Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma

PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign.     

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of ODG. We studied 19 patients with proven ODG, comparing standardized uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas-Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas-Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake. In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.     

Evaluation of early response to radiotherapy in head and neck cancer measured with [11C]methionine-positron emission tomography.

PURPOSE: To evaluate whether positron emission tomography (PET) with carbon-11-methionine (MET) can be used for detection of early response to external beam radiotherapy (RT) in untreated head and neck cancer using locoregional control and survival as study endpoints. MATERIALS: Fifteen patients with head and neck cancer underwent a MET PET study before RT and after a median dose of 24 Gy. Fractionation was standard (n = 6) or hyperfractionated (n = 9), and 13 out of 15 patients had planned surgery after RT. SUV was calculated for primary tumor (n = 13) or largest lymph node metastasis in two patients of whom one had his primary excised before study enrollment and one presented with unknown primary tumor syndrome. METHODS: Attenuation corrected PET scans acquired 20-40 min from tracer injection were used for evaluation of MET uptake in tumors. A quantitative MET uptake index was expressed as standardized uptake value (SUV) or SUV(lean) (corrected for lean body mass). The PET results were correlated with clinical follow-up data. The median follow-up time is currently 28 months (range 22-34). RESULTS: A total of 13 primary tumors and 12 metastatic lymph nodes were visually identified in MET PET. In the first PET study the median SUV in tumor was 8.6 (range, 5.5-14.0). In the second PET study performed during RT the median SUV decreased to 5.7 (range, 3.1-8.2, P = 0.001). Two out of 15 patients showed no radiation-induced decrease in SUV. The median tumor SUV ratio of patients remaining in local control (CR) after RT was 0.7 (range 0.6-0.8, n = 6), and that of relapsing patients similarly 0.7 (range 0.5-1.0, n = 9, NS). The SUV ratio was not associated with survival time. The MET uptake of submandibular salivary glands decreased in all patients during the first two or three weeks of RT (P = 0.03). CONCLUSIONS: MET uptake in tumor shows a significant decrease during the first two to three weeks of RT of head and neck cancer. It appears that the rate of decrease in tracer uptake is comparable in relapsing patients and those who remain locally controlled and thus the use of MET PET for prediction of response to RT is limited.     

Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[f]fluoro-2-deoxy-d-glucose

PURPOSE: Tumor uptake of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) may relate to outcome in cancer patients. Pretreatment FDG uptake was evaluated as a predictor of local control (LC) and disease-free survival (DFS) in patients with head-and-neck cancer managed primarily either by radiotherapy (RT) or surgery. PATIENTS AND METHODS: Tumor FDG uptake using the Standardized Uptake Value (SUV) was measured in 120 patients studied prospectively using positron emission tomography (PET). Treatment consisted of either radical RT with or without chemotherapy (73 patients) or radical surgery with or without postoperative RT (47 patients). Median follow-up of the surviving patients was 48 months. RESULTS: The median SUV was higher in 46 patients who failed treatment than in the remaining controlled patients (5.8 vs. 3.6, p = 0.002). In monovariate analysis, patients with tumors having high FDG uptake (SUV > median, 4.76) had poorer LC (p = 0.003) and DFS (p = 0.005). This difference was also observed when the RT and surgery groups were analyzed separately. In the multivariate analysis T-category (p = 0.005) and SUV (p = 0.046) remained independent adverse factors for LC, whereas N-category (p = 0.004), T-category (p = 0.02) and SUV (p = 0.05) were independent determinants of DFS. CONCLUSION: These results suggest that pretreatment tumor FDG uptake represents an independent prognostic factor in patients with head-and-neck cancers, whatever the primary treatment modality. Tumors having high FDG uptake are at greater risk of failure and should be considered for more aggressive multimodality therapy.     

