Purpose
To investigate the value of whole-body positron emission tomography/computed tomography (PET/CT) as a screening tool for patients with uveal metastasis.
Design
Retrospective observational case series.
Methods
setting: Clinical practice. study population: Eighteen patients with uveal metastatic tumors were evaluated. Patients had no history of malignancy or a past medical history of malignancy without known active metastasis or known systemic cancer. intervention: Whole-body PET/CT was used as a screening tool to evaluate the intraocular tumor, to evaluate for multi-organ metastatic disease, and for cancer staging. main outcome measures: Detection and PET/CT uptake of primary tumors and metastatic disease.
Results
PET/CT imaging uncovered previously occult primary nonocular cancers (11/18, 61%), revealed progression of known primary systemic cancer (7/18, 39%), and confirmed multi-organ metastases in all cases (18/18, 100%). PET/CT findings were used to direct nonocular, confirmatory biopsy in 67% of cases (12/18). No uveal biopsies were required. PET/CT revealed lymph nodes and bone as the most common metastatic sites. The intraocular tumor was detectable in 28% of cases. Small, non-avid tumors and those within the hypermetabolic, PET-avid brain were falsely negative.
Conclusion
This study suggests that whole-body PET/CT can be useful for clinical evaluation of patients with uveal metastases. It allowed for screening of the entire body and directed extraocular biopsy. Commonly used for tumor staging, PET/CT aided in the detection of the primary cancer in patients with metastatic uveal tumors.
Metastatic choroidal tumors are the most common intraocular malignancy. Detection of the primary malignancy typically precedes ocular findings. However, in a relatively small subset of these patients, ocular findings can be the first sign of metastatic disease. These patients typically present to the ophthalmologist with foveal invasion or secondary macular retinal detachment with associated symptoms of blurred vision, metamorphopsia, and photopsia.
There are 3 common clinical presentations for patients with uveal metastatic tumors. When uveal metastasis is clinically apparent in the setting of known disseminated metastatic disease, ophthalmic treatment can be initiated. When there exists a history of primary cancer without known metastatic disease, restaging is necessary. Lastly, when there is no known primary cancer and uveal metastasis is suspected, a systemic evaluation is also necessary.
Given that most cases of uveal metastasis are from a breast primary in women and from lung in men, radiographic surveys have focused on these 2 areas. However, alternate primaries such as prostate, gastrointestinal, kidney, thyroid, and others have been described. Further, multifocal nonocular sites may be overlooked by focal, limited radiographic imaging. Computed tomography (CT) allows for anatomic views that may not distinguish between benign and malignant tumors. Positron emission tomography (PET) allows for physiological views with poor anatomic localization. Magnetic resonance imaging (MRI) is associated with a number of contraindications (including body size, metallic implants, and renal insufficiency) and has been shown to be inferior in staging of tumors when compared to PET/CT.
For these reasons, whole-body 18-fluoro-2-deoxyglucose (18F FDG) PET/CT is gaining worldwide use for the staging, screening, and management of patients with cancer. PET/CT combines the functional metabolism revealed by PET with the anatomic characteristics found on CT, putting form and function on the same diagnostic page. In this study, we have evaluated PET/CT for initial staging of patients with uveal metastasis.
Methods
A retrospective observational case review of consecutive patients at a single clinical practice was performed. Entry criteria included a clinical diagnosis of uveal metastasis, and at the initial visit, patients had either no history of malignancy, a history of cancer thought to be in remission, or a known solitary nonocular metastasis. When necessary, nonocular systemic lesions were confirmed by biopsy.
Ophthalmic examinations included a best-corrected visual acuity, pupillary, ocular motor, and confrontational visual field assessment. Slit-lamp biomicroscopy and indirect ophthalmoscopy were performed. Ancillary testing included ultrasound imaging (USG), photography, fluorescein angiography (FA), fundus autofluorescence (FAF), and optical coherence tomography (OCT). Once the clinical diagnosis of metastatic choroidal tumor was established, a whole-body 18F FDG PET/CT was obtained to evaluate the intraocular tumor, define the primary, and discover multi-organ metastatic disease.
