Jinbo Yue

Measuring Tumor Cell Proliferation with 18F-FLT PET During Radiotherapy of Esophageal Squamous Cell Carcinoma: A Pilot Clinical Study

The primary aim of this study was to use serial 18F-3′-deoxy-3′-fluorothymidine (FLT) PET/CT to measure tumor cell proliferation during radiotherapy of squamous cell carcinoma (SCC) of the esophagus. Methods: Twenty-one patients with inoperable locally advanced SCC of the esophagus underwent serial 18F-FLT PET/CT during radiotherapy. Each patient received a pretreatment scan, followed by 1–3 scans after delivery of 2, 6, 10, 20, 30, 40, 50, or 60 Gy to the tumor. Results: Among the 19 patients who completed radiotherapy without interruption, parameters reflecting 18F-FLT uptake in the tumor (i.e., maximum tumor standardized uptake value [SUVmax] and proliferation target volume) decreased steadily. All patients demonstrated an almost complete absence of proliferating esophageal tumor after 30 Gy and a complete absence after 40 Gy. In the 2 patients whose radiotherapy course was interrupted, 18F-FLT uptake in the tumor was greater after the interruption than before the interruption. Marked early reduction of 18F-FLT uptake in irradiated bone marrow was observed in all patients, even after only 2 Gy. All showed a complete absence of proliferating marrow in irradiated regions after 10 Gy. Both patients who underwent scans after completing the entire radiotherapy course showed no tumor uptake on 18F-FLT PET/CT but high uptake on 18F-FDG PET/CT. Pathologic examination of these regions revealed inflammatory infiltrates but no residual tumor. Conclusion: 18F-FLT uptake can be used to monitor the biologic response of esophageal SCC and normal tissue to radiotherapy. Increased uptake of 18F-FLT after treatment interruptions may reflect accelerated repopulation. 18F-FLT PET/CT may have an advantage over 18F-FDG PET/CT in differentiating inflammation from tumor.

Mediastinal lymph nodes staging by 18F-FDG PET/CT for early stage non-small cell lung cancer: A multicenter study

PURPOSE Accurate staging of mediastinal lymph nodes metastases is critical for determining the application of stereotactic body radiation therapy (SBRT) for patients with early stage non-small cell lung cancer (NSCLC). In this multicenter study the accuracy of (18)F-FDG PET/CT to detect lymph node metastases was evaluated for early stage NSCLC. MATERIALS AND METHODS The data from the patients with stage1 NSCLC who received preoperative (18)F-FDG PET/CT staging and radical surgery was retrospectively reviewed of five centers from February 2004 to August 2010. The lymph node metastases were confirmed histopathologically after radical surgery. And the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for PET/CT staging. RESULTS Two hundred patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for lymph node metastases on PET/CT were 44%, 83%, 78%, 29% and 91%, respectively. There were eight and 19 cases positive for lymph node metastases with central (n=62) and peripheral (n=138) NSCLC (P>0.05), respectively. CONCLUSION (18)F-FDG PET/CT was specific in N(0) staging for T(1-2) NSCLC. The NPV was about 91% in clinical N(0) patients, suggested that (18)F-FDG PET/CT may help to accurately stage N(0) patients and thus identify patients for SBRT.

Prognostic value of serial [18F]fluorodeoxyglucose PET-CT uptake in stage III patients with non-small cell lung cancer treated by concurrent chemoradiotherapy.

