The efficacy and roles of combining temozolomide with whole brain radiotherapy in protection neurocognitive function and improvement quality of life of non-small-cell lung cancer patients with brain metastases.

BACKGROUND: Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). The efficacy and roles of combining temozolomide (TMZ) with whole brain radiotherapy (WBRT) in protection neurocognitive function (NCF) and improvement quality of life (QOL) were investigated and compared with WBRT alone in the treatment of NSCLC patients with BM. METHODS: A total of 238 NSCLC patients with BM were reviewed and categorized into WBRT plus TMZ (RCT) arm and WBRT alone (RT), respectively. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. NCF was assessed by using revised Hopkins Verbal Learning Test (HVLT-R), Controlled Oral Word Association (COWA) test and Trail-making Test (TMT). QOL was assessed by the Functional Assessment of Cancer Treatment-Lung (FACT-L) Chinese version 4.0 questionnaire. RESULTS: The average intracranial objective response (ORR) and disease control rate (DCR) for all the patients were 26.9 and 95.8%, respectively. The intracranial ORR and DCR for RCT and RT arm were 34.9% vs. 20.2% (p = 0.01) and 98.4% vs. 92.7% (p = 0.03), respectively. The median intracranial progression-free survival (PFS) and overall survival (OS) of NSCLC patients with BM were 5.2 and 7.3 months, respectively. The median PFS of RCT arm was significantly longer than that of RT arm (5.9 vs. 4.9 months, p = 0.002). The median OS of the RCT arm was also slightly longer than that of the RT arm (8.5 vs. 5.9 months), but without statistical significance (p = 0.11). Multivariate analysis indicated that TMZ was a significant factor for PFS. Statistically significant differences on NCF and QOL were observed between CRT and RT arms at 5 months. RCT showed a trend of toxicities increase compared with RT, however, the toxicities were tolerable and manageable. CONCLUSIONS: Adding TMZ to WBRT in the treatment of NSCLC patients with BM could improve the intracranial ORR, DCR, and median PFS compared with WBRT alone. Although no remarkable difference on median OS was found, adding TMZ could prevent NCF and QOL from worsening. The side effects increased by adding TMZ, but the difference was not statistical significance and toxicities were well tolerated.

Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer.

Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678-0.800, P < 0.01]. Kaplan-Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation.

Upregulated expression of long noncoding RNA SNHG15 promotes cell proliferation and invasion through regulates MMP2/MMP9 in patients with GC.

Accumulation of data indicates that misregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be served as diagnosis and prognosis biomarker or potential therapeutic targets. Identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are significant for understanding the development and progression of cancer. In this study, we identified a novel lncRNA SNHG15, whose expression was upregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, increased SNHG15 expression was positively correlated with invasion depth (P < 0.001), advanced tumor node metastasis (TNM) stage (P = 0.001), and lymph node metastasis (P = 0.019). SNHG15 levels were robust in differentiating GC tissues from controls (area under the curve (AUC) = 0.722; 95 % confidence interval (CI) = 0.657-0.782, P < 0.01). Kaplan-Meier analysis demonstrated that elevated SNHG15 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that SNHG15 could be an independent prognostic marker. Furthermore, knockdown of SNHG15 expression by siRNA could inhibit cell proliferation and invasion and induce apoptosis, while ectopic expression of SNHG15 promoted cell proliferation and invasion in GC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that elevated lncRNA SNHG15 could be identified as a poor prognostic biomarker in GC and regulate cell invasion.

Benefit of radiotherapy on survival in resectable gastric carcinoma: a meta-analysis.

