DOI: 10.1148/rg.232025705
(Radiographics. 2003;23:315-340.)
© RSNA, 2003
Clinical Role of FDG PET in Evaluation of Cancer Patients1
Lale Kostakoglu, MD,
Harry Agress, Jr, MD and
Stanley J. Goldsmith, MD
1 From the Division of Nuclear Medicine, Department of Radiology, New York Presbyterian Hospital, Weill Cornell Medical Center, 525 E 68th St, Starr No. 221, New York, NY 10021 (L.K., S.J.G.); and the Division of Nuclear Medicine, Department of Radiology, Hackensack University Medical Center, Hackensack, NJ (H.A.). Received April 25, 2002; revision requested August 5 and received October 7; accepted October 8. H.A. has given lectures sponsored by CTI (Knoxville, Tenn), PETNET (Knoxville, Tenn), and Alliance Imaging (Anaheim, Calif) on use of PET. Address correspondence to L.K. (e-mail: lak2005@med.cornell.edu).
 |
Abstract
|
|---|
Positron emission tomography (PET) is a diagnostic imaging technique that allows identification of biochemical and physiologic alterations in tumors. Use of PET performed with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) significantly improves the accuracy of tumor imaging. In terms of oncologic applications, FDG PET has already gained widespread acceptance in the initial staging of cancer, management of recurrent cancer, and monitoring the response to therapy. With conventional imaging modalities, size criteria are used to distinguish between benign and malignant disease in lymph nodes; conversely, FDG PET is based on identification of fundamental aspects of tumor metabolism. FDG uptake in tumors is proportional to the metabolic rate of viable tumor cells, which have an increased demand for glucose. The high sensitivity and high negative predictive value of FDG PET in most malignant tumors enable this technique to play an even greater role in tumor management at initial staging and follow-up.
© RSNA, 2003
Index Terms: Fluorine, radioactive • Neoplasms, PET, **.121632, **.30 • Neoplasms, staging • Positron emission tomography (PET), **.12163
|
LEARNING OBJECTIVES FOR TEST 2
|
|---|
After reading this article and taking the test, the reader will be able to:
- Discuss the value of FDG PET in comparison with those of conventional imaging modalities in initial staging and restaging of cancers.
- Describe the advantages of FDG PET over conventional imaging modalities in predicting therapy outcome or monitoring response to therapy.
- Identify the pitfalls of FDG PET in staging and in monitoring response to therapy.
|
Introduction
|
|---|
Positron emission tomography (PET) is an advanced imaging tool for diagnosis, staging, and restaging of cancer. The method is based on identifying the increased glycolytic activity in malignant cells, in which glucose is preferentially concentrated due to an increase in membrane glucose transporters as well as to an increase in some of the principal enzymes, such as hexokinase, responsible for phosphorylation of glucose (1,2). 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) is transported into tumor cells, similarly to glucose, by means of glucose transporter proteins known as GLUT transporters and subsequently phosphorylated by hexokinase to FDG 6-phosphate. FDG 6-phosphate is not efficiently metabolized further and therefore accumulates within the cell. This process of "metabolic trapping" of FDG in the cell constitutes the basis for imaging the in vivo distribution of the tracer with FDG PET. It is possible to image the entire body in a single session, increasing the opportunity for finding unsuspected disease sites.
At present, the Centers for Medicare and Medicaid Services (formerly the Health Care Financing Administration) has approved expanded Medicare coverage for FDG PET for the following indications: diagnosis, initial staging, and restaging of non–small cell lung cancer, colorectal cancer, Hodgkin and non-Hodgkin lymphoma, esophageal cancer, melanoma, head and neck cancers, and breast cancer as well as characterization of solitary pulmonary nodules (Table). However, the current Medicare coverage does not include central nervous system, thyroid, hepatocellular, pancreatic, and genitourinary neoplasms.
This review considers the applications of FDG PET in management of primary and recurrent malignancies approved by the Centers for Medicare and Medicaid Services for reimbursement at this time. All of the FDG PET scans were obtained with a dedicated PET system with attenuation correction (ECAT EXACT HR +; CTI/Siemens, Knoxville, Tenn) except those in Figure 16, which were obtained with a dual-head coincidence camera (MCD-AC; ADAC Laboratories, Milpitas, Calif).
|
Normal Distribution of FDG
|
|---|
There are several sites of normal physiologic accumulation of FDG, hence FDG distribution is not limited to neoplastic tissues (Fig 1). The brain uses glucose as its primary substrate; consequently, accumulation is physiologically high in the cortex, basal ganglia, thalamus, and cerebellum. Although the myocardium uses free fatty acids as its primary substrate, it also uses glucose as an alternate substrate; up to 4% of the injected dose can accumulate within the myocardium depending on the relative availability of free fatty acids versus glucose. The biodistribution of FDG can be affected by blood glucose levels via the competitive displacement of FDG by the circulating glucose. There is no agreement as to adjusting glucose levels in diabetic patients. In type I diabetes, insulin is not recommended and FDG PET should be performed in the morning after an overnight fast. In type II diabetes, insulin may be used to manipulate glucose levels, although this requires patient monitoring and exaggerates physiologic muscle uptake. All patients should fast for at least 4–6 hours prior to the study to enhance and standardize tumor FDG uptake as well as to avoid the interference of the cardiac uptake for lesions in the chest.