Correlation of 18-F-fluorodeoxyglucose (FDG) accumulation with glucose transporter (Glut-1) expression in esophageal squamous cell carcinoma

BACKGROUND: We previously reported that positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) might be a useful tool for evaluating the stage of esophageal squamous cell carcinoma (SCC), and that FDG-PET shows greater accuracy in the diagnosis of lymph node metastasis than computed tomography. Further, we elucidated the relationships among FDG-PET performance, glucose transporter (Glut)-1 expression and serum levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA) and squamous cell carcinoma antigen (SCC-Ag) in esophageal SCC. PATIENTS AND METHODS: We studied 44 patients with thoracic esophageal SCC who had undergone radical esophagectomy. Immunohistochemical analysis was used to detect the expression of Glut-1 in resected specimens and FDG accumulation was assessed by FDG-PET scan. RESULTS: FDG uptake in the primary tumor was found in 34 out of 44 (77.3%) patients. No significant correlation was observed between SUVs and the tumor markers CEA, CYFRA and SCC-Ag. The survival rate in patients with high FDG uptake (SUV > 3) was significantly lower than in cases with low FDG uptake (SUV < 3) (p < 0.01). A significant correlation was observed between SUV and Glut-1 expression (p < 0.05). The prognosis in patients with both low Glut-1 expression and low FDG uptake tended to be more favorable than in patients with high Glut-1 expression and/or high FDG uptake. CONCLUSION: Glut-1 expression was related to FDG uptake, and assessment of both FDG uptake and Glut-1 expression might be useful for providing prognostic information in patients with esophageal SCC.     

Prognostic significance of [(18)F]fluorodeoxyglucose uptake on positron emission tomography in patients with pathologic stage I lung adenocarcinoma

BACKGROUND: [(18)F]Fluoro-2-deoxyglucose uptake on positron emission tomography (FDG-PET) has been frequently used for diagnosis and staging of lung cancer. The prognostic significance of FDG uptake on PET was evaluated in patients with pathologic Stage I lung adenocarcinoma (tumor stages were based on the TNM classification of the International Union Against Cancer). METHODS: Disease-free survival of 98 patients with pathologic Stage I lung adenocarcinoma who were treated by curative resection was examined in relation to sex, age, histologic grade of differentiation, surgical procedure, tumor stage, and FDG uptake measured as the maximum standardized uptake value (SUV). RESULTS: Sixty-three patients were had Stage IA disease and 35 patients had Stage IB disease. Six patients each with Stage IA and Stage IB disease developed disease recurrence after a mean postsurgical follow-up period of 31 months. Ten (23%) of the 43 patients with SUV > or = 3.3 developed a recurrence compared with 2 (4%) of the 55 patients with SUV < 3.3 (P = .020). Ten (20%) of the 51 patients with moderately or poorly differentiated adenocarcinoma developed disease recurrence, compared with 2 (4%) of the 47 patients with well-differentiated adenocarcinoma (P = .056). Multivariate analysis demonstrated that histologic grade of differentiation was not correlated with the frequency of tumor recurrence (P = .286), whereas SUV was found to be marginally correlated (P = .079). CONCLUSIONS: FDG uptake appears to be predictive of disease-free survival in patients with Stage I lung adenocarcinoma. FDG uptake could yield important information for determining the likely value of postoperative adjuvant chemotherapy in such patients.     

