Matthias R. Benz

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after the Initial Cycle of Neoadjuvant Chemotherapy in High-Grade Soft-Tissue Sarcomas

Purpose: In patients with soft-tissue sarcoma (STS), the early assessment of treatment responses is important. Using positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose (FDG), we determined whether changes in tumor FDG uptake predict histopathologic treatment responses in high-grade STS after the initial cycle of neoadjuvant chemotherapy. Experimental Design: From February 2006 to March 2008, 50 patients with resectable high-grade STS scheduled for neoadjuvant therapy and subsequent tumor resection were enrolled prospectively. FDG-PET/CT before (baseline), after the first cycle (early follow-up), and after completion of neoadjuvant therapy (late follow-up) was done. Tumor FDG uptake and changes were measured by standardized uptake values. Histopathologic examination of the resected specimen provided an assessment of treatment response. Patients with ≥95% pathologic necrosis were classified as treatment responders. FDG-PET/CT results were compared with histopathologic findings. Results: At early follow-up, FDG uptake decreased significantly more in 8 (16%) responders than in the 42 (84%) nonresponders (−55% versus −23%; P = 0.002). All responders and 14 of 42 nonresponders had a ≥35% reduction in standardized uptake value between baseline and early follow-up. Using a ≥35% reduction in FDG uptake as early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively. Applying a higher threshold at late follow-up improved specificity but not sensitivity. CT had no value at response prediction. Conclusion: A 35% reduction in tumor FDG uptake at early follow-up is a sensitive predictor of histopathologic tumor response. Early treatment decisions such as discontinuation of chemotherapy in nonresponding patients could be based on FDG-PET criteria.

Quantitative F18-fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign

Correct pretreatment classification is critical for optimizing diagnosis and treatment of patients with peripheral nerve sheath tumors (PNSTs). The aim of this study was to evaluate whether F18‐fluorodeoxyglucose positron emission tomography (FDG PET) can differentiate malignant (MPNST) from benign PNSTs.

Treatment Monitoring by 18F-FDG PET/CT in Patients with Sarcomas: Interobserver Variability of Quantitative Parameters in Treatment-Induced Changes in Histopathologically Responding and Nonresponding Tumors

Measurements of tumor glucose use by 18F-FDG PET need to be standardized within and across institutions. Various parameters are used for measuring changes in tumor glucose metabolic activity with 18F-FDG PET in response to cancer treatments. However, it is unknown which of these provide the lowest variability between observers. Knowledge of the interobserver variability of quantitative parameters is important in sarcomas as these tumors are frequently large and demonstrate heterogeneous 18F-FDG uptake. Methods: A total of 33 patients (16 men, 17 women; mean age, 47 ± 18 y) with high-grade sarcomas underwent 18F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Two independent investigators measured the following parameters on the pretreatment and posttreatment scans: maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), SUVmean in an automatically defined volume (SUVauto), and tumor-to-background ratio (TBR). The variability of the different parameters was compared by concordance correlation coefficient (CCC), variability effect coefficient, and Bland–Altman plots. Results: Baseline SUVmax, SUVpeak, SUVmean, SUVauto, and TBR averaged 10.36, 7.78, 4.13, and 6.22 g/mL and 14.67, respectively. They decreased to 5.36, 3.80, 1.79, and 3.25 g/mL and 6.62, respectively, after treatment. SUVmax, SUVpeak, and SUVauto measurements and their changes were reproducible (CCC ≥ 0.98). However, SUVauto poorly differentiated between responding and nonresponding tumors. The high intratumoral heterogeneity of 18F-FDG resulted in frequent failure of the thresholding algorithm, which necessitated manual corrections that in turn resulted in a higher interobserver variability of SUVmean (CCCs for follow-up and change were 0.96 and 0.91, respectively; P < 0.005). TBRs also showed a significantly higher variability than did SUVpeak (CCCs for follow-up and change were 0.94 and 0.86, respectively; P < 0.005). Conclusion: SUVmax and SUVpeak provided the most robust measurements of tumor glucose metabolism in sarcomas. Delineation of the whole-tumor volume by semiautomatic thresholding did not decrease the variability of SUV measurements. TBRs were significantly more observer-dependent than were absolute SUVs. These findings should be considered for standardization of clinical 18F-FDG PET/CT trials.