View larger version (70K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1. Normal distribution of FDG. Coronal FDG PET image shows physiologic uptake in the cerebral cortex, vocal cords (arrow), liver, kidneys, intestine, and urinary bladder. Also note the minimal uptake in the breasts, mediastinum, and bone marrow.
|
|
In the resting state, the muscular uptake of FDG is negligible. After exercise, however, significant uptake is observed in the skeletal muscles. Hyperventilation may induce uptake in the diaphragm, and stress-related muscle uptake is often observed in the cervical, trapezius, and paraspinal muscles. Uptake in the tonsils, parotid glands, and muscles of mastication may also be seen as a normal variant. FDG also accumulates in laryngeal muscles in proportion to contractile activity during vocalization (3). FDG is filtered by the glomerulus and not reabsorbed, so significant FDG is seen in the renal collecting system, ureters, and bladder, which may interfere with identification of renal or pelvic tumors. Hydration should be encouraged to promote diuresis and decrease activity in the renal collecting system and bladder. Uptake in the gastrointestinal tract is variable. The wall of the stomach is usually faintly seen. Uptake in the cecum may be related to abundant lymphoid tissue in this region. The normal colon and small intestine may demonstrate increased FDG uptake probably due to smooth muscle activity, bacterial uptake, and metabolically active mucosa (4). FDG uptake in the bone marrow is normally modest. Patients undergoing treatment with granulocyte-stimulating factor have diffuse intense FDG uptake in the bone marrow (5). In addition, granulomatous inflammation and recent surgical intervention may cause FDG to accumulate.
In this review, potential sources of false-positive and false-negative findings are discussed under each disease category.
Quantitative evaluation of FDG PET images: FDG PET also provides quantitative data in the form of the standardized uptake value (SUV) or standardized uptake ratio (SUR). This is an uptake measurement that provides a means of comparison of FDG uptake between different lesions. Measurement of SUV requires attenuation correction to avoid the variability in FDG uptake due to the differences in tumor depth within the body. This value normalizes the tumor FDG uptake with the injected activity (Qinj) and the body weight (W) (SUV = Q x W/Qinj). However, SUV is dependent on the body weight. Therefore, correction with the lean body mass (SUVLBM) is required to avoid erroneous comparisons that can stem from changes in pre- and posttherapy body weight in the same patient. In calculating SUVs, the administered dose, corrected for residual activity in the syringe and tubing, must also be accurately determined and the dose must be decay corrected to the time of imaging.
|
Solitary Pulmonary Nodules
|
|---|
There is no size criterion that allows reliable distinction of benign from malignant solitary pulmonary nodules. Although 80% of benign solitary pulmonary nodules are less than 2 cm in diameter, small size is not consistent with benignity, since approximately 42% of malignant nodules are less than 2 cm in diameter (6). The overall sensitivity and specificity of FDG PET are 92% and 90%, respectively, for detection of malignancy in nodules between 0.7 and 4 cm in diameter (7) (Fig 2). FDG PET has been approved by the Centers for Medicare and Medicaid Services as a substitute for CT-directed needle biopsy. In a recent meta-analysis, FDG PET was reported to have a sensitivity of 97% and a specificity of 78% in characterizing solitary pulmonary nodules (8). In this analysis, no difference was found in the accuracy of FDG PET between nodules 1 cm in diameter and those larger than 1 cm, although few data exist for nodules smaller than 1 cm. Notwithstanding the controversial views, SUVs of 2.5 or greater have been used as a cutoff value indicative of malignancy (7,9). In brief, evaluation of solitary pulmonary nodules with FDG PET allows patients to be followed up with sequential imaging rather than invasive procedures.
View larger version (100K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2a. Primary carcinoid nodule of the left upper lung. (a) Computed tomographic (CT) scan shows a 1.5-cm-diameter solitary pulmonary nodule (arrow) in the left upper lobe adjacent to the aortic arch. (b) Axial FDG PET image shows hypermetabolism in the lesion (arrow) (mean SUV = 1.9). Histologic evaluation demonstrated that the mass was a pulmonary carcinoid tumor.
|
|
View larger version (92K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2b. Primary carcinoid nodule of the left upper lung. (a) Computed tomographic (CT) scan shows a 1.5-cm-diameter solitary pulmonary nodule (arrow) in the left upper lobe adjacent to the aortic arch. (b) Axial FDG PET image shows hypermetabolism in the lesion (arrow) (mean SUV = 1.9). Histologic evaluation demonstrated that the mass was a pulmonary carcinoid tumor.
|
|
|
Lung Cancer
|
|---|
Lung cancer is among the most commonly occurring malignancies in the world and one of the few that continue to show increasing incidence. Histologically, non–small cell lung cancers (NSCLCs) constitute about 80% of lung cancers and small cell lung cancers constitute about 20%. The Centers for Medicare and Medicaid Services approved FDG PET for evaluation of NSCLC.
