Early determination of primary tumor site, extent of metastatic lesions, and best location for biopsy are critical issues for patients with BM-CUPS . There is only one retrospective study of 16 patients that showed a high capability of PET/CT to localize the primary lesion in patients presented with brain metastasis .
This study included 39 patients with brain metastasis confirmed by histopathological analysis and/or imaging modalities with unknown primary tumor. The aim of this study was to assess the diagnostic efficiency of PET/CT in detection of the unknown primary tumors in patients presented with brain metastases as first manifestation and its impact on survival.
There was no significant difference between patients and PET/CT lesions regarding gender and age (P = 0.362, P = 0.075); the same result was seen in the result of Bakhshayeshkaram et al. who stated that mean age did not show significant different between male (61.10 ± 10.91 years) and female (57.84 ± 13.10) (P = 0.36) .
Some reports have stated that in spite of complete diagnostic work up, PET/CT may not add any significant benefits in either detection of occult primary tumor or help in patient’s management and the additional value of PE/CT in CUP patients may be overestimated . However, identification of primary tumor is not the only problem in CUP patients. Determination of the lesion extent is not helpful in recognition of the small population of CUP patients with favorable outcome but may also help in optimizing treatment planning including field of radiation therapy and also evaluation of response to treatment .
Wolpert et al. investigated the diagnostic value of PET/CT in 64 patients with BM of unknown primary and detected additional lesions suspicious of extracerebral metastases in 27 of 64 patients (42%) mainly in lymph nodes and concluded that PET/CT improves the accuracy of tumor staging by detecting more metastases that resulted in adjustment of the therapeutic strategy .
In another retrospective study by Koc et al. which included 31 patients with brain metastasis according to histopathology and/or MRI, they showed that PET/CT detected additionally 13 patients with additional metastatic sites mainly in the lung. They concluded that although the lung was the most frequent primary tumor in patients with BM, there may be unexpected metastatic tumors all over the body .
In Bakhshayeshkaram et al.’s study which included sixty-two CUP patients, PET/CT revealed additional metastasis in 56.4% (35/62) patients. The most frequent sites were mediastinal, hilar, and retroperitoneal lymph nodes .
Our results agreed with Wolpert and Bakhshayeshkaram et al. as PET/CT detected additional extracerebral metastatic sites in 12/19 patients (63%) mainly in lymph nodes.
In the same study of Bakhshayeshkaram et al., they found that the lung was the most frequent primary source of brain metastasis in 4.93% patients . The same result was detected by Kung et al. in their study which included 40 patients with BM; they found that bronchogenic carcinoma was common primary source in 62.5% (25/40) patients . Our results matched with both studies as the primary tumor was correctly detected by PET/CT in 31.6% (6/19) patients, mostly from the lung.
A study by Gutzeit et al. has shown that CT alone can detect the primary tumor in 8/45 patients (18%), while this percent was 33% (15/45 patients) when used PET/CT .
Roh et al. showed the sensitivity of PET/CT (87.5%) was significantly higher than that of CT (43.7%) in detection of the primary tumor in patients with brain metastases .
Han et al. in their study which included 162 CUP patients presented mainly with brain metastases concluded that sensitivity, specificity, and accuracy of 18F-FDG PET/CT was 91.5%, 85.2%, and 88.3%, respectively .
In another study by Riaz et al. which included 100 patients, the sensitivity, specificity, and accuracy of 18F-FDG PET/CT in detection of primary tumor were reported as 80%, 74%, and 78% .
In our study, the primary tumor could not be detected in (41%) 16/39 patients. Fifteen patients showed true-negative results and one patient was a false-negative result; the tumor was detected by histopathological analysis to be cancer pancreas and showed low uptake of FDG. Four patients showed false-positive results, two of them were diagnosed falsely by PET/CT to be pulmonary carcinoma but one of them was pulmonary hamartoma and the other one was pulmonary inflammatory pseudotumor. The remaining 2 patients were diagnosed by PET/CT to be cancer colon but by colonoscopic biopsy, one patient was diagnosed as polyp and other one was sigmoid diverticulosis. As a result, we found that PET/CT had specificity, sensitivity, and accuracy in detection of primary tumor as 95%, 79%, and 87%, respectively.
During the follow-up period which ranged between 6 and 25 months with a median of 12 months, median OS in patients with identified primary tumor were (12 months) versus (13 months) in patients with no identified primary tumor with no significant difference (P = 0.217)
In a study cohort by Reinert et al. which included 155 patients to detect the effect of PET/CT on clinical management in CUP patients, he concluded that there was no significant differences in estimated overall survival time could be noticed between patients with an identified primary tumor and patients with unidentified primary tumor . This result is in concordance with other studies; their explanation was that for many patients with identified primary tumor, no management can be provided that improves their overall survival .