Combined Assessment of Metabolic and Volumetric Changes for Assessment of Tumor Response in Patients with Soft-Tissue Sarcomas

By allowing simultaneous measurements of tumor volume and metabolic activity, integrated PET/CT opens up new approaches for assessing tumor response to therapy. The aim of this study was to determine whether combined assessment of tumor volume and metabolic activity improves the accuracy of 18F-FDG PET for predicting histopathologic tumor response in patients with soft-tissue sarcomas. Methods: Twenty patients with locally advanced high-grade soft-tissue sarcoma (10 men and 10 women; mean age, 49 ± 17 y) were studied by 18F-FDG PET/CT before and after preoperative therapy. CT tumor volume (CTvol) was measured by delineating tumor borders on consecutive slices of the CT scan. Mean and maximum 18F-FDG standardized uptake value within this volume (SUVmean and SUVmax, respectively) were determined. Two indices of total lesion glycolysis (TLG) were calculated by multiplying tumor volume by SUVmean (TLGmean) and SUVmax (TLGmax). Changes in CTvol, SUVmean, SUVmax, TLGmean, and TLGmax after chemotherapy were correlated with histopathologic tumor response (≥95% treatment-induced tumor necrosis). Accuracy for predicting histopathologic response was compared by receiver-operating-characteristic (ROC) curve analysis. Results: Baseline SUVmax, SUVmean, CTvol, TLGmean, and TLGmax were 11.22 g/mL, 2.84 g/mL, 544.1 mL, 1,619.8 g, and 8852.9 g, respectively. After neoadjuvant therapy, all parameters except CTvol showed a significant decline (ΔSUVmax = −51%, P < 0.001; ΔSUVmean = −40%, P < 0.001; ΔCTvol = −14%, P = 0.37; ΔTLGmean = −44%, P = 0.006; and ΔTLGmax = −54%, P = 0.001). SUV changes in histopathologic responders (n = 6) were significantly more pronounced than those in nonresponders (n = 14) (P = 0.001). Histopathologic response was well predicted by changes in SUVmean and SUVmax (area under ROC curve [AUC] = 1.0 and 0.98, respectively) followed by TLGmean (AUC = 0.77) and TLGmax (AUC = 0.74). In contrast, changes in CTvol did not allow prediction of treatment response (AUC = 0.48). Conclusion: In this population of patients with sarcoma, TLG was less accurate in predicting tumor response than were measurements of the intratumoral 18F-FDG concentration (SUVmax, SUVmean). Further evaluation of TLG in larger patient populations and other tumor types is necessary to determine the value of this conceptually attractive parameter for assessing tumor response.

Utilization of positron emission tomography in the management of patients with sarcoma.

Purpose of review 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is being used with increased frequency in the care of patients with sarcoma. In this review, the recent literature covering all aspects of PET imaging in the management of patients with soft tissue and bone sarcomas will be discussed. Recent findings In a prospective multicenter study, PET imaging accurately detected primary tumors as well as lymph node and bone metastases in patients with sarcoma. Limitations in detecting lung metastasis can be overcome by using a hybrid PET/CT scanner. In patients with neurofibromatosis, 18F-FDG-PET demonstrated its application to detect and monitor for the malignant transformation of neurofibromas. Changes in tumor 18F-FDG uptake correlate significantly with histopathologic response and survival in patients with sarcoma. Summary PET imaging is emerging as an important imaging modality in the management of patients with sarcoma. Its applications include tumor grading, staging, therapeutic monitoring, and prognostication in adult and pediatric populations.