Initial Staging of NSCLC
In the staging of NSCLC, FDG PET is not recommended for determination of tumor size or invasion into adjacent tissues (T3 status of the tumor). However, FDG PET has been successfully used in mediastinal nodal staging and detection of distant metastases (Fig 3). Staging with CT and magnetic resonance (MR) imaging has been reported to have a sensitivity of 50%–60%, whereas mediastinoscopy has a sensitivity and specificity of 87% and 91%, respectively (10,11). A recent comprehensive study reported a sensitivity of 93% and specificity of 99% for FDG PET versus 72% and 94% for CT, respectively (12). The sensitivity and specificity of FDG PET for nodal involvement are comparable with those of mediastinoscopy; however, its sensitivity is limited for micrometastases, which require tissue biopsy (13). Owing to its high negative predictive value (approximately 94%), FDG PET combined with chest CT preoperatively may alleviate the need for surgical staging in FDG PET–negative cases. However, with a positive FDG PET result, further diagnostic procedures should still be pursued to avoid overstaging.
View larger version (71K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3a. NSCLC of the right upper lobe with metastatic involvement of the ipsilateral hilum, bilateral adrenal glands, and bone. Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe. Additional foci are seen in the right hilum (short arrow in b), bilateral adrenal glands (long arrows) (with greater activity in the right gland than in the left), and left acetabulum (arrowhead in b); these foci represent distant metastases.
|
|
View larger version (62K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3b. NSCLC of the right upper lobe with metastatic involvement of the ipsilateral hilum, bilateral adrenal glands, and bone. Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe. Additional foci are seen in the right hilum (short arrow in b), bilateral adrenal glands (long arrows) (with greater activity in the right gland than in the left), and left acetabulum (arrowhead in b); these foci represent distant metastases.
|
|
Metastatic disease: At least 10% of patients are found to have unsuspected metastatic disease at FDG PET when results of routine CT are not definitive for metastasis (14) (Fig 4). In addition, some false-positive findings at CT, including adrenal nodules, are correctly interpreted as negative with FDG PET (15). Thus, FDG PET has a substantial role in identifying patients as surgical candidates who might otherwise be considered to have unresectable tumors. Accordingly, patient treatment can be altered in up to 41% of cases on the basis of the FDG PET findings (16,17).
View larger version (112K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4a. NSCLC of the right upper lobe staged with FDG PET and CT. (a, b) Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe, as well as in right hilar, paratracheal, subcarinal, and right supraclavicular (arrow in b) lymph nodes. The original CT report mentioned all of these findings except the right supraclavicular node. (c) CT scan shows a large mass in the right upper lobe. (d) CT scan of the thoracic inlet shows right supraclavicular adenopathy (arrow), which was initially overlooked, thus changing the stage from 3A (potential surgical candidate) before FDG PET to 3B (inoperable disease) after FDG PET.
|
|
View larger version (109K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4b. NSCLC of the right upper lobe staged with FDG PET and CT. (a, b) Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe, as well as in right hilar, paratracheal, subcarinal, and right supraclavicular (arrow in b) lymph nodes. The original CT report mentioned all of these findings except the right supraclavicular node. (c) CT scan shows a large mass in the right upper lobe. (d) CT scan of the thoracic inlet shows right supraclavicular adenopathy (arrow), which was initially overlooked, thus changing the stage from 3A (potential surgical candidate) before FDG PET to 3B (inoperable disease) after FDG PET.
|
|
View larger version (99K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4c. NSCLC of the right upper lobe staged with FDG PET and CT. (a, b) Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe, as well as in right hilar, paratracheal, subcarinal, and right supraclavicular (arrow in b) lymph nodes. The original CT report mentioned all of these findings except the right supraclavicular node. (c) CT scan shows a large mass in the right upper lobe. (d) CT scan of the thoracic inlet shows right supraclavicular adenopathy (arrow), which was initially overlooked, thus changing the stage from 3A (potential surgical candidate) before FDG PET to 3B (inoperable disease) after FDG PET.
|
|
View larger version (119K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4d. NSCLC of the right upper lobe staged with FDG PET and CT. (a, b) Coronal FDG PET images show intense hypermetabolism in an NSCLC of the right upper lobe, as well as in right hilar, paratracheal, subcarinal, and right supraclavicular (arrow in b) lymph nodes. The original CT report mentioned all of these findings except the right supraclavicular node. (c) CT scan shows a large mass in the right upper lobe. (d) CT scan of the thoracic inlet shows right supraclavicular adenopathy (arrow), which was initially overlooked, thus changing the stage from 3A (potential surgical candidate) before FDG PET to 3B (inoperable disease) after FDG PET.
|
|
Recurrent NSCLC and Evaluation of Response to Therapy
Posttherapy tissue changes such as scarring and necrosis may obscure the identification of recurrent tumor with CT. A negative biopsy result for tumor may well be a false-negative finding due to sampling errors. Equivocal radiographic findings suggestive of tumor recurrence can be accurately characterized with FDG PET.
FDG PET can demonstrate changes in metabolism after treatment and may be a better indicator of a favorable response to therapy than the decrease in tumor size determined with CT. However, it has been suggested that a relative decrease in FDG uptake may indicate only a partial response resulting from destruction of cells sensitive to chemotherapy while resistant cells continue to grow (18). Nevertheless, normalization of FDG uptake after treatment appears to be an indicator of a good prognosis (19) (Fig 5). In a recent study, all patients with negative posttherapy FDG PET scans were alive 2 years after the completion of treatment, whereas 50% of patients with residual FDG uptake did not survive within that same period (16,17,19) (Fig 6).
