Detection of lung cancer by FDG-PET cancer screening program: a nationwide Japanese survey.

AIM: The aim of this study was to analyze the lung cancer detection rate in asymptomatic individuals by the Fluorine-18 fluorodeoxyglucose-positron emission tomography FDG-PET cancer screening program in Japan. MATERIALS AND METHODS: A total of 153,775 asymptomatic individuals underwent the FDG-PET cancer screening program; the 854 cases with findings that indicated suspected lung cancer by any detection method were analyzed. RESULTS: Among the 854 cases, 319 were verified as lung cancer. The relative sensitivity and positive predictive value (PPV) of FDG-PET were 86.5% and 38.9% for lung cancer, respectively. The sensitivity of PET/computed tomography (CT) scanner was higher than that of dedicated PET (100.0% vs. 63.2%), indicating that CT imaging was effective for lung cancer screening. The majority of lung carcinomas detected by FDG-PET screening were UICC stage IA or IB, but detection of smaller or less invasive carcinomas was limited. CONCLUSION: The FDG-PET screening program in Japan detected lung cancer at an early stage.

The current status of an FDG-PET cancer screening program in Japan, based on a 4-year (2006-2009) nationwide survey.

OBJECTIVE: The aim of this study was to survey the 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening program conducted in Japan. METHODS: The "FDG-PET cancer screening program" included both FDG-PET and positron emission tomography with computed tomography (PET/CT) with or without other combined screening tests that were performed for cancer screening in asymptomatic subjects. A total of 155,456 subjects who underwent the FDG-PET cancer screening program during 2006-2009 were analyzed. RESULTS: Of the 155,456 subjects, positive findings suggesting possible cancer were noted in 16,955 (10.9 %). The number of cases with detected cancer was 1,912 (1.23 % of the total screened cases, annual range 1.14-1.30 %). Of the 1,912 cases of detected cancer, positive findings on FDG-PET were present in 1,491 cases (0.96 % of the total number of screened cases). According to the results of further examinations, the true positive rate for subjects with suggested possible cancer (positive predictive value) was 32.3 % with FDG-PET. Cancers of the colon/rectum, thyroid, lung, and breast were most frequently found (396, 353, 319, and 163 cases, respectively) with high PET sensitivity (85.9, 90.7, 86.8, 84.0 %, respectively). Prostate cancer and gastric cancer (165 and 124 cases, respectively) had low PET sensitivity (37.0 and 37.9 %, respectively). The Union for International Cancer Control (UICC) clinical stage of cancer found with the FDG-PET cancer screening program was mainly Stage I. CONCLUSIONS: The FDG-PET screening program in Japan has detected a variety of cancers at an early stage. However, several cancers were found in repeated FDG-PET cancer screening program, indicating the limitation of a one-time FDG-PET cancer screening program. The value of the FDG-PET cancer screening program is left to the judgment of individuals with regard to its potentials and limitations.

Radiation exposure and risk-benefit analysis in cancer screening using FDG-PET: results of a Japanese nationwide survey.

OBJECTIVE: The aim of this study was to estimate radiation exposure and evaluate the risks and benefits of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in cancer screening. METHODS: A nationwide survey of FDG-PET cancer screening was conducted in 2006, and the results were analyzed with a common index, "extension/shortening of the average life expectancy." RESULTS: The average estimated effective dose was 4.4 mSv (male 4.7 mSv; female 4.0 mSv) for dedicated PET and 13.5 mSv (male 14.2 mSv; female 12.8 mSv) for PET/computed tomography (CT). The risk-benefit break-even age from the viewpoint of radiation exposure was in the 40s for men and 30s for women for dedicated PET and in the 50s for men and 50s (variable injection dose) or 60s (constant injection dose) for women for PET/CT. CONCLUSIONS: FDG-PET cancer screening is beneficial for examinees above the break-even ages. The risks and benefits should be explained to examinees because of the larger radiation used in cancer FDG-PET screening compared with other X-ray tests.