18F-FDOPA PET and PET/CT Accurately Localize Pheochromocytomas

Successful treatment of pheochromocytoma requires accurate diagnosis and localization of tumors. Herein, we investigated the accuracy of PET using 3,4-dihydroxy-6-18F-fluoro-phenylalanine (18F-FDOPA), an amino acid transporter substrate, as an independent marker for detection of benign and malignant pheochromocytomas. Methods: The study comprised 25 consecutive patients (9 men, 16 women) whose median age was 51 y (range, 25–68 y), with known or suspected pheochromocytoma. Eleven patients underwent standardized 18F-FDOPA PET and 14 patients underwent 18F-FDOPA PET/CT studies, with a median of 511 MBq of 18F-FDOPA (range, 206–625 MBq). Two readers, unaware of the reports of other imaging studies and clinical data, analyzed all scans visually and quantitatively (maximum standardized uptake value [SUVmax] and maximum transverse diameter). Histology and long-term clinical follow-up served as the gold standard. Correlation between SUVmax of tumors and biochemical markers was evaluated. SUVmax of the benign and malignant tumors was compared. Results: Seventeen patients underwent surgery. Histology confirmed pheochromocytoma or paraganglioma in 11 cases (8 adrenal, including 2 malignant tumors, and 3 extraadrenal, including 1 malignant tumor). The diagnosis of pheochromocytoma was established by follow-up in 2 additional patients (1 adrenal and 1 unknown location) and ruled out in 6 patients. Visual analysis detected and localized pheochromocytoma in 11 of 13 patients without false-positive results (sensitivity, 84.6%; specificity, 100%; accuracy, 92%). These lesions had an SUVmax of 2.3–34.9 (median, 8.3). Evaluation of the false-negative cases revealed a 13 × 5 mm lesion with an SUVmax of 1.96 in 1 case; no lesion was localized in the second case using multiple additional modalities. Spearman nonparametric analysis did not show statistically significant correlation between SUVmax of the tumors and biochemical markers. The Mann–Whitney nonparametric test did not demonstrate a statistically significant difference between the SUVmax of 18F-FDOPA in malignant and benign tumors. Conclusion: 18F-FDOPA PET and PET/CT are highly sensitive and specific tools that can provide additional independent information for diagnosis and localization of benign and malignant pheochromocytomas.

18F-FDG PET/CT for Monitoring Treatment Responses to the Epidermal Growth Factor Receptor Inhibitor Erlotinib

Response rates of unselected non–small cell lung cancer (NSCLC) patients to the epidermal growth factor receptor inhibitor erlotinib are low and range from 10% to 20%. Early response assessments are needed to avoid costs and side effects of inefficient treatments. Here we determined whether early changes in tumor uptake of 18F-FDG can predict progression-free and overall survival in NSCLC patients who are treated with erlotinib. Methods: Twenty-two patients (6 men, 16 women; mean age ± SD, 64 ± 13 y) with stage III or stage IV NSCLC who received erlotinib treatment were enrolled prospectively. 18F-FDG PET/CT was performed before the initiation of treatment (n = 22), after 2 wk (n = 22), and after 78 ± 21 d (n = 11). Tumor maximum standardized uptake values were measured for a maximum of 5 lesions for each patient. Tumor responses were classified using modified PET Response Criteria in Solid Tumors (use of maximum standardized uptake values). Median overall survival by Kaplan–Meier analysis was compared between groups using a log-rank test. Results: The overall median time to progression was 52 d (95% confidence interval, 47–57 d). The overall median survival time was 131 d (95% confidence interval, 0–351 d). Patients with progressive metabolic disease on early follow-up PET showed a significantly shorter time to progression (47 vs. 119 d; P < 0.001) and overall survival (87 vs. 828 d; P = 0.01) than patients classified as having stable metabolic disease or partial or complete metabolic response. Conclusion: These data suggest that 18F-FDG PET/CT performed early after the start of erlotinib treatment can help to identify patients who benefit from this targeted therapy.

