Whole-Body versus Routine Skull Base to Mid-thigh 18F-Fluorodeoxyglucose Positron Emission Tomography/ Computed Tomography in Patients with Malignant Melanoma
Objectives:The objectives of this study are to assess the utility of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) (skull vertex to toes) imaging relative to the standard field of view (skull base to mid-thigh) in patients with primary melanoma site that is not located in the lower extremities.
Material and Methods:The primary site of the melanoma and metastatic disease was determined based on 18F-FDG PET/CT findings in 26 patients. The FDG avid sites were tabulated as the primary site, lower extremity, brain, and other sites. The hypothesis is that routine skull base to mid-thigh versus whole-body 18F-FDG PET/CT in patients with malignant melanoma will not change management.
Results:Patients (26) were divided into those with primary melanoma site in either the lower extremities (six patients) or other site (20 patients). Four of the six patients with the primary site in the lower extremities also had positive findings in the ipsilateral inguinal lymph nodes. One of the patients with a positive inguinal lymph node had metastatic sites in the external iliac region and lungs on the initial study. On follow-up imaging, this patient also exhibited diffuse metastatic disease, including a lower extremity. None of the remaining patients in this group had positive findings other than the primary site in the lower extremity. Of the remaining 20 patients with the primary site not in the lower extremity, one had diffuse metastatic disease that included a lower extremity. However, lower extremity involvement would not change patient management in this case. A second patient in this group had diffuse metastatic disease that also involved the brain. However, no metastatic disease was present in the lower extremities in this patient. None of the remaining 18 patients in this group had metastatic disease in a lower extremity. Two patients in the entire study group of 26 had brain metastasis on contrast-enhanced head CT, with one having multiple brain metastasis. PET failed to demonstrate some of the brain lesions. In the other patient with solitary brain metastasis detected on contrast-enhanced head CT, PET was negative.
Conclusion:18F-FDG PET/CT imaging of the lower extremity may not be justified if the primary neoplasm is not located in the lower extremities. Elimination of lower extremity imaging will reduce scanning time and additional radiation exposure. Similarly, PET/CT imaging of the brain may not be justified if contrast-enhanced CT or magnetic resonance imaging of the head is already obtained since these are more sensitive.
In the United States, cutaneous melanoma is the fifth most common type of new cancer diagnosis in men and the seventh most common in women, with continually increasing new cases. The estimated new melanoma cases for 2020 are 100,350, which are 5.6% of all new cancer cases. Estimated death from cutaneous melanoma for 2020 is 6850, which is 1.1% of all cancer-related deaths. Although
18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) is inferior to sentinel lymph node biopsy in the evaluation of regional disease, it could be useful in the detection of distant metastases in patients with advanced-stage or high-risk melanoma.[2-5] It has a high diagnostic value in the routine follow-up of melanoma. There is also an improved prediction of patient survival with PET/CT imaging.
MATERIAL AND METHODS
Patients selected for inclusion received whole-body 18F-FDG PET/CT from January 10, 2007, to January 1, 2018, with a diagnosis of malignant melanoma. These patients were identified by running a query of the PACS system. All 18F-FDG PET/CT images were acquired using Siemens Biograph 40 TruePoint PET/CT (Knoxville, TN). The PET component was composed of lutetium oxyortho-silicate (LSO) crystals. The CT component had 40 slice multidetector-row with 70 cm transverse field of view. The acquisition parameters consist of 120 kV, 60 mAs, 0.5 s rotation time, 5 mm slice thickness, and 0.8 pitch.
The image acquisition involved two fields, one from the vertex of the skull to pelvis with 3–4 min per bed position (range for incubation period 56–102 min, mean 113 min) and second from the pelvis to toes with 1–2 min per bed position (range for incubation period 90–207 min, and mean 121 min). The time interval between the two fields of the study ranged from 29 to 56 min (mean 37 min). The patient’s arms were positioned down during acquisition.