View larger version (83K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5a. Large cell lung cancer in a 71-year-old woman. (a) Pretherapy coronal FDG PET image shows intense hypermetabolism in a lung neoplasm in the superior segment of the left lower lobe, as well as in the bilateral hilar and mediastinal lymph nodes. (b) FDG PET image obtained 4 months after therapy shows normal FDG distribution with physiologic uptake in the heart, renal collecting system, intestine, and bladder.
|
|
View larger version (76K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5b. Large cell lung cancer in a 71-year-old woman. (a) Pretherapy coronal FDG PET image shows intense hypermetabolism in a lung neoplasm in the superior segment of the left lower lobe, as well as in the bilateral hilar and mediastinal lymph nodes. (b) FDG PET image obtained 4 months after therapy shows normal FDG distribution with physiologic uptake in the heart, renal collecting system, intestine, and bladder.
|
|
View larger version (81K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6a. NSCLC of the left parahilar region evaluated with FDG PET before and after therapy (left pneumonectomy and radiation therapy). (a) Pretherapy coronal FDG PET image shows left parahilar hypermetabolism in an NSCLC (arrow). (b) FDG PET image obtained 8 months after therapy shows multiple new hypermetabolic foci in the aortopulmonary window, subcarinal, and right-sided lymph nodes, findings consistent with progression of disease.
|
|
View larger version (84K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6b. NSCLC of the left parahilar region evaluated with FDG PET before and after therapy (left pneumonectomy and radiation therapy). (a) Pretherapy coronal FDG PET image shows left parahilar hypermetabolism in an NSCLC (arrow). (b) FDG PET image obtained 8 months after therapy shows multiple new hypermetabolic foci in the aortopulmonary window, subcarinal, and right-sided lymph nodes, findings consistent with progression of disease.
|
|
However, there are pitfalls in the posttherapy setting. Treatment, in particular radiation therapy, may result in therapy-induced inflammatory changes that may be difficult to differentiate from persistent tumor (9,19). FDG PET scans are therefore more reliable when obtained at least 12 weeks after completion of radiation therapy. In addition, FDG PET allows differentiation of recurrent tumor from radiation-induced benign pleural thickening, whereas pleural biopsy is relatively unreliable when performed percutaneously (20). Postirradiation changes on FDG PET images also include radiation esophagitis and diminished marrow activity in the spine (Fig 7).
View larger version (81K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7a. NSCLC treated with radiation therapy and followed up with posttherapy FDG PET. (a, b) Projection and coronal FDG PET images show midesophageal activity secondary to radiation esophagitis (arrow). In addition, there is asymmetric activity in the laryngeal muscles (arrowhead in a), which is decreased on the left side secondary to paralysis of the vocal cord and disruption of the left recurrent laryngeal nerve. (c) Sagittal FDG PET image shows decreased activity in the marrow of the thoracic spine (arrowheads) secondary to radiation therapy.
|
|
View larger version (73K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7b. NSCLC treated with radiation therapy and followed up with posttherapy FDG PET. (a, b) Projection and coronal FDG PET images show midesophageal activity secondary to radiation esophagitis (arrow). In addition, there is asymmetric activity in the laryngeal muscles (arrowhead in a), which is decreased on the left side secondary to paralysis of the vocal cord and disruption of the left recurrent laryngeal nerve. (c) Sagittal FDG PET image shows decreased activity in the marrow of the thoracic spine (arrowheads) secondary to radiation therapy.
|
|
View larger version (53K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7c. NSCLC treated with radiation therapy and followed up with posttherapy FDG PET. (a, b) Projection and coronal FDG PET images show midesophageal activity secondary to radiation esophagitis (arrow). In addition, there is asymmetric activity in the laryngeal muscles (arrowhead in a), which is decreased on the left side secondary to paralysis of the vocal cord and disruption of the left recurrent laryngeal nerve. (c) Sagittal FDG PET image shows decreased activity in the marrow of the thoracic spine (arrowheads) secondary to radiation therapy.
|
|
False-positive and False-negative Findings
Granulomas that occur in patients with sarcoidosis, tuberculosis, histoplasmosis, aspergillosis, and coccidioidomycosis as well as Mycobacterium avium-intracellulare infection and other infectious processes such as pneumonia may result in false-positive findings (21).
Tumors with low metabolic activity such as bronchioloalveolar carcinoma and carcinoid tumors can give rise to false-negative results. Occasionally, well-differentiated adenocarcinomas have relatively less intense FDG accumulation, particularly lesions smaller than 1.0 cm in diameter.
|
Colorectal Cancer
|
|---|
Adenocarcinoma of the large intestine is the third most common malignancy in the United States, representing 15% of all cancers. If diagnosed in its early stage, this common malignancy is highly curable with surgical treatment.
Initial Staging of Colorectal Cancer
FDG PET is sensitive for primary colorectal carcinoma; however, it does not supplant the current morphologic imaging modalities at initial staging, as FDG PET scanners lack the resolution required to evaluate the depth of tumor penetration through the bowel wall. At the primary site, the negative predictive value of FDG PET is greater than the positive predictive value (100% vs 90%) due to the false-positive FDG PET findings of inflammatory processes (22).
