Anqin Han

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.

Using 18F-Fluorodeoxyglucose Positron Emission Tomography to Estimate the Length of Gross Tumor in Patients With Squamous Cell Carcinoma of the Esophagus

PURPOSE To determine the optimal method of using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) to estimate gross tumor length in esophageal carcinoma. METHODS AND MATERIALS Thirty-six patients with esophageal squamous cell carcinoma treated with radical surgery were enrolled. Gross tumor volumes (GTVs) were delineated using three different methods: visual interpretation, standardized uptake value (SUV) 2.5, and 40% of maximum standard uptake value (SUV(max)) on FDG-PET imaging. The length of tumors on PET scan were measured and recorded as Length(vis), Length(2.5), and Length(40), respectively, and compared with the length of gross tumor in the resected specimen (Length(gross)). All PET data were reviewed again postoperatively, and the GTV was delineated using various percentages of SUV(max). The optimal-threshold SUV was generated when the length of PET matched the Length(gross). RESULTS The mean (+/-SD) Length(gross) was 5.48 +/- 1.98 cm. The mean Length(vis), Length(2.5), and Length(40) were 5.18 +/- 1.93 cm, 5.49 +/- 1.79 cm, and 4.34 +/- 1.54 cm, respectively. The mean Length(vis) (p = 0.123) and Length(2.5) (p = 0.957) were not significantly different from Length(gross), and Length(2.5) seems more approximate to Length(gross.) The mean Length(40) was significantly shorter than Length(gross) (p < 0.001). The mean optimal threshold was 23.81% +/- 11.29% for all tumors, and it was 19.78% +/- 8.59%, 30.92% +/- 12.28% for tumors >/=5 cm, and <5 cm, respectively (p = 0.009). The correlation coefficients of the optimal threshold were -0.802 and -0.561 with SUV(max) and Length(gross), respectively. CONCLUSIONS The optimal PET method to estimate the length of gross tumor varies with tumor length and SUV(max); an SUV cutoff of 2.5 provided the closest estimation in this study.

Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small-cell lung cancer

PurposeTo compare the diagnostic efficacies of 18F-FLT and 18F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index.MethodsA total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry.ResultsThe sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively (p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG (p<0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index (r=0.644; p<0.01), but the SUV of FDG was not significantly correlated (r=0.293; p>0.05).ConclusionIn terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs.

Value of dual-time-point FDG PET/CT for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity.

Purpose: To evaluate the efficacy of dual-time-point F-18 fluorodeoxyglucose positron emission tomography (FDG PET)/ computed tomography (CT) for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity. Materials and Methods: Fifty-three pathologically proven non-small-cell lung cancer patients with pulmonary comorbidity and 49 patients as controlled group without comorbidity were enrolled. PET/CT was performed at 1-hour (whole body) post-FDG injection and repeated 2 hours (thoracic) after injection. All patients received radical surgery with system mediastinal lymph node (LN) dissection. The results of LN detection by single-time-point and dual-time-point scan were compared with the histopathologic findings. Results: On a per-patient basis, in patients with pulmonary comorbidity, the sensitivity, specificity, accuracy, and positive predictive values (PPV), and negative predictive values of single-time-point scan were 87.5%, 59.5%, 67.9%, 48.3%, and 91.7%, respectively. Those values of dual-time-point scan were 93.8%, 67.6%, 75.5%, 55.6%, and 96.2%, respectively. In patients without comorbidity, dual-time-point scan was similar in those values to single-time-point. On a per-nodal station basis, the specificity, accuracy, and PPV of dual-time-point scan were better than those of single-time-point with statistically significant differences (P = 0.017, 0.002, and 0.027, respectively) in patients with pulmonary comorbidity, but the difference was not statistically significant in patients with no pulmonary comorbidity. Conclusions: Dual-time-point FDG PET/CT is more effective for mediastinal nodal staging than single-time-point in patients with pulmonary comorbidity. Dual-time-point scan was useful for diagnosis of mediastinal LN metastases in reducing the false-positive results in all patients, but improved specificity, accuracy, and PPV only in patients with pulmonary comorbidity.

The prognostic value of 18F-fluorodeoxyglucose uptake by using serial positron emission tomography and computed tomography in patients with stage III nonsmall cell lung cancer.

Objectives:To determine the prognostic value of standardized uptake value (SUV) of 18F-fluorodeoxyglucose by serial positron emission tomography and computed tomography (PET/CT) in nonsmall cell lung cancer (NSCLC). Methods:Forty-seven patients (37 male, 10 female) with NSCLC in stage III were enrolled. All patients had at least 2 serial 18F-fluorodeoxyglucose PET/CT scans, both before and after therapy, and the maximum standardized uptake value (SUVmax) of the primary lung lesion was calculated. The value changes of SUVmax before and after treatment were calculated according to the following equation: &Dgr;SUV = (SUVbefore − SUVafter) × 100%/SUVbefore. Results:Of the 47 eligible patients, after a median follow-up of 23.5 months (range, 13–34 months), 26 patients had local and regional recurrence or metastasis and 21 remained disease-free. Significant differences in SUVmax were observed either before (P1 = 0.003) or after (P2 = 0.002) treatment between the 2 groups. However, the percent change of SUVmax before and after therapy were not significantly different (P = 0.054). Conclusions:SUV from 2 serial PET/CT scans, before and after concurrent chemoradiotherapy were significant predictors for local and regional recurrence or metastasis. SUV is a significant predictor for local and regional recurrence or metastasis in patients of NSCLC.