Does adding FDG-PET to MRI improve the differentiation between primary cerebral lymphoma and glioblastoma? Observer performance study.

OBJECTIVE: It is sometimes difficult to distinguish between primary central nervous system lymphomas (PCNSL) and glioblastoma multiforme (GBM). The aim of this study was to investigate whether the addition of (18)F-2-fluoro-2-deoxy-D: -glucose positron emission tomography ([(18)F]FDG-PET) and apparent diffusion coefficients (ADC) to conventional MRI improves diagnostic accuracy for distinguishing between PCNSL and GBM with similar MRI findings. METHODS: We used conventional- and diffusion-weighted MRI and FDG-PET scans of 21 patients with histologically confirmed brain tumors exhibiting similar MRI findings (PCNSL, n = 14, GBM, n = 7) in our observer performance study that consisted of 3 interpretation sessions. ADC and maximum standard uptake values (SUV(max)) of the tumors were calculated. Three radiologists first interpreted conventional MRI (1st session), then they read images to which the ADC value had been added (2nd session), and finally they interpreted images supplemented with SUV(max) (3rd session). Observer performance was evaluated using κ statistic and receiver operating characteristics analyses. RESULTS: The addition of ADC values to conventional MRI failed to improve the differentiation between PCNSL and GBM. The addition of SUV(max) at the third session improved the diagnostic accuracy of all 3 readers and resulted in higher interobserver agreement; mean accuracy was 95% (range 93-100%). In one observer the accuracy of tumor differentiation was significantly improved at the third compared to the second session (p = 0.017). CONCLUSIONS: In a selected group of PCNSL and GBM with similar MRI findings, the addition of quantitative FDG-PET to MRI may improve their differentiation. ADC measurement did not allow further discrimination.

Analysis of various malignant neoplasms detected by FDG-PET cancer screening program: based on a Japanese Nationwide Survey.

OBJECTIVE: The most distinctive feature of FDG-PET cancer screening program is the ability to find various kinds of malignant neoplasms in a single test. The aim of this survey is to clarify the range and frequency of various malignant neoplasms detected by FDG-PET cancer screening performed in Japan. METHODS: "FDG-PET cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. This survey was based on a questionnaire regarding FDG-PET cancer screening. We analyzed the situation of 9 less frequently found malignant neoplasms including malignant lymphoma, malignancy of head and neck, esophagus, hepatobiliary and gallbladder, pancreas, kidney, cervical and uterine, ovary, and bladder. RESULTS: The detailed information of subjects with the suspected 9 kinds of malignant neoplasms mentioned above in the FDG-PET cancer screening program was studied in a total of 1,219 cases from 212 facilities. A statistical significance between PET/CT and PET was found in relative sensitivity and PPV for renal cell cancer. Malignant lymphoma was frequently of indolent type, suspected head and neck cancers had many false-positive results, and pancreatic cancer detected in this program was often in the advanced stage even in asymptomatic subjects. The recommendation of combined screening modality to PET or PET/CT was as follows: gastric endoscopy for assessing early esophageal cancer; abdominal ultrasound for screening hepatobiliary and gallbladder cancer; pelvic magnetic resonance imaging for assessing gynecological and pelvic cancers; and the CA125 blood test for screening ovarian cancer. Delayed image was helpful depending on the type of suspected malignant neoplasm. CONCLUSION: We analyzed various types of malignant neoplasms detected by the FDG-PET cancer screening program and presented recommended combination of examinations to cover FDG-PET and PET/CT.

[Assessment of diagnostic criteria for FDG-PET cancer screening program according to the interpretation of FDG-PET and combined examination].

