Zicheng Zhang

Value of Metabolic Tumor Volume on Repeated 18F-FDG PET/CT for Early Prediction of Survival in Locally Advanced Non–Small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

The aim of this study was to investigate the value of standardized uptake values (SUVs) and metabolic tumor volume (MTV) in 18F-FDG PET/CT to predict the survival of patients with locally advanced non–small cell lung cancer during the early stage of concurrent chemoradiotherapy. Methods: A total of 53 patients were included in the prospective study. All patients were evaluated by 18F-FDG PET before and after 40 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy regimen. Semiquantitative assessment was used to determine the maximum and mean SUVs (SUVmax and SUVmean, respectively) and MTV of the primary tumor. The cutoffs for changes in SUVmax, SUVmean, and MTV (37.2%, 41.7%, and 29.7%, respectively) determined in a previous study were used with Kaplan–Meier curves to separate the groups. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analysis. Results: Overall survival (OS) at 1 and 2 y was 83.0% (46/53) and 52.8% (28/53), respectively. Survival curves for SUVmean and MTV were significantly different using the cutoffs. However, Cox regression analysis showed that the only prognostic factor for OS was a decrease in MTV. Conclusion: The use of repeated 18F-FDG PET to assess survival early during concurrent chemoradiotherapy is possible in patients with locally advanced non–small cell lung cancer. A decrease in MTV according to 18F-FDG uptake by the primary tumor correlates with higher long-term OS.

CYFRA21-1 and CEA are useful markers for predicting the sensitivity to chemoradiotherapy of esophageal squamous cell carcinoma.

Background: Chemoradiotherapy (CRT) is currently performed for patients with advanced esophageal carcinoma. Sensitivity of tumours to CRT differs from one case to another and may be influenced by the expression of biological molecules. The aim of this study was to identify biological markers which could predict sensitivities of esophageal squamous cell carcinoma (ESCC) to CRT. Methods: A total of 84 patients with stage I–IV ESCC were evaluated. The cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) levels were measured before CRT by enzyme-linked immunosorbent assays in patients with primary ESCCs using 3.4 ng ml−1 and 3.3 ng ml−1, respectively, as cut-off values. The relationships between pretreatment expression of CYFRA 21-1 and CEA and the effectiveness of CRT were analysed. Results: The complete response (CR) rates of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 and CEA were 10% (3/30) and 4.2% (1/24), while in cases with low CYFRA21-1 and CEA the CR rates were 50% (27/54) and 48.3% (29/60), respectively (p = 0.002 and 0.003). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 60% (18/30) and 96.3% (52/54), while in CEA high and low groups they were 58.3% (14/24) and 93.3% (56/60), respectively (p = 0.013 and 0.013). Conclusion: CYFRA21-1 and CEA may be helpful in predicting the responsiveness in ESCC of primary lesions to CRT, although the results should be confirmed in larger, more homogeneous studies.

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer.

ObjectivesConcurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy. MethodsThe chemotherapy was cisplatin (25 mg/m2×3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m2. The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [18F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%. ResultsNine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m2 level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m2. ConclusionsThe combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.

The early predictive value of a decrease of metabolic tumor volume in repeated 18F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

PURPOSE The aim of this study is to investigate the value of [(18)F] fluorodeoxyglucose positron emission tomography/computed tomography ((18)F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). METHODS A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan-Meier curves. RESULTS Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan-Meier curve successfully. CONCLUSION The prospective study has reinforced the early predictive value of MTV in repeated (18)F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who underwent CCRT. A decrease of MTV in (18)F-FDG uptake by the primary tumor correlates with higher LRFS.

Clinical and dosimetric risk factors of acute esophagitis in patients treated with 3-dimensional conformal radiotherapy for non-small-cell lung cancer.