The main role of FDG PET in staging colorectal cancer is the assessment of regional lymph node involvement and distal metastases. In a recent study, the sensitivity of both FDG PET and CT in detecting involved regional lymph nodes was 29%, whereas the specificity of FDG PET was higher (96% vs 85%) (22,23). False-negative findings in regional metastatic lymph nodes are usually due to the intense FDG uptake by the primary site, which obscures the adjacent structures. At initial surgery for primary colorectal carcinoma, hepatic metastases are present in 10%–25% of patients (24). FDG PET is superior to CT for identification of hepatic metastases, with a sensitivity of 88% versus 38% and a specificity of 100% versus 97% (22).
Recurrent Colon Cancer and Evaluation of Response to Therapy
The recurrence rate after curative resection of the primary tumor is 10%–40% (25). Approximately 25% of first colorectal cancer recurrences are isolated locoregional failures. An additional 15%–20% are detected as metastatic deposits and are potentially resectable for cure (26). Despite the convenience of CT in the detection of pelvic recurrences, this technique is limited by low specificity (27). The use of T1- and T2-weighted MR imaging may help differentiate local recurrences from scar tissue, although there are still limitations with respect to the tumor size and specificity (28). A correlation has been observed between reduction of the tumor FDG metabolism 5 weeks after systemic treatment and therapy outcome, with sensitivities of 100% and 75%, respectively (29,30). In patients treated with novel therapies such as radio-frequency ablation or a combination of cryotherapy and hepatic artery chemotherapy, FDG PET may be more accurate than CT in distinguishing posttherapy changes from recurrent or residual tumor (31) (Fig 8).
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8a. Colorectal carcinoma with a solitary hepatic metastasis in the left lobe. The metastasis was treated with radio-frequency ablation; FDG PET and CT were performed to evaluate the response to therapy. (a) Posttherapy CT scan shows a low-attenuation lesion with deformity and central increased attenuation (arrow) secondary to the radio-frequency ablation. (b) Baseline FDG PET image shows hypermetabolism in the metastasis (arrow). (c) Posttherapy FDG PET image shows only partial ablation of the lesion medially with residual metabolism noted laterally (arrow).
|
|
View larger version (92K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8b. Colorectal carcinoma with a solitary hepatic metastasis in the left lobe. The metastasis was treated with radio-frequency ablation; FDG PET and CT were performed to evaluate the response to therapy. (a) Posttherapy CT scan shows a low-attenuation lesion with deformity and central increased attenuation (arrow) secondary to the radio-frequency ablation. (b) Baseline FDG PET image shows hypermetabolism in the metastasis (arrow). (c) Posttherapy FDG PET image shows only partial ablation of the lesion medially with residual metabolism noted laterally (arrow).
|
|
View larger version (89K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8c. Colorectal carcinoma with a solitary hepatic metastasis in the left lobe. The metastasis was treated with radio-frequency ablation; FDG PET and CT were performed to evaluate the response to therapy. (a) Posttherapy CT scan shows a low-attenuation lesion with deformity and central increased attenuation (arrow) secondary to the radio-frequency ablation. (b) Baseline FDG PET image shows hypermetabolism in the metastasis (arrow). (c) Posttherapy FDG PET image shows only partial ablation of the lesion medially with residual metabolism noted laterally (arrow).
|
|
The timing of FDG PET after therapy is crucial, as the so-called flare phenomenon may cause a temporary increase in FDG metabolism in responding lesions shortly after initiation of chemotherapy (29). It is therefore recommended that response to chemotherapy be evaluated at least after completion of therapy to avoid false-positive results.
Local-Pelvic Recurrence.—
FDG PET accurately demonstrates recurrent colorectal cancer in patients who have indeterminate findings at CT or MR imaging (32–35) (Fig 9). In a meta-analysis of 366 patients, the sensitivity and specificity of FDG PET for local-pelvic recurrences were 95% and 97%, respectively (36). Nonetheless, correlation with CT is recommended to avoid misinterpretations in cases of inflammatory lesions and bladder diverticula.
View larger version (133K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 9a. Colorectal carcinoma in a 78-year-old man who underwent surgical resection. CT and FDG PET were performed for evaluation of recurrence. (a) CT scan shows a presacral soft-tissue mass (arrow), but it is difficult to determine whether this finding represents postoperative fibrosis or tumor recurrence. (b) Axial FDG PET image shows circumferential hypermetabolism in the presacral space (solid arrow), which represents recurrent tumor (proved at biopsy) with central necrosis. Normal bladder activity is noted anteriorly (arrow with dotted tail). FDG PET can help identify the optimal site for biopsy within a mass by highlighting the area of maximum tumor activity.
|
|
View larger version (77K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 9b. Colorectal carcinoma in a 78-year-old man who underwent surgical resection. CT and FDG PET were performed for evaluation of recurrence. (a) CT scan shows a presacral soft-tissue mass (arrow), but it is difficult to determine whether this finding represents postoperative fibrosis or tumor recurrence. (b) Axial FDG PET image shows circumferential hypermetabolism in the presacral space (solid arrow), which represents recurrent tumor (proved at biopsy) with central necrosis. Normal bladder activity is noted anteriorly (arrow with dotted tail). FDG PET can help identify the optimal site for biopsy within a mass by highlighting the area of maximum tumor activity.
|
|
In a study by Schiepers et al (37), FDG PET allowed differentiation of pelvic recurrence from fibrosis and proved superior to CT, with a sensitivity of 93% versus 60%, specificity of 97% versus 72%, and accuracy of 95% versus 65%.
