Prevalence of clinically significant extraosseous findings on unenhanced CT portions of ¹8F-fluoride PET/CT bone scans.

OBJECTIVE: Due to the frequently interrupted supply of (99m)Tc-methylene diphosphonate, the use of ¹8F-fluoride positron emission tomography (PET)/computed tomography (CT) has become more popular. The study aims to determine the percentage of extraosseous findings from the unenhanced CT portion of F ¹8F-fluoride PET/CT scans. MATERIALS AND METHODS: We retrospectively collected ¹8F-fluoride PET/CT studies between March 2010 and February 2011. The unenhanced CT portions of ¹8F-fluoride PET/CT were reviewed for each patient. Significant extraosseous findings related to malignancy from the unenhanced CT were recorded. RESULTS: A total of 158 patients (110 females, 48 males) were included in the study. Clinically significant extraosseous findings from the unenhanced CT were found in 43 patients (27.2%). Previously unknown extraosseous findings were identified in 17 patients (10.8%) after a review of the ¹8F-fluoride PET/CT scan results. Most of the extraosseous findings were small pulmonary metastases or enlarged metastatic lymph nodes. CONCLUSION: It is not rare to identify new clinically significant extraosseous findings from the unenhanced CT of ¹8F-fluoride PET/CT studies. Therefore the clinical management of patients may be altered by the results, and a careful review of the unenhanced CT portion of ¹8F-fluoride PET/CT is mandatory.

Comparative benefits and limitations of 18F-FDG PET and CT-MRI in documented or suspected recurrent cervical cancer.

PURPOSE: The purpose of this study was to assess the comparative benefits and limitations of (18)F-fluorodeoxyglucose (FDG) PET and CT-MRI in documented or suspected recurrence of cervical cancer after primary treatment. METHODS: Three patient groups were enrolled. Group A patients had biopsy-documented recurrent or persistent cervical cancer. Group B patients had suspicion of recurrent tumour on CT-MRI without biopsy proof and were potentially curable. Group C patients were in complete remission after previous definitive treatment for histologically confirmed cervical carcinoma but had elevated serum squamous cell carcinoma antigen (tumour marker) levels despite negative CT-MRI. Clinical management decisions were recorded with CT-MRI alone and with additional FDG PET. Discordances and concordances between CT-MRI and FDG PET results were identified and related to final diagnosis as based on histopathology or follow-up. RESULTS: A total of 150 patients (ten regions per patient) were eligible for analysis, with 58 in group A, 52 in group B and 40 in group C. For the 149 discordant regions, 126 (84.6%) had final diagnoses. Of these final diagnoses, there was additional benefit from FDG PET over CT-MRI in 73.8% (93/126), with FDG PET correcting false negatives (FNs) on CT-MRI in 74.2% (69/93) and correcting false positives (FPs) on CT-MRI in 25.8% (24/93). Among lesions confirmed by FDG PET, 75.4% (52/69) were extra-pelvic. There was additional benefit of CT-MRI compared with FDG PET in 26.2% (33/126): in nine (27.3%) CT-MRI results were shown to be true positive (TP) whereas FDG PET yielded FN results, while in 24 (72.7%) CT-MRI corrected FP results on FDG PET. Among the nine FNs on FDG PET that were identified by CT-MRI, four were extra-pelvic. Among the FPs on FDG PET that were excluded by CT-MRI, 79.2% (19/24) were extra-pelvic. CONCLUSION: For recurrent cervical cancer, the benefits of FDG PET exceed those of CT-MRI owing to the ability of FDG PET to identify extra-pelvic metastases and its higher sensitivity and specificity.

Low value of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in primary staging of early-stage cervical cancer before radical hysterectomy.

PURPOSE: The role of positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND). PATIENTS AND METHODS: Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (< or = 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) -defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m-sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report. RESULTS: There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 x 3.0 mm (range, 0.5 x 0.5 to 7 x 6 mm). The second stage of this trial will be continued without PET. CONCLUSION: This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.

Radioguided sentinel lymph node biopsy in early breast cancer: experience at Chang Gung Memorial Hospital.

