Jiro Ishida

Clinicopathological and Prognostic Relevance of Uptake Level using 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Fusion Imaging (18F-FDG PET/CT) in Primary Breast Cancer

OBJECTIVE Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer. METHODS Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC). RESULTS High SUV level was significantly correlated with tumor invasive size (< or = 2 cm) (P < 0.0001), higher score of nuclear grade (P < 0.0001), nuclear atypia (P < 0.0001) and mitosis counts (P < 0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P < 0.0001,< 0.0001, and < 0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P < 0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P < 0.0001). CONCLUSIONS High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pre-therapeutically predict biological characteristics and baseline risk of breast cancer.

Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer

BackgroundAccurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC).MethodsOne hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging.ResultsIn a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03).ConclusionThe diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis.

Early Reduction in Standardized Uptake Value After One Cycle of Neoadjuvant Chemotherapy Measured by Sequential FDG PET/CT is an Independent Predictor of Pathological Response of Primary Breast Cancer

To the Editor: F-fluorodeoxyglucose (FDG) levels on positron emission tomography (PET) reflect glucose metabolism in cancer cells (1). Currently, FDG PET combined with computed tomography (FDG PET ⁄ CT) has become employed as a non-invasive method for imaging glucose metabolism in tumors (2,3). The aim of the present study was to evaluate whether early metabolic changes after one cycle of neoadjuvant chemotherapy in FDG uptake evaluated by maximal standardized uptake value (SUVmax) could predict a pathological response of primary breast cancers. Thirty-two tumors in 30 patients having primary invasive breast cancer were investigated. All patients had received a standard neoadjuvant chemotherapy regimen comprising four cycles of epirubicine (90 mg ⁄ m) and cyclophosphamide (600 mg ⁄ m) on a triweekly basis and sequential use of 12 cycles of weekly paclitaxel (80 mg ⁄ m) (25 patients) or four cycles of triweekly docetaxel (60 mg ⁄ m) (five patients). The procedure of FDG PET ⁄ CT has been described (4). Sequential FDG PET ⁄ CT (Biograph LSO Emotion; 3D model, Siemens, Germany) was performed at the baseline (baseline PET ⁄ CT), after one cycle of chemotherapy (PET ⁄ CT2), after four cycles of chemotherapy (PET ⁄ CT3), and prior to surgery (PET ⁄ CT4). Tumors showing a 40% reduction or more in SUVmax on PET ⁄ CT2, when compared with the baseline PET ⁄ CT, were defined as metabolic responders and those showing a change of less than 40% in SUVmax were considered to be metabolic nonresponders (Fig. 1). Baseline characteristics of patients and tumors, determined by conventional modalities, are shown in Table 1. Baseline SUVmax was significantly higher in metabolic responders [10.2 ± 6.4 SD] than nonresponders (6.7 ± 3.1 SD) (p = 0.05). The percentage of tumors with nuclear grade 3 was significantly higher among the metabolic responders (71%) than among the nonresponders (16%) (p = 0.03). There were no significant differences between metabolic responders and nonresponders with regard to patient age, T-stage, nodal status, hormone receptor status, or HER2 status. The average degree of decrease in SUVmax at PET ⁄ CT2 in comparison with the baseline SUVmax was 57.9% (±11.7 SD) in metabolic responders and 10.3% (±15.7 SD) in metabolic nonresponders (p < 0.0001). Clinical response after completion of chemotherapy was measured using ultrasound or CT combined with FDG PET, and evaluated based on RECIST. On the basis of clinical response, five (71%) and two (29%) of the seven tumors with a metabolic response exhibited partial response (PR) and complete response (CR), respectively, while 18 (72%) of the 25 nonresponding tumors had PR. No nonresponding tumors showed CR. Metabolic responders showed a significantly excellent clinical response rate (100%) in terms of PR or CR in comparison with that (72%) for non-responding tumors (p = 0.001) (Table 2a). Histological criteria for assessment of therapeutic response were based on General Rules for Clinical and Pathological Recording of Breast Cancer 2008 (5). Among a total of 32 tumors, six (19%) and two (6%) were found to have grade 3, or pathological complete response (pCR), and to have grade 2b, or near pCR, where only a few residual invasive cancer cells were seen, respectively. Among the seven tumors with a metabolic response, three (43%) and two (29%) showed pCR and near pCR, respectively. Among the 25 tumors without metabolic response, Address corresopondence and reprint requests to: Hitoshi Tsuda, MD, PhD, Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan, or e-mail: hstsuda@ gmail.com.