We aimed to perform a meta-analysis to assess the impact of radiotherapy (RT) on both 3- and 5-year survival in patients with resectable gastric cancer. Relevant studies were identified by using PubMed, Embase and the Cochrane Controlled Trials Register through May 2013. We included randomized clinical trials (RCTs) that compared survival of surgery combined with RT (preoperative and/or postoperative) to surgery alone or surgery plus chemotherapy. Meta-analysis was performed using risk ratios (RRs). Both fixed- and random-effects models were used to calculate the summary risk estimates. Fourteen RCTs involving 2,853 participants were included in this meta-analysis. The addition of RT significantly increased the 3-year (RR 1.19; 95% confidence interval (CI) 1.05-1.35) and 5-year survival (RR 1.25; 95% CI 1.12-1.40). A significant advantage was also observed in subgroup analysis of preoperative RT for both 3-year (RR 1.56; 95% CI 1.19-2.05) and 5-year overall survival (RR 1.40; 95% CI 1.13-1.73). There was no evidence that preoperative RT increased postoperative mortality (RR 0.85; 95% CI 0.42-1.72). Surgery combined with RT or chemoradiotherapy compared to surgery alone improved the 3-year (RR 1.18; 95% CI 1.01-1.38) and 5-year survival rate (RR 1.38; 95% CI 1.18-1.61). Although the quality of the studies was variable, the data were consistent, and no substantial publication bias was observed. In patients with resectable gastric carcinoma, adjuvant RT significantly increased the 3-year and 5-year survival. Preoperative RT is safe and definitely improves overall survival. Available evidence is insufficient to determine the benefit of postoperative RT after an extended lymphadenectomy and radical resection.

Intraperitoneal recombinant human endostatin combined with chemotherapy for refractory malignant ascites due to gastrointestinal cancer: a pilot study.

BACKGROUND/AIMS: To evaluate the efficacy, safety and consequent impact on quality of life of a combined-modality using intraperitoneal recombinant human endostatin, Endostar and chemotherapy in patients with refractory malignant ascites caused by gastrointestinal cancer. METHODOLOGY: Patients received combined intraperitoneal therapy repeated 3 weeks, which consisted of 5-fluorouracil 600 mg/m2 and cisplatin 30 mg/m2 on day 1-3 followed by Endostar 60 mg on day 4. RESULTS: A total of 18 patients were treated. The overall response rate was 55.6%, with a complete remission rate of 22.2%. The malignant ascites controlled rate was 77.8%. The median time to progression and overall survival was 2.6 and 4.9 months, respectively. Therapy-associated toxicities were generally mild to moderate treatment-related deaths. The mean Karnofsky performance status score was significantly improved from 59.4±2.49 at enrollment to 69.4±3.18 at 2 weeks after the first cycle of therapy (p=0.001). The mean score for overall ascites-associated symptoms was improved from 5.3±0.35 to 4.0±0.23 (p=0.004). Significant improvements of 6 individual symptoms were also observed. CONCLUSIONS: The combined-modality using intraperitoneal Endostar and chemotherapy is effective and safe in selected patients with refractory malignant ascites due to gastrointestinal cancer and significantly improves patient's quality of life with encouraging survival, which merits further investigation.

[Effects end mechanisms of curcumol beta-cyclodextrin compound on the proliferation and apoptosls of esophageal carcinoma cell line TE-1].

OBJECTIVE: To investigate the effects and mechanisms of Curcumol beta-cyclodextrin Compound (CbetaC) on the proliferation and apoptosis of esophageal carcinoma cell line TE-1. METHODS: The CbetaC was prepared by saturated solution and confirmed by infrared absorption spectroscopy. The effects of CbetaC (at 25, 50, 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro was analyzed by MTT assay. The cell cycles and apoptosis were detected by flow cytometer. The relative expression of survivin mRNA was detected by real-time fluorescent quantitative PCR and calculated by the 2(-deltaCt) method. The protein expression of survivin was measured by Western blot. RESULTS: Compared with the control group, results of MTT showed that CbetaC at each dose significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (P < 0.05). The results of flow cytometry showed that CbetaC resulted in the cell cycle arrest at G0/G1 and G2/M phase, and promoted the cell apoptosis. Besides, when compared with the control group, the protein and mRNA expressions of survivin obviously decreased in each CbetaC group (P < 0.05). CONCLUSIONS: CbetaC could inhibit the proliferation of esophageal carcinoma cell TE-1 and promote the apoptosis. Its inhibition on the survivin expression was correlated with its inhibition on the malignant phenotypes of esophageal carcinoma cells.

