purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease.

Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy

PurposeSilent myocardial ischaemia—as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain—is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion.MethodsThe patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, 99mTc-sestamibi, 201Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS).ResultsAbnormal MPS (SSS≥4) was observed in 49 (37%) patients (SSS=4.9±8.4, SDS=2.4±4.7), reversible perfusion defects (SDS≥2) in 40 (30%) patients [SSS=13.3±10.9; SDS=8.0±5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21–42%) presented reversible defects (SSS=13.9±11.3; SDS=7.4±1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress [odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02).ConclusionSilent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify these patients with a potentially increased risk of cardiovascular events.

Dosimetry of 90Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial

The objective of this analysis was to assess the radiation exposure associated with 90Y-ibritumomab tiuxetan when used as consolidation therapy in adults with low or minimal tumor burden after first-line therapy of advanced follicular lymphoma (FL). Methods: The patients who were enrolled in the phase 3 first-line indolent trial were 18 y or older, with CD20+ grade 1 or 2 stage III or IV FL, and a partial response, complete response, or unconfirmed complete response to first-line chemotherapy. The patients were allocated randomly to receive a single infusion of unlabeled rituximab 250 mg/m2 on day −7 and consolidation on day 0 with a single dose of 90Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after unlabeled rituximab, 250 mg/m2, or no further treatment. On day −7, a subset of patients received an injection of 185 MBq of 111In-ibritumomab tiuxetan immediately after unlabeled rituximab, 250 mg/m2, for central dosimetry analysis. Correlations were assessed between organ radiation absorbed dose and toxicity, body weight, body mass index, and progression-free survival. Results: Central dosimetry evaluations were available from 57 of 70 patients. Median radiation absorbed doses were 100 cGy (range, 28–327 cGy) for the red marrow and 72 cGy (range, 46–106 cGy) for the whole body. Radiation absorbed doses did not differ significantly between patients who had a partial response or complete response to initial therapy. Progression-free survival correlated significantly with the whole-body (r = 0.4401; P = 0.0006) and bone marrow (r = 0.2976; P = 0.0246) radiation dose. Body weight was significantly negatively correlated with whole-body radiation dose (r = −0.4971; P < 0.0001). Neither the whole-body radiation dose nor the bone marrow radiation dose correlated with hematologic toxicity. Conclusion: In patients with low or minimal residual tumor burden after first-line chemotherapy of advanced FL, whole-body and bone marrow exposure after 90Y-ibritumomab tiuxetan consolidation showed a significant positive correlation with progression-free survival, whereas dosimetric data could not predict hematologic toxicity.

The Role of Interval Nodes in Sentinel Lymph Node Mapping and Dissection for Melanoma Patients

In sentinel node (SN) biopsy, an interval SN is defined as a lymph node or group of lymph nodes located between the primary melanoma and an anatomically well-defined lymph node group directly draining the skin. As shown in previous reports, these interval SNs seem to be at the same metastatic risk as are SNs in the usual, classic areas. This study aimed to review the incidence, lymphatic anatomy, and metastatic risk of interval SNs. Methods: SN biopsy was performed at a tertiary center by a single surgical team on a cohort of 402 consecutive patients with primary melanoma. The triple technique of localization was used—that is, lymphoscintigraphy, blue dye, and γ-probe. Otolaryngologic melanoma and mucosal melanoma were excluded from this analysis. SNs were examined by serial sectioning and immunohistochemistry. All patients with metastatic SNs were recommended to undergo a radical selective lymph node dissection. Results: The primary locations of the melanomas included the trunk (188), an upper limb (67), or a lower limb (147). Overall, 97 (24.1%) of the 402 SNs were metastatic. Interval SNs were observed in 18 patients, in all but 2 of whom classic SNs were also found. The location of the primary was truncal in 11 (61%) of the 18, upper limb in 5, and lower limb in 2. One patient with a dorsal melanoma had drainage exclusively in a cervicoscapular area that was shown on removal to contain not lymph node tissue but only a blue lymph channel without tumor cells. Apart from the interval SN, 13 patients had 1 classic SN area and 3 patients 2 classic SN areas. Of the 18 patients, 2 had at least 1 metastatic interval SN and 2 had a classic SN that was metastatic; overall, 4 (22.2%) of 18 patients were node-positive. Conclusion: We found that 2 of 18 interval SNs were metastatic: This study showed that preoperative lymphoscintigraphy must review all known lymphatic areas in order to exclude an interval SN.

