Effect of SPAG9 on migration, invasion and prognosis of prostate cancer.

PURPOSE: The present study was designed to explore the expression of sperm associated antigen 9 (SPAG9) in patients with prostate cancer and estimate the correlation between SPAG9 mRNA expression and prognosis of prostate cancer patients. Moreover, we also investigated the role of SPAG9 in migration and invasion of prostate cancer cell lines. METHODS: Quantitative real-time PCR (qRT-PCR) was adopted to detect the expression of SPAG9 mRNA in prostate cancer tissues. Chi-square was used to evaluate the relationship between SPAG9 expression and the clinical features of prostate cancer patients. Tranwell assay was performed to detect the migration and invasion of prostate cancer cells. Kaplan-Meier curve and Cox regression analysis were used to evaluate the prognostic value of SPAG9 in prostate cancer patients. RESULTS: The qRT-PCR results showed that SPAG9 mRNA was highly expressed in prostate cancer tissues than the control group (P<0.05). There was tight relationship between SPAG9 mRNA expression and clinical characteristics such as Gleason score, NED rate and radical prostatectomy (P<0.05). Overexpression of SPAG9 in vitro significantly promoted the migration and invasion of prostate cancer cells (P<0.05). Kaplan-Meier survival analysis demonstrated that patients with high SPAG9 mRNA expression had higher mortality than those with low expression (P<0.001). Both univariate and multivariate analyses revealed that SPAG9 was a prognostic factor for prostate cancer patients (P=0.000, HR=4.878, 95% CI=2.422-9.825). CONCLUSION: In a word, SPAG9 is a novel prognostic biomarker for prostate cancer patients.

Spect-guidance to reduce radioactive dose to functioning lung for stage III non-small cell lung cancer.

OBJECTIVE: To investigate the treatment effect of additional information obtained by single photon emission computed tomography (SPECT) lung perfusion imaging (LPI) in the radiotherapy planning process for patients with stage III non-small cell lung cancer (NSCLC). METHODS: 39 patients with stage III NSCLC were enrolled. Gross tumor volume (GTV) was outlined by SPECT/CT images, SPECT-LPIs being used to define functional lung (FL) and non-functional lung (NFL) regions. Two sets of IMRT plans were designed to deliver 64Gy to PTV. One was a regular IMRT plan using CT images only (Plan 1), and the other was a corresponding IMRT plan using co-registered images (Plan 2). FLVx (the % volume of functional lung receiving ≥x Gy) and WLVx (% volume of whole lung to receive ≥x Gy) were compared by paired Student's t test. Kendalls correlation was used to analyze the factor (s) related with the FLV20 decrease. RESULTS: Compared with plan 1, both WLVx and FLVx were decreased in plan 2. WLV10, WLV15, WLV20, WLV25, WLV30 and WLV35 decreased 9.7%, 13.8%, 17.2%, 12.9%, 9.8% and 9.8%, and FLV10, FLV15, FLV20, FLV25, FLV30 and FLV35 decreased 10.8%, 14.6%, 17.3%, 14.5%, 14.5% and 10.5%. FLVx decreased significantly compared with WLVx. There were significant differences in WLV10, WLV15, WLV20, WLV25, WLV3 and FLV10, FLV15, FLV20, FLV25, FLV30 between plan 1 and plan 2 (P=0.002, 0.000, 0.000, 0.005, 0.027 and 0.002, 0.000, 0.000, 0.006, 0.010). According to Kendall correlation analysis, NFL had a negative relation with the percentage FLV20 decrease (r=-0.559, P<0.01), while the distance of PTV and NFL center had a significantly positive relation with the percentage of FLV20 decrease (r=0.768, P<0.01). CONCLUSION: Routine use of SPECT-LPI for patients undergoing radiotherapy planning for stage III NSCLC appears warranted.

Feasibility of shrinking field radiation therapy through 18F-FDG PET/CT after 40 Gy for stage III non-small cell lung cancers.

OBJECTIVE: To explore the feasibility of shrinking field technique after 40 Gy radiation through 18F-FDG PET/ CT during treatment for patients with stage III non-small cell lung cancer (NSCLC). METHODS: In 66 consecutive patients with local-advanced NSCLC, 18F-FDG PET/CT scanning was performed prior to treatment and repeated after 40 Gy. Conventionally fractionated IMRT or CRT plans to a median total dose of 66 Gy (range, 60-78 Gy) were generated. The target volumes were delineated in composite images of CT and PET. Plan 1 was designed for 40 Gy to the initial planning target volume (PTV) with a subsequent 20-28 Gy-boost to the shrunken PTV. Plan 2 was delivering the same dose to the initial PTV without shrinking field. Accumulated doses of normal tissues were calculated using deformable image registration during the treatment course. RESULTS: The median GTV and PTV reduction were 35% and 30% after 40 Gy treatment. Target volume reduction was correlated with chemotherapy and sex. In plan 2, delivering the same dose to the initial PTV could have only been achieved in 10 (15.2%) patients. Significant differences (p<0.05) were observed regarding doses to the lung, spinal cord, esophagus and heart. CONCLUSIONS: Radiotherapy adaptive to tumor shrinkage determined by repeated 18F-FDG PET/CT after 40 Gy during treatment course might be feasible to spare more normal tissues, and has the potential to allow dose escalation and increased local control.

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

OBJECTIVES: Concurrent 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. METHODS: The chemotherapy was cisplatin (25 mg/m(2) × 3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m(2). The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [(18)F] 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%. RESULTS: Nine 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/m(2) 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/m(2). CONCLUSIONS: The 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.

[Impact of the pattern of lymph node metastasis on the clinical target volume in radiotherapy for thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To study the pattern of lymph node metastasis of thoracic esophageal squamous cell carcinoma (ESCC) after esophagectomy and its impact on the clinical target volume (CTV) delineation in radiotherapy fpr thoracic ESCC. METHODS: The pattern of lymph node metastasis was retrospectively analyzed in 1077 patients with primary thoracic ESCC. All patients received esophagectomy with two- or three-field lymphadenectomy. The clinicopathologic factors related to lymph node metastasis were then analyzed using logistic regression analysis. RESULTS: The rates of cervical, upper mediastinal, middle mediastinal, lower mediastinal and abdominal cavity lymph node metastasis were 16.7%, 33.3%, 11.1%, 5.6% and 5.6%, respectively. The rates of those node metastasis in the middle thoracic ESCC were 4.0%, 3.8%, 28.5%, 7.1% and 17.1%, respectively, and the rates of those node metastasis in the lower thoracic ESCC were 1.5%, 3.0%, 22.7%, 37.0% and 33.2%, respectively. The depth of tumor invasion, histologic differentiation and the length of tumor were showed to be statistically most significant risk factors of lymph node metastasis of ESCC (P < 0.001). CONCLUSION: The depth of tumor invasion, histologic differentiation, and length of tumor were closely correlated with lymph node metastasis of ESCC. All these factors and tumor location should be considered comprehensively when designing the target volume for radiotherapy.

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 > or =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.

Phase I study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and Capecitabine, Cisplatin for locally advanced esophageal squamous cell carcinoma.

Twelve patients with locally advanced esophageal squamous cell carcinoma were enrolled to evaluate the safety and efficacy of concurrent chemo-radiotherapy. Dose-limiting toxicity was mainly observed at Capecitabine 1500 mg. The maximum-tolerated dose/recommended dose of Capecitabine was 1000 mg. The Kaplan-Meier estimated overall l-year survival rate was 100%.