[Phase II study of radiotherapy plus erlotinib for elder patients with esophageal carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of radiation plus erlotinib in patients with esophageal cancer older than 70 years. METHODS: Radiotherapy was prescribed at a daily fraction of 2.0 Gy up to a total dose of 60 Gy over 6 weeks. Concurrent erlotinib was administrated at a dose of 150 mg daily at days 1-42. Acute toxicities were assessed by the criteria of Radiation Therapy Oncology Group (RTOG) and National Cancer Institute (NCI). The results were analyzed by the software SPSS 17.0. RESULTS: A total of 33 patients were enrolled. The median survival time was 16.3 ± 8.6 months (95%CI 0.0 - 33.3) and the 1-and 2-year overall survival rates were 66.3% and 49.7% respectively. The media progression-free survival was 16.7 ± 7.1 months (95%CI 2.9 - 30.5) and the 1- and 2-year local control rates 73.3% and 54.9% respectively. Most toxicities were of grade 1-2 and manageable. CONCLUSION: The combined regimen of radiation and erlotinib is effective and safe in elder patients aged > 70 years with esophageal cancer. However the results of our study should be confirmed in randomized controlled trials of a larger sample size.

[The effect on life quality of nasopharyngeal cancer patients through xerostomia decrease after intensity-modulated radiotherapy].

OBJECTIVE: To evaluate the gain on the life quality of NPC from efforts to reduce the radiotherapy-induced xerostomia after IMRT. METHODS: From August 2002 to December 2008, 235 patients with nasopharyngeal carcinoma were treated with IMRT in the First Affiliated Hospital of Wenzhou Medical College. Ninety-one patients with minimum 2 years of survival and no replaces and metastasis were enlisted. XQ and QOL questionnaires were completed at baseline, then 0, 3, 6, 9, 12, 18 and 24 months after IMRT. RESULTS: The XQ scores were substantially higher at the end of IMRT compared with baseline and descended over time. At 9 months post-RT, the XQ scores improved significantly (P = 0.024) and recovered nearly to baseline at 18 months post-RT. Likewise, the QOL scores were significantly higher at the end of IMRT compared with baseline (P = 0.012) and had a sequential trend towards improvement over the study period. At 18 months post-RT, the QOL scores almost recover to baseline (P = 0.020). Multiple comparisons testing revealed that communication, eating and pain sub-scale scores were significantly higher at the end of IMRT compared with baseline(P < 0.05) with the exception of emotion domain. There was a significant correlation between XQ scores and QOL scores in general in all the study time (r = 0.976, P < 0.001), also a significant position correlation was found between XQ scores and communication, eating sub-scale scores and overall bother scores. CONCLUSIONS: IMRT technique can reduce the incidence of postradiation xerostomia significantly and can improve the quality of life in many domains.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

[Concurrent standard dose of cisplatin, paclitaxel, and radiotherapy followed by surgery in treatment of thoracic esophageal carcinoma].