OBJECTIVE: The aim of this study is to establish the diagnostic criteria for FDG-PET cancer screening program of four kinds of organ (breast, thyroid, lung and colon/rectum) according to the interpretation of FDG-PET cancer screening program of the case with proved clinical outcome. METHODS: Among FDG-PET cancer screening examinations performed in two PET centers during 2003 to 2006, two hundreds of examinations with proved clinical outcome were evaluated. Interpretation of breast ultrasonography, thyroid ultrasonography, chest CT and fecal occult blood testing, which were regarded as combined examinations, were performed together with the interpretation of FDG-PET images. RESULTS: As a result of the interpretation, localized FDG accumulating site in all four organs should be recommended for further inspections. In addition, essential point for diagnosis was considered as follows; (1) check over the slight localized FDG accumulation with screening of breast region, (2) combine chest CT with FDG-PET for the evaluation of lung region and (3) check up the shift of FDG accumulation between early and delayed phase with screening of colon/rectum region. CONCLUSIONS: According to the interpretation results of this study, we establish diagnostic criteria of FDG-PET and combined examination of four kinds of organ.

11C-acetate for positron emission tomography imaging of clinical stage IA lung adenocarcinoma: comparison with 18F-fluorodeoxyglucose for imaging and evaluation of tumor aggressiveness.

BACKGROUND: To determine the usefulness of positron emission tomography (PET) with (11)C-acetate (AC) for imaging lung adenocarcinoma and evaluating its tumor aggressiveness, AC- and (18)F-fluorodeoxyglucose (FDG)-PET were compared. METHODS: One hundred and sixty-nine adenocarcinomas with clinical stage IA and 53 benign nodules were examined by both AC- and FDG-PET before surgery. The sensitivity and specificity for discriminating benign/adenocarcinoma were compared between AC- and FDG-PET. The AC and FDG uptakes were examined to determine the relationship with tumor aggressiveness, i.e., pathological tumor stage, lymphatic, vascular, or pleural involvement, and proliferative activity determined by Ki-67 staining score. RESULTS: While the sensitivity of AC-PET was significantly higher than FDG-PET for bronchioloalveolar carcinoma (BAC) and well-differentiated (W/D) adenocarcinoma (p < 0.001 and 0.006, respectively), there was no significant difference for moderately or poorly differentiated adenocarcinoma. The specificity was not different between them. While FDG uptakes were significantly higher in tumors with pathological advanced stages or those with lymphatic, vascular and/or pleural involvements than in tumors with pathological stage IA or those without these tumor involvements (p = 0.04 to p < 0.001), AC uptake did not show significant differences between the respective sub-groups except according to the tumor stage. While both AC and FDG uptakes showed a significant correlation with Ki-67 staining scores (p = 0.03 and p < 0.001, respectively), the correlation coefficient of former was lower than that of latter (p = 0.07). CONCLUSIONS: While AC-PET can image BAC and W/D adenocarcinoma with a higher sensitivity than FDG-PET, it cannot evaluate tumor aggressiveness of clinical stage IA lung adenocarcinoma as well as FDG-PET.

18F-fluorodeoxyglucose and 11C-acetate positron emission tomography are useful modalities for diagnosing the histologic type of thymoma.

BACKGROUND: The objective of this study was to clarify the usefulness of positron emission tomography (PET) using(18)F-fluorodeoxyglucose (FDG) and carbon 11-labeled acetate (AC) for predicting the histologic types and tumor invasiveness of thymoma in a multicenter study. METHODS: Forty thymomas were examined using both FDG-PET and AC-PET before surgery. The histologic types were type A in 1 thymoma, type AB in 12 thymomas, type B1 in 11 thymomas, type B2 in 7 thymomas, type B3 in 6 thymomas, and type C in 3 thymomas. Tumor invasiveness was assessed by pathologic tumor stage and was identified as stage I in 17 tumors, stage II in 17 tumors, stage III in 4 tumors, and stage IV in 2 tumors. FDG and AC uptake was measured as the maximum standard uptake value (SUV). RESULTS: The FDG-SUV in type C thymomas was significantly higher than that in the other types (A-B3; P = .001 - P = .048). The AC-SUV in type A/AB thymomas was significantly higher than that in the other tumor types (B1-C; P < .001 - P = .002). All 3 type C tumors had an FDG-SUV >or=6.3, and all 13 type A/AB tumors had an FDG-SUV <6.3 and an AC-SUV >or=5.7. All 17 thymomas that had an FDG-SUV <6.3 and an AC-SUV <5.7 were type B1, B2, or B3. Neither the FDG-SUV nor the AC-SUV differed significantly between the stages I/II tumors and stage III/IV tumors. CONCLUSIONS: Although neither the FDG-SUV nor the AC-SUV can predict the invasiveness of thymomas assessed by tumor stage, they are useful for predicting histologic types of thymoma. Thymomas with an FDG-SUV <6.3 and an AC-SUV >or=5.7 almost certainly are types A/AB, which is of considerable prognostic and management significance.