A new in vivo model to analyze hepatic metastasis of the human colon cancer cell line HCT116 in NOD/Shi-scid/IL-2Rγnull (NOG) mice by 18F-FDG PET/CT

Clinically, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) is useful in the evaluation of various types of human cancers. While PET analysis has been established to evaluate subcutaneous lesions of human cancers in mice, its applications for internal lesions are still being developed. We are currently evaluating new PET approaches for the effective evaluation of in vivo metastatic lesions in the internal organs of small experimental animals. In this study, we analyzed in vivo hepatic metastases of human colonic cancer in immunodeficient mice (NOD/Shi-scid/IL-2Rγ(null), NOG) using PET imaging. This new PET approach has been proposed for the evaluation of in vivo metastatic lesions in internal organs. The human colon cancer line HCT116 (1.0x10(5) and 1.0x10(6) cells/mouse) was transplanted by intrasplenic injection. (18)F-FDG-PET/CT scans were performed 2 weeks after transplantation. After PET/CT scans, histopathological examinations were performed. PET/CT analysis disclosed multiple metastatic foci and increased standardized uptake values (SUV) of FDG in the livers of NOG mice (control, SUVmean 0.450±0.033, SUVmax 0.635±0.017; 1.0x10(5) cells, 0.853±0.087, 1.254±0.237; 1.0x10(6) cells, 1.211±0.108, 1.701±0.158). There were significant differences in FDG uptakes between the three groups (ANOVA, P=0.017 in SUVmean; P=0.044 in SUVmax, n=2). We clearly and quantitatively detected images of hepatic metastasis in the livers of NOG mice by (18)F-FDG-PET/CT in vivo. PET/CT analysis of internal organ lesions of human cancerous xenografts is a new reliable experimental system to simulate metastases. This model system is useful for analyzing metastatic mechanisms and for developing new novel drugs targeting hepatic metastases of cancer.

Lung Cancer: Computer-aided Diagnosis with Computed Tomography

Publisher Summary This chapter presents the computer-aided diagnosis (CAD) system to detect pulmonary nodules used for lung cancer screening with low-dose helical computed tomography (LDHCT) scanning and discusses the usefulness and pitfalls of the CAD system in mass screening for lung cancer. Lung cancer screening with LDHCT scan was performed on 518 participants (376 men, 142 women; age range 20-85 years, mean age 57.9 years). All 518 procedures were baseline screenings, and no repeat screenings were made. A helical CT scanner was used for this study. The scanning parameters were 120 kilovolt peaks, 50 mA, 10 mm collimation, and 2.0 pitches. Computer-aided diagnosis software includes a detection algorithm for pulmonary nodules and a user interface. The detection algorithm includes a complex segmentation of lung parenchyma, followed by the detection of structures with soft tissue density within the lung parenchyma and a region analysis to evaluate the detected structures in the three-dimensional (3D) data set. All images were obtained at window settings appropriate for lung parenchyma. As for the CADs performance, the time required to obtain images and diagnose them was ∼7 min. The CAD could not simultaneously provide images from a CT scan when it was running another thoracic examination. Three respiratory physicians separately interpreted all cases according to the General Rule for the Clinical and Pathological Record of Lung Cancer (GRCPRLC) edited by the Japan Lung Cancer Society (JLCS) (2003) (“a,” undetermined, “b,” within normal limit, “c,” old inflammatory lesion, “d,” suspicion of disease other than lung cancer, “e,” suspicion of lung cancer). All three physicians independently judged 46/75 (61.3%) participants as “e,” while one or two physicians judged 29 other participants as “e.”