OBJECTIVE: To investigate the curative effect of incorporation of the regimen of standard dose of paclitaxel combined with cisplatin into concurrent radiotherapy as pre-operative treatment for patients with esophageal carcinoma. METHODS: Twenty-six patients with primary diagnosis of esophageal carcinoma, 17 in stage II and 9 in stage III, underwent conventional fractionated radiotherapy with a total dosage of 40 Gy (2 Gy per day, 5 doses per week). Paclitaxel were given intravenously at a dose of 135 mg/m(2) for 3 h on day1 and day 22. Cisplatin was given intravenously at a dose of 20 mg/m(2) on D1-D3 and D22-24. 4 - 6 weeks after the completion of chemo-radiotherapy, left thoracic incision and transhiatal esophagectomy with anastomosis in the neck was performed. The patients were followed up for 42.28 months. Kaplan-Meier method was used to analyze the overall survival (OS) and disease-free survival (DFS), and Log-rank test was performed to assess the survival rates statistical significance among groups. RESULTS: The radical resection rate was 96.15%. The pathologic response to chemoradiotherapy were grade I in 9 patients, grade II in 6 patients, and grade III in 11 patients. The pathological complete remission (PCR) rate was 42.31% (11/26). Toxicity grade 3 - 4 included leucopenia (7.69%, 2/26), thrombocytopenia (7.69%, 2/26), and radiation esophagitis (11.54%, 3/26). Surgery-related complications included anastomotic leakage (3.85%, 1/26), recurrent laryngeal nerve injury (7.69%, 2/26), and chylothorax (3.85%, 1/26). The 3- and 5-year overall survival rates were 62.96% and 54.56% respectively. The 3- and 5-year disease-free survival rates were 59.94% and 55.65% respectively. The 3-year overall survival rates of the patients with different pathologic responses were 25.40% (for those of grade I), 60% (for grade II), and 90.91% (for grade III) respectively (P < 0.05). The 5-year overall survival rates were 0 (for grade I), 60% (for grade II), and 81.82% (for grade III) respectively (P < 0.05). CONCLUSION: Preoperative chemoradiotherapy containing full dose of paclitaxel and cisplatin increases the 5-year overall survival for the patients with postoperative pathologic response grade II and above, and does not increase the treatment-related complications.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

[Concurrent chemoradiation with paclitaxel and platinum for locally advanced esophageal cancer].

UNLABELLED: OBJECTIVE To assess the efficacy of concurrent chemoradiation with paclitaxel and platinum and external irradiation, and to compare the effect of extensive regional field irradiation with conventional local field irradiation for locally advanced esophageal cancer. METHODS: From Oct. 2000 to Jan. 2006, 89 patients with locally advanced esophageal cancer were registered in this study. All patients were inoperable or refused to undergo operation. Patients were divided into two groups: extensive regional field group (51 patients) and conventional field group (38 patients). Patients received radiotherapy at a total dose of 60 Gy in 30 fractions within 7 weeks,and concurrent paclitaxel 125 mg/m2 on D1, cisplatin 20 mg/m2 on D1-D3, or oxaliplatin 130 mg/m2 on D2 in the fist and fourth week of external radiation. RESULTS: Of these patients, 87.6% completed the treatment regimen with a response rate of 75.5% and 66.7% in the extensive regional field group and conventional field group, respectively. Grade 3 or severe toxicities of leucopenia (33.3% vs. 23.7%), thrombocytopenia (76.0% vs. 2.6%), and esophagitis (17.7% vs. 26.3%) were observed in extensive regional field group and conventional field group, respectively. Major late toxic effect was lung fibrosis. There were no statistically significant differences in the incidence of the toxicity profile between two groups. The overall 3-year survival rates was 32.8%, and the overall 3-year recurrence and metastasis-free survival rates was 34.5%. The overall 3-year locoregional control rate was 44.0%. No significant difference was found between two groups in the 3-year survival (38.2% % vs. 28.1%, P = 0.59). For the patients with stage II and stage III cancers who completed the planned treatment, large regional field radiotherapy significantly improved the 3-year survival (57.3% vs. 22.2% , P = 0.03) or 3-year recurrent and metastasis-free survival (55.5% vs. 23.0%, P = 0.03) or 3-year locoregional control (65.9% vs. 30.2%, P = 0.02) than conventional field radiotherapy. CONCLUSION: historical results, the combination of paclitaxel/platinum and radiation in this study can improve the survival for locally advanced esophageal, and the side effect is well tolerated. Compared with the conventional field group, concurrent chemoradiotherapy with the large regional field can significantly improve 3-year survival and locoregional control for stage II or stage III esophageal cancer.