Detection of an Asymptomatic Right-Ventricle Cardiac Metastasis from a Small-Cell Lung Cancer by F-18-FDG PET/CT

A right heart metastasis of a small-cell lung cancer was found on the whole-body 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) of a 69-year-old smoker investigated for a right pulmonary mass discovered on chest radiography after a fracture of the right humerus. The PET scan showed an increased FDG uptake by the mass in the right lung and an intense, atypical focal activity of the right ventricle strongly suggestive of a neoplastic process. CT-guided lung biopsy revealed a small-cell lung cancer and myocardial biopsy confirmed the presence of a cardiac metastasis. The patient was treated with six cycles of chemotherapy followed by radiation therapy, which included the heart lesion. At follow-up PET/CT 2 months after the end of treatment, the abnormal cardiac uptake had disappeared, whereas increased FDG uptake persisted in the pulmonary residual mass.

Radiolabelled monoclonal antibodies in tumour imaging and therapy: out of fashion?

The initial enthusiasm for the development of diagnostic and therapeutic studies involving the use of monoclonal antibodies was replaced by scepticism as hopes remained unfulfilled. Against this background one needs to ask whether immunoscintigraphy (IS) serves clinical needs effectively and whether radioimmunotherapy (RIT) has a future. The current review considers these questions by reference to relevant studies. Taking colorectal cancer as an example, an appraisal is offered of the ability of IS to detect disease at an early stage and thereby to reduce mortality, and of the influence of the results of IS on patient management. It is concluded that in a limited number of cases of colorectal cancer and other solid tumors, IS will allow surgery to be performed at a stage where cure is still possible because of its ability to detect early recurrence. Turning to RIT, the results of studies in respect of various tumour types are reviewed, with due attention to reported toxicity. As regards colorectal cancer, no consistent therapeutic effects have been achieved, and myelotoxicity is typically the dose-limiting factor. Thus many questions remain to be answered, regarding antigens to be targeted, fractionation schedule, the use of “humanised” antibodies, choice of radionuclide and the use of intact immunoglobulins or fragments. These questions are considered. Overall it is concluded that the most promising application of RIT is as adjuvant therapy in patients with minimal residual disease, and a controlled multicentre trial is recommended. The development of more potent radioimmunoconjugates for therapeutic and ultimately diagnostic purposes will contribute to the improvement and development of IS by increasing its potential to influence prognosis.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study

Purpose18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and MRI are used for detecting liver metastases from uveal melanoma. The introduction of new treatment options in clinical trials might benefit from early response assessment. Here, we determine the value of FDG-PET/CT with respect to MRI at diagnosis and its potential for monitoring therapy. Material and methodsTen patients with biopsy-proven liver metastases of uveal melanoma enrolled in a randomized phase III trial (NCT00110123) underwent both FDG-PET coupled with unenhanced CT and gadolinium-diethylene triamine pentaacetic acid-enhanced liver MRI within 4 weeks. FDG-PET and MRI were evaluated blindly and then compared using the ratio of lesion to normal liver parenchyma PET-derived standardized uptake value (SUV). The influence of lesion size and response to chemotherapy were studied. ResultsOverall, 108 liver lesions were seen: 34 (31%) on both modalities (1–18 lesions/patient), four (4%) by PET/CT only, and 70 (65%) by MRI only. SUV correlated with MRI lesion size (r=0.81, P<0.0001). PET/CT detected 26 of 33 (79%) MRI lesions of more than or equal to 1.2 cm, whereas it detected only eight of 71 (11%) lesions of less than 1.2 cm (P<0.0001). MRI lesions without PET correspondence were small (0.6±0.2 vs. 2.1±1.1 cm, P<0.0001). During follow-up (six patients, 30 lesions), the ratio lesion-to-normal-liver SUV diminished in size-stable lesions (1.90±0.64–1.46±0.50, P<0.0001), whereas it increased in enlarging lesions (1.56±0.40–1.99±0.56, P=0.032). ConclusionMRI outweighs PET/CT for detecting small liver metastases. However, PET/CT detected at least one liver metastasis per patient and changes in FDG uptake not related to size change, suggesting a role in assessing early therapy response.