OBJECTIVE To evaluate (18)FDG PET-CT for the assessment of therapy response and prediction of patient outcome after concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC). METHODS Forty-six patients with pathologically proven stage III NSCLC had 2 serial FDG PET-CT scans, before and during CCRT. The maximum standardized uptake value (SUV(max)) of the primary lung lesion was calculated. The value changes of SUV(max) before and during treatment were calculated according to the following equation: SUV=(SUV(before)-SUV(during))100%/SUV(before). The relationship between changes of the SUV(max) and the therapy response as well as long-term survival was studied in the responsive and non-responsive groups after CCRT. RESULTS Of the 46 enrolled patients, after a medicine follow-up of 2 years, the initial SUV(max) in the responsive and non-responsive groups was 7.59±3.14 and 14.72±4.67, respectively. The SUV(max) during treatment in the two groups was 2.89±1.39 and 9.82±3.31, respectively. Significant difference (P=0.001; P=0.001) in SUV(max) was observed either before or during treatment. Furthermore, the percent change of SUV(max) before and during treatment was 61.91±86.69 and 33.56±90.37, respectively. There was significant difference between these two groups (P=0.007). In addition, the 1-year survival rate in the responsive and non-responsive group was 73% and 69%, respectively. The 2-year survival rate in the two groups was 40% and 37%, respectively. There was significant difference between these two groups (P=0.001). CONCLUSIONS (18)FDG PET-CT is an effective method in the prediction of therapy response in patients with stage III NSCLC. The analysis of percent change of SUV(max) provides additional value in early prediction of therapy response and patient outcome.

Early detection of radiation-induced heart disease using 99mTc-MIBI SPECT gated myocardial perfusion imaging in patients with oesophageal cancer during radiotherapy

BACKGROUND AND PURPOSE The primary aim of this prospective study was to investigate the value of (99m)Tc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) in the detection of radiation-induced heart disease (RIHD) as early as during radiotherapy (RT) for oesophageal cancer (EC). The second aim was to analyse the correlation between cardiac toxicity and the dose-volume factors. MATERIALS AND METHODS The (99m)Tc-MIBI SPECT GMPI was performed both pre-RT and during RT (40Gray). The results of the SPECT were quantitatively analysed with QGS/QPS software and read by two experienced nuclear medicine physicians. The correlation between the changes in the SPECT parameters and the RT dosimetric data was analysed. RESULTS Eighteen patients with locally advanced EC were enrolled in the study. Compared with the baseline, the imaging during RT showed not only significant decreases in the wall motion (WM) (1/20 segments), wall thickening (WT) (2/20 segments), end-diastolic perfusion (EDP) (5/20 segments) and end-systolic perfusion (ESP) (8/20 segments) (p<0.05) but also a significant increase in the heart rate (74.63±7.79 vs 81.49±9.90, p=0.036). New myocardial perfusion defects were observed in 8 of the 18 patients. The V37-V40 was significantly higher (p<0.05) in the patients with the new perfusion defects during RT than in the patients who did not exhibit these defects. CONCLUSIONS Radiotherapy for EC induces cardiac damage from an early stage. (99m)Tc-MIBI SPECT GMPI can detect the occurrence of cardiac impairment during RT. The WM, WT, EDP and ESP may be valuable as early indicators of RIHD. The percentage of the heart volume that receives a high dose is an important factor that is correlated with RIHD.

Histopathologic validation of 3′-deoxy-3′-18F-fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice18F-FLT PET repopulation -->

BACKGROUND AND PURPOSE FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing (18)F-FLT PET. MATERIAL AND METHODS Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm]=3.0 Gy), either daily or every second day. (18)F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. RESULTS Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P<0.05) and 18 fractions in 18 days (P<0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P>0.05) and 18 fractions in 36 days (P>0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P<0.05), and increases with every-second-day irradiation (P>0.05). (18)F-FLT parameters correlated strongly with proliferation markers (r(2): 0.679-0.879, P<0.001). CONCLUSIONS (18)F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for (18)F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.

Clinical value of 18F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma

OBJECTIVE To evaluate the clinical value of (18)F-FDG PET/CT in postoperative monitoring for patients with colorectal carcinoma. METHODS 66 postoperative patients with colorectal carcinoma underwent whole-body FDG PET/CT. The final histopathological and formal clinical follow-up findings were used as gold standard to determine the sensitivity and specificity of FDG PET/CT and enhanced CT of the same periods. RESULTS The sensitivity and specificity of FDG PET/CT in detecting recurrence are 96.30%, 94.87% (while enhanced CT are 70.37% and 87.18% respectively). The sensitivity and specificity in detecting metastasis are 95.35%, 82.61% (enhanced CT are 61.90%, 75.00%). SUVmax was significantly higher in malignant lesions [range 4.16-22.00, mean±standard deviation (x±s) 8.06±4.30] than in benign ones (range 1.18-6.25, x±s 2.82±1.02). CONCLUSION At present, whole-body (18)F-FDG PET/CT is an advanced diagnostic imaging technique in detecting loco-regional recurrence and metastasis in postoperative patients with colorectal carcinoma for its higher sensitivity and specificity.