In patients suspected of having recurrent colorectal cancer, FDG PET can favorably influence therapeutic management in up to 31% of patients by indicating a change in the surgical decision (38).
Hepatic and Abdominal Metastases.—
Surgical resection is the only potential cure in patients with intrahepatic metastases, whereas extrahepatic disease excludes curative surgery. FDG PET has a greater sensitivity and specificity than conventional imaging modalities in depicting hepatic and extrahepatic recurrent colorectal cancer (33,39). The sensitivity and specificity of FDG PET in detection of recurrences in the liver are 96% and 97%, respectively (Fig 10). FDG PET may reveal unexpected extrahepatic metastases leading to patient treatment changes in 18%–43%of patients with suspected recurrent or metastatic colorectal cancer (33,37).
View larger version (102K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 10a. Colorectal carcinoma in a 42-year-old man who underwent resection of colon cancer; the patient was undergoing chemotherapy for multiple hepatic metastases. Initial and follow-up FDG PET was performed to evaluate the response to therapy. (a) Pretherapy coronal FDG PET images show new metastases in the right lobe (arrows and small arrowhead) and left lobe (large arrowhead) of the liver. (b) Coronal FDG PET images obtained 5 months after therapy show increased intensity in the right lobe metastases (arrows and arrowhead) and resolution of the left lobe metastasis.
|
|
View larger version (98K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 10b. Colorectal carcinoma in a 42-year-old man who underwent resection of colon cancer; the patient was undergoing chemotherapy for multiple hepatic metastases. Initial and follow-up FDG PET was performed to evaluate the response to therapy. (a) Pretherapy coronal FDG PET images show new metastases in the right lobe (arrows and small arrowhead) and left lobe (large arrowhead) of the liver. (b) Coronal FDG PET images obtained 5 months after therapy show increased intensity in the right lobe metastases (arrows and arrowhead) and resolution of the left lobe metastasis.
|
|
Distant Metastases.—
Whole-body FDG PET is superior to conventional staging techniques in the evaluation of distant metastases in patients with resected colorectal carcinoma (40–42) (Fig 11). In a meta-analysis of 127 patients, the sensitivity and specificity of FDG PET in the whole body were 97% and 77%, respectively (36). In one study, FDG PET showed additional tumor sites in 29% of preoperative cases in which CT showed a single site of recurrence (41). FDG PET may alter surgical decision making in 25%–29% of patients with unexpected extrahepatic malignant lesions (40,41).
View larger version (130K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 11a. Colorectal carcinoma in a 55-year-old man who underwent tumor resection and in whom recurrence was clinically suspected. FDG PET was performed to evaluate the extent of disease; CT showed no evidence of recurrence. (a) Anterior (left) and posterior (right) coronal FDG PET images show intense hypermetabolism in the left side of the midabdomen (solid arrow), a finding consistent with tumor recurrence. In addition, a subtle nonspecific focus is seen in the liver (arrow with dotted tail). (b) Axial FDG PET image shows the focus of intense hypermetabolism in the left side of the abdomen (arrow). (c) CT scan shows soft-tissue attenuation adjacent to the pancreatic tail (arrow) with adjacent stranding, an appearance consistent with tumor recurrence. In retrospect, this appearance corresponded to the FDG PET finding.
|
|
View larger version (89K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 11b. Colorectal carcinoma in a 55-year-old man who underwent tumor resection and in whom recurrence was clinically suspected. FDG PET was performed to evaluate the extent of disease; CT showed no evidence of recurrence. (a) Anterior (left) and posterior (right) coronal FDG PET images show intense hypermetabolism in the left side of the midabdomen (solid arrow), a finding consistent with tumor recurrence. In addition, a subtle nonspecific focus is seen in the liver (arrow with dotted tail). (b) Axial FDG PET image shows the focus of intense hypermetabolism in the left side of the abdomen (arrow). (c) CT scan shows soft-tissue attenuation adjacent to the pancreatic tail (arrow) with adjacent stranding, an appearance consistent with tumor recurrence. In retrospect, this appearance corresponded to the FDG PET finding.
|
|
View larger version (138K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 11c. Colorectal carcinoma in a 55-year-old man who underwent tumor resection and in whom recurrence was clinically suspected. FDG PET was performed to evaluate the extent of disease; CT showed no evidence of recurrence. (a) Anterior (left) and posterior (right) coronal FDG PET images show intense hypermetabolism in the left side of the midabdomen (solid arrow), a finding consistent with tumor recurrence. In addition, a subtle nonspecific focus is seen in the liver (arrow with dotted tail). (b) Axial FDG PET image shows the focus of intense hypermetabolism in the left side of the abdomen (arrow). (c) CT scan shows soft-tissue attenuation adjacent to the pancreatic tail (arrow) with adjacent stranding, an appearance consistent with tumor recurrence. In retrospect, this appearance corresponded to the FDG PET finding.
|
|
Rising Level of Carcinoembryonic Antigen.—
Conventional imaging studies frequently fail to identify the site of recurrence despite rising carcinoembryonic antigen levels. At second-look surgery, up to 60% of patients are found to be ineligible for curative resection (43). FDG PET has been found to be helpful in identifying early recurrence when CT findings are subtle (Fig 12) (34,42,44). As a result of useful information supplied by FDG PET, clinical management may change substantially in patients with suspected local recurrence.
