Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

Purpose

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma.

Material & Methods

Fifty-two patients with malignant melanoma (female: n =?30, male: n =?22, mean age 50.5?±?16.0 years, mean tumor thickness 2.28?±?1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard.

Results

Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased.

Conclusion

In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

     

Clinical role of (18)F-FDG PET for initial staging of patients with extrahepatic bile duct cancer

In extrahepatic bile duct cancer, preoperative evaluation is important because only surgical excision of all detectable tumours is associated with improvement in 5-year survival. However, morphological imaging techniques, including computed tomography (CT), are still insufficient for accurate staging. The purpose of this study was to assess the additional value, in relation to CT, of 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography ((18)F-FDG PET) for the evaluation of extrahepatic bile duct cancer. Thirty patients with extrahepatic bile duct cancer underwent both (18)F-FDG PET and CT for initial staging. The results of the two modalities for evaluation of primary tumours and regional lymph nodes were compared with the final diagnoses based on pathological or clinical findings. The primary tumours were interpreted as malignant on the basis of CT in 24 (80%) of the patients, while (18)F-FDG PET revealed increased (18)F-FDG uptake in 18 (60%) of them. On the other hand, (18)F-FDG PET showed focal accumulation of (18)F-FDG in the bile duct in three of the six patients with equivocal findings on CT. The sensitivity, specificity and accuracy of CT for regional lymph node metastases were 54%, 59% and 57%, while those of (18)F-FDG PET were 38%, 100% and 73%, respectively. The specificity of (18)F-FDG PET for regional lymph node metastases was significantly higher than that of CT ( P<0.01). Of 14 patients with N1 or N2 disease diagnosed by CT, only seven (50%) had a final diagnosis of regional lymph node metastasis. In these 14 patients, (18)F-FDG PET accurately evaluated the N component of the disease in 12 patients (86%). In conclusion, in the initial staging of patients with extrahepatic bile duct cancer, (18)F-FDG PET offers additional value in relation to CT in evaluating both the primary tumour and regional lymph nodes.     

18F-FLT和18F-FDG PET/CT对胸段食管癌淋巴结分期诊断的对比研究

目的 评价18F-脱氧胸苷（FLT）PET/CT对未经治疗的胸段食管癌淋巴结分期诊断的价值,并与18F-脱氧葡萄糖（FDG）PET/CT进行比较.方法 选择22例拟行手术治疗的胸段食管癌患者,术前行双显像剂PET/CT检查及淋巴结分期诊断,术后以病理学诊断为＂金标准＂,比较18F-FLT和18F-FDG PET/CT对胸段食管癌淋巴结分期的灵敏度、特异性、准确性、阳性预测值和阴性预测值.应用SPSS 13.0软件进行x2检验.结果 患者均行食管癌切除和淋巴结清扫术,病理检查结果显示16例患者存在淋巴结转移,N0期7例,N1期15例,M1a期6例（其中1例为N0M1a,另外5例为N1M1a）,全组均无M1b期.共检出424枚淋巴结,其中47枚为转移淋巴结.18F-FDG PET/CT诊断呈假阳性的淋巴结14枚,而18F-FLT诊断呈假阳性的淋巴结为3枚;18F-FDG假阴性的淋巴结8枚,18F-FLT假阴性的淋巴结12枚.18F-FLT PET/CT的诊断灵敏度、特异性、准确性、阴性预测值和阳性预测值分别为74.47%（35/47）、99.20%（374/377）、96.46%（409/424）、96.89%（374/386）和92.11%（35/38）,18F-FDG分别为82.98%（39/47）、96.29%（363/377）、94.81%（402/424）、97.84%（363/371）和73.58%（39/53）;两者比较的x2值分别为0.572,6.018,1.017,0.348,3.852,P值分别＞0.05,＜0.05、＞0.05、＞0.05和＞0.05.结论 18F-FLT对食管癌区域淋巴结的诊断灵敏度与18F-FDG显像接近,特异性高于18F-FDG,但仍存在一定的局限性.     

