Comparison between FDG PET Imaging, Gallium Planar and SPECT Imaging in a Case of Relapsed Hodgkin s Disease Kung-Chu Ho 1, Cheng-Chien Tsai 1, Po-Nan Wang 2, Feng-Yuan Liu 1 1 Department of Nuclear Medicine, Chang Gung Memorial Hospital and University, Taoyuan, Taiwan 2 Department of Hematology Oncology, Chang Gung Memorial Hospital and University, Taoyuan, Taiwan Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and 67 Ga scan are superior to computed tomography (CT) in the detection of recurrence of lymphoma because identification of tumor viability as opposed to simple visualization of a mass is essential for these applications. Herein, we reported a case of relapsed Hodgkin s disease, in which FDG PET and 67 Ga scan detected the recurrent tumor nine months earlier than CT. Besides, FDG PET provided more information than 67 Ga scan for nodal identification at para-aortic region. Key words: tomography, emission-computed, 18 F- fludeoxyglucose, gallium radioisotope, lymphoma Ann Nucl Med Sci 2004;17:109-113 Ten to thirty percent of Hodgkin s disease (HD) has potential to relapse after complete remission [1]. The earlier the HD relapse, the worse the outcome [2]. Besides, the earlier use of high dose chemotherapy (HDCT) for early recurrence, the better prognosis could be expected [3]. Traditionally, diagnosis of relapse is usually assessed by clinical symptoms, laboratory and radiographic image such as computed tomography (CT). Unfortunately, under-diagnosis is not uncommon [4]. In comparison with CT, 67 Ga scan is a Received 1/20/2004; revised 2/3/2004; accepted 2/5/2004. For correspondence or reprints contact: Feng-Yuan Liu, M.D., Department of Nuclear Medicine, Department of Nuclear Medicine, Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kueishan, Taoyuan 333, Taiwan. Tel: (886)3-3281200 ext. 2673, Fax: (886)3-2110052, E-mail: billliu@adm.cgmh.org.tw more sensitive and specific tool for restaging patients with lymphoma recurrence [5]. However, 67 Ga scan has some limitations, such as noisy image quality, poor detection of abdominal lesion and low grade tumor. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG PET) imaging showed significant greater value than CT and 67 Ga scan in both HD and non-hodgkin s lymphoma of all grades at either primary or recurrent disease [4,6]. Herein, we reported a case of relapsed HD detected nine months earlier by FDG PET and 67 Ga scan than CT. Moreover, FDG PET scan provided more nodal metastatic information than conventional imaging. Case Report An 18-year-old male with a huge mediastinal tumor was first diagnosed as small cell lung cancer in Dec. 2000 in this hospital. However, considering his clinical presentation of asthma and atopic dermatitis which was not typical for small cell lung cancer, a repeated mediastinal biopsy was performed in Feb. 2001. The final pathologic result showed HD, nodular sclerosis type. The clinical stage was IVA according to Ann Arbor system due to involvements of mediastinum, cervical lymph nodes, right lung, and pleurae, with pericardial effusion. Pretreatment 67 Ga scan showed compatible findings of neck and chest regions (Figure 1). He received eight courses chemotherapy of biweekly adriamycin, bleomycin, vincristine and dacarbazine regimens (ABVD) with partial response. He was then given radiotherapy to whole lung and bilateral axillary regions with total dose of 3,120 cgy. Since then, the mediastinal lesions were stationary by regular follow-up CT at out patient clinics. In Aug.