Effect of celecoxib on inhibiting tumor repopulation during radiotherapy in human FaDu squamous cell carcinoma

Aim of the study FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrated accelerated tumor repopulation during fractionated irradiation with pathological validation in a xenograft model system. Previous studies showed that the selective cyclooxygenase (COX)-2 inhibitor celecoxib can enhance the tumor response to radiotherapy. So we aimed to explore the effect of celecoxib in inducing apoptosis and inhibiting repopulation of FaDu tumors in nude mice during fractionated radiotherapy. Material and methods FaDu-hSCC was transplanted into the right hind leg of BALB/C nude mice. Mice were treated with celecoxib and/or fractionated irradiation. Celecoxib (100 mg/kg/day) was administered by daily gavage. Irradiation was delivered with 12 to 18 fractions of 3.0 Gy daily or every second day based on Petersens repopulation model. At different time points, tumors were excised for immunohistochemistry staining. Results Significant tumor repopulation occurred after about 18 days of radiotherapy. On average, Ki-67 and bromodeoxyuridine (BrdUrd) labeling indices (LI) decreased with daily irradiation (both p < 0.05) and increased with every-second-day irradiation (both p > 0.05), suggesting accelerated repopulation. Ki-67 LI decreased in celecoxib concurrent with radiotherapy for 12 fractions in 24 days and 18 fractions in 36 days compared with irradiated alone (p = 0.004 and 0.042, respectively). BrdUrd LI values were lower in the concurrent groups than irradiated alone (p = 0.001 and 0.006, respectively). Epithelial growth factor receptor (EGFR) expression score decreased in the concurrent groups than irradiated alone (p = 0.037 and 0.031, respectively). Caspase-3 expression scores were higher in the concurrent groups than irradiated alone (p = 0.05 and 0.006, respectively). Conclusions Celecoxib concurrent radiotherapy could inhibit tumor repopulation and increase tumor apoptosis during the treatment in FaDu squamous cell carcinoma.

Risk of brain metastasis reduced after erlotinib treatment in advanced pulmonary adenocarcinoma patients with sensitive EGFR mutation

Purpose Brain metastasis (BM) is associated with impaired quality of life and increased mortality. The study aimed to compare BM risk after erlotinib administration and chemotherapy in stage IIIB/IV pulmonary adenocarcinoma patients harboring epidermal growth factor receptor (EGFR) mutation. Patients and methods Eligible patients underwent match pair process with matching factors, including age, sex, performance status score, first-line or second-line treatment, first-line chemotherapy regimen (for the second-line treatment subgroup), stage IIIB or IV, and genotypes of EGFR mutation. BM and mortality risk of both groups were recorded and compared. Results In total 129 matched pairs were included for analysis. During a median follow-up of 21.5 months, time to BM risk was longer and incidences of BM within 2 years were lower in patients who received erlotinib than chemotherapy in total population, as well as subgroups of first-line treatment, second-line treatment, stage IIIB, stage IV, exon 19 deletion mutation, and exon 21 L858R mutation. Similar overall survival time and 2-year survival rates were seen in two groups totally or in any subgroup. Multivariate analysis showed that BM was retarded in patients who received erlotinib administration (hazard ratio, 1.695; P=0.001) and in patients who were in stage IIIB (hazard ratio, 1.751; P=0.001). Conclusion Erlotinib administration decreases BM risk in advanced pulmonary adenocarcinoma patients harboring sensitive EGFR mutations.