The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma

PURPOSE: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer. This study examines the ability of post-RT FDG PET imaging to predict the tumor status of residual lymphadenopathy after nonsurgical management of regionally advanced neck disease. METHODS AND MATERIAL: From February 2000 to October 2002, 41 patients were treated definitively by radiation (with or without chemotherapy) and underwent FDG PET and computed tomography (CT) imaging after treatment to assess response. Patients with negative CT and FDG PET scans were observed and did not undergo neck dissection. Patients with radiographically persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration of the lymph nodes using ultrasound guidance. The results of the FDG PET scans were correlated with the pathologic findings. RESULTS: Twelve patients with persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration. Four of the 12 were found to have viable residual tumor in the cervical lymph nodes. The pathology did not correlate with the size of the lymph nodes in the pre-RT or post-RT CT studies. However, the pathology correlated strongly with the post-RT FDG PET studies. All patients with a negative post-RT FDG PET or those with a maximum standardized uptake value (SUV(max)) of less than 3.0 in the post-RT FDG PET were found to be free of residual viable tumor. Using an SUV(max) of less than 3.0 as the criterion for a negative FDG PET study, the negative predictive value was 100% and the positive predictive value was 80%. CONCLUSIONS: A negative post-RT FDG PET scan is very predictive of negative pathology in neck dissection or fine-needle aspiration even with large residual lymphadenopathy. Therefore, if the post-RT FDG PET scan is negative, neck dissection might not be required for regional control. A prospective study with longer follow-up and greater patient numbers is needed to determine whether a policy of deferring neck dissection based on a negative FDG PET is supported.     

Utility of FDG PET in patients with squamous cell carcinomas of the oral cavity

Background

The utility of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer has received little attention in a clinician's perspective. We systematically evaluated the clinical roles of FDG PET in patients with oral cavity squamous cell carcinomas (SCCs).

Methods

Between August 2001 and February 2005, 82 new patients with resectable oral cavity SCCs underwent CT/MRI and FDG PET at initial staging and follow-up. The sensitivity and specificity of CT/MRI and FDG PET for neck metastases were compared with histopathologic reference of 67 patients who underwent neck dissection. The relationships between the maximal standardized uptake value (SUV) of primary tumors and clinicopathologic parameters, such as gender, age, tumor thickness, local invasiveness, T and N categories, tumor-node-metastasis stage, and histological grade, as well as with disease-free survival (DFS), were assessed.

Results

FDG PET was more sensitive than CT/MRI for detecting cervical metastases on a level-by-level basis (38/43 vs. 28/43; P = 0.002). Age, T and N categories, tumor thickness (>8 mm) and SUV (>5.0) were also significant variables of 3-year DFS in univariate analysis. T category was an independent determinant of DFS in multivariate analysis (P < 0.05). During a mean follow-up of 36 months, FDG PET correctly diagnosed locoregional recurrences in 20 patients, distant metastases in six and second cancers in five.

Conclusion

FDG PET may have potential roles in initial staging, survival prediction, and the detection of recurrences and second cancers.     

18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors.

PURPOSE: Response to neoadjuvant chemotherapy is a significant prognostic factor for the Ewing sarcoma family of tumors (ESFTs). [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that accurately predicts histopathologic response in several malignancies. To determine the prognostic value of FDG PET response for progression-free survival (PFS) in ESFTs, we reviewed the University of Washington Medical Center experience. PATIENTS AND METHODS: Thirty-six patients with ESFTs were evaluated by FDG PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG PET standard uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with chemotherapy response, as assessed by histopathology in surgically excised tumors. Thirty-four patients had both SUV1 and SUV2. RESULTS: The mean SUV1, SUV2, and ratio of SUV2 to SUV1 (SUV2:1) were 7.9 (range, 2.3 to 32.8), 2.1 (range, 0 to 4.3), and 0.36 (range, 0.00 to 1.00), respectively. Good FDG PET response was defined as SUV2 less than 2.5 or SUV2:1 < or = 0.5. FDG PET response by SUV2 or SUV2:1 was concordant with histologic response in 68% and 69% of patients, respectively. SUV2 was associated with outcome (4-year PFS 72% for SUV2 < 2.5 v 27% for SUV2 > or = 2.5, P = .01 for all patients; 80% for SUV2 < 2.5 v 33% for SUV2 > or = 2.5, P = .036 for localized at diagnosis patients). SUV2:1 < or = 0.5 was not predictive of PFS. CONCLUSION: FDG PET imaging of ESFTs correlates with histologic response to neoadjuvant chemotherapy. SUV2 less than 2.5 is predictive of PFS independent of initial disease stage.     