Ho KC et al Figure 1. 67 Ga scan and CT were performed in a 19 y/o patient with Hodgkin s disease for initial staging. 67 Ga scan of (A) planar, and (B) selected transaxial SPECT imaging revealed 67 Ga avid lesions involving the mediastinum (arrows) and left lower cervical lymph nodes. (C) Corresponding CT imaging showed a large hypodense infiltrative tumor (arrow) and invasion to the pericardium and pleura was highly suspected. Ultrasound-guided biopsy of the mediastinal mass and left lower neck open biopsy confirmed the diagnosis. Bone marrow biopsy showed no evidence of bone marrow involvement. Figure 2. One year after completion of chemotherapy and radiotherapy, 67 Ga scan of (A) planar, and (B) selected transaxial SPECT imaging revealed 67 Ga avid right mediastinal lesion (arrows). As compared with previous study, the mediastinal lesion was smaller in size and extent, and the left lower neck lesion was not evident. Right mediastinal residual tumor was impressed. (C) Corresponding CT image showed abnormal soft tissue mass with calcification (arrow) in anterior mediastinum and no improved change when compared with previous study. (D) Follow-up CT image three months after showed that the mediastinal lesion (arrow) was stationary in size and extent. 2002, 67 Ga scan was performed and showed 67 Ga avid right mediastinal lesions (Figure 2). However, due to stationary in size in the following chest CT, the patient was therefore suggested to follow up at our out patient clinics. In May 2003, the mediastinal lesion progressed by CT scan, he thus underwent a whole body 67 Ga scan with additional SPECT studies in chest and abdomen. Besides, a FDG PET scan was also performed to evaluate the relapse condition. The planar 67 Ga scan revealed 67 Ga avid right lung and right mediastinal lesions, 67 Ga SPECT revealed two additional lesions in paraaortic regions (Figure 3). FDG PET found more lesions in para-aortic lymph nodes. Discussion Though advances in the treatment of HD have resulted in cure rates of greater than 80%, still 10-30% of patients will relapse after achieving complete remission [1,7]. The earlier the recurrence, the worse prognosis could be expected, especially for those relapses within one year after first line chemotherapy [2]. Though HDCT is considered to be the treatment of choice in all relapses after complete remission, a considerable number of good-risk patients (mainly late relapses) might be overtreated with HDCT. Besides, the time to relapse is one of the prognostic factors for choosing the best treatment for HD patients at relapse [1]. Due to earlier use of HDCT may produce a better result [3], it is worthwhile in the detection of recurrence as early as possible. At least 60% of patients with HD have already had mediastinal involvement before primary treatment, especially for bulky tumor [8]. Once tumor recurrence, residual tumor is another important issue. About 60% patients still bore residual/recurrent tumor at mediastinum after the com- Ann Nucl Med Sci 2004;17:109-113 Vol. 17 No. 2 June 2004 110
FDG-PET 67 Ga FDG-PET and 67 Ga in Hodgkin s disease Figure 3. (A) Regularly follow-up CT revealed the mediastinal lesion (arrow) progressively enlarged, and therefore 67 Ga scan and FDG PET were arranged for further study. (B)The planar 67 Ga scan revealed 67 Ga avid right lung and right mediastinum lesions (arrows). (C) There were two additional lesions in paraaortic region (arrows) detected on 67 Ga SPECT study as compared with planar image. (D) Selected coronal FDG PET images showed multiple lung and mediastinal lesions and three left para-aortic nodes (arrow) involvement and a small metastatic chest wall lesion (arrowhead). FDG PET revealed more lymph node lesions than 67 Ga scan in this case. pletion of treatment [8]. CT has limitation in differentiating fibrosis from relapsed tumor in a residual mass before complete resolution at CT, especially for those large lymphomatous masses that might have necrosis and fibrosis [4]. 