Norbert Avril

Prediction of Response to Preoperative Chemotherapy in Adenocarcinomas of the Esophagogastric Junction by Metabolic Imaging

PURPOSEnPreoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy.nnnPATIENTS AND METHODSnForty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically.nnnRESULTSnThe reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04).nnnCONCLUSIONnPET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Positron Emission Tomography Using [18F]Fluorodeoxyglucose for Monitoring Primary Chemotherapy in Breast Cancer

PURPOSE: To address the role of positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard. RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P < .05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responde...

Breast Imaging With Positron Emission Tomography and Fluorine-18 Fluorodeoxyglucose: Use and Limitations

PURPOSEnTo evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer.nnnPATIENTS AND METHODSnPreoperatively, 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast. To identify breast cancer by increased metabolic activity, parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading (CIR) and sensitive image reading (SIR). One hundred eighty-five breast tumors were evaluated by histology, revealing 132 breast carcinomas and 53 benign masses.nnnRESULTSnBreast carcinomas were identified with an overall sensitivity of 64.4% (CIR) and 80.3% (SIR). The increase in sensitivity (SIR) resulted in a noticeable decrease in specificity, from 94.3% (CIR) to 75.5% (SIR). At stage pT1, only 30 (68.2%) of 44 breast carcinomas were detected, compared with 57 (91.9%) of 62 at stage pT2. A higher percentage of invasive lobular carcinomas were false-negative (65.2%) compared with invasive ductal carcinomas (23.7%). Nevertheless, positive PET scans provided a high positive-predictive value (96.6%) for breast cancer.nnnCONCLUSIONnPartial volume effects and varying metabolic activity (dependent on tumor type) seem to represent the most significant limitations for the routine diagnostic application of PET. The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography. However, the high positive-predictive value, resulting from the increased metabolic activity of malignant tissue, may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response.

Neoadjuvant therapy of esophageal squamous cell carcinoma: Response evaluation by positron emission tomography

ObjectiveTo evaluate the use of positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy and chemotherapy in patients with locally advanced esophageal cancer. Summary Background DataImaging modalities, including endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging, currently used to evaluate response to neoadjuvant treatment in esophageal cancer do not reliably differentiate between responders and nonresponders. MethodsTwenty-seven patients with histopathologically proven squamous cell carcinoma of the esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant therapy consisting of external-beam radiotherapy and 5-fluorouracil as a continuous infusion. FDG-PET was performed before and 3 weeks after the end of radiotherapy and chemotherapy (before surgery). Quantitative measurements of tumor FDG uptake were correlated with histopathologic response and patient survival. ResultsAfter neoadjuvant therapy, 24 patients underwent surgery. Histopathologic evaluation revealed less than 10% viable tumor cells in 13 patients (responders) and more than 10% viable tumor cells in 11 patients (nonresponders). In responders, FDG uptake decreased by 72% ± 11%; in nonresponders, it decreased by only 42% ± 22%. At a threshold of 52% decrease of FDG uptake compared with baseline, sensitivity to detect response was 100%, with a corresponding specificity of 55%. The positive and negative predictive values were 72% and 100%. Nonresponders to PET scanning had a significantly worse survival after resection than responders. ConclusionFDG-PET is a valuable tool for the noninvasive assessment of histopathologic tumor response after neoadjuvant radiotherapy and chemotherapy.

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.

PURPOSEnTo evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors.nnnPATIENTS AND METHODSnFifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake.nnnRESULTSnPrimary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information.nnnCONCLUSIONnPET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.

Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer

PURPOSEnThe aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer.nnnPATIENTS AND METHODSnThirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference.nnnRESULTSnA significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival.nnnCONCLUSIONnSequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.

Relevance of positron emission tomography (PET) in oncology.