BTG2 Overexpression Increases the Radiosensitivity of Breast Cancer Cells In Vitro and In Vivo

Antiproliferative gene B-cell translocation gene, member 2 (BTG2) is a member of the BTG/TOB antiproliferative gene family. In this study, we investigated the effect of BTG2 gene overexpression on the radiosensitivity of breast cancer cells in vitro and in vivo. Results show that in human breast cancer cell line MCF-7 stably overexpressing BTG2 gene, cell sensitivity to ionizing radiation increased. The MCF-7-BTG2 cells were more susceptible to radiation-caused apoptosis with decreased cyclin B1, cyclin D1, Ku70, FEN-1, and XRCC1 protein expression as well as increased BAX protein expression. The findings indicate for the first time that BTG2 can improve the radiosensitivity of breast cancer cells by affecting cell cycle distribution, enhancing radiation-induced apoptosis, and inhibiting DNA repair-related protein expression.

Prediction of the outcome of definitive chemoradiation by decrease in F-18 FDG uptake in nonsurgical esophageal squamous cell cancer.

Purpose: To analyze the predictive value of fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake using positron emission tomography and computed tomography to assess the outcome of definitive chemoradiation in nonsurgical esophageal squamous cell carcinoma. Materials and Methods: A retrospective review of 61 patients with clinical stage T1–4, N0/1, and M0 was performed. Chemoradiation included chemotherapy with fluorouracil plus cisplatin and irradiation with a total dose of 5600 to 6400 centigray (cGy). Positron emission tomography combined with computed tomography scans were acquired before and during the therapy. The correlation between a decrease in FDG uptake and 5-year progression-free survival (PFS) was analyzed by a receiver operating characteristic curve method to determine a cutoff value. A 5-year overall survival (OS), PFS, and cancer-specific survival (CSS) were evaluated by Kaplan-Meier method. Results: The mean of standardized uptake value decreased significantly during chemoradiation (P = 0.001). Using 51% reduction of FDG uptake as a cutoff value provided a sensitivity of 76.9% and a specificity of 79.2% in predicting PFS (P = 0.000). The positive predictive value and negative predictive value were 50% and 95%, respectively. PFS, CSS, and OS were significantly different when grouped by this cutoff value (P < 0.05), and when dichotomized by stage T1–2 and T3–4 (P < 0.05), simultaneously with a decrease of 51% or more in FDG uptake. Conclusions: This study showed that a 51% decrease in FDG uptake during chemoradiation was a sensitive and accurate cut-point for predicting PFS. Stage T and decrease in FDG uptake were 2 independent predictive factors for 5-year PFS, CSS, and OS.

Prognostic Value of Metabolic Parameters of Metastatic Lymph Nodes on 18F-FDG PET/CT in Patients With Limited-stage Small-cell Lung Cancer With Lymph Node Involvement

Introduction We assessed the prognostic value of the metabolic parameters of different lesions, including primary tumors and metastatic lymph nodes (LNs), measured by fluorine‐18 fluorodeoxyglucose positron emission tomography (PET)/computed tomography in patients with limited‐stage small‐cell lung cancer (LS‐SCLC) with LN metastasis. Materials and Methods The present retrospective study included 46 patients with clinical stage II‐III N1‐N2 LS‐SCLC who had undergone pretreatment fluorine‐18 fluorodeoxyglucose PET/computed tomography scanning from January 2011 to December 2014. All patients underwent complete first‐line therapy (concurrent chemoradiotherapy and prophylactic cranial irradiation). The metabolic parameters, including maximal standardized uptake value, mean standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values of the PTs and metastatic LNs were measured on PET. Kaplan‐Meier survival curves were used for evaluation of progression‐free survival (PFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors. Results The median OS and PFS were 25.9 months (range, 8.2‐63.5 months) and 21 months (range, 6.4‐55.3 months), respectively. Univariate analysis demonstrated that the Eastern Cooperative Oncology Group performance status, N1 station involvement, subcarinal LN metastasis, LN MTV, LN TLG, sum of the MTV, and summary of the TLG were significant predictive factors (P < .05). The Eastern Cooperative Oncology Group performance status, subcarinal nodal metastasis, LN MTV, and LN TLG were independent predictive factors of PFS and OS on multivariate analysis. Conclusion The metabolic parameters of metastatic LNs, other than lung lesions, are independent prognostic factors in patients with LS‐SCLC with LN metastasis. These parameters could further stratify the prognosis of these patients, and these findings might provide functional imaging evidence for the future study of the mechanisms of metastasis. Micro‐Abstract Increasing evidence has suggested that positron emission tomography/computed tomography‐related parameters have prognostic implications for patients with small‐cell lung cancer (SCLC). However, the results seem to be inconsistent for limited‐stage (LS)‐SCLC, and those studies did not explore the prognostic role of metastatic lymph nodes (LNs). We assessed the prognostic value of metabolic parameters of different lesions, including primary tumors and metastatic LNs in patients with LS‐SCLC with LN metastasis. Our results suggest that the volume metabolic parameters of metastatic LNs, other than lung lesions, are promising imaging biomarkers in patients with LS‐SCLC with LN metastasis. These parameters could further stratify the prognosis of these patients, and these findings might provide functional imaging evidence for the future study of the mechanisms of metastasis.