^18F-FDG PET／CT在胰腺癌诊断中的价值

目的评价^18F-脱氧葡萄糖（FDG）PET／CT鉴别诊断胰腺良恶性病变及检测淋巴结和（或）远处转移的价值。方法回顾性分析上海交通大学医学院附属仁济医院行^18F—FDGPET／CT检查的46例临床疑胰腺肿瘤患者的影像学检查资料和临床资料,其中胰腺癌患者26例,良性病变者20例,比较分析PET和CT的特征。结果当选择最大标准摄取值（SUVmax）=2．95为判断良恶性的界值时,对胰腺癌诊断的灵敏度是88．5％（23／26）,特异性是85．0％（17／20）。^18F—FDGPET／CT显像假阳性3例,假阴性3例。同时发现16例检查前未确定的肝、肺、骨及淋巴结转移患者。根据显像结果,11例患者治疗方案得以修正。结论根据现有资料分析,^18F—FDGPET／CT是鉴别诊断胰腺良恶性病变及检测胰腺癌患者淋巴结和（或）远处转移一种较好的方法。     

Evaluation of head and neck cancer with 18F-FDG PET: a comparison with conventional methods

The aim of this study was to evaluate the usefulness of 18F-FDG PET in the diagnosis and staging of primary and recurrent malignant head and neck tumours in comparison with conventional imaging methods [including ultrasonography, radiography, computed tomography (CT) and magnetic resonance imaging (MRI)], physical examination, panendoscopy and biopsies in clinical routine. A total of 54 patients (13 female, 41 male, age 61.3+/-12 years) were investigated retrospectively. Three groups were formed. In group I, 18F-FDG PET was performed in 15 patients to detect unknown primary cancers. In group II, 24 studies were obtained for preoperative staging of proven head and neck cancer. In group III, 18F-FDG PET was used in 15 patients to monitor tumour recurrence after radiotherapy and/or chemotherapy. In all patients, imaging was obtained at 70 min after the intravenous administration of 180 MBq 18F-FDG. In 11 of the 15 patients in group I, the primary cancer could be found with 18F-FDG, yielding a detection rate of 73.3%. In 4 of the 15 patients, CT findings were also suggestive of the primary cancer but were nonetheless equivocal. In these patients, 18F-FDG showed increased 18F-FDG uptake by the primary tumour, which was confirmed by histology. One patient had recurrence of breast carcinoma that could not be detected with 18F-FDG PET, but was detected by CT. In three cases, the primary cancer could not be found with any imaging method. Among the 24 patients in group II investigated for staging purposes, 18F-FDG PET detected a total of 13 local and three distant lymph node metastases, whereas the conventional imaging methods detected only nine local and one distant lymph node metastases. The results of 18F-FDG PET led to an upstaging in 5/24 (20.8%) patients. The conventional imaging methods were false positive in 5/24 (20.8%). There was one false positive result using 18F-FDG PET. Among the 15 patients of group III with suspected recurrence after radiotherapy and/or chemotherapy, 18F-FDG was true positive in 7/15 (46.6%) and true negative in 4/15 (26.6%). The conventional imaging methods were true positive in 5/15 (33.3%) and true negative in 4/15 (26.6%). One false negative (6.6%) and three false positive findings (20%) on 18F-FDG PET were due to inflamed tissue. The conventional imaging methods were false positive in three (20%) and false negative in three cases (20%). It is concluded that in comparison to conventional diagnostic methods, 18F-FDG PET provides additional and clinically relevant information in the detection of primary and metastatic carcinomas as well as in the early detection of recurrent or persistent head and neck cancer after radiotherapy and/or chemotherapy. 18F-FDG PET should therefore be performed early in clinical routine, usually before CT or MRI.     

Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer

The aims of this study were to investigate the detection of cervical lymph node metastases of head and neck cancer by positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) and to perform a prospective comparison with computed tomography (CT), magnetic resonance imaging (MRI), sonographic and histopathological findings. Sixty patients with histologically proven squamous cell carcinoma were studied by PET imaging before surgery. Preoperative endoscopy (including biopsy), CT, MRI and sonography of the cervical region were performed in all patients within 2 weeks preceding ¹⁸F-FDG whole-body PET. FDG PET images were analysed visually and quantitatively for objective assessment of regional tracer uptake. Histopathology of the resected neck specimens revealed a total of 1284 lymph nodes, 117 of which showed metastatic involvement. Based on histopathological findings, FDG PET correctly identified lymph node metastases with a sensitivity of 90% and a specificity of 94% (P<10^–6). CT and MRI visualized histologically proven lymph node metastases with a sensitivity of 82% (specificity 85%) and 80% (specificity 79%), respectively (P<10^–6). Sonography revealed a sensitivity of 72% (P<10^–6). The comparison of ¹⁸F-FDG PET with conventional imaging modalities demonstrated statistically significant correlations (PET vs CT, P = 0.017; PET vs MRI, P = 0.012; PET vs sonography, P = 0.0001). Quantitative analysis of FDG uptake in lymph node metastases using body weight-based standardized uptake values (SUV_BW) showed no significant correlation between FDG uptake (3.7±2.0) and histological grading of tumour-involved lymph nodes (P = 0.9). Interestingly, benign lymph nodes had increased FDG uptake as a result of inflammatory reactions (SUV_BW-range: 2–15.8). This prospective, histopathologically controlled study confirms FDG PET as the procedure with the highest sensitivity and specificity for detecting lymph node metastases of head and neck cancer and has become a routine method in our University Medical Center. Furthermore, the optimal diagnostic modality may be a fusion image showing the increased metabolism of the tumour and the anatomical localization. Received 17 February and in revised form 12 June 1998     