[Simultaneous modulated accelerated radiation therapy in the treatment of nasopharyngeal cancer].

OBJECTIVE: To evaluate the toxicity and clinical efficacy of simultaneous modulated accelerated radiation therapy (SMART) technique for nasopharyngeal carcinoma. METHODS: 110 patients with nasopharyngeal carcinoma underwent boost treatment with SMART at the dose of 2.5 Gy/time for 28 times for gross tumor volume (GTV) with the total dose of 70 Gy and the dose of 2.0 Gy/time once a day and 5 times a week, totally 28 times, with the total dose of 56 Gy for the clinical treatment volume (CTV). The GTV dose for 36 of these patients was boosted to 80 Gy. Follow-up was conducted for 24 months (7 - 44 months). RESULTS: Follow-up showed that the 1, 2, and 3-year survival rates were 97.02%, 88.72%, and 78.27%, respectively. The 1 - 3 year local relapse-free survival rate was 97.94% (95.10% - 100%). The 1, 2, and 3-yea local-regional relapse-free rates and distant metastasis-free rates were 95.21%, 89.83%, 76.10% and 95.38%, 85.71%, and 79.67%, respectively. According to the Fuzhou staging, the 3-year overall survival rate of the stage I - II patients was 100%, while the 3-year survival rate of the stage III patients was 74.33% and the 3-year survival rate of stage IV a patients was 62.96%. The acute toxicity was well tolerated except for the high incidence of severe mucositis. No grade 4 side effects occurred. Most of the patients showed Grade 0 to 1 late toxicity and xerostomia was a common side effect. No increase of toxicity was seen when the GTV dose was increased to 80 Gy. CONCLUSION: SMART yields superior dose distribution over the traditional radiotherapy in nasopharyngeal carcinoma at the early or advanced stages. The local-regional control was excellent and distant metastasis remains the main risk. Dose escalation to 80 Gy was safe and feasible. Toxicity of SMART is acceptable and tolerable.

[The relationship between the parotid glands function and the dose-volume effect in nasopharyngeal carcinoma patients with intensity-modulated radiation therapy].

OBJECTIVE: To study the preservation of parotid glands function and relationship between parotid glands function and dose-volume histogram (DVH) in nasopharyngeal carcinoma (NPC) patients treated by intensity modulated radiation therapy (IMRT). METHODS: From August 2002 to December 2004, the excretion index (EI) and uptake index (UI) of parotids in 48 NPC patients underwent radical IMRT was examined by ECT at the beginning, the end of and the 3 months after radiotherapy. The relationship between parotid function (EI and UI) and DVH were analyzed. RESULTS: The mean doses to the contralateral parotid and ipsilateral parotid were 22.8 +/- 4.5 Gy and 31.9 +/- 4.1 Gy, respectively. The symptom of xerostomia was mild at the end of radiotherapy. ECT showed EI of contralateral parotid were 0.35 +/- 0.25, 0.31 +/- 0.24 and 0.33 +/- 0.22 at the beginning, the end of and 3 months after radiotherapy (RT), respectively. UI were 7.12 +/- 3.56, 5.81 +/- 2.25 and 5.72 +/- 2.81 at the same intervals. This shows no statistical difference. The EI and UI of ipsilateral parotid at the completion of radiotherapy declined significantly (0.21 +/- 0.16 and 4.87 +/- 2.45, respectively) compared with those of pre-treatment (0.36 +/- 0.27 and 8.02 +/- 3.89, respectively) (P < 0.05). DVH showed: at the end of RT, the EI was significant difference between mean dose < 26 Gy and > or = 26 Gy group (P = 0.009) and decreased significantly in the group of V25 (the percentages of parotid volume irradiated with < 25 Gy) > or = 50% compared with the group of V25 < 50% (P < 0.01). The UIs were no significant difference in two groups (P > 0.05). CONCLUSION: 26 Gy is a threshold dose for the preservation of parotid glands function. There is also a threshold volume irradiated for the preservation of the parotid glands function. Based on the precondition of assuring significant dose to the target volume (PTV), we should reduce the irradiated volume and dose to parotid glands as possible as we can so as to preserve its function.