This retrospective study was approved by the Institutional Review Board of University of Florida – Jacksonville. A query of the PACS system identified 42 patients that received whole- body 18F-FDG PET/CT (skull vertex to toes) from January 10, 2017, to January 1, 2018. Of these, 26 patients were identified as patients with malignant melanoma with PET/CT imaging used for initial staging or restaging. The age of the patients ranged from 48 to 83, with the median age of 57 and mean age of 60 years old. There was an equal female to male ratio. The patients fasted a minimum of 4 h (range 4–20 h, mean 12.7 h) before intravenous injection of the prescribed dose of 555 MBq [15 mCi] of 18F-FDG (range 476.93–604.95 MBq [12.89–16.35 mCi], and mean 560.55 MBq [15.15 mCi]). Blood glucose levels of the patients were measured before the injection of 18F-FDG (range 4.67–11.28 mmol/l, and mean 6.29 mmol/l). All 18F-FDG PET/CT images were acquired using Siemens Biograph 40 TruePoint PET/CT (Knoxville, TN). The PET component was composed of LSO crystals. The CT component had 40 slice multidetector-row with 70 cm transverse field of view. The acquisition parameters consisted of 120 kV, 60 mAs, 0.5 s rotation time, 5 mm slice thickness, and 0.8 pitch. The image acquisition consisted of two fields, one from the vertex of the skull to pelvis with 3–4 min per bed position (range for incubation period 56– 102 min, and mean 113 min) and second field from the pelvis to toes with 1 to 2 min per bed position (range for incubation period 90–207 min, and mean 121 min). The time interval between the two parts of the study ranged from 29 to 56 min (mean 37 min).
The results consisted of identifying and tabulating the primary site of melanoma and the presence of metastatic disease in the lower extremities and other locations [Table 1].
|Patient number||Primary melanoma site||Metastatic sites excluding lower extremities and brain||Lower extremity metastasis||Brain metastasis PET||Brain metastasis head CT||Date of head CT|
|1||Left axilla||None||No||No||No||Same day|
|2||Right and left groin||None||No||No|
|3||Left groin||None||No||No||No||Same day|
|4||Upper back||Multiple diffuse metastasis||Yes||No|
|5||Left cheek||None||No||No||No||27 days prior|
|9||Vulva||Multiple metastasis||No||Yes||Yes||2 days prior|
|11||Left foot||Left inguinal node||No||No|
|12||Right thigh||Right inguinal, right external iliac nodes and lungs metastasis on the initial study, diffuse metastasis including lower extremities on follow-up study||Yes||No|
|14||Left-arm||Left axillary node||No||No||No||Same day|
|15||Left neck||None||No||No||No||Same day|
|16||Left face||None||No||No||No||Same day|
|17||Left back||None||No||No||No||Same day|
|20||Left thigh||Right inguinal node, Right breast (primary versus metastasis)||No||No||Yes||Same day|
|21||Right temporal region||None (Incidentally found colon cancer)||No||No|
|22||Left ear||Bilateral neck nodes||No||No|
|23||Left anterior chest and back||None||No||No|
|24||Right foot||Right inguinal node||No||No|
|25||Left upper arm||Left axillary node||No||No||No||Same day|
|26||Right and left upper extremity||Right axillary node||No||No|
PET: Positron emission tomography, CT: Computed tomography
Six of the 26 patients had the primary site of melanoma in the lower extremities (three in thighs, one in calf, and two in feet). Four of these six patients had metastatic disease. Three patients with metastatic disease had ipsilateral inguinal lymph node involvement. The fourth patient had ipsilateral inguinal nodes, ipsilateral external iliac nodes, and lungs metastasis on the initial study and diffuse metastasis, including a lower extremity on a follow-up study.
In the remaining 20 patients with the primary site not involving the lower extremity, four had the primary site in the upper extremities, seven in the head and neck, and nine in torso. One of these patients had a primary site located in the upper back also had a diffuse metastatic disease that involved the lower extremity [Figure 1]. However, this would not have changed management due to metastatic disease. Another patient in this group had primary vulvar melanoma with diffuse metastatic disease, including brain temporal lobe involvement. Additional brain metastatic foci were visible on contrast-enhanced head CT but were not discernible on PET [Figure 2]. However, no metastatic disease was present in the lower extremities in this patient. None of the remaining 18 patients in this group had metastatic disease in the lower extremities. In summary, whole-body imaging would not have changed patient management in the two patients that exhibited involvement outside standard PET/CT field of view, one in the lower extremity with diffuse metastatic disease and one in the brain already detected with contrast-enhanced head CT.
Ten patients of the entire group of 26 had head CT within 1 month of the whole-body 18F-FDG PET/CT (eight of them on the same day, one 2 days prior, and one 27 days before whole 18F-FDG PET/CT). Two patients had metastatic disease involving the brain. In one patient, as discussed above, 18F-FDG PET was positive only in one cerebral lesion and failed to demonstrate additional lesions. In the second case, 18F-FDG PET did not demonstrate the solitary lesion detected on contrast-enhanced head CT.