BACKGROUND: Sentinel lymph node (SLN) biopsy can identify regional metastases and provides an alternative to axillary dissection that avoids arm morbidity. This investigation assessed the accuracy of SLN biopsy for predicting axillary node status. METHODS: A total of 174 clinical node-negative breast cancer patients and 165 SLN biopsies were enrolled. SLN biopsy was performed in a two-day protocol with backup axillary dissection: subdermally injected technetium-99 sulfur colloid to detect and localize SLN on day one; sentinel node harvesting under gamma-counter guidance on day two. Clinicopathological factors were statistically analyzed to assess the accuracy of the SLN biopsy. RESULTS: The SLN was identified in 94.3% (165 of 175) of cases. SLN biopsy had an accuracy of 98.2%, with sensitivity of 93.7%, specificity of 100%, negative predictive value of 97.5% and positive predictive value of 100%. Three SLN negative cases had non-SLN metastasis representing a false-negative rate of 6.3% (3 of 48). Tumor size was the only factor statistically correlated with the accuracy of the SLN biopsy. The diagnostic accuracy for tumors sized 2 cm or below was 100%. Hematoxylin-eosin stain followed by immunohistochemical stain increased the diagnosis of axillary metastasis from 25.5% to 29.1%. CONCLUSION: SLN biopsy can accurately forecast axillary node status in early breast cancer, particularly in patients with tumor sizes of no more than 2 cm.

Clinical relevance of nonvisualized sentinel lymph nodes in unselected breast cancer patients during lymphoscintigraphy.

BACKGROUND: Sentinel lymph node (SLN) biopsy in breast cancer is an effective technique with a high degree of accuracy and low false-negative rate to replace axillary lymph node dissection (ALND). This study analyzed the major clinicopathological factors associated with nonvisualized sentinel nodes during preoperative lymphoscintigraphy. METHODS: Breast cancer patients who underwent preoperative lymphoscintigraphy and sentinel node biopsy between 2000 and 2003 were retrospectively reviewed. Sentinel node biopsy was performed with a two-day protocol. On day one, a filtered (45 micro m Millipore) technetium-99m sulfur colloid isotope with a mean radioactive dose of 37 MBq (1 mCi) in a diluted volume of 1 ml was injected subdermally just above the primary breast tumor site. Serial dynamic images were taken with a high-resolution collimator and a static image was acquired after the SLN was identified. No hot spot identified two hours after injection was classified as nonvisualization unless lymphatic drainage channels were viewed by the lymphoscintigraphy and a prolonged two hour scan was obtained. Sentinel nodes were harvested on day two. The cases with nonvisualized sentinel nodes were analyzed according to clinical histopathologic parameters to determine the clinical significance. RESULTS: A total of two hundred thirty-two breast cancer patients were enrolled in this study. Twenty-four of these cases presented with advanced breast cancer prior to neoadjuvant chemotherapy. The sentinel node was nonvisualized in twenty-seven of two hundred thrity-two cases (11.6%). Tumor size (p = 0.025) and lymph node metastasis (p = 0.001) were two factors associated with nonvisualized sentinel node in univariate analysis. Multivariate logistic regression analysis showed that more than three nodes (p = 0.001) and more than ten nodes (p = 0.001) metastasis were independent factors associated with nonvisualized sentinel node. CONCLUSIONS: Patients with more than three axillary nodes metastasis is an independent factor associated with nonvisualized sentinel node during lymphoscintigraphy.

Exclusion of lung metastases in placental site trophoblastic tumor using [18F]fluorodeoxyglucose positron emission tomography: a case report.

BACKGROUND: We present the first case using [18F]fluorodeoxyglucose positron emission tomography (PET) for the evaluation of multiple lung nodules in a woman with placental site trophoblastic tumor (PSTT) and history of pulmonary tuberculosis. CASE: PSTT was diagnosed by endometrial biopsy in a 38-year-old female, 11 months after an abortion. She had received medical treatment for pulmonary tuberculosis 8 years ago. Nodular lung lesions in upper and lower lung fields were noted on the chest X-ray and computed tomography, which was not shown on PET. She then received hysterectomy and complete remission of serum beta-hCG titer with stationary lung lesions in follow-up images were noticed thereafter. CONCLUSION: PET, as adjuvant study to conventional images, may help in the differentiation of chest lesions in PSTT.

