Lung cancer and positron emission tomography with fluorodeoxyglucose

Over the past years, positron emission tomography (PET) with fluoro-2-deoxy-D-glucose (FDG) has emerged as an important imaging modality. In the thorax, FDG-PET has been shown to differentiate benign from malignant pulmonary lesions and stage lung cancer. Preliminary studies have shown its usefulness in assessing tumor recurrence, and assisting in radiotherapy planning. FDG-PET is often more accurate than conventional imaging studies, and has been proven to be cost-effective in evaluating lung cancer patients. This review will discuss the current applications of FDG-PET as compared with conventional imaging in diagnosing, staging, and following patients with lung cancer.     

Anal cancer maximum F-18 fluorodeoxyglucose uptake on positron emission tomography is correlated with prognosis

Purpose

To evaluate anal cancer uptake of F-18 fluorodeoxyglucose (FDG) measured as the maximum standardized uptake value (SUV_max) by positron emission tomography (PET) and its correlation with prognostic factors.

Patients and methods

The study population consisted of 77 patients with stages 0-IIIB anal cancer who underwent pre-treatment FDG-PET. Tumor histology included 65 squamous cell, 11 basaloid, and 1 small cell cancers. SUV_max and sites of lymph node metastasis were recorded. We analyzed the association between SUV_max and prognostic factors.

Results

The mean SUV_max was 10.0 (range 1.0-43.1). The stage distribution included: 2 stage 0, 7 stage I, 49 stage II, 10 stage IIIA, 9 stage IIIB. SUV_max and clinical tumor size were not associated (R² = 0.338). Histology did not significantly influence SUV_max (mean SUV_max 10.0 for squamous versus 9.90 for basaloid). Higher SUV_max was associated with an increased risk of nodal metastasis at diagnosis (p < 0.0001). Higher SUV_max was associated with worse disease-free survival (p = 0.05). Patients with high anal tumor SUV_max at diagnosis were at an increased risk of persistent or recurrent disease on post-therapy FDG-PET performed less than 4 months after completing therapy (p = 0.0402).

Conclusions

SUV_max is a valuable biomarker of anal cancer prognosis, predicting increased risk of lymph node metastasis and worse disease-free survival.     

Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography.

Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.     

18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.     

Gangliocytoma of the medulla oblongata demonstrating high tracer uptake on positron emission tomography

Journal of Neuro-Oncology -     

Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma.

PURPOSE: (18)Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease. MATERIALS AND METHODS: PET studies of 97 patients with non-Hodgkin's lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology. RESULTS: FDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 +/- 3.1 v 19.6 +/- 9.3; P < .01) and relapsed (SUV, 6.3 +/- 2.7 v 18.1 +/- 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher. CONCLUSION: FDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.     

Methods to delineate tumour for radiotherapy by fluorodeoxyglucose positron emission tomography

Numerous articles have been published showing the interest to delineate tumours using fluorodeoxyglucose positron emission tomography/computed tomography images in radiotherapy planning. This imaging is used to identify tumour tissues with increased glucose metabolism compared to healthy surrounding tissues. This volume corresponds to the metabolic tumour volume. Despite extensive research on metabolic tumour volume segmentation methods, there is currently no consensus on the optimal segmentation method to use. In this review, the main methods proposed in the literature are presented, as well as their advantages and disadvantages in the context of radiotherapy.     

Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography.

PURPOSE: Variable uptake of the glucose analog (18)fluorodeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared (18)FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. PATIENTS AND METHODS: Preoperative (18)FDG-PET scans were performed in 55 patients. (18)FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1alpha); vascular endothelial growth factor (VEGF(165)); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. RESULTS: There were positive correlations between (18)FDG uptake and Glut-1 expression (P <.001), MAI (P =.001), amount of necrosis (P =.010), number of tumor cells/volume (P =.009), expression of HK I (P =.019), number of lymphocytes (P =.032), and microvessel density (r =.373; P =.005). HIF-1alpha, VEGF(165), HK II, HK III, and macrophages showed no univariate correlation with (18)FDG. In logistic regression, however, HIF-1alpha and HK II added value to MAI and Glut-1. CONCLUSION: (18)FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of (18)FDG into the cell, HK for entering (18)FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1alpha for upregulating Glut-1. Together, these features explain why breast cancers vary in (18)FDG uptake and elucidate the low uptake in lobular breast cancer.     

Pancreatic cancer: Preliminary experience with sodium iodide fluorodeoxyglucose positron emission tomography in Australia

Previous studies of fluorodeoxyglucose positron emission tomography (FDG‐PET) in pancreatic cancer have used Bismuth Germinate detector systems. This preliminary Australian study aims to confirm the accuracy of FDG‐PET in pancreatic cancer using a dedicated sodium iodide (NaI) PET system. Fifteen consecutive patients underwent FDG‐PET using a GE QUEST dedicated NaI PET scanner. The indications were the characterization of a pancreatic mass seen on CT or ultrasonographic imaging (nine cases), diagnosis or exclusion of recurrent disease following surgery and adjuvant therapy (four cases) and presurgical staging of primary pancreatic cancer (two cases). The final diagnosis was determined from histology or, when no histology was available, by radiological and clinical follow up. The FDG‐PET accurately characterized eight out of nine pancreatic masses (seven were true negative, one was true positive and one was false positive). Of the four cases performed to determine recurrent disease, three were accurately diagnosed (two true negatives and one true positive). In the fourth case, PET accurately detected a liver metastasis but did not detect the local recurrence. Results in the two cases where PET was performed for preoperative staging comprised one true positive and one false negative. Sodium iodide FDG‐PET is useful in the diagnosis of pancreatic cancer, particularly in the presence of a previously detected mass.     