Association between single nucleotide polymorphisms of the transforming growth factor-ß1 gene and overall survival in unresectable locally advanced non-small-cell lung cancer patients treated with radio(chemo)therapy in a Chinese population.

The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-ß1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-ß1 C-509T and T+869C. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-ß1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-ß1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-ß1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.

Simultaneous modulated accelerated radiation therapy and concurrent weekly Paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma.

OBJECTIVES: To evaluate the feasibility and efficacy of simultaneous accelerated radiation therapy (SMART) and concurrent weekly paclitaxel in the treatment of locally advanced nasopharyngeal carcinoma. METHODS: Forty- one patients with pathologically confirmed nasopharyngeal carcinoma were treated by SMART with concurrent weekly paclitaxel. Daily fraction doses of 2.5 Gy and 2.0 Gy were prescribed to the gross tumor volume (GTV) and clinical target volume (CTV) to a total dose of 70 Gy and 56 Gy, respectively. Paclitaxel of 45 mg/m2 was administered concurrently with radiation therapy every week. Adjuvant chemotherapy was given four weeks after the completion of the radiotherapy (RT) if the tumor demonstrated only a partial response (PR). RESULTS: All patients completed the radiotherapy (RT) course. Adjuvant chemotherapy was administered to 12 patients due to PR. The CR (complete remission) rate was 82.9% three months after RT. Thirty-nine (95.1%) patients completed the concurrent weekly chemotherapy with paclitaxel, and two patients skipped their sixth course. Seven patients had a 15% dosage reduction at the fifth and sixth course due to grade 3 mucositis. The median follow-up was 30 (range, 14-42) months. The three-year overall survival (OS), metastases-free survival (MFS), and local control rates were 77.0%, 64.4%, and 97.6%, respectively. No correlation between survival rate and T or N stage was observed. Grade 3 acute mucositis and xerostomia were present in 17.1% and 7.1%, respectively. CONCLUSION: SMART with concurrent weekly paclitaxel is a potentially effective and toxicity tolerable approach in the treatment of locally advanced NPC.

Adjuvant combined systemic chemotherapy and intraperitoneal chemotherapy for locally advanced gastric cancer.

The optimal adjuvant treatment modality for gastric cancer has not been well defined. The aim of this study was to evaluate the efficacy and feasibility of adjuvant combined systemic and intraperitoneal chemotherapy (ACSIP) in high-risk patients with locally advanced gastric cancer. Between June 2003 and December 2008, 62 eligible patients with serosa-infiltrating and/or node-positive gastric cancer following curative gastrectomy with D2 lymphadenectomy received ACSIP, consisting of intravenous oxaliplatin 85 mg/m(2) on day 1 followed by leucovorin (LV) 200 mg/m(2) and 5-fluorouracil (5-FU) 450 mg/m(2) on days 1-3, intraperitoneal 5-FU 600 mg/m(2) on days 4-5 and cisplatin (CDDP) 40 mg/m(2) on day 5. Survival rates, the sites of first treatment failure and safety were analyzed. At a median follow-up of 45 months (range 7-101), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 66.1 and 74.2%, respectively. Initial peritoneal and hepatic failures were found in 6 (24.0%) and 3 (12.0%) of the 25 patients with recurrence, respectively. Neutropenia, gastrointestinal side effects and peripheral neuropathy were the most common grade 3-4 toxicities; however, they were all infrequent and manageable. No serious surgical complications or treatment-related mortality was observed. The results of this study indicate that ACSIP is effective and feasible for locally advanced gastric cancer with encouraging survival rates and possibly decreased peritoneal and hepatic recurrences. The benefits of this promising combined adjuvant treatment modality warrant further studies.

Baseline plasma proteomic analysis to identify biomarkers that predict radiation-induced lung toxicity in patients receiving radiation for non-small cell lung cancer.