Defining the priority of using 18F-FDG PET for recurrent cervical cancer.

UNLABELLED: PET with 18F-FDG has shown its potential in cervical cancer. For maximizing the benefits of this new imaging technology, we aimed to define the prognostic features of recurrent cervical cancer patients for selecting appropriate candidates using 18F-FDG PET. METHODS: Patients enrolled were from 2 independent prospective studies investigating the role of 18F-FDG PET in cervical cancer patients after definitive treatment with documented failure (CTRP-018) or unexplained elevated tumor marker serum levels (CTRP-016) and proven relapse after PET. A total of 55 eligible patients received PET and CT or MRI. Lesion status was determined from pathologic results or clinical follow-up. The benefits calculated were based on treatment that was modified because of the PET findings. The Cox proportional hazards ratio (HR) was used to select independent prognostic covariates. RESULTS: Thirty-six (65.5%) patients had treatment that was modified due to PET. Primary radiation (HR = 14.62; 95% confidence interval [CI] = 2.74-77.92), squamous cell carcinoma antigen (SCC-Ag) > or = 4 ng/mL (HR = 5.82; 95% CI = 1.53-22.04), and presence of symptoms (HR = 6.24; 95% CI = 1.99-19.61) at recurrence were significant factors associated with poor survival. A scoring system using these covariates defined 3 distinct prognostic groups: score < or = 1 (HR = 1.00); score = 2 (HR = 6.91; 95% CI = 1.49-32.14); and score = 3 (HR = 60.46; 95% CI = 9.68-378.09) (P < 0.0001). CONCLUSION: Using this risk score, 18F-FDG PET may offer maximal benefits by selecting appropriate recurrent cervical cancer patients for salvage therapy with precise restaging information.

Positron emission tomography for unexplained elevation of serum squamous cell carcinoma antigen levels during follow-up for patients with cervical malignancies: a phase II study.

BACKGROUND: During follow-up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC-Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting. METHODS: Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC-Ag levels > or = 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence. RESULTS: Twenty-seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET-positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow-up. Overall, PET detected FDG-avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC-Ag levels as a first sign of recurrence. CONCLUSIONS: PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC-Ag levels. Such expedited detection may have positive effects on patient survival.

18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression.

UNLABELLED: This prospective study investigates the relationship between glucose transporter-1 (Glut-1) expression and PET images using (18)F-FDG and its uptake and compares them with the tumor status (primary vs. recurrent or persistent), initial grade of histologic differentiation, and International Federation of Gynecologic Obstetrics (FIGO) staging for cervical cancer patients. METHODS: A dual-phase (18)F-FDG PET scan was performed on 51 participants within the 2 wk before surgery or biopsy. (18)F-FDG uptake was quantified by calculating standardized uptake values (SUVs). After (18)F-FDG PET scanning, 51 histologically proven squamous cell carcinoma specimens were examined to determine their degree of differentiation, using hematoxylin and eosin staining, and the expression of Glut-1 by an immunohistochemical stain. Twenty normal cervical and 20 cervical intraepithelial neoplasia (CIN) sets of tissue were also used to compare the results of Glut-1 expression in these tissues. The expression of Glut-1 was the product of (the intensity [with grades 0-3, defined qualitatively]) with (percentages of the lesion area that were positive). The results of Glut-1 expression were analyzed in combination with the SUVs (SUV1 was that at 40 min and SUV2 was that at 3 h), tumor status, initial cell differentiation, and FIGO staging. RESULTS: Significant overexpression of Glut-1 was noted in 48 of the 51 (94.1%) cancer specimens. None or only minimal expression of Glut-1 was observed in basal layers of normal and CIN tissues. Significant positive correlation was observed between Glut-1 expression and the SUVs in cervical cancer specimens (r = 0.74, P < 0.000 for SUV1 and r = 0.65, P < 0.000 for SUV2). In recurrent or persistent tumor, tumor size was significantly associated with both Glut-1 expression (r = 0.508, P = 0.011) and SUV1 (r = 0. 456, P = 0.025). For recurrent or persistent tumor, only SUV1 reached statistical significance when compared with lymph node metastasis (P = 0.0226). CONCLUSION: Glut-1 expression was related to (18)F-FDG uptake in cervical cancer patients. Recurrent or persistent cervical cancer tumor had significantly higher Glut-1 expression than metastatic lymph nodes. The values of SUV and the expression of Glut-1 did not correlate with the initial grade of histologic differentiation and FIGO staging.