Purpose:To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non–small-cell lung cancer (NSCLC) patients treated with 3-dimensional conformal radiotherapy (3D-CRT). Methods and Materials:One hundred two NSCLC patients treated with 3D-CRT were retrospectively analyzed. Forty of these 102 patients analyzed were treated with concurrent chemotherapy (CCT). The median biologic effective dose of radiotherapy was 72.0 Gy. AE was scored according to the Radiation Therapy Oncology Group criteria. The clinical and dosimetric factors associated with grade 2 or worse AE were analyzed using univariate and multivariate binary logistic analysis. Results:There were no grade 4 or 5 AE observed in the 102 patients analyzed. Thirty-four of 102 patients (33.3%) developed grade 2 or 3 AE. Univariate analysis showed that clinical factors, such as lymph nodes stage (N 0/1 vs. N 2/3), pretreatment weight loss ≥5%, CCT, and the use of late-course hyperfractionated radiotherapy were significantly associated with grade 2 and 3 AE. Dose volume parameters of esophagus including mean esophageal dose, maximal esophageal dose, rV15, rV20, rV25, rV30, rV35, rV40, rV45, rV50, rV55, rV60 were also associated with AE. On multivariate forward step-wise logistic analysis, CCT, lymph nodes stage, and rV55 emerged as the statistically most significant factors of AE with OR parameters of 8.911, 4.832, and 1.083, respectively. Conclusion:CCT, lymphatic status, and rV55 were strong predictors of grade 2 or worse AE in NSCLC treated with 3D-CRT.

Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin-based chemotherapy for esophageal squamous cell carcinoma: a phase II study

BackgroundIn this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC).MethodsPatients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT.ResultsThe median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II–III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%.ConclusionsENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway.Trial registrationChiCTR-TRC-09000568

MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1:

Cervical cancer is the fourth most commonly occurring malignancy in females worldwide. Accumulated studies have demonstrated that the aberrant expression of microRNAs plays important roles in tumorigenesis and tumor development and potentially serves as therapeutic targets in various cancers including cervical cancer. Therefore, the identification of specific microRNAs contributed to cervical cancer formation and progression would provide critical clues for the treatments for patients with this disease. In this study, we aimed to detect microRNA-337 expression pattern and investigate the biological roles of microRNA-337 in the regulation of the malignant phenotypes of cervical cancer and its underlying mechanisms. We found that microRNA-337 expression was significantly downregulated in cervical cancer tissues and cell lines. In addition, its aberrant expression levels were positively correlated with tumor size, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis of cervical cancer. The ectopic expression of microRNA-337 suppressed cell proliferation and invasion of cervical cancer in vitro. Furthermore, specificity protein 1 was identified as a direct target of microRNA-337 in cervical cancer. The expression of specificity protein 1 increased in cervical cancer tissues and negatively correlated with microRNA-337 expression level. Moreover, rescue experiments revealed that upregulation of specificity protein 1 could rescue the effects of microRNA-337 on cervical cancer cells. Taken together, these findings collectively demonstrate that microRNA-337 exerts its tumor-suppressing roles in cervical cancer by directly targeting specificity protein 1, thereby indicating a potential novel potential therapeutic target for patients with cervical cancer.

Phase III study of cisplatin with pemtrexed or vinorelbine plus concurrent late course accelerated hyperfractionated radiotherapy in patients with unresectable stage III non-small cell lung cancer

Our aim was to evaluate the efficacy and safety of cisplatin with pemtrexed or vinorelbine and concurrent late course accelerated hyperfractionated radiotherapy (LCAHRT). Patients with unresectable stage III non-small-cell lung cancer (NSCLC) were randomly assigned to two regimens. The experimental (PP) arm included cisplatin, pemtrexed and concurrent LCAHRT based on bilateral lung V20 = 33%. The control (NP) arm used cisplatin, vinorelbine with the same radiotherapy protocol. The primary endpoint was overall survival. Median survival times were 26.0 months (95% CI 23.2 to 28.7 months) and 28.5 months (95% CI 17.1 to 39.9 months) for the NP and PP arms, respectively (P = 0.26). Median progression-free survival was 12.5 months and 17.5 months in the NP and PP arms (P = 0.07). In both arms of the study, there were no differences in overall survival between patients with squamous and nonsquamous NSCLC. The incidences of grade 3 or 4 toxicity were higher in NP than PP arm. With concurrent LCAHRT, pemetrexed/cisplatin was equally as efficacious as vinorelbine/cisplatin, but showed a more favorable toxicity profile.