Prognostic PET 18F-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non-Small Cell Lung Cancer

Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis. Cancer Res; 72(15); 3725-34. ?2012 AACR.     

Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy

Background

Fluorine-18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine (¹¹C MET) has little uptake under normal conditions. We prospectively investigated the uptake of ¹⁸F FDG and ¹¹C MET PET in patients with craniopharyngioma prior to proton therapy.

Methods

Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using ¹⁸F FDG and ¹¹C MET. PET and MRI studies were registered to help identify tumor volume. Measurements of maximum standardized uptake value (SUV_max) were taken of the tumor and compared with noninvolved left frontal background white matter using a paired t-test. Uptake was graded using a 4-point scale.

Results

Median patient age was 9 years (range 5–19). Seven patients were diagnosed by pathology, 1 by cyst fluid aspiration, and 2 by neuroimaging. Median FDG SUV_max for tumor and background were 2.65 and 3.2, respectively. Median MET SUV_max for tumor and background were 2.2 and 1, respectively. There was a significant difference between MET tumor SUV_max and MET background SUV_max (P = .0001). The difference between FDG tumor SUV_max and FDG background SUV_max was not significant (P = .3672).

Conclusion

¹¹C MET PET uptake is significantly greater within the tumor compared with noninvolved background white matter, making it more useful than FDG PET in identifying active tumor in patients with craniopharyngioma. Future work will focus on using ¹¹C MET PET to discriminate between active and inactive tumor after irradiation.     

Serial 2-[<Superscript>18</Superscript>F] fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP)

Background The response of bone-dominant (BD) breast cancer to therapy is difficult to assess by conventional imaging. Our preliminary studies have shown that quantitative serial 2-[¹⁸F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) correlates with therapeutic response of BD breast cancer, but the relationship to long-term outcome measures is unknown. Our goal was to evaluate the prognostic power of serial FDG PET in BD breast cancer patients undergoing treatment. Methods We reviewed medical records of 405 consecutive breast cancer patients referred for FDG PET. Of these, 28 demonstrated metastatic BD breast cancer, were undergoing treatment, had at least 2 serial PET scans, and had abnormal FDG uptake on the first scan. Standardized uptake value (SUV) for the most conspicuous bone lesion at the initial scan, absolute change in SUV over an interval of 1–17 months, and percent change in SUV were considered as predictors of time-to-progression (TTP) and time to skeletal-related event (t-SRE). Results Using proportional hazards regression, smaller percentage decreases in SUV (or increases in SUV) were associated with a shorter TTP (P < 0.006). A patient with no change in SUV was twice as likely to progress compared to a patient with a 42% median decrease in SUV. A higher SUV on the initial FDG PET predicted a shorter t-SRE (hazard ratio = 1.30, P < 0.02). Conclusions Changes in serial FDG PET may predict TTP in BD metastatic breast cancer patients. However, larger prospective trials are needed to validate changes in FDG PET as a surrogate endpoint for treatment response.     

Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma.

PURPOSE: To establish the predictive potential of 2-18fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses > or = 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 < or = 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (< or = or > 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.     

Evaluation of Early Response to SU101 Target-based Therapy in Patients with Recurrent Supratentorial Malignant Gliomas Using FDG PET and Gd-DTPA MRI