Delayed (18)F-FDG PET for detection of paraaortic lymph node metastases in cervical cancer patients.

UNLABELLED: This prospective study investigated the usefulness of dual-phase (18)F-FDG PET scans (40 min and 3 h) in detecting paraaortic lymph node (PALN) metastasis for cervical cancer. METHODS: One hundred four consecutive cervical cancer patients (International Federation of Gynecology and Obstetrics staging Ib-IVb, recurrent or persistent tumors) were included. All patients received a whole-body (18)F-FDG PET scan at 40 min and an additional scan from the T11 level to the inguinal region at 3 h after injection of 370 MBq (18)F-FDG. The maximum standardized uptake value (SUV) and retention index (RI [%], obtained by subtracting the normalized SUV value obtained at 40 min from that at 3 h) of the lesions were determined. RESULTS: In all, 38 of the 104 patients were confirmed to have PALN metastases. For 31 patients (81.6%) with 13 upper (L1-L2 level) and 30 lower (L3-L4 level) PALNs, these metastases were detected with the 40-min scan. In addition, for 7 patients (18.4%) with 7 lower PALNs, metastases were found with the 3-h scan (RI = 12.6%). Two patients (3.0%) had 2 false-positive lesions initially (40 min) but were classified as benign with the 3-h scan. The sensitivity, specificity, and accuracy of (18)F-FDG PET scans at 40 min were 81.6%, 97.0%, and 91.3%, respectively. These quantities were all 100% when both the 40-min and 3-h scans were taken together. Eight patients (21.1%) had their treatment planning changed. We divided the 38 patients into 2 subgroups. Subgroup A included those with either only upper or only lower PALN metastases, and subgroup B included those with both upper and lower PALN metastases. In subgroup A, the SUV values were greater in the upper than in the lower PALNs in both the 40-min and 3-h images (P = 0.077). In subgroup B, there was no significant difference of SUV values between upper and lower PALNs in the 40-min (P = 0.433) and 3-h (P = 0.937) images. CONCLUSION: Our results showed that an additional 3-h scan is helpful for PALN detection of cervical cancer patients. A delayed image (3 h) is especially useful for lower PALN metastases.

Value of dual-phase 2-fluoro-2-deoxy-d-glucose positron emission tomography in cervical cancer.

PURPOSE: The role of positron emission tomography (PET) with fluorine-18-labeled fluoro-2-deoxy-d-glucose (FDG) in cervical cancer has not yet been well defined. We conducted a prospective study to investigate its efficacy in comparison with magnetic resonance imaging and/or computed tomography (MRI-CT). MATERIALS AND METHODS: Patients with untreated locally advanced (35%) or recurrent (65%) cervical cancer were enrolled onto this study. In the first part of this study, 41 patients had a conventional FDG-PET (40 minutes after injection), and in the second part, 94 patients received dual-phase PET (at both 40 minutes and 3 hours after injection). The overall results of PET scans were compared with MRI-CT, and the two protocols of PET were also compared with each other. Lesion status was determined by pathology results or clinical follow-up. The receiver operating characteristic curve method with area under the curve (AUC) calculation was used to evaluate the discriminative power. RESULTS: Overall (N = 135), FDG-PET was significantly superior to MRI-CT in identifying metastatic lesions (AUC, 0.971 v 0.879; P =.039), although the diagnostic accuracy was similar for local tumors. Dual-phase PET was also significantly better than the 40-minute PET (n = 94). The latter accurately recognized 70% of metastatic lesions and the former detected 90% (AUC, 0.943 v 0.951; P =.007). Dual-phase FDG-PET changed treatment of 29 patients (31%; upstaging 27% and downstaging 4%). CONCLUSION: This study shows that dual-phase FDG-PET is superior to conventional FDG-PET or MRI-CT in the evaluation of metastatic lesions in locally advanced or recurrent cervical cancer.