Gerald Antoch

Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET

PURPOSE To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases. PATIENTS AND METHODS This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards of reference. RESULTS PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively. CONCLUSION Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.

Radioembolization with yttrium‐90 glass microspheres in hepatocellular carcinoma: European experience on safety and long‐term survival

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium‐90 (Y‐90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan‐Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue‐syndrome. Conclusion: Radioembolization with Y‐90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (HEPATOLOGY 2010;52:1741‐1749)

False-Positive FDG PET Uptake−the Role of PET/CT

Positron emission tomography (PET) is a powerful molecular imaging technique for the human body-imaging applications currently available. As altered glucose metabolism is characteristic for many malignancies, FDG-PET is mostly used in oncology for staging and therapy control. Although PET is a sensitive tool for detecting malignancy, FDG uptake is not tumor specific. It can also be seen in healthy tissue or in benign disease as inflammation or posttraumatic repair and could be mistaken for cancer. The experienced nuclear medicine physician mostly manages to differentiate malignant from non-malignant FDG uptake, but some findings may remain ambiguous. In these cases, the difficulties in differentiating physiologic variants or benign causes of FDG uptake from tumor tissue can often be overcome by combined PET and CT (PET/CT) as anatomic information is added to the metabolic data. Thus, PET/CT improves the diagnostic accuracy compared to PET alone and helps to avoid unnecessary surgery/therapy. However, PET/CT involves other sources of artifacts that may occur when using CT for attenuation correction of PET or by patient motion caused by respiration or bowel movements.

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

Value of 18F-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography in Non–Small-Cell Lung Cancer for Prediction of Pathologic Response and Times to Relapse after Neoadjuvant Chemoradiotherapy

Purpose: To determine the value of combined positron emission tomography/computed tomography (PET/CT) during induction chemotherapy (CTx) followed by chemoradiotherapy (CTx/RTx) for non–small-cell lung cancer to predict histopathologic response in primary tumor and mediastinum and prognosis of the patient. Experimental Design: Fifty consecutive patients with locally advanced non–small-cell lung cancer received induction therapy and, if considered resectable, proceeded to surgery (37 of 50 patients). Patients had at least two repeated 18F-2-fluoro-2-deoxy-d-glucose (FDG)-PET/CT scans either before treatment (t0) or after induction CTx (t1) or CTx/RTx (t2). Variables from the PET/CT studies [e.g., lesion volume and corrected maximum standardized glucose uptake values (SUVmax,corr)] were correlated with histopathologic response (graded as 3, 2b, or 2a: 0%, >0-10%, or >10% residual tumor cells) and times to failure. Results: Primary tumors showed a percentage decrease in SUVmax,corr during induction significantly larger in grade 2b/3 than in grade 2a responding tumors (67% versus 34% at t1, 73% versus 49% at t2; both P < 0.005). SUVmax,corr at t2 was significantly correlated with histopathologic response in tumors smaller than the median volume (7.5 cm3; r = −0.54, P = 0.02). In the mediastinal lymph nodes, SUVmax,corr values at t2 predicted an ypN0 status with a sensitivity and specificity of 73% and 89%, respectively (SUVmax,corr threshold of 4.1, r = −0.54, P = 0.0005). Freedom from extracerebral relapse was significantly better in grade 2b/3 patients (86% at 16 months versus 20% in 2a responders; P = 0.003) and in patients with a greater percentage decrease in SUVmax,corr in the primary tumor at t2 in relation to t0 than in patients with lesser response (83% at 16 months versus 43%; P = 0.03 for cutoff points between 0.45 and 0.55). Conclusions: SUVmax,corr values from two serial PET/CT scans, before and after three chemotherapy cycles or later, allow prediction of histopathologic response in the primary tumor and mediastinal lymph nodes and have prognostic value.

Combined PET/MRI: a new dimension in whole-body oncology imaging?

IntroductionHybrid imaging systems providing morphological and functional data in a single session have been available for oncological imaging for some time. So far, computed tomography (CT) has been the morphological method-of-choice for inclusion into these hybrid imaging systems. However, recently, research has focused on hardware-based fusion of function with magnetic resonance imaging (MRI) rather than CT.ObjectivesNow that the first head-only positron emission tomography (PET)/MRI systems have been installed and whole-body systems are to be expected in the near future, potential indications in clinical oncology have to be addressed.DiscussionThis article discusses potential indications of PET/MRI in whole-body oncology imaging. Potential advantages and disadvantages compared with currently available hybrid imaging systems will be reviewed.