Breast cancer staging in a single session: whole-body PET/CT mammography

Our objective was to compare the diagnostic accuracy of an all-in-one protocol of whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the diagnostic accuracy of a multimodality algorithm for initial breast cancer staging. METHODS: Forty women (mean age, 58.3 y; range, 30.8-78.4 y; SD, 12 y) with suspected breast cancer were included. For the primary tumor, we compared 18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm. Histopathology and clinical follow-up served as the standard of reference. The Fisher exact test evaluated the significance of differences (P < 0.05). Alterations in patient management caused by 18F-FDG PET/CT were documented. RESULTS: No significant differences were found in the detection rate of breast cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly classified lesion focality significantly more often than did MRI (18F-FDG PET/CT, 79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG PET/CT detected axillary lymph node metastases in 80% of cases; clinical investigation/ultrasound, in 70%. This difference was not statistically significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in 100% of cases, and the multimodality algorithm identified distant metastases in 70%. This difference was not statistically significant (P = 1). Three patients had extraaxillary lymph node metastases that were detected only by PET/CT (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT changed patient management in 12.5% of cases. CONCLUSION: Our data suggest that a whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast cancer in a single session. This initial assessment of the 18F-FDG PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions. Although MRI seems to be more accurate when assessing the T stage of the tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality. Although 18F-FDG PET/CT mammography was able to detect axillary lymph node metastases with a high sensitivity, this method cannot soon be expected to replace the combination of clinical examination, ultrasound, and sentinel lymph node biopsy for axillary assessment.     

18F-FDG PET/CT for staging of penile cancer.

The value of PET or PET/CT with (18)F-FDG for the staging of penile cancer has yet to be determined. The objective of this study was to investigate the pattern of (18)F-FDG uptake in the primary malignancy and its metastases and to determine the diagnostic value of (18)F-FDG PET/CT in the staging and restaging of penile cancer. METHODS: Thirteen patients (mean +/- SD age, 64 +/- 14.0 y) with suspected penile cancer or suspected recurrent disease were examined with a Gemini PET/CT system (200 MBq of (18)F-FDG). The reference standard was based on histopathologic findings obtained at biopsy or during surgery. RESULTS: Both the primary tumor and regional lymph node metastases exhibited a pattern of (18)F-FDG uptake typical for malignancy. Sensitivity in the detection of primary lesions was 75% (6/8), and specificity was 75% (3/4). On a per-patient basis, sensitivity in the detection of lymph node metastases was 80% (4/5), and specificity was 100% (8/8). On a nodal-group basis, PET/CT showed a sensitivity of 89% (8/9) in the detection of metastases in the superficial inguinal lymph node basins and a sensitivity of 100% (7/7) in the deep inguinal and obturator lymph node basins. The mean +/- SD maximum standardized uptake value for the 8 primary lesions was 5.3 +/- 3.7, and that for the 16 lymph node metastases was 4.6 +/- 2.0. CONCLUSION: According to our results, the main indication for (18)F-FDG PET in the primary staging or follow-up of penile cancer patients may be the prognostically crucial search for lymph node metastases. With the use of a PET/CT unit, the additional information provided by CT may be especially useful for planning surgery. Implementing (18)F-FDG PET and PET/CT in future staging algorithms may lead to a more precise and stage-appropriate therapeutic strategy. Furthermore, invasive procedures with a high morbidity rate, such as general bilateral lymphadenectomy, may be avoided.     

Lymph node staging of gastric cancer using (18)F-FDG PET: a comparison study with CT.