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.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations.

PURPOSE: To evaluate the diagnostic value of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) for the diagnosis of primary breast cancer. PATIENTS AND METHODS: Preoperatively, 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. RESULTS: Breast 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. CONCLUSION: Partial 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.     

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.     

Initial staging impact of fluorodeoxyglucose positron emission tomography/computed tomography in locally advanced breast cancer

Purpose.

Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may reveal distant metastases more accurately than conventional imaging (CT, skeletal scintigraphy, chest radiography). We hypothesized that patients diagnosed with stage III noninflammatory breast cancer (non-IBC) and IBC by conventional imaging with PET/CT have a better prognosis than patients diagnosed without PET/CT.

Patients and Methods.

We retrospectively identified 935 patients with stage III breast cancer in 2000–2009. We compared the relapse-free survival (RFS) and overall survival (OS) times of patients diagnosed by conventional imaging with those of patients diagnosed by conventional imaging plus PET/CT. Univariate and multivariate Cox proportional hazards regression models were used to assess associations between survival and PET/CT.

Results.

RFS and OS times were not significantly different between patients imaged with PET/CT and those imaged without PET/CT. However, the RFS time in IBC patients was significantly different between patients imaged with PET/CT and those imaged without PET/CT on both univariate (hazard ratio [HR], 0.43; p = .014) and multivariate (HR, 0.33; p = .004) analysis. There was a trend for a longer OS duration in IBC patients imaged with PET/CT.

Conclusion.

Among IBC patients, adding PET/CT to staging based on conventional imaging might detect patients with metastases that were not detected by conventional imaging. The use of conventional imaging with PET/CT for staging in non-IBC patients is not justified on the basis of these retrospective data. The use of conventional imaging plus PET/CT in staging IBC needs to be studied prospectively to determine whether it will improve prognosis.     

Lymphadenopathy resulting from acute toxoplasmosis mimicking relapse of non-Hodgkin's lymphoma on fluorodeoxyglucose positron emission tomography/computed tomography

We report a case documenting fluorodeoxyglucose (FDG) accumulation in cervical, supraclavicular and axillary lymph nodes resulting from acute toxoplasmosis. A 50-year-old Indian female with history of non-Hodgkin's lymphoma (NHL) of left breast, postchemotherapy status, was found to have hypermetabolic right cervical, supraclavicular and axillary lymph nodes on a surveillance FDG positron emission tomography/computed tomography (PET/CT) scan. Her previous two PET/CT scans were unremarkable with no evidence of metabolically active disease. Therefore, a differential diagnosis of relapse of NHL versus infectious/inflammatory pathology was raised in the report. Biopsy of axillary lymph node demonstrated features characteristic of toxoplasmosis. The serological test results were also compatible with acute toxoplasmosis infection. Infective and inflammatory diseases are known to accumulate FDG, resulting in false positives for malignancy. This case demonstrates lymph nodal toxoplasmosis as a potential cause of false positive FDG PET/CT findings in patients with known malignancy and highlights the importance of histopathological and laboratory correlation for the accurate interpretation of FDG PET/CT scans.     

Brain tumor iron uptake measured with positron emission tomography and 52Fe-citrate

Summary Iron and transferrin are required for DNA synthesis and cell division. Cellular iron uptake is mediated by transferrin receptors. In order to investigate whether iron uptake in brain tumors is associated with their histological grade, we studied 24 patients (5 astrocytoma, 11 glioblastoma, 8 meningioma) using positron emission tomography and 12 Fe-citrate. Tracer uptake from blood into brain and tumor tissue was assessed 1. using multiple time graphical analysis yielding a measure for unidirectional net tracer uptake (Ki and 2.) testing a one- and two-tissue kinetic compartment model, where K1 denotes tracer uptake from blood into tissue, k2 efflux from tissue into plasma, and 0 specific tracer binding. In the plasma, ⁵²Fe was bound to a 80 kD protein (transferrin). Ki (in units of 10^–5/min) was higher in glioblastomas (Ki mean ± SD 13.6 ± 6.1) compared with astrocytomas (4.8 ± 3.5, Mann Whitney p = 0.015) and contralateral brain (2.2 ± 0.9, Mann Whitney p = 0.009). Highest values were found in meningiomas (no blood-brain barrier (BBB); Ki 33.4 ± 16.5, Mann Whitney p = 0.008 compared with glioblastomas). Among the compartment models, fitting with Kl1 and regional plasma volume explained the data best (one-tissue model), data fits were not significantly improved by addition of a k2 or k3 parameter. K1 and Ki values were significantly correlated (Spearman Rank, p = 0.0006). We conclude that ⁵²Fe accumulation in tumors is governed by tracer uptake at the BBB, and does not reflect number of transferrin receptors at the level of tumor cells.