PET/CT imaging: The incremental value of assessing the glucose metabolic phenotype and the structure of cancers in a single examination

PET/CT with the glucose analogue FDG is emerging as the most important diagnostic imaging tool in oncology. More than 2000 PET/CT scanners are operational worldwide and its unique role for diagnosing, staging, restaging and therapeutic monitoring in cancer is undisputed. Studies conducted in thousands of cancer patients have clearly indicated that the combination of molecular PET with anatomical CT imaging provides incremental diagnostic value over PET or CT alone. State of the art imaging protocols combine fully diagnostic CT scans with quality whole body PET surveys. The current review briefly describes the biological alterations of cancer cells that result in their switch to a strongly glycolytic phenotype. Different whole body imaging protocols are discussed. We summarize the evidence for the incremental value of PET/CT over CT and PET alone using imaging of sarcoma as an example. Following this section we discuss the performance of FDG-PET/CT imaging for staging, restaging and monitoring of head and neck cancer, solitary lung nodules and lung cancer, breast cancer, colorectal cancer, lymphoma and unknown primary tumors. Finally, the recently emerging evidence of a substantial impact of PET/CT imaging on patient management is presented.

18F-FDG-PET/CT Imaging as an Early Survival Predictor in Patients with Primary High-Grade Soft Tissue Sarcomas Undergoing Neoadjuvant Therapy

Purpose: Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 2[18F]fluoro-2-deoxy-d-glucose (18F-FDG)-PET/computed tomographic (CT) imaging after the initial cycle of neoadjuvant therapy could predict overall survival in these patients. Experimental Design: Thirty-nine patients underwent 18F-FDG-PET/CT before and after one cycle of neoadjuvant therapy. Fifty-six patients underwent end-of-treatment PET. Overall survival was, among others, correlated with changes of SUVpeak and histopathology. Results: One-, two-, and five-year survival rates were 95% ± 3.0%, 86% ± 4.6%, and 68% ± 6.6%, respectively. Median time to death was 30.9 months (mean, 27.7; range, 6.9–50.1). Optimal cutoff values for early and late decreases in SUVpeak (26% and 57%, respectively) were significant predictors of survival in univariate survival analysis [P = 0.041; HR, 0.27; 95% confidence interval (CI), 0.08–0.95 and P = 0.045; HR, 0.31; 95% CI, 0.10–0.98]. Seven of 15 early PET nonresponders but only four of 24 early PET responders died during follow-up (P = 0.068). The only other significant survival predictor was surgical margin positivity (P = 0.041; HR, 3.31; 95% CI, 1.05–10.42). By multivariable analysis, early metabolic response (P = 0.016) and positivity of surgical margins (P = 0.036) remained significant survival predictors. Conclusion: 18F-FDG-PET predicted survival after the initial cycle of neoadjuvant chemotherapy in patients with STS and can potentially serve as an intermediate endpoint biomarker in clinical research and patient care. Clin Cancer Res; 18(7); 2024–31. ©2012 AACR.

Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil.

PurposeTo evaluate the value of dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) without endorectal coil (EC) in the detection of local recurrent prostate cancer (PC) after radical prostatectomy (RP).Material and methodsThirty-three patients with recurrent PC underwent DCE-MRI without EC before salvage radiotherapy (RT). At median 15 (mean 16±4.9, range 12–27) months after completion of RT all patients showed complete biochemical response. Additional follow up post RT DCE-MRI scans were available. Prostate specific antigen (PSA) levels at the time of imaging were correlated to the imaging findings.ResultsIn 22/33 patients (67%) early contrast enhancing nodules were detected in the post-prostatectomy fossa on pre-RT DCE-MRI images. The average pre-RT PSA level of the 22 patients with positive pre-RT DCE-MRI findings was significantly higher (mean, 0.74±0.64 ng/mL) compared to the pre-RT PSA level of the 11 patients with negative pre-RT DCE-MRI (mean, 0.24±0.13 ng/mL) (p<0.001). All post-RT DCE-MRI images showed complete resolution of initial suspicious lesions. A pre-RT PSA cut-off value of ≥0.54 ng/ml readily predicted a positive DCE-MRI finding.ConclusionsThis is the first study that shows that DCE-MRI without EC can detect local recurrent PC with an estimated accuracy of 83% at low PSA levels. All false negative DCE-MRI scans were detected using a PSA cut-off of ≥0.54 ng/mL.