This study was performed to compare (18)F-FDG PET with CT for the evaluation of primary tumors and lymph node metastases in gastric cancer. METHODS: Eighty-one patients (28 women and 53 men; mean age, 56.6 y; age range; 32-82 y) who had undergone radical (n = 74) or palliative (n = 7) gastrectomy and lymph node dissection for the management of gastric cancer were included. Preoperative (18)F-FDG PET and CT were reviewed retrospectively for primary tumors of the stomach and lymph node metastases. Any increased (18)F-FDG uptake exceeding that of the adjacent normal gastric wall was considered positive for the primary tumor. Lymph nodes were classified into 3 groups based on their anatomic sites. Because perigastric lymph nodes (N1) were often not clearly differentiated from primary tumors, N1 lymph node metastases were determined when possible. Lymph nodes were considered positive or negative on the basis of the group as a whole. Final conclusions for primary tumors and lymph node metastases were based on histopathologic specimens in all patients. RESULTS: There were 17 patients with early gastric cancer (EGC) and 64 patients with advanced gastric cancer (AGC). For primary tumors, both PET and CT showed a sensitivity of 47% (8/17) for EGC and 98% (63/64) for AGC. The sensitivity of CT for N1 disease was significantly higher than that of PET. (18)F-FDG PET had a sensitivity, specificity, and accuracy of 34% (11/32), 96% (47/49), and 72% (58/81), respectively, for N2 metastases, whereas the corresponding CT values were 44% (14/32), 86% (42/49), and 69% (56/81). For N3 metastases, PET and CT had the same sensitivity, specificity, and accuracy: 50% (3/6), 99% (74/75), and 95% (77/81), respectively. Overall, the sensitivity, specificity, and accuracy of (18)F-FDG PET were not significantly different from those of CT for primary tumors or for N2 and N3 metastases. CONCLUSION: (18)F-FDG PET is as accurate as CT for the detection of primary tumors of either EGC or AGC. The low sensitivities of PET and CT were insufficient to allow decision making on the extent of lymphadenectomy. In contrast, the high specificity of PET for N disease appeared valuable, and the presence of N disease on PET may have a clinically significant impact on the choice of initial therapy.     

A case of renal pelvic tumor visualized by<Superscript>18</Superscript>F-FDG-PET imaging

18F fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging is a useful modality in detecting various tumors, including renal cell carcinoma. We evaluated a patient with renal pelvic tumor (transitional cell carcinoma) with multiple metastases using 18F-FDG PET imaging and detected abnormal increased uptake of a right renal pelvic tumor extending to the renal cortex with liver metastasis and paraaortic lymph node metastases. These results suggest that 18F-FDG PET imaging may be useful in detecting primary and metastatic lesions of renal pelvic tumor (transitional cell carcinoma).     

Preoperative assessment of cervical lymph nodes in head and neck cancer with fluorine-18 fluorodeoxyglucose using a dual-head coincidence camera: a pilot study.

The aim of this study was to investigate whether in patients with head and neck cancer, staging is possible with fluorine-18 fluorodeoxyglucose (18F-FDG) using a dual-head positron emission tomography (PET) camera. Twenty patients (ten men, ten women; mean age: 60 years) were studied using 185 MBq (5 mCi) 18F-FDG. Two of these patients who were suspected of having recurrence in the neck were restaged 19 and 12 months, respectively, after the resection of the primary tumour. The images were visually analyzed and the results were correlated with computed tomography (CT) (n = 18), ultrasonography (n = 17) and pathological findings. With respect to the primary tumour, FDG dual-head PET and CT revealed a sensitivity of 100% and 59%, respectively (P < 0.001). In seven patients lymph node metastases were found in the neck specimen. Two of them had bilateral metastases. FDG dual-head PET correctly identified all nine pathological neck sides whereas CT and ultrasonography depicted eight of nine and seven of eight pathological sides, respectively. In three patients, false-positive FDG uptake was seen, which was due to a preceding biopsy in two cases. The sensitivity of FDG dual-head PET, CT and ultrasonography in the identification of pathological neck sides was 100%, 89% and 87%, respectively, and the specificity was 90%, 93% and 50%, respectively. With knowledge of the preceding biopsies, the specificity of FDG dual-head PET would have been 97%. The smallest lymph node metastasis detected by FDG dual-head PET that was missed by CT had a diameter of 0.6 cm. Measurement of 18F-FDG with a dual-head PET camera is very sensitive in the detection of primary head and neck cancers and accurate in the preoperative assessment of lymph node metastases. The results justify a prospective study on the identification of metastases in patients with head and neck cancer. In addition, it is justified to start a study on the detection of unknown primary tumours in patients with cervical metastases.     

Additional value of PET/CT over PET in assessment of locoregional lymph nodes in thoracic esophageal squamous cell cancer.