Positron Emission Tomography/Computed Tomography Imaging
Each patient in this study received PET/CT imaging at different institutions in the New York area. Each imaging center was called to ensure that the protocols for PET/CT met the guidelines provided by the American College of Radiology. Briefly, the protocol was as follows and has been previously described. Imaging requires that patients refrain from eating a carbohydrate-based dinner the night before testing and fast 4 to 6 hours before the injection of 18F FDG (radioactive tracer). These measures diminish physiological glucose utilization and reduce insulin serum levels to baseline.
Imaging was initiated approximately 60 minutes after injection of 18F FDG. The whole-body noncontrast CT is performed first. The CT portion (General Electric Discovery ST, Discovery STE, Fairfield, Connecticut, USA) with BGO (bismuth germanate) consists of a multi-detector helical scanner. It is initiated at the top of the head and ends at the bottom of the feet. Whole-body PET scanning is then performed. Patients are asked to lie in 6 to 9 bed positions. The resolution of the PET scan is 4 mm. The PET scan reconstructs the images and uses the CT scan to correct for attenuation. Xeleris or Advantage Workstation (General Electric software) computer software was used to fuse and display the PET and CT images simultaneously on 1 diagnostic page. A radiologist who specializes in nuclear medicine at each facility evaluated the images. The data collection was gathered from the reports.
Standardized maximum uptake (SUV) represents the metabolic activity of a lesion. Lesions that are SUV positive are clinically correlated and evaluated for the suspicion of malignancy vs benign causes. In all of the centers in this study, tumors were graded as positive with tracer uptake of 2.5 or more (comparison with the surrounding structures). The standardized maximum SUV was calculated at each site by employing the conventional formula using body weight normalization.
Results
Eighteen patients (10 male and 8 female) with a mean age of 65.4 years (range 41–85) diagnosed with intraocular metastatic tumors were screened with whole-body PET/CT. Eight patients (44%) had no prior history of malignancy and 3 patients (17%) had a history of unrelated cancer. Seven patients (39%) had a history of cancer found to be metastatic to the eye; of these 7 patients, 4 were thought to be in remission and 3 were thought to have a solitary nonocular lesion. In patients with a previous history of cancer, the average number of years from initial diagnosis of nonocular cancer to presentation of ocular symptoms was 6.6 years ( Table 1 ).
| Patient | Age, Years | Sex | History of Any Cancer | Years Since Diagnosis | Previous Treatment | Known Metastasis |
|---|---|---|---|---|---|---|
| 1 | 80 | M | None | — | None | None |
| 2 | 52 | F | None | — | None | None |
| 3 | 64 | M | None | — | None | None |
| 4 | 71 | M | None | — | None | None |
| 5 | 70 | F | None | — | None | None |
| 6 | 55 | M | None | — | None | None |
| 7 | 42 | F | None | — | None | None |
| 8 | 69 | M | Multiple myeloma | 10 | None | None |
| 9 | 78 | M | Cutaneous melanoma | Unknown | Excision | None |
| 10 | 85 | M | Cutaneous melanoma | 9 | Excision | None |
| 11 | 41 | M | Colon | 6 | Resection | Lung |
| 12 | 52 | F | Breast | 12 | Mastectomy/chemotherapy/radiation | None |
| 13 | 63 | F | Breast | 7 | Mastectomy | None |
| 14 | 81 | F | Breast | 8 | Mastectomy/chemotherapy/radiation | None |
| 15 | 70 | M | Pancreatic | 1 | Chemotherapy | Liver |
| 16 | 73 | M | Lung | 2 | Resection/chemotherapy | Brain |
| 17 | 74 | F | Lung | 10 | Resection | None |
| 18 | 57 | F | None | — | None | None |
| Mean | 65.4 | — | — | 6.6 | — | — |
There were 17 unifocal posterior choroidal tumors ( Figure 1 ) and 1 unifocal anterior iris metastasis ( Figure 1 ). Uveal metastases affected the right eye in 9 patients and were primarily located in the macula (n = 12), but were also located in the mid-peripheral retina (n = 4), juxtapapillary retina (n = 1), and iris (n = 1) ( Table 2 ). Ultrasound showed either variable (n = 11) or moderate (n = 7) reflective tumors, and most had a secondary retinal detachment (n = 12). One tumor exhibited extrascleral extension on ultrasonography ( Table 2 ).
