The value of F-18 FDG PET-CT for detecting primary foci in the metastatic cancer of unknown primary origin

Abstract

Introduction: Metastatic cancers of unknown primary origin (CUP) have poor prognosis and the median survival for patients with CUP is approximately 1 year. This survival can be extended by the identification of the primary origin and treating with specific therapy.

Material-Methods: F-18 FDG PET/CT scans of 75 patients (39 female, 36 male, mean age 60 ±12) with metastatic cancers of unknown primary origin referred to our clinic between January 2009 and January 2011 were evaluated retrospectively. Whole body images were obtained 60 minutes after the injection of approximately 370 MBq (10 mCi) F-18 FDG by PET/CT (Gemini-TOF-Philips). Emission scans were obtained for 1.5 min per bed position and transmission scans were obtained with low dose CT using 50 mA and 120 kvp.

Results: The tumor was identified histopathologically in 58 of 75 patients. 4 of 58 patients were treated as CUP. 17 of 75 patients could not be followed, so final diagnosis could not be made. In 54 patients, the primary was identified as 17 lung, 8 colorectal, 7 breast, 3 stomach, 3 pancreas, 2 endometrial, 2 nasopharynx, 2 gallbladder cancers, 2 lymphoma, 2 peritoneum, 1 maxillary sinus, 1 salivary gland carcinoma, 1 brain tumor, 1 leiomyosarcoma, 1 ovary cancer and 1 multiple myeloma. If reports are considered, F-18 FDG PET/CT helped to detect primary origin in 65% of these 58 patients, 38 of 54 primary sites were true positive (70%). There were 6 false positive sites (10.3%), 16 false negative (27.5%) results in F-18 FDG PET/CT. After the retrospective evaluation of the false negative patients, we have seen that primary sites were ignored in 5 of 14 patients, so actually F-18 FDG PET/CT helped in 74% of the patients showing 43 of 54 primary sites (80%). F-18 FDG PET/CT could not detect 2 breast cancers, 1 lymphoma, 1 colon cancer and 1 intra maxillary sinus cancer.

Discussion: F-18 FDG PET/CT is an important imaging tool for detecting primary origin in the patients with CUP. Besides, F-18 FDG PET/CT can help to determine the extent of the disease and help to evaluate the therapy response. In the patients with CUP, lung, breast, colon and the physiologic uptake areas should be scrutinized carefully for any tumor location.

Keywords

• F-18 FDG, unknown primary origin, metastatic cancer

References

1. Ries LAG, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review. Bethesda, National Cancer Institute, 1999.
2. Levi F, Te VC, Erler G, Randimbison L, La Vecchia C. Epidemiology of unknown primary tumors. Eur J Cancer 2002; 38: 1810-1812.
3. Van de Wouw AJ, Janssen-Heijnen MLG, Coebergh JWW, Hillen HF. Epidemiology of unknown primary tumors; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984–1992. Eur J Cancer 2002; 38: 409-413.
4. Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN. Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol 1995; 13: 2094-2103.
5. Jordan III WE, Shildt RA. Adenocarcinoma of unknown primary site. The Brooke Army Medical Center experience. Cancer 1985; 55: 857-860.
6. Califano J, Westra WH, Koch W, et al. Unknown primary head and neck squamous cell carcinoma:molecular identification of the site of origin. J Natl Cancer Inst 1999; 91: 599-604.
7. Le Chevalier T, Cvitkovic E, Caille P, et al. Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med 1988; 148: 203520
8. Raber MN, Faintuch J, Abbruzzese JL, Sumrall C, Frost P. Continuous infuse on 5-fluorouracil, etoposide and cis-diamminedichloroplatinum in patients w ith metastatic carcinoma of unknown primary origin. Ann Oncol 1991; 2: 519-520.

9. Haas I, Hoffmann TK, Engers R, Ganzer U. Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol 2002; 259: 325-333.
10. Kwee TC, Basu S, Cheng G, Alavi A. FDG PET/CT in carcinoma of unknown primary. Eur J Nucl Med Mol Imaging 2010; 37: 635-644.
11. Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 2004; 101: 2641-2649.
12. Seve P, Billotey C, Broussolle C, Dumontet C, Mackey JR. The role of 2-deoxy-2-(F-18)fluoro-Dglucose positron emission tomography in disseminated carcinoma of unknown primary site. Cancer 2007; 109: 292-299.
13. Kwee TC, Kwee RM. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol 2009; 19: 7317
14. Park JS, Yim JJ, Kang WJ, et al. Detection of primary sites in unknown primary tumors using FDG-PET or FDG-PET/CT. BMC Res Notes 2011; 4: 56.
15. Lenzi R, Hess KR, Abbruzzese MC, et al. Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma? J Clin Oncol 1997; 15: 2056-2066.
16. Naresh KN. Do metastatic tumours from an unknown primary reflect angiogenic incompetence of the tumour at the primary site?--a hypothesis. Med Hypotheses 2002; 59: 357-360.
17. Pelosi E, Pennone M, Deandreis D, et al. Role of whole body positron emission tomography/computed tomography scan with 18F-fluorodeoxyglucose in patients with biopsy proven tumor metastases from unknown primary site. Q J Nucl Med Mol Imaging 2006; 50: 15-22.
18. Gutzeit A, Antoch G, Kühl H, et al. Unknown primary tumors: detection with dual-modality PET/CT--initial experience. Radiology 2005; 234: 227-234.
19. Kaya AO, Coskun U, Unlu M, et al. Whole body 18FFDG PET/CT imaging in the detection of primary tumours in patients with a metastatic carcinoma of unknown origin. Asian Pac J Cancer Prev 2008; 9: 683-6
20. Kole AC, Nieweg OE, Pruim J, et al. Detection of unknown occult primary tumors using positron emission tomography. Cancer 1998; 82: 1160-1166.
21. Alberini JL, Belhocine T, Hustinx R, Daenen F, Rigo P. Whole-body positron emission tomography using fluorodeoxyglucose in patients with metastases of unknown primary tumours (CUP syndrome). Nucl Med Commun 2003; 24: 1081-1086.
22. Bohuslavizki KH, Klutmann S, Kröger S, et al. FDG PET detection of unknown primary tumors. J Nucl Med 2000; 41: 816-822.
23. Nanni C, Rubello D, Castellucci P, et al. Role of 18FFDG PET-CT imaging for the detection of an unknown primary tumour: preliminary results in 21 patients. Eur J Nucl Med Mol Imaging 2005; 32: 5895
24. Chang JM, Lee HJ, Goo JM, et al. False positive and false negative FDG-PET scans in various thoracic diseases. Korean J Radiol 2006; 7: 57-69.