Changes in [¹⁸F]-2-fluoro-2-deoxyglucose (FDG) uptake and gadopentetate dimeglumine (Gd-DTPA) enhancement before and after the first course of treatment with a cytostatic agent SU101 (N-[(4-trifluoromethyl)-phenyl]-5-methylisoxazole-4-carboxamide, SUGEN) were assessed using positron emission tomography (PET) and magnetic resonance imaging (MRI) in a pilot study of 8 patients with recurrent supratentorial malignant gliomas. The localization and the volume of Gd-DTPA enhancement and FDG hypermetabolism were analyzed. PET and MRI studies were performed one week before and 7.6±3.7 weeks after administration of SU101. The ratios of mean tumor nobreak activity to mean contralateral white matter and ipsilateral cerebellar activity were calculated for tumor regions, and SUV values corrected to the subjects' body surface area and glucose level (SUVbsa^*glu) were calculated for non-tumor regions. Five patients had a substantial increase of tumor volume on both PET and MRI during the first course of SU101. PET and MRI showed roughly equivalent volume changes. Large tumor volume increases were associated with a short time to clinical progression. The metabolic change in the tumor following the first course of SU101 varied from patient to patient, ranging from a 31% reduction to a 43% increase in FDG uptake ratio. Changes in FDG uptake were not predictive of time to progression or survival. In 2 patients with marked clinical deterioration and rapid tumor growth, there were differences in localization of Gd-DTPA enhancement and FDG hypermetabolism suggesting that hypermetabolism beyond the area of contrast enhancement may be of value in predicting rapid progression of high-grade glioma. SU101 did not induce any appreciable changes in SUVbsa^*glu for non-tumor brain in 6 of 8 patients.     

2-[18F]-Fluoro-2-deoxy-D-glucose positron emission tomography as guidance for primary treatment in patients with advanced-stage resectable squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: High uptake of 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) is associated with unfavorable results. Pretreatment FDG uptake was evaluated as a predictor of survival and guidance for primary surgery or radiotherapy (RT) in patients with squamous cell carcinoma (SCC) of the larynx and hypopharynx. MATERIALS AND METHODS: Seventy-nine consecutive patients with newly diagnosed advanced resectable SCC of the larynx and hypopharynx underwent FDG positron emission tomography (PET) before surgical resection plus RT and chemotherapy (surgery group, n=40) or RT with chemotherapy and surgical salvage (RT group, n=39). Age, tumor stage, histological grade, treatment strategy, and standardized uptake value (SUV) were analyzed for association with local control and survival. RESULTS: Overall local control and survival in the two groups did not differ (P>0.1). In univariate analysis, nodal positivity (P=0.014) and SUV>8.0 (P=0.007) were associated with poorer disease-free survival (DFS). In multivariate analysis, SUV remained an independent determinant of DFS (P=0.014). When patients with SUV>8.0 in the two treatment groups were analyzed separately, those in the surgery group tended to have a higher 3-year DFS than those in the RT group, despite no statistical significance (48% vs. 27%, P=0.085). CONCLUSIONS: High FDG uptake is associated with poor survival in patients with advanced laryngopharyngeal SCC. Patients with high FDG uptake may be better treated by surgical resection followed by RT and chemotherapy.     

Metabolic flare: indicator of hormone responsiveness in advanced breast cancer.

PURPOSE: The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [(18)F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[(18)F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS: Forty women with biopsy-proved advanced ER-positive (ER(+)) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS: In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% +/- 23.3% (mean +/- SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% +/- 16.2%; P =.0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 +/- 2.4) than those of nonresponders (SUV, 1.8 +/- 1.3; P =.0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% +/- 14.2%) than in the nonresponders (mean percentage decrease, 19.4% +/- 17.3%; P =.0003). CONCLUSION: The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER(+) breast cancer.     

Detection of histological anaplasia in gliomas with oligodendroglial components using positron emission tomography with 18F-FDG and 11C-methionine: report of two cases

Gliomas are regionally heterogeneous tumors. Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) and ¹¹C-methionine (MET) evaluates the heterogeneity of histological malignancy within the tumor. We present two patients with oligodendrocytic tumors that showed discrepancies in the highest uptake areas with these two tracers. PET studies with MET and FDG were performed on the same day, 2 weeks before surgery. In both cases, biopsy specimens were separately obtained from the highest MET and FDG uptake areas guided by intraoperative neuronavigation. Histological examinations demonstrated that the specimens from the highest MET uptake area revealed low-grade oligoastrocytoma or oligodendroglioma, whereas histological anaplasias were contained in the specimens from the highest FDG uptake area. With gliomas with oligodendroglial components, the MET uptake ratio does not always correspond to histological anaplasia, which can be detected only by FDG PET. Sole application of MET PET for preoperative evaluation may lead to misunderstanding of histological heterogeneity in gliomas, especially those with oligodendroglial components. FDG and MET tracers play complementary roles in preoperative evaluation of gliomas.     