| Tumor | B-Scan | ||||||
|---|---|---|---|---|---|---|---|
| Patient | Eye | Location | Color | Focality | Reflectivity | ESE | RD |
| 1 | OD | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 2 | OS | Iris | Amelanotic | Unifocal | Variable | No | No |
| 3 | OS | Macula | Amelanotic | Unifocal | Variable | No | No |
| 4 | OD | Macula | Amelanotic | Unifocal | Moderate | Yes | Yes |
| 5 | OD | Nasal retina | Amelanotic | Unifocal | Moderate | No | No |
| 6 | OS | Superior retina | Lightly pigmented | Unifocal | Variable | No | Yes |
| 7 | OS | Macula | Amelanotic | Unifocal | Moderate | No | No |
| 8 | OD | Macula | Amelanotic | Unifocal | Variable | No | No |
| 9 | OS | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 10 | OD | Macula | Amelanotic | Unifocal | Moderate | No | Yes |
| 11 | OS | Nasal retina | Amelanotic | Unifocal | Variable | No | Yes |
| 12 | OD | Macula | Amelanotic | Unifocal | Moderate | No | Yes |
| 13 | OD | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 14 | OD | Nasal retina | Lightly pigmented | Unifocal | Moderate | No | No |
| 15 | OD | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 16 | OS | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 17 | OS | Macula | Amelanotic | Unifocal | Variable | No | Yes |
| 18 | OS | Juxtapapillary | Amelanotic | Unifocal | Moderate | No | Yes |
PET/CT imaging revealed widespread metastasis (involving 2 or more metastatic foci) in 16 of 18 (89%) patients. The remaining 2 PET/CT scans (Patients 5 and 18) revealed only the primary cancer but no other metastatic lesions. The primary tumor was not visible in 7 patients, 6 attributed to previous resection of the cancer and 1 because it was not detectable on PET/CT. The mean SUV for the primary tumor was 9.7, range 1.9–17 ( Table 3 ).
| Patient No. | Primary Tumor | Primary Tumor SUV | Sites of Metastasis and SUVs | Tissue Biopsy Site | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Globe | Rib | Spine | Other Osseous | Lymph Node | Lung | Chest Wall | Brain | Liver | Other | ||||
| 1 | Lung | 12.7 | 8.3 | 16.2 | 8.3, 5.9 | 7.2, 6.2, 5.9 | 7.3, 4.8 | Lung | |||||
| 2 | Lung | 17 | 6.7 | N/A | 15.9, 7.3 | Kidney | |||||||
| 3 | Lung | 13.3 | 2.7 | 5.0, 8.0 | 6.6 | Lung | |||||||
| 4 | Lung | 6.8 | 3.5 | 9.0, 4.1, 3.6 | 5.4 | 5.5, 5.6 | Chest wall | ||||||
| 5 | Breast | 1.9 | Breast | ||||||||||
| 6 | Esophagus | 14.3 | 4.4 | 3.8 | 8.0,10.7 | 14.3 | 8.7, 4.9, 6.0 | Not done | |||||
| 7 | Lung | 3.8 | 6.5 | 6.2, 5.2, 4.4 | 4.9, 3.3, 4.1 | 4.1 | Bone | ||||||
| 8 | Lung | 9.8 | 3.8 | 3.0 | N/A | Not done | |||||||
| 9 | Lung | 12.8 | N/A | 4.5 | 21.1 | Lung | |||||||
| 10 | Prostate | Not detected | 3.1 | 4.0 | 6.1, 4.6 | 4.0, 6.5 | 3.1, 4,4, 5.2 | Bone | |||||
| 11 | Colon | Resected | 8.8 | 5.5 | 7.7 | 6.6 | Not done | ||||||
| 12 | Breast | Resected | 4.6, 4.7 | 5.0 | 6.0 | Bone | |||||||
| 13 | Breast | Resected | 7.5, 5.9. 3.2 | 7.8 | 9.0 | Bone | |||||||
| 14 | Breast | Resected | N/A | N/A | N/A | 7.2, 8.1, 6.2 | Lymph node | ||||||
| 15 | Pancreas | Resected | 2.6, 3.5 | N/A | 2.2 | Not done | |||||||
| 16 | Lung | Resected | 19.3 | 23.1 | Not done | ||||||||
| 17 | Lung | 7.4 | 3.2 | 7.8 | 7.6,5.5 | 6.9,10.5, 10.4 | 7.7 | 4.9 | Not done | ||||
| 18 | Lung | 6.8 | Lung | ||||||||||
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