The purpose of this study was to assess the value of PET/CT for diagnosis, restaging, and follow-up of MM patients with curative intend. It was analyzed through a retrospective design. It aimed to develop a medical algorithm for PET in regular follow-up programs of CMM.
CMM staging is required for appropriate treatment decision-making. Autopsies of patients with known CMM revealed a higher frequency of metastases than regularly clinically reported, indicating that clinical evaluation and conventional imaging techniques (chest radiography, ultrasonography, computed tomography [CT], and magnetic resonance [MR] imaging) lead to underestimation of disease extent. Conventional imaging techniques will only reveal metastases when they are morphologically different from normal tissue in terms of size or structure [3, 11].
The present study revealed that malignant melanoma is much more common in males (n = 28.56%) than females (n = 22.44%) with mean age 55.94 + 13.04 years. The great number of cases was between 66 and 74 years more in males (9 cases) than females (8 cases). This is in harmony with the previous findings of Malik et al. [12], who showed during studying 54 patients that the clinical risk factors for malignancy are related to age and the mean age of their studied patients was 51.3 + 16.4 years. Previously, Frary et al. [13] showed during studying of 46 cases of MM that males were more common than females (26 males “56.53%” and 20 “43.47%” females), similar to our present findings.
The male sex predilection of skin cancer in Egypt could be explained by the fact that men represent the main workforce (outdoor work) with more risk for ultra violet exposure (predisposing factor of melanoma) than women as had previously mentioned by Hussein [14].
The primary sites for MM in our study were the head and neck (face) (36%), trunk (30%), extremities (30%), and groin (4%). This is in harmony with the previous findings of Daniesen et al. [15], who showed during studying 167 cases that the primary sites for MM were the head and neck (35.3%), trunk (32%), and extremities (33%).
The present study showed that the vast majority of the patients had nodular melanoma (84%) followed by acral lentiginous melanoma (10%) then finally superficial spreading (6%). This was in harmony with the previous findings of Hussein [14] who found that compared to Western societies, melanomas among Egyptians differ in being: (1) rare neoplasms, (2) have a definite male sex predilection with older age incidence, and (3) of nodular growth pattern.
As in all cancers, accurate initial staging is essential for developing the appropriate treatment strategy. 18F-FDG PET/CT findings of G1, 21 patients, in our study for initial staging were compared with the reference standards and showed the sensitivity of 93.33%, specificity of 60%, and accuracy of 85.71% for primary staging.
SUVmean and SUVmax in all the 21 patients of initial staging were significantly higher in true positive more than true negative or false-positive patients diagnosed by PET/CT with high sensitivity 82.88%.
The two false-positive cases in our study were one inflamed epidermal cyst and the other had popliteal neurinoma. Our findings were similar to Essler et al. [16], who detected two false-positive patients, one had a popliteal neurinoma, and the other false-positive patient had a chromic lymphatic leukemia. The false-negative patient in our study had brain focal lesion which could not be detected due to the high physiological glucose metabolism in the brain. Such findings supported the previous finding of Essler et al. [16], who detected false-negative results in two patients of brain metastases. This may be explained by brain hyperthermia. Hyperthermia might alter the follow-up of patient by ET–CT. We can overcome this problem by newly cooling system used practically in the brain cooling named by a zero-heat-flux Spot On sensor [17].
All G1 patients, n = 21, had surgical excision of lesions at primary sites, and 12 patients who had high SUVmax also received either chemotherapy or combination of chemotherapy and radiotherapy in addition to the surgical treatment according to level of metabolic activity. Our findings were nearly similar to those of Malik et al. [12], who found that in 54 patients that all of them had surgical excision of lesions at primary sites and 10 patients also received either chemotherapy or combination of chemotherapy and radiotherapy in addition to the surgical treatment.
18F-FDG PET/CT scan was done in the present study for 11 clinical suspicion patients of relapse after treatment (G2) and showed the sensitivity of 100%, specificity of 66.66%, positive predictive value 88.88%; negative predictive value 100%; and accuracy of 90.90%.
The reported maximum value (SUVmax) was 22, while the recorded minimum value was 6.26. SUVmax in all the suspicion patients of relapse was above 2.9 in recurrent cases with high sensitivity of 100%. Our findings coincided with those of Malik et al. [12], who showed the sensitivity, specificity, positive predictive value, and negative predictive value of 91.2%, 80%, 88.6%, and 84.2%, respectively, for detection of recurrence. They recorded SUVmax above 2.7 in all their examined recurrent and metastatic cases.