The aim of this study was to compare the value of reviewing combined 18F-FDG PET/CT images with that of reviewing side-by-side PET and CT images in the diagnosis of locoregional lymph node metastases in patients with esophageal squamous cell cancer. METHODS: From November 2003 to December 2005, 45 patients with thoracic esophageal squamous cell cancer underwent 18F-FDG PET/CT before surgery. The results of reviewing combined PET/CT images and side-by-side PET and CT images for the diagnosis of locoregional lymph node metastases were compared prospectively in relation to pathologic findings. RESULTS: All patients underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 32 patients and 82 of 397 excised nodal groups. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 93.90% (77/82 nodal groups), 92.06% (290/315), 92.44% (367/397), 75.49% (77/102), and 98.31% (290/295), respectively, whereas those of PET were 81.71% (67/82), 87.30% (275/315), 86.15% (342/397), 62.62% (67/107), and 94.83% (275/290), respectively. P values were 0.032, 0.067, 0.006, 0.063, and 0.037, respectively. The differences in sensitivity, accuracy, and negative predictive value between PET and PET/CT were statistically significant. CONCLUSION: PET/CT improves the sensitivity, accuracy, and negative predictive value of 18F-FDG imaging in the assessment of locoregional lymph nodes in thoracic esophageal squamous cell cancer and provides data of diagnostic significance.     

18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation.

Accurate evaluation of primary tumors and cervical lymph node status of squamous cell carcinoma (SCC) of the oral cavity is important to treatment planning and prognosis prediction. In this prospective study, we evaluated the use of 18F-FDG PET, CT/MRI, and their visual correlation for the identification of primary tumors and cervical nodal metastases of SCC of the oral cavity with histologic correlation. METHODS: One hundred twenty-four patients with pathologically proven diagnoses of oral cavity SCC underwent 18F-FDG PET and CT/MRI within 2 wk before surgery. We interpreted 18F-FDG PET, CT/MRI, and visually correlated 18F-FDG PET and CT/MRI separately to assess the primary tumors and their regional lymph node status. We recorded lymph node metastases according to the neck level system of imaging-based nodal classification. Histopathologic analysis was used as the gold standard for assessment of the primary tumors and lymph node involvement. We analyzed differences in sensitivity and specificity among the imaging modalities using the McNemar test. The receiver-operating-characteristic (ROC) curve and calculation of the area under the curve were used to evaluate their discriminative power. RESULTS: The accuracy of 18F-FDG PET, CT/MRI, and their visual correlation for the identification of primary tumors was 98.4%, 87.1%, and 99.2%, respectively. The sensitivity of 18F-FDG PET for the identification of nodal metastases on a level-by-level basis was 22.1% higher than that of CT/MRI (74.7% vs. 52.6%, P < 0.001), whereas the specificity of 18F-FDG PET was 1.5% lower than that of CT/MRI (93.0% vs. 94.5%, P = 0.345). The sensitivity and specificity of the visual correlation of 18F-FDG PET and CT/MRI were 3.2% and 1.5% higher than those of 18F-FDG PET alone (77.9% vs. 74.7%, P = 0.25; 94.5% vs. 93.0%, P = 0.18, respectively). The area under the curve obtained from the ROC curve showed that 18F-FDG PET was significantly superior to CT/MRI for total nodal detection (0.896 vs. 0.801, P = 0.002), whereas the visual correlation of 18F-FDG PET and CT/MRI was modestly superior to 18F-FDG PET alone (0.913 vs. 0.896, P = 0.28). CONCLUSION: 18F-FDG PET is superior to CT/MRI in the detection of cervical status of oral cavity SCC. The sensitivity of 18F-FDG PET for the detection of cervical nodal metastasis on a level-by-level basis was significantly higher than that of CT/MRI, whereas their specificities appeared to be similar. Visual correlation of 18F-FDG PET and CT/MRI showed a trend of increased diagnostic accuracy over 18F-FDG PET alone but without a statistically significant difference, and its sensitivity was still not high enough to replace pathologic lymph node staging based on neck dissection.     