Evaluation of semiquantitative assessments of fluorodeoxyglucose uptake on positron emission tomography scans for the diagnosis of pulmonary malignancies 1 to 3 cm in size.

BACKGROUND: To determine the optimal method of evaluating fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) for the diagnosis of pulmonary malignancies, the sensitivity and specificity of visual assessment and the several semiquantitative analyses were compared. METHODS: Positron emission tomography data were analyzed for 130 pulmonary nodules from 1 to 3 cm in size (101 malignant and 29 benign nodules). The FDG uptake was measured by maximum standard uptake value (SUVmax), the contrast ratio (CR) of the SUV to the cerebellum (CR brain), and the CR of the SUV to the contralateral lung (CR lung). The CR lung was calculated from the SUV of the tumor (T) and that of the contralateral normal lung (N) and then was measured by two formulas, namely, T-N/T+N and T/N. RESULTS: The sensitivities of both CR lung T-N/T+N and CR lung T/N were significantly higher than those of visual assessment, SUVmax, and CR brain (p = 0.01 to p < 0.001). No significant difference in sensitivity was observed between the CR lung T-N/T+N and CR lung T/N. Both CR lung T-N/T+N and CR lung T+N successfully imaged well-differentiated lung adenocarcinoma more frequently than the visual assessment, SUVmax, and CR brain (p = 0.002 to p < 0.001), whereas there were no significant differences of sensitivity among those five methods for the diagnosis of other histologic types of pulmonary malignancies. CONCLUSIONS: The FDG uptake evaluated by the CR lung is superior to that evaluated using the visual assessment, SUVmax, and CR brain for the diagnosis of pulmonary malignancies, especially for well-differentiated lung adenocarcinoma. The simplified formula of CR lung with T/N can be used in place of that with T-N/T+N.

11C-Acetate can be used in place of 18F-fluorodeoxyglucose for positron emission tomography imaging of non-small cell lung cancer with higher sensitivity for well-differentiated adenocarcinoma.

OBJECTIVES: Although positron emission tomography (PET) using F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for slow-growing tumors, C-acetate (AC)-PET has been reported to be able to detect them. To determine the usefulness of AC-PET for imaging non-small cell lung cancers (NSCLCs), the sensitivity and specificity were compared between the AC-PET and FDG-PET with a multicenter study. MATERIALS AND METHODS: A total of 284 pulmonary lesions (227 NSCLCs and 57 benign lesions) were examined using both AC-PET and FDG-PET before surgery at seven Japanese institutes. The AC- or FDG-uptake in each lesion were quantitatively measured using the contrast ratio of the standard uptake value between the lesions and the contralateral lung. RESULTS: The sensitivity of AC-PET for diagnosing NSCLC was 0.71, which was significantly higher than the value of 0.57 obtained by FDG-PET (p < 0.001). No significant difference in the specificity was seen between AC- and FDG-PET. For the 146 well-differentiated adenocarcinomas, the sensitivity of AC-PET was 0.62, which was significantly higher than the value of 0.37 obtained by FDG-PET (p < 0.001). Of the 51 moderately- or poorly-differentiated adenocarcinomas and 30 nonadenocarcinomas, there was no significant difference of sensitivity between AC- and FDG-PET. CONCLUSIONS: AC-PET could be used in place of FDG-PET for imaging NSCLC, with higher sensitivity for well-differentiated adenocarcinoma compared with FDG-PET.

Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey.