View larger version (93K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12a. Colorectal carcinoma in a 35-year-old man who underwent resection and in whom the level of carcinoembryonic antigen was rising. CT was originally performed, as there was no evidence of metastases. FDG PET was performed to detect a possible site of recurrence. (a, b) Coronal (a) and axial (b) FDG PET images show a subtle focus of hypermetabolism in the left lower quadrant of the abdomen (arrow in a, arrowhead in b). Findings from rotating three-dimensional (cine) images (not shown) strongly suggested extraluminal uptake. (c) CT scan shows subtle increased attenuation in the mesentery (arrow and arrowhead), which was identified only in retrospect after correlation with the FDG PET scan. The surgical decision was based solely on the FDG PET findings. Surgical exploration yielded recurrent metastatic peritoneal implants in the area of FDG uptake. FDG PET in conjunction with anatomic imaging can significantly assist location of early tumor recurrence by guiding exploratory surgery.
|
|
View larger version (91K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12b. Colorectal carcinoma in a 35-year-old man who underwent resection and in whom the level of carcinoembryonic antigen was rising. CT was originally performed, as there was no evidence of metastases. FDG PET was performed to detect a possible site of recurrence. (a, b) Coronal (a) and axial (b) FDG PET images show a subtle focus of hypermetabolism in the left lower quadrant of the abdomen (arrow in a, arrowhead in b). Findings from rotating three-dimensional (cine) images (not shown) strongly suggested extraluminal uptake. (c) CT scan shows subtle increased attenuation in the mesentery (arrow and arrowhead), which was identified only in retrospect after correlation with the FDG PET scan. The surgical decision was based solely on the FDG PET findings. Surgical exploration yielded recurrent metastatic peritoneal implants in the area of FDG uptake. FDG PET in conjunction with anatomic imaging can significantly assist location of early tumor recurrence by guiding exploratory surgery.
|
|
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12c. Colorectal carcinoma in a 35-year-old man who underwent resection and in whom the level of carcinoembryonic antigen was rising. CT was originally performed, as there was no evidence of metastases. FDG PET was performed to detect a possible site of recurrence. (a, b) Coronal (a) and axial (b) FDG PET images show a subtle focus of hypermetabolism in the left lower quadrant of the abdomen (arrow in a, arrowhead in b). Findings from rotating three-dimensional (cine) images (not shown) strongly suggested extraluminal uptake. (c) CT scan shows subtle increased attenuation in the mesentery (arrow and arrowhead), which was identified only in retrospect after correlation with the FDG PET scan. The surgical decision was based solely on the FDG PET findings. Surgical exploration yielded recurrent metastatic peritoneal implants in the area of FDG uptake. FDG PET in conjunction with anatomic imaging can significantly assist location of early tumor recurrence by guiding exploratory surgery.
|
|
False-positive and False-negative Findings
Approximately 25% of FDG uptake can occur in nontumor tissues such as macrophages, neutrophils, fibroblasts, and granulation tissue (45). Delaying FDG PET studies for 2–3 months after radiation therapy is recommended to accurately assess therapy response in colorectal cancer (46).
False-negative FDG PET results may occur in lesions smaller than 1 cm in diameter, particularly in the liver (47). MR imaging techniques such as breath-hold contrast material–enhanced arterial phase imaging may demonstrate subtle metastases undetected with FDG PET. Also, false-negative results in metastatic lymph nodes appear to stem from the lesser extent of the involvement (micrometastases) and the proximity of the involved lymph node to the primary site.
|
Lymphoma
|
|---|
Non-Hodgkin lymphomas are the sixth most common cause of cancer-related deaths in the United States. Non-Hodgkin lymphomas are more than five times as common as Hodgkin disease. Both types of lymphoma are potentially curable, and treatment options vary greatly with the initial stage of the disease.
Initial Staging of Lymphoma
Nodal Involvement.—
FDG PET demonstrates disease sites equally in both non-Hodgkin lymphoma and Hodgkin disease (48–55). FDG PET has a high sensitivity for detecting nodal disease regardless of the lesion site and size (48). FDG uptake is usually comparable in all grades of non-Hodgkin lymphoma. However, low-grade lymphomas may have a lower degree of FDG uptake compared with high-grade lymphomas. Qualitative interpretation is sufficient for staging, whereas quantitative analysis may be useful in determining the malignancy grade in non-Hodgkin lymphoma (55).
The diagnostic efficiency of FDG PET is equivalent or superior to that of CT in staging malignant lymphoma prior to therapy (56). FDG PET may "upstage" patients by revealing additional disease sites. FDG PET has been reported to demonstrate significantly more lesions than gallium-67 single photon emission CT, indicating higher sensitivity for FDG PET (48).