67 Ga citrate is taken up by viable cancer cell and not by fibrotic and necrotic masses, it may help in differentiating a viable tumor, either residual or recurrence, from fibrosis or necrosis [5]. For early diagnosis of recurrence, 67 Ga scan is also helpful. Even at the time of clinical relapse, the sensitivity of CT is only 45% for the chest and 55% for the abdomen. As for 67 Ga scan, the sensitivity and specificity of 67 Ga imaging in identifying recurrence are 95% and 89% [5]. Not only higher sensitivity of 67 Ga scan than CT for early recurrence, a much earlier diagnosis (average 6.8 months) was also observed [5]. Thus, the management for HD patients might be altered. SPECT is a popular technique for nuclear medicine worldwide. It can provide better contrast resolution than planar images [9]. According to the literature, the sensitivity and specificity for planar and SPECT studies in HD patients in the chest is 66% and 66% vs. 96% and 100%, respectively. For abdomen, the sensitivity and specificity for planar was 69% and 87%, and 85% and 100% for SPECT studies [9]. Therefore 67 Ga-SPECT is superior to 67 Ga-planar studies for HD in both sensitivity and specificity. In this case report, it also clearly demonstrated that 67 Ga-SPECT imaging revealed subdiaphragmatic lesions of para-aortic lymph nodes, which were not shown in the planar imaging (Figure 3). It offered crucial clinical information since appearance of another lesion on the opposite site of diaphragm would upstage the disease. As SPECT imaging improves anatomic localization and detection of deep structures, we thus suggested that SPECT imaging should be recommended at both thorax and abdomen for high risk group. FDG PET is gradually replacing 67 Ga scan for assessment of lymphoma since 1998 [10]. 67 Ga scan has limitations such as suboptimal photon energy lead to noisy images, variable uptake of gallium by tumor, particularly low grade NHL, limited detection of abdominal disease secondary to marked physiologic hepatic and colonic activity, and multiple visits to the imaging facility on consecutive days [4]. In contrast to 67 Ga scan, FDG imaging is a half-day procedure associated with a higher resolution and provides a good solution for non-ga-avid lymphomas [10]. It is useful in re-staging of primary disease, to search for early recurrence and predict therapeutic outcome [11-12]. In this case, FDG PET provided the best diagnostic accuracy due to revealing more subdiaphragmatic lymph node metastases than 67 Ga scan and CT did (Figure 3) and thus upstaging of CT finding. 2004;17:109-113 2004 6 17 2 111
Ho KC et al In conclusion, early diagnosis of relapse is essential not only for treatment planning but also for outcome evaluation in HD. CT has limitation in differentiating relapsed tumor from fibrosis in residual mass. 67 Ga scan is superior to CT since it reveals recurrence much earlier than the radiological abnormalities. SPECT technique is useful in leading to a higher certainty of detecting abnormalities. Compared with the limitation of conventional imaging, FDG PET provided the best imaging among all, especially for nodal identification. References 1. Cavalli FG. Hodgkin s disease: treatment of relapsed disease. Ann Oncol 2002;13 Suppl 4:159-162. 2. Lohri A, Barnett M, Fairey RN, et al. Outcome of treatment of first relapse of Hodgkin s disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988. Blood 1991;77:2292-2298. 3. Diehl V, Stein H, Hummel M, Zollinger R, Connors JM. Hodgkin s Lymphoma: Biology and Treatment Strategies for Primary, Refractory, and Relapsed Disease. Hematology (Am Soc Hematol Educ Program) 2003; 225-247. 4. Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med 2000;27:1564-1578. 5. Front D, Bar-Shalom R, Epelbaum R, et al. Early detection of lymphoma recurrence with gallium-67 scintigraphy. J Nucl Med 1993;34:2101-2104. 6. Guay C, Lepine M, Verreault J, Benard F. Prognostic value of PET using 18 F-FDG in Hodgkin s disease for posttreatment evaluation. J Nucl Med 2003;44:1225-1231. 7. Eghbali H, Soubeyran P, Tchen N, de Mascarel I, Soubeyran I, Richaud P. Current treatment of Hodgkin s disease. Crit Rev Oncol Hematol 2000;35:49-73. 8. Kostakoglu L, Yeh SD, Portlock C, et al. Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin s disease in the mediastinum. J Nucl Med 1992;33:345-350. 9. Tumeh SS, Rosenthal DS, Kaplan WD, English RJ, Holman BL. Lymphoma: evaluation with Ga-67 SPECT. Radiology 1987;164:111-114. 10. Even-Sapir E, Israel O. Gallium-67 scintigraphy: a cornerstone in functional imaging of lymphoma. Eur J Nucl Med Mol Imaging 2003;30 Suppl 1:S65-81. 11. Friedberg JW, Chengazi V. PET scans in the staging of lymphoma: current status. Oncologist 2003;8:438-447. 12. Kostakoglu L, Leonard JP, Kuji I, Coleman M, Vallabhajosula S, Goldsmith SJ. Comparison of fluorine- 18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma. Cancer 2002;94:879-888. Ann Nucl Med Sci 2004;17:109-113 Vol. 17 No. 2 June 2004 112
FDG-PET 67 Ga FDG-PET and 67 Ga in Hodgkin s disease 1 1 2 1 1 2-18 -67-67 -67-18 2004;17:109-113 93 1 20 93 2 3 93 2 5 333 5 (03)-3281200 2673 (03)-2110052 billliu@adm.cgmh.org.tw 2004;17:109-113 2004 6 17 2 113