OBJECTIVE: The aim of this study is to survey the situation of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile. METHODS: "FDG-PET for cancer screening" was defined as FDG-PET or positron emission tomography and computed tomography (PET/CT) scan with or without other tests performed for cancer screening of healthy subjects. We sent questionnaires regarding FDG-PET cancer screening to 99 facilities in which FDG-PET tests were performed during the fiscal year 2005. Replies were obtained from 68 of the 99 facilities, of which 46 facilities performed FDG-PET cancer screening. The total number of subjects who underwent FDG-PET cancer screening was 50 558. From 38 of 46 facilities, reliable results of thorough examinations were obtained for the subjects who were positive by FDG-PET and/or one or more of the combined screening tests was performed and were referred for further evaluation. The total number of subjects in these 38 facilities amounted to 43 996. RESULTS: A total of 50,558 healthy subjects underwent FDG-PET (including PET/CT) scanning with or without other tests for cancer screening in 46 PET centers during the fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases as a result of positive findings suggesting possible cancer. On analyzing 43 996 cases from 38 PET centers from which detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% were PET positive and 0.24% were PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of the thyroid, colon/rectum, lung, and breast were most frequently found (107, 102, 79, and 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, and 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had a better detection rate, sensitivity, and positive predictive value than dedicated PET (P < 0.01). CONCLUSIONS: We were able to clarify the performance profile of "FDG-PET for cancer screening" on the basis of a Japanese nationwide survey. The number of facilities possessing PET is increasing steadily, highlighting the necessity of evaluating the usefulness of "FDG-PET cancer screening" as soon as possible by undertaking long-term investigations of large series of subjects.

[Performance profile of FDG-PET and PET/CT for cancer screening based on a Japanese nationwide survey].

A total of 50,558 healthy subjects underwent an FDG-PET (including PET/CT) scan with or without combination of other tests for cancer screening in 46 PET centers during fiscal year of 2005 in Japan. Thorough examination was indicated for 9.8% of the cases due to positive findings suggesting possible cancer. On analyzing 43,996 cases from 38 PET centers, where detailed information was obtained, 500 cases of cancers (1.14%) were found, of which 0.90% was PET positive and 0.24% was PET negative, resulting in the relative sensitivity of PET being 79.0%. Cancers of thyroid, colon/rectum, lung and breast were most frequently found (107, 102, 79, 35 cases, respectively) with high PET sensitivity (88%, 90%, 80%, 92%). PET showed an overall positive predictive value of 29.0%. PET/CT had better detection rate, sensitivity, and positive predictive value than dedicated PET (p<0.01).

Emphysema detected by lung cancer screening with low-dose spiral CT: prevalence, and correlation with smoking habits and pulmonary function in Japanese male subjects.

OBJECTIVE: Screening with low-dose spiral CT is a promising new tool for early lung cancer detection. A study was undertaken to assess the prevalence of emphysema detected by CT screening, and to assess the correlation between the extent of emphysema and the severity defined according to the recently published Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. METHODS: After informed consent, CT screening and pulmonary function tests were performed on 615 men between the ages of 40 and 69. Severity of emphysema was assessed visually. Only the pulmonary function data for male subjects were analysed because there were too few female subjects with emphysema. RESULTS: Emphysema was detected in 30.5% of current smokers, 14.1% of former smokers and 3.0% of non-smokers. In male current smokers, airflow obstruction (FEV(1)/FVC < 0.7) was seen in 18.1% of subjects with mild emphysema, and in 33.3% of subjects with moderate emphysema. FEV(1) values were less than 80% of the predicted normal in 8.5% of subjects with mild emphysema, and 28.6% of subjects with moderate emphysema. The percentage of male subjects with emphysema equivalent to GOLD stage 0 was 90.0% for subjects in their 40s, 82.5% for those in their 50s, and 68.2% for those in their 60s. CONCLUSION: A considerable percentage of the subjects with emphysema as detected by CT screening had GOLD stage 0. CT screening assists in detecting early-stage emphysema.