PURPOSE: To identify new plasma proteomic markers before radiotherapy start to predict later grade ≥2 radiation-induced lung toxicity (RILT2). METHODS: Fifty-seven patients with non-small cell lung cancer received radiotherapy (RT) were eligible. Forty-eight patients with minimum follow-up of 1 year, nine with RILT2 with tumor stage matched to 39 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained within 2 weeks before radiotherapy. The plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography, and nano liquid chromatography electrospray ionization tandem mass spectrometry. Z scores and Bonferroni-adjusted p values for the two-sample mean comparison were used to identify the differential protein expression between patients with and without RILT2. RESULTS: More than 200 proteins were identified and quantified. After excluding proteins that were not detected in at least 40% of the 48 patient samples, C4b-binding protein alpha chain and vitronectin had significantly higher (p < 0.001 and p = 0.02) expression levels in patients with RILT2 compared with patients without RILT2. These two proteins were validated by Western blot. Ingenuity pathway analysis revealed that they both play important roles in the inflammatory response and are associated with the known pathways of radiation-induced lung damage. CONCLUSIONS: This proteomic approach demonstrates new plasma protein biomarkers before treatment for future studies on RILT2 prediction.

Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab.

BACKGROUND AND PURPOSE: The purpose of our study is to examine the capacity of cetuximab to reverse radiation resistance and investigate molecular mechanisms in human radiation-resistant esophageal carcinoma cell line KYSE-150R. MATERIALS AND METHODS: The radioresistant cell line KYSE-150R was established by using fractionated irradiation (FIR). The KYSE-150R cell line was exposed to radiation, treatment with cetuximab, and combined treatment. Cell cycle distribution and apoptosis were analyzed using flow cytometry. Radiation survival was analyzed using clonogenic assays. RT(2) profiler PCR array was performed to analyze EGF/PDGF signaling pathway genes. RESULTS: The established esophageal carcinoma cell line KYSE-150R showed higher radioresistance than parental cell line. Cetuximab could reverse the radiation resistance of KYSE-150R cells. Cell cycle analysis showed that combination with radiation and cetuximab resulted in the accumulation of cells in G1 and G2/M phases, with the reduction of cells within the S phase. Cetuximab enhanced the apoptosis induced by radiation. RT(2) profiler array showed that some intracellular signaling genes deriving from EGF/PDGF signaling pathway regulated by cetuximab. CONCLUSIONS: Irradiation combined with EGFR blocked by cetuximab may reverse the resistance to radiation in radioresistant esophageal carcinoma cell. The mechanisms may include cell cycle perturbation and enhancement of radiation-induced apoptosis. Further studies are needed to evaluate the role of cetuximab in combination with radiotherapy in the management of esophageal carcinoma.

[Efficacy of combined paclitaxel and oxaliplatin therapy in patients with pretreated advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: No chemotherapeutic regimen and agent are effective for patients with pretreated advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and toxicity of the combination of paclitaxel and oxaliplatin in this subset of patients. METHODS: Twenty-two patients who had been pretreated with platinum-based chemotherapy were enrolled into this study. All received paclitaxel (135 mg/m2, intravenous infusion over 3 hours on day 1) and oxaliplatin (130 mg/m2, intravenous infusion over 2 hours on day 1) every 28 days. The whole course of treatment consisted at least 2 cycles. RESULTS: Of 22 patients, 5 achieved partial response with the overall response rate of 22.7%. Nearly all lesions shrank or remained stable after the first 2 cycles, except for those of 3 patients who showed progressive diseases. Median progression-free duration time was 4 months, and median survival time was 8 months. Commonly encountered toxicities included nausea and vomiting, myalgia/arthralgta, peripheral neuropathy, and myelosuppression. CONCLUSION: Paclitaxel plus oxaliplatin combination was a safe and active regimen for patients with pretreated advanced NSCLC and deserves further evaluation.