Extranodal Involvement.—
In 20%–30% of patients, infradiaphragmatic disease (mainly splenic) is diagnosed only at staging laparotomy (57). The sensitivity of CT is 15%–37% for splenic infiltration and 19%–33% for liver infiltration (57). Ga-67 imaging is limited in evaluation of the abdomen due to the physiologic bowel uptake. Despite the physiologic FDG accumulation in the liver, FDG PET is able to demonstrate liver lesions (58). Several studies have illustrated the superiority of FDG PET over CT in the detection of hepatic and splenic extranodal lesions (55,59).
Central nervous system lymphomas have considerably high FDG uptake compared with the adjacent gray matter. FDG PET can be used to differentiate primary central nervous system lymphoma from infectious lesions associated with acquired immunodeficiency syndrome (59).
Detection of bone marrow involvement with FDG PET is controversial. Physiologic bone marrow uptake can be observed on FDG PET images. Diffusely increased uptake is not specific to bone marrow involvement and is usually observed in reactive bone marrow, particularly following chemotherapy and administration of growth factor (eg, granulocyte colony-stimulating factor) (5,60,61) (Fig 13). In addition, in patients with limited involvement of the bone marrow, FDG PET findings may be false-negative.
View larger version (74K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 13. Hodgkin disease. After chemotherapy, FDG PET was performed to evaluate the response to therapy. Posttherapy coronal FDG PET image shows diffusely increased activity in the marrow of the axial and appendicular skeleton, a finding consistent with reactive bone marrow.
|
|
Recurrent Lymphoma and Evaluation of Response to Therapy
Although residual abnormalities are observed after therapy in a significant number of patients, only 10%–18% of residual masses are reported to be positive for lymphoma at biopsy (62). In addition, biopsy is limited in large masses due to potential mixing of fibrosis and tumor. Ga-67 scintigraphy has proved useful in restaging and determining the need for further therapy in posttreatment evaluation (63,64). Nevertheless, Ga-67 imaging is less sensitive in intraabdominal and low-grade lymphoma; thus, its value in monitoring response to therapy in these cases is limited. FDG PET is at least as sensitive as CT and more specific (50,51,53) (Fig 14). In one study, FDG PET was reported to have a sensitivity of 88% and a specificity of 83% for detection of residual disease. The corresponding values for CT were 84% and 31%, respectively (65) (Fig 15).
View larger version (97K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 14a. Non-Hodgkin lymphoma in the mediastinum in a 29-year-old man. After chemotherapy, FDG PET was performed to evaluate the response to therapy. (a) Posttherapy CT scan shows a residual mediastinal mass (arrow). (b) Coronal FDG PET image shows circumferential hypermetabolism in the region of the mass with central absence of activity (arrows), an appearance consistent with residual lymphoma and central necrosis.
|
|
View larger version (104K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 14b. Non-Hodgkin lymphoma in the mediastinum in a 29-year-old man. After chemotherapy, FDG PET was performed to evaluate the response to therapy. (a) Posttherapy CT scan shows a residual mediastinal mass (arrow). (b) Coronal FDG PET image shows circumferential hypermetabolism in the region of the mass with central absence of activity (arrows), an appearance consistent with residual lymphoma and central necrosis.
|
|
View larger version (93K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 15a. Hodgkin disease involving the mediastinal and right cervical lymph nodes. (a, b) CT scans of the neck (a) and chest (b) show marked adenopathy of the right side of the neck and the mediastinum. (c) Coronal FDG PET image shows multiple foci of intense hypermetabolism in the right cervical lymph nodes and mediastinal lymph nodes (with greater activity on the right side than on the left), which represent extensive nodal involvement. (d) CT scan obtained 2 months after chemotherapy shows a persistent right mediastinal mass. It is not possible to determine whether it represents posttherapy fibrosis or residual tumor. (e) Contemporaneous FDG PET image shows resolution of the previously noted intense uptake seen in c, with no evidence of residual tumor.
|
|
View larger version (89K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 15b. Hodgkin disease involving the mediastinal and right cervical lymph nodes. (a, b) CT scans of the neck (a) and chest (b) show marked adenopathy of the right side of the neck and the mediastinum. (c) Coronal FDG PET image shows multiple foci of intense hypermetabolism in the right cervical lymph nodes and mediastinal lymph nodes (with greater activity on the right side than on the left), which represent extensive nodal involvement. (d) CT scan obtained 2 months after chemotherapy shows a persistent right mediastinal mass. It is not possible to determine whether it represents posttherapy fibrosis or residual tumor. (e) Contemporaneous FDG PET image shows resolution of the previously noted intense uptake seen in c, with no evidence of residual tumor.
|
|
View larger version (72K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 15c. Hodgkin disease involving the mediastinal and right cervical lymph nodes. (a, b) CT scans of the neck (a) and chest (b) show marked adenopathy of the right side of the neck and the mediastinum. (c) Coronal FDG PET image shows multiple foci of intense hypermetabolism in the right cervical lymph nodes and mediastinal lymph nodes (with greater activity on the right side than on the left), which represent extensive nodal involvement. (d) CT scan obtained 2 months after chemotherapy shows a persistent right mediastinal mass. It is not possible to determine whether it represents posttherapy fibrosis or residual tumor. (e) Contemporaneous FDG PET image shows res | |
Top
Abstract
LEARNING OBJECTIVES FOR TEST...