Whole body PET-CT was done in the present study for G3, n = 18, case come with stage IV melanoma for detection of metastasis and show sensitivity of 100%, specificity of 66.66%, and overall accuracy of 94.44%. SUVmax was above 2.9 ranging from 22.4 to 34.6 in patients with distant metastasis. Our finding coincided with those of Holder et al. [18] who showed that PET is sensitive, 94.2%, and very specific, 83.3%, for identifying malignant melanoma; also, Akcali et al. [19] showed that PET is efficient in detecting melanoma with a high overall specificity of 92%, sensitivity of 91%, and accuracy of 92%. The false-positive results in our metastatic group (G3) were due to increased accumulation of FDG in some benign processes as inflammation or infection as had been previously detected by Long and Smith [20].
A number of study had suggested that for early stage of MM (I–II), PET-CT was of limited diagnostic value, due to its low sensitivity in detecting microscopic lymphatic disease. It had been posted that in danced stage of MM (III–IV) can be of great value by locating distant metastasis, thereby influencing treatment decision and informing prognosis [21].
Six of our 18 MM (G3) died within 24 months; the dead patients were aged above 50 years, primary site of tumor located in the head and neck. All six patients were stage IV and had distant metastases. Five of the patients had multiple metastases; this finding matched with Robinson and Roenigk [22] who showed that the old age was more affected which could be as a result of weakening of the immune system.
In our wok, we found that the overall survival (OS) of MM depended on the age, site, histological type, stage of tumor, number of metastasis as well as the SUVmax which present prognostic factor. This is similar to the finding of de Vries et al. [23].
Thus, melanoma specific survival (MSS) of MM patients with multiple metastasis was associated with a significantly shorter MSS than in the single metastatic nodule as shown in our results 24.2 ± 2.6 vs 38.8 ± 7.8 months, P = 0.01. In the present study, SUVmax ≥ 2.9 was a significant prognostic factor for shorter MSS (23.4 ± 3.5 vs 44.2 ± 4.6 months, P = 0.01). We found that survival analysis after combining both multiple metastasis and SUVmax ≥ 2.9 demonstrated significantly shorter MSS; this is matched with Malik et al. [12].
We found that five of our dead patients had multiple metastases. This was similar to the findings of Essler et al. [16] who compared the melanoma associated mortality risk of patients with different numbers of metastases.
From the forgoing, PET/CT scanning has high sensitivity and specificity for detecting late stages as III and IV metastatic melanomas. The CT component of PET/CT helps to establish the correct anatomical location of the lesions and to differentiate between physiological and non-physiological 18F-FDG uptake, thus facilitating appropriate interpretation of the PET scan and decreasing the numbers of false-positive and false-negative results.
Therefore, the main indication of PET/CT in cutaneous melanoma is to detect recurrence or to restage disease following the detection of recurrence, particularly in patients with high-risk melanoma who are candidates for resection with curative intent. As patients therapy that showed no responce could be changed, saving the patients from ineffective therapy and associated toxicities and costs.
When patients are being considered for surgical resection of isolated distant metastatic lesions, FDG-PET/CT imaging is used to accurately assess disease extent. Additional lesions identified on FDG-PET/CT imaging make surgical resection unwarranted.
Advanced melanoma carries a poor prognosis, mandating development of new therapies. FDG-PET/CT imaging can provide an early indicator of response to therapy for melanoma patient.
Malignant melanoma patients need continuous follow-up by PET/CT which enhanced diagnostic performance in detection of the primary malignancy, in follow-up of high-risk patients and patients with suspected or known local or distant recurrence, and in restaging of patients with known distant metastatic disease to assess tumor response; thus, it is highly recommended to be imaging of choice especially in follow-up or postoperative. If PET/CT will be adding to routine follow-up program of CMM patients, it would be strongly helpful if the radiation could be restricted to an absolute minimum. New dosimetry studies performed with phantoms of identical characteristics, using thermoluminescent dosimeters (TLDs) placed in regions close to the region where this study conducted, and identified lower dose values [24]
This study had many limitations: the nature of study as a retrospective, small number size of studied patients in each group, and high dose of radiation; we should use low-dose radiation CT if follow-up done as a protocol, high cost of PET-CT epically in developing countries.
One of most important limitation of the study did not identify the patients needed, and the other excluded from follow-up by PET-CT and did not identify the time schedule of follow-up; surveillance part of study is also needed to be extended over large number of patients.