Background: The clinical use of positron emission tomography (PET) for detection and staging of malignant tumors is rapidly increasing. Furthermore, encouraging results for monitoring the effects of radio- and chemotherapy have been reported.nn Methods: This review describes the technical principles of PET and the biological characteristics of tracers used in oncological research and patient studies. The results of clinical studies published in peer reviewed journals during the last 5 years are summarized and clinical indications for PET scans in various tumor types are discussed.nn Results and Conclusions: Numerous studies have documented the high diagnostic accuracy of PET studies using the glucose analogue F-18-fluordeoxyglucose (FDG-PET) for detection and staging of malignant tumors. In this field, FDG-PET has been particularly successful in lung cancer, colorectal cancer, malignant lymphoma and melanoma. Furthermore, FDG-PET has often proven to be superior to morphological imaging techniques for differentiation of tumor recurrence from scar tissue. Due to the high glucose utilization of normal gray matter radiolabeled amino-acids like C-11-methionine are superior to FDG for detection and delineation of brain tumors by PET. In the future, more specific markers of tumor cell proliferation and gene expression may allow the application of PET not only for diagnostic imaging also but for non-invasive biological characterization of malignant tumors and early monitoring of therapeutic interventions.Hintergrund: Die Positronenemissionstomographie (PET) wird zunehmend in der Diagnostik onkologischer Erkrankungen eingesetzt. Auch in der Therapiekontrolle von Strahlen- und Chemotherapie maligner Tumoren wurde vielversprechende Ergebnisse berichtet.nn Methodik: Diese Übersicht beschreibt die technischen Grundlagen von PET-Untersuchungen und die biologischen Eigenschaften von Markern, die in der onkologischen Forschung und klinischen Diagnostik eingesetzt werden. Ergebnisse von in den letzten fünf Jahren in “peer-reviewed” Zeitschriften veröffentlichten klinischen Studien sind zusammengestellt, und klinische Indikationen für PET-Untersuchungen werden diskutiert.nn Ergebnisse und Schlußfolgerungen: In zahlreichen Studien wurde eine hohe diagnostische Genauigkeit der PET beim Nachweis und Staging maligner Tumoren unter Verwendung des Glucoseanalogons F-18-Fluordeoxyglucose (FDG) nachgewiesen. Die Anwendung der FDG-PET erwies sich als besonders erfolgreich bei Kopf-Hals-Tumoren, Bronchialkarzinomen, kolorektalen Karzinomen, malignen Melanomen und Lymphomen. Es wurde außerdem gezeigt, daß die FDG-PET bei der Differenzierung von Tumorrezidiven und therapiebedingten Veränderungen häufig der konventionellen bildgebenden Diagnostik überlegen ist. Bei der Diagnostik von Hirntumoren bieten radioaktiv markierte Aminosäuren wie C-11-Methionin aufgrund des hohen Glucosestoffwechsels der normalen grauen Stubstanz Vorteile gegenüber FDGT. Neue spezifische Marker für Tumorzellproliferation und Genexpression sind vielversprechende Ansätze für eine biologische Charakterisierung von Tumoren und Kontrolle von Therapieeffekten mittels PET.

Quantitative assessment of tumor metabolism using FDG-PET imaging.

Positron emission tomography using the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) provides a unique means of non-invasive assessment of tumor metabolism. Several approaches, of varying complexity, can be applied for quantitative image analysis. Previous studies have demonstrated that standardized uptake values (SUV) and simplified tracer kinetic modeling, using the Patlak-Gjedde-analysis, provide highly reproducible parameters of tumor glucose utilization. Quantification of regional FDG uptake gives complementary information to visual image interpretation and provides objective criteria for differentiation between benign and malignant lesions. Moreover, quantification of tumor glucose metabolism is essential for assessment of therapy induced changes. Clinical studies in breast cancer and lymphoma suggest that serial FDG-PET studies allow the prediction of response early in the course of chemotherapy. Therefore, FDG-PET may be helpful in patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose intense regimes. In addition, FDG-PET allows non-invasive assessment of tumor viability following chemo- and radiotherapy which permits individualized therapy management.

Preoperative Evaluation of Pancreatic Masses with Positron Emission Tomography Using 18F-fluorodeoxyglucose: Diagnostic Limitations

Abstract Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue 18F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n= 38) or follow-up (n= 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.

Whole-body positron emission tomography in clinical oncology : comparison between attenuation-corrected and uncorrected images

The clinical need for attenuation correction of whole-body positron emission tomography (PET) images is controversial, especially because of the required increase in imaging time. In this study, regional tracer distribution in attenuation-corrected and uncorrected images was compared in order to delineate the potential advantages of attenuation correction for clinical application. An ECAT EXACT scanner and a protocol including five to seven bed positions, emission scans of 9 min and post-injection transmission scans of 10 min per bed position were used. Uncorrected and attenuation-corrected images were reconstructed by filtered backprojection. In total, 109 areas of focal fluorine-18 fluorodeoxyglucose (FDG) uptake in 34 patients undergoing PET for the staging of malignancies were analysed. To measure focus contrast, a ratio of focus (target) to background average countrates (t/b ratio) was obtained from transaxial slices using a region of interest technique. Calculation of focus diameters by a distance measurement tool and visual determination of focus borders were performed. In addition, images of a body phantom with spheres to simulate focal FDG uptake were acquired. Transmission scans with and without radioactivity in the phantom were used with increasing transmission scanning times (2–30 min). The t/b ratios of the spheres were calculated and compared for the different imaging protocols. In patients, the t/b ratio was significantly higher for uncorrected images than for attenuation-corrected images (5.0±3.6 vs 3.1±1.4;P<0.001). This effect was independent of focus localization, tissue type and distance to body surface. Compared with the attenuation-corrected images, foci in uncorrected images showed larger diameters in the anterior-posterior dimension (27±14 vs 23±12 mm;P<0.001) but smaller diameters in the leftright dimension (19±11 vs 21±11 mm;P<0.001). Phantom data confirmed higher contrast in uncorrected images compared with attenuation-corrected images. It is concluded that, although distortion of foci was demonstrated, uncorrected images provided higher contrast for focal FDG uptake independent of tumour localization. In most clinical situations, the main issue of whole-body PET is pure lesion detection with the highest contrast possible, and not quantification of tracer uptake. The present data suggest that attenuation correction may not be necessary for this purpose.