Oncologic PET/MRI, Part 1: Tumors of the Brain, Head and Neck, Chest, Abdomen, and Pelvis

In oncology, staging forms the basis for prognostic consideration and directly influences patient care by determining the therapeutic approach. Cross-sectional imaging techniques, especially when combined with PET information, play an important role in cancer staging. With the recent introduction of integrated whole-body PET/MRI into clinical practice, a novel metabolic–anatomic imaging technique is now available. PET/MRI seems to be highly accurate in T-staging of tumor entities for which MRI has traditionally been favored, such as squamous cell carcinomas of the head and neck. By adding functional MRI to PET, PET/MRI may further improve diagnostic accuracy in the differentiation of scar tissue from recurrence of tumors such as rectal cancer. This hypothesis will have to be assessed in future studies. With regard to N-staging, PET/MRI does not seem to provide a considerable benefit as compared with PET/CT but provides similar N-staging accuracy when applied as a whole-body staging approach. M-staging will benefit from MRI accuracy in the brain and the liver. The purpose of this review is to summarize the available first experiences with PET/MRI and to outline the potential value of PET/MRI in oncologic applications for which data on PET/MRI are still lacking.

Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long‐term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted.

Secondary rise in blood pressure after renal denervation.

In July, 2011, a 58-year-old man with type II diabetes and hypertension resistant to treatment was referred to our hospital for renal denervation. He had had hypertension for 30 years and his antihypertensive medication dose had been increased over several years. In 2001, he had a minor stroke, and in 2009, a carotid artery stent was implanted. On examination, his blood pressure was 170/90 mm Hg despite treatment with seven antihypertensive drugs (appendix). Resistant hypertension was confi rmed by 24 h ambulatory blood pressure measurement. He also had sleep apnoea which was treated with continuous positive airway pressure therapy. Aldosteronism, phaeochromocytoma, and renal artery stenosis were ruled out. Renal resistive indices (RI) on both sides were similar. Normal renal function with microalbuminuria was present. Magnetic resonance angiography (appendix) done before renal denervation showed early ramifi cation but no relevant stenosis on either side. In August, 2011, six ablations were applied on the left side (three in each branch) and six on the right side, including two at proximal superior positions 4 mm and 9 mm distal to the ostium (fi gure). Ablations were applied in a spiral pattern at a minimum distance of 5 mm. Renal artery alterations were not visible im mediately after denervation. Duplex sonography the next day did not show any abnormalities. 3 months later his blood pressure had decreased to 140/70 mm Hg. A routine follow-up duplex sonography showed turbulences and increased renal blood fl ow velocity on the right side. At this time no diff erences in RI were detectable, excluding

68Ga-DOTATOC Versus 68Ga-DOTATATE PET/CT in Functional Imaging of Neuroendocrine Tumors

Radiolabeled somatostatin analogs represent valuable tools for both in vivo diagnosis and therapy of neuroendocrine tumors (NETs) because of the frequent tumoral overexpression of somatostatin receptors (sst). The 2 compounds most often used in functional imaging with PET are 68Ga-DOTATATE and 68Ga-DOTATOC. Both ligands share a quite similar sst binding profile. However, the in vitro affinity of 68Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately 10-fold higher than that of 68Ga-DOTATOC. This difference may affect their efficiency in the detection of NET lesions because it is the sst2 that is predominantly overexpressed in NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs (68Ga-DOTATATE and 68Ga-DOTATOC) in the same NET patients. Methods: Forty patients with metastatic NETs underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT as part of the work-up before prospective peptide receptor radionuclide therapy. The performance of both imaging methods was analyzed and compared for the detection of individual lesions per patient and for 8 defined body regions. A region was regarded positive if at least 1 lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. Results: Seventy-eight regions were found positive with 68Ga-DOTATATE versus 79 regions with 68Ga-DOTATOC (not significant). Overall, however, significantly fewer lesions were detected with 68Ga-DOTATATE than with 68Ga-DOTATOC (254 vs. 262, P < 0.05). Mean 68Ga-DOTATATE SUVmax across all lesions was significantly lower than 68Ga-DOTATOC (16.0 ± 10.8 vs. 20.4 ± 14.7, P < 0.01). Mean SUVmax for renal parenchyma was not significantly different between 68Ga-DOTATATE and 68Ga-DOTATOC (12.7 ± 3.0 vs. 13.2 ± 3.3). Conclusion: 68Ga-DOTATOC and 68Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions, with 68Ga-DOTATOC having a potential advantage. The approximately 10-fold higher affinity for the sst2 of 68Ga-DOTATATE does not prove to be clinically relevant. Quite unexpectedly, SUVmax of 68Ga-DOTATOC scans tended to be higher than their 68Ga-DOTATATE counterparts.