A seldom case of primary urethral malignant melanoma and breast cancer detected by (18)F-FDG PET/CT

In the 1(st )issue of HJNM for 2012 we read with interest a case where 3 different cancers were detected. Synchronous second malignancy can be incidentally detected in routine fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography ( (18)F-FDG PET/CT) imaging in approximately 1% of cancer patients with lungs being the most frequent site. We report the (18)F-FDG PET/CT scan for staging of the primary malignant melanoma of the urethra and for the detection of another malignancy in the breast in the same patient, since primary malignant melanoma of urethra is very seldom. A 65 years old post-menopausal woman presented with increased frequency of micturition, dysuria and a gradually enlarging mass protruding from the external urethral meatus. Fine needle aspiration cytology (FNAC) performed from the mass revealed malignant melanoma. On cystourethrescopy examination, a 4x4 cm blackish mass was noted at the external urethral meatus with a satellite nodule in the bladder trigone. Contrast enhanced CT (CeCT) of the pelvis showed soft tissue thickening along the urethra infiltrating urinary bladder neck and vagina. Analysis of (18)F-FDG PET/CeCT was performed to assess the extent of the disease. Intensely (18)F-FDG avid soft tissue mass (SUV(max): 20.1) was noticed along the entire length of the urethra with hypermetabolic right inguinal and left external iliac lymph nodes. In addition to (18)F-FDG uptake in the bladder wall and the vaginal wall, intense (18)F-FDG uptake was also seen in two soft tissue nodules in the right breast and in the axillary lymph nodes suggestive of a second primary in the breast. Cytological diagnosis of intraductal breast carcinoma was made after FNAC from the breast nodule. Urethral melanoma was treated with anterior exenteration and ileal conduit. Histopathology confirmed the diagnosis of primary malignant melanoma of urethra infiltrating the urinary bladder and anterior vaginal wall. Postoperative histopathology from the right inguinal and left external iliac lymph nodes revealed metastatic disease. The diagnostic contribution of PET/CT was crucial. Melanotic melanoma cells have a distinctive MRI signal, which may be helpful in diagnosis. In this case whole body MRI could have been of equal value for accurate staging of urethral melanoma, but whole body MRI is a cumbersome procedure and often is not practical. Primary urethral carcinoma is very rare and an annual ageadjusted incidence rate of 4.3 per 106 in males and 1.5 per 106 in females has been reported in USA. Primary malignant melanoma of the urethra is rare, representing less than 1% of all melanomas and 4% of urethral cancers. Furthermore, the incidence of two primary cancers is rare and is reported to be between 0.3% and 4.3%. Primary malignant melanoma of the urethra has a worse prognosis than its cutaneous counterpart, partly due to delayed diagnosis. At the time of diagnosis, urethral melanoma is usually deeply invasive and locally extended to the vagina or vulva or the corpora cavernosa. Inguinal lymph node metastases are present at diagnosis in half of the cases and distant metastases in one third of them. Positron emission tomography demonstrates specificity and accuracy of 94.7% and 73% respectively in detecting lymph nodal metastases. Sensitivity, specificity and accuracy of (18)F-FDG PET/CT in detecting metastases in high risk patients were 85%, 96%, 91% while for (18)F-FDG PET/CT with dedicated CT interpretation were 98%, % and 96%, respectively. Recently, the role of (18)F-FDG PET/CT in treatment response evaluation of melanoma patients has also been demonstrated. Incidental (18)F-FDG uptake in the breasts is rare, and the lesion may be malignant in up to 57% of the cases. To our knowledge no published literature is available on synchronous breast carcinoma and urethral melanoma. The reason why some patients are more prone to develop multiple cancers remains obscure. One possibility may be of a genetic predisposition linking the two cancers. Research suggests that mutations in CDKN2A, a gene that indicates high risk of developing melanoma, also puts carriers at an up to 3.8 times greater risk of breast cancer. Similarly, mutations in the gene of breast cancer susceptibility, BRCA2, increase carriers' risk of melanoma by as much as 2.58 times. In conclusion, we describe a case of two primary carcinomas: a unique urethral malignant melanoma and a breast carcinoma, detected and staged by (18)F-FDG PET/CT.     

Evaluation of head and neck cancer with 18F-FDG PET: a comparison with conventional methods