The most commonly used protocol for oncologic 18F-FDG PET/CT imaging is routine skull base to mid-thigh imaging. However, whole-body imaging is frequently obtained in patients with malignant melanoma. The rationale for whole-body imaging in patients with malignant melanoma is that it can metastasize to any organ.[8,9] Earlier reports in the literature demonstrate the effectiveness of this approach. Whole-body imaging may reveal unsuspected malignancy outside the typical skull base to mid-thigh field of view in patients with various cancers.[11,12] However, although 18F-FDG PET/ CT imaging of the head may reveal additional lesions, the sensitivity of contrast-enhanced CT or magnetic resonance imaging (MRI) of the head is reported to be superior to 18F-FDG PET/CT. 18F-FDG PET/CT did not demonstrate additional lesions in the two patients with brain metastasis that CT already detected, and it failed to demonstrate some of the lesions detected on head CT. Therefore, a dedicated CT or MRI of the head is usually obtained for accurate staging regardless of whether the head is included or not with the 18F-FDG PET/CT.
Imaging of the lower extremities requires more time, usually several additional bed positions. Although, more lesions can be detected by this approach, it may not necessarily change patient management. In our series, no metastatic disease was present in the lower extremities in 19 of 20 patients who had primary sites other than the lower extremities. Only one of the 20 patients had involvement of the lower extremities. However, this finding did not change patient management since diffuse metastatic disease was already present. Elimination of the brain and lower extremity imaging will reduce the length of scanning time and additional radiation exposure.
Although 18F-FDG PET/CT is a sensitive technique for staging malignant melanoma, the value of lower extremity imaging remains controversial unless the primary site is located in the lower extremities. Similarly, its use for detecting brain metastasis is questionable since contrast- enhanced CT or MR has better sensitivity. Our findings support the hypothesis that whole-body imaging in patients with melanoma with the primary site not involving the lower extremity does not change patient management. There are many other studies that question the utility of including lower extremity and brain imaging in patients with melanoma. Niederkohr et al. found no unanticipated isolated lesions in brain/scalp or lower extremities to change the clinical management in their retrospective analysis of 296 PET/CT examination of 173 patients. Querellau et al. found no additional benefit of the lower extremity imaging in therapeutic decision-making in a retrospective study of 122 patients. Additional lesions in the lower extremities were either part of the disseminated metastatic disease or benign lesions. Lazaga et al. found only three scans had positive findings in the lower extremities in their 200 patient series, one of the findings within the field of view of standard skull base to mid-thigh, one benign finding, and one incidental squamous cell carcinoma. Plouznikoff et al. found 21 scans demonstrating findings attributed to melanoma in the lower limbs in their series of 461 whole-body scans. However, none of the lesions upstaged a patient. Tan et al. found only four unexpected brain/scalp abnormalities and only five lower extremity abnormalities in their series of 398 PET/CT examinations of 361 patients. There are, however, other studies that support whole-body imaging for the detection of unsuspected metastasis that results in a change in patient management. Osman et al. found that 59 of 500 patients had FDG PET/CT findings suggestive of malignancy outside the routine skull base to mid-thigh field of view in their retrospective study. However, their case series was not confined to melanoma patients. Within the 55 melanoma cases, only four of them had unexpected findings outside the skull base to mid-thigh field of view with no change in staging. In this study, whole-body PET/CT had a greater impact in changing staging and patient management in other malignancies such as lung cancer. Bronstein et al. evaluated whole-body PET/CT in 32 patients with oligometastatic Stage IV and clinically evident Stage III patients with malignant melanoma who already had contrast-enhanced CT of the chest, abdomen, and pelvis and MRI of the brain. PET/CT changed the management of four patients because of unanticipated findings. In two of these cases, the findings were within gastric wall and bones, remaining within the fields of view of a standard skull base to mid-thigh PET/ CT. In the third case, there were two unanticipated lower extremity findings with the larger one located in the upper thigh also within a standard field of view. The remaining additional finding was in a below the knee lower extremity and would probably not have changed patient management. However, in a final fourth case, a finding was detected in the soft tissue of the below the knee leg that did change management by adding adjuvant isolated limb perfusion.
This study supports our hypothesis and also existing reports that demonstrate a very small benefit of whole-body PET/ CT compared with the standard skull base to mid-thigh PET/CT if the primary melanoma is not located in the lower extremities. The main benefits of the standard field of view include reduced scanner time and radiation dose. The limitations of this study include a small sample size and lack of pathologic correlation for each 18F-FDG avid finding. Recent developments of mutation-driven therapy, immunotherapy, and targeted therapies such as BRAF blockade therapy have significantly improved survival of the patients with malignant melanoma. 18F-FDG PET/ CT plays an integral role in the treatment and evaluation of therapy response with these new novel therapies. Prospective studies incorporating a larger number of patients and longer- term follow-up are needed to determine the optimal imaging protocol for patients with malignant melanoma.
AcknowledgmentsThe authors would like to thank editing by Dr. Ashley Way, M.D.
Declaration of patient consentInstitutional Review Board (IRB) permission obtained for the study.
Financial support and sponsorshipNone.
Conflicts of interestThere are no conflicts of interest.
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