The role of PET in the surgical management of malignant pleural mesothelioma

Current imaging modalities fail to define precisely the extent of disease in MPM and are inaccurate in selecting patients for treatment. Previous studies have shown that CT and MRI provide anatomical information that is often imprecise in the preoperative staging of MPM. Consequently, about 25% of patients are found to have unresectable tumor at the time of exploratory thoracotomy. PET is now widely recognized as an important staging modality in many cancers, and PET SUV is reported as a prognostic indicator in several malignancies. However, only a few previous studies have investigated the utility of FDG PET scan in MPM. From 1998 to 2003, 65 patients with MPM underwent PET scans. Median PET SUV in the primary tumor was 6.6 (range, 2-23). The median follow-up for all surviving patients was 16 months. Median survivals were 14 and 24 months for the high and low SUV groups, respectively. In a multivariable analysis, high SUV tumors were associated with a 3.3 times greater risk of death than low SUV tumors (p = 0.03). Mixed histology carried a 3.2 times greater risk of death than epithelial histology (p = 0.03). SUV of >4 and mixed histology are poor risk factors in malignant pleural mesothelioma. These findings suggest that FDG-PET can be used to stratify patients for treatment and clinical trials.     

Prediction of Pathology and Survival by FDG PET in Gliomas

Objectives: Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-d-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. Methods: All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. Results: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for >1 year (median survival of 28 months) and 19% survived for >5 years. Only 29% (48/165) of patients with high uptake survived for >1 year, (median survival of 11 months) and none survived for >5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. Conclusions: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.     

[F‐18]‐fluorodeoxy‐D‐glucose–positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults

BACKGROUND:

Response to neoadjuvant chemotherapy is 1 of the most powerful prognostic factors for extremity osteosarcoma. [F‐18]‐fluorodeoxy‐D‐glucose–positron emission tomography (FDG‐PET) is a noninvasive imaging modality that is used to predict histopathologic response. To determine the prognostic value of FDG‐PET response for progression‐free survival (PFS) in osteosarcoma, the authors of this report reviewed the University of Washington Medical Center experience.

METHODS:

Forty patients with extremity osteosarcoma were evaluated by FDG‐PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG‐PET standard uptake values (SUVs) before neoadjuvant chemotherapy (SUV1) and after neoadjuvant chemotherapy (SUV2) were analyzed and correlated with histopathologic response.

RESULTS:

The median SUV1 was 6.8 (range, 3.0‐24.1), the median SUV2 was 2.3 (range, 1.2‐12.8), and the median SUV2 to SUV1 ratio (SUV2:1), was 0.36 (range, 0.12‐1.10). A good FDG‐PET response was defined as anSUV2 <2.5 or an SUV2:1 ≤0.5. FDG‐PET responses according to SUV2 and SUV2:1 were concordant with histologic response in 58% and 68% of patients, respectively. SUV2 was associated with outcome (4‐year PFS, 73% for SUV2 <2.5 vs 39% for SUV2 ≥2.5; P = .021). Both the initial disease stage and the histologic response were associated with outcome.

CONCLUSIONS:

FDG‐PET imaging of extremity osteosarcoma was correlated only partially with a histologic response to neoadjuvant chemotherapy. An SUV2 <2.5 was associated with improved PFS. Future prospective studies are warranted to determine whether FDG‐PET imaging may be used as a predictor of outcome independent of initial disease stage. Cancer 2009. © 2009 American Cancer Society.