The aim of this study was to evaluate the usefulness of ¹⁸F-FDG PET in the diagnosis and staging of primary and recurrent malignant head and neck tumours in comparison with conventional imaging methods [including ultrasonography, radiography, computed tomography (CT) and magnetic resonance imaging (MRI)], physical examination, panendoscopy and biopsies in clinical routine. A total of 54 patients (13 female, 41 male, age 61.3ᆠ years) were investigated retrospectively. Three groups were formed. In group I, ¹⁸F-FDG PET was performed in 15 patients to detect unknown primary cancers. In group II, 24 studies were obtained for preoperative staging of proven head and neck cancer. In group III, ¹⁸F-FDG PET was used in 15 patients to monitor tumour recurrence after radiotherapy and/or chemotherapy. In all patients, imaging was obtained at 70 min after the intravenous administration of 180 MBq ¹⁸F-FDG. In 11 of the 15 patients in group I, the primary cancer could be found with ¹⁸F-FDG, yielding a detection rate of 73.3%. In 4 of the 15 patients, CT findings were also suggestive of the primary cancer but were nonetheless equivocal. In these patients, ¹⁸F-FDG showed increased ¹⁸F-FDG uptake by the primary tumour, which was confirmed by histology. One patient had recurrence of breast carcinoma that could not be detected with ¹⁸F-FDG PET, but was detected by CT. In three cases, the primary cancer could not be found with any imaging method. Among the 24 patients in group II investigated for staging purposes, ¹⁸F-FDG PET detected a total of 13 local and three distant lymph node metastases, whereas the conventional imaging methods detected only nine local and one distant lymph node metastases. The results of ¹⁸F-FDG PET led to an upstaging in 5/24 (20.8%) patients. The conventional imaging methods were false positive in 5/24 (20.8%). There was one false positive result using ¹⁸F-FDG PET. Among the 15 patients of group III with suspected recurrence after radiotherapy and/or chemotherapy, ¹⁸F-FDG was true positive in 7/15 (46.6%) and true negative in 4/15 (26.6%). The conventional imaging methods were true positive in 5/15 (33.3%) and true negative in 4/15 (26.6%). One false negative (6.6%) and three false positive findings (20%) on ¹⁸F-FDG PET were due to inflamed tissue. The conventional imaging methods were false positive in three (20%) and false negative in three cases (20%). It is concluded that in comparison to conventional diagnostic methods, ¹⁸F-FDG PET provides additional and clinically relevant information in the detection of primary and metastatic carcinomas as well as in the early detection of recurrent or persistent head and neck cancer after radiotherapy and/or chemotherapy. ¹⁸F-FDG PET should therefore be performed early in clinical routine, usually before CT or MRI.     

Routine (18)F-FDG PET preoperative staging of colorectal cancer: comparison with conventional staging and its impact on treatment decision making.

The preoperative staging of colorectal cancer (CRC) with (18)F-FDG PET is not as yet generally considered to be evidence based. We have found only 1 study that evaluated (18)F-FDG PET in a nonselected population with proven CRC. Several other studies have concentrated on more advanced disease. The aim of this study was to assess the potential clinical benefit of (18)F-FDG PET in the routine staging of CRC. METHODS: Thirty-eight consecutive patients who had had CRC histologically proven by colonoscopy underwent prospective preoperative staging by plain chest radiography, sonography, CT, and (18)F-FDG PET. Sensitivity, specificity, and accuracy were retrospectively assessed by comparison with the histologic results after surgery (36 patients) or clinical follow-up (2 inoperable cases-both patients died within 1 y of the PET examination). The impact of (18)F-FDG PET on therapeutic decision making was evaluated by comparing medical records before and after (18)F-FDG PET. RESULTS: (18)F-FDG PET correctly detected 95% of primary tumors, whereas CT and sonography correctly detected only 49% and 14%, respectively. Lymph nodes were involved in 7 patients. The sensitivity, specificity, and accuracy of (18)F-FDG PET were 29%, 88%, and 75%, respectively. CT and sonography did not reveal any lymph node involvement. Liver metastases were present in 9 patients. (18)F-FDG PET, CT, and sonography had a sensitivity of 78%, 67%, and 25%, respectively; a specificity of 96%, 100%, and 100%, respectively; and an accuracy of 91%, 91%, and 81%, respectively. (18)F-FDG PET revealed further lesions in 11 patients. Levels of carcinoembryonic antigen and carbohydrate antigen 19-9 tumor markers were elevated in, respectively, only 33% and 8% of cases of proven CRC. (18)F-FDG PET changed the treatment modality for 8% and the range of surgery for 13% of patients. In total, (18)F-FDG PET changed the method of treatment for 16% of patients. CONCLUSION: Plain chest radiography and sonography did not bring any clinical benefits. No correlation was found between the level of tumor markers and the stage of disease. CT is necessary for confirmation of PET findings at extraabdominal sites (PET-guided CT) and for their morphologic specification at abdominal and pelvic sites before an operation. (18)F-FDG PET is the best method for the staging of CRC in all localities, despite the high rate of false-negative PET findings in patients with lymph node involvement. PET should be performed as a first examination after verification of CRC. We propose a PET/CT hybrid system as optimal in the staging of CRC.     

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.     

Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging.

The aim of this investigation was to evaluate the influence and accuracy of (18)F-FDG PET in target volume definition as a complementary modality to CT for patients with head and neck cancer (HNC) using dedicated PET and CT scanners. METHODS: Six HNC patients were custom fitted with head and neck and upper body immobilization devices, and conventional radiotherapy CT simulation was performed together with (18)F-FDG PET imaging. Gross target volume (GTV) and pathologic nodal volumes were first defined in the conventional manner based on CT. A segmentation and surface-rendering registration technique was then used to coregister the (18)F-FDG PET and CT planning image datasets. (18)F-FDG PET GTVs were determined and displayed simultaneously with the CT contours. CT GTVs were then modified based on the PET data to form final PET/CT treatment volumes. Five-field intensity-modulated radiation therapy (IMRT) was then used to demonstrate dose targeting to the CT GTV or the PET/CT GTV. RESULTS: One patient was PET-negative after induction chemotherapy. The CT GTV was modified in all remaining patients based on (18)F-FDG PET data. The resulting PET/CT GTV was larger than the original CT volume by an average of 15%. In 5 cases, (18)F-FDG PET identified active lymph nodes that corresponded to lymph nodes contoured on CT. The pathologically enlarged CT lymph nodes were modified to create final lymph node volumes in 3 of 5 cases. In 1 of 6 patients, (18)F-FDG-avid lymph nodes were not identified as pathologic on CT. In 2 of 6 patients, registration of the independently acquired PET and CT data using segmentation and surface rendering resulted in a suboptimal alignment and, therefore, had to be repeated. Radiotherapy planning using IMRT demonstrated the capability of this technique to target anatomic or anatomic/physiologic target volumes. In this manner, metabolically active sites can be intensified to greater daily doses. CONCLUSION: Inclusion of (18)F-FDG PET data resulted in modified target volumes in radiotherapy planning for HNC. PET and CT data acquired on separate, dedicated scanners may be coregistered for therapy planning; however, dual-acquisition PET/CT systems may be considered to reduce the need for reregistrations. It is possible to use IMRT to target dose to metabolically active sites based on coregistered PET/CT data.     

Nodal status of malignant lymphoma in pelvic and retroperitoneal lymphatic pathways: comparison of integrated PET/CT with or without contrast enhancement

AIM: To determine the diagnostic accuracy of integrated contrast-enhanced positron emission tomography (PET) and computed tomography (CT), as compared with non-contrasted PET/CT, in evaluating nodal status of malignant lymphoma in pelvic and retroperitoneal lymphatic pathways. MATERIALS AND METHODS: Sixty-six patients (33 men and 33 women) with malignant lymphoma underwent staging with integrated CT and fluorine-18-fluorodeoxyglucose ((18)FDG) PET. Tumor types were diffuse large B-cell lymphoma (n=26, 39%), follicular lymphoma (n=20, 30%), Hodgkin disease (n=16, 24%), and marginal zone B-cell lymphoma (n=4, 6%). Both non-contrasted PET/CT and contrast-enhanced PET/CT images were examined separately by two different qualified physicians for each imaging modality, and nodal status of pelvic and retroperitoneal lymphatic pathways was evaluated. Reference standard included follow-up with clinical, laboratory, and conventional CT findings. We compared diagnostic accuracy retrospectively on basis of per-patient and per-lesion analyses between two modalities using McNemar test, respectively. RESULTS: Nodal status of pelvic and retroperitoneal lymphatic pathways was more accurately determined on contrast-enhanced PET/CT (n=52, 79%) compared with non-contrasted PET/CT (n=47, 71%). Difference in the accuracy of nodal staging between non-contrasted PET/CT and contrast-enhanced PET/CT was significant (p=0.048). On basis of per-lesion analysis, contrast-enhanced PET/CT determined more accurately the status of external iliac lymph node (p=0.002), internal iliac lymph node (p<0.0001), and common iliac lymph node (p=0.002) compared with non-contrasted PET/CT. Diagnostic accuracies of paraaortic lymph node, aortocaval lymph node, and paracaval lymph node were similar by either non-contrasted PET/CT or contrast-enhanced PET/CT. CONCLUSION: Integrated contrast-enhanced PET/CT improves the diagnostic accuracy in evaluating nodal status of pelvic and retroperitoneal lymphatic pathways in patients with malignant lymphoma.     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.