Radiotherapy (RT) is one main method for the treatment of esophageal squamous cell carcinoma (ESCC), and the radioresistance is the predominant cause of patients with local recurrence. The previous results of gene microarray and subsequent verification showed that NRAGE might be involved in radiation resistance of ESCC cells. In this study, we reestablished human esophageal carcinoma radioresistant cell lines TE13R120 and ECA109R60 with gradient dose irradiation as previously reported, respectively. NRAGE expression was high in TE13R120 and ECA109R60 cells and was correlative with ionizing radiation (IR) resistance in clinic. However, the radiosensitivity of TE13R120 cells had a remarkable increase detected by colony formation assays after siRNA against NRAGE (siNRG) transfection into TE13R120 cells. Compared with TE13 cells, an increasing number of TE13R120 cells with NRAGE overexpression in S phase and a lower ratio in G2/M were observed by flow cytometry method (FCM). Intriguingly, the above changes were partially reversed in TE13R120 cells treated with siNRG. More importantly, the ectopic subcellular localization of NRAGE mediated nuclear translocation of β-catenin which may be one reason of IR resistance of esophageal carcinoma cell. These data indicate that NRAGE extremely may be a pivotal factor involved in Wnt/β-catenin signal pathway, mediating nuclear translocation of β-catenin and then facilitating the formation of radioresistance of ESCC.

The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy for patients with non-small cell lung cancer (NSCLC); however, it was unclear whether this dose could be safely administered to Asian patients due to differences in their physique compared to Western patients. We therefore conducted a modified Phase I trial to determine whether 70 Gy could be safely delivered to Chinese patients with NSCLC undergoing 3D-conformal radiation therapy (3D-CRT) with concurrent chemotherapy. Previously untreated NSCLC patients received 3D-CRT (2 Gy/day, 5 fractions per week). Three dose levels were examined: 62, 66 and 70 Gy. Two cycles of concurrent chemotherapy (vinorelbine and carboplatin) were started on the first day of radiation therapy. Dose-limiting toxicity (DLT) was defined as severe or life-threatening side effects that altered the continued implementation of chemoradiotherapy. Among the 19 patients recruited in this study, most of the haematologic and non-haematologic toxicities were mild to moderate and clinically manageable. Only one patient, in the 70 Gy cohort, experienced a DLT of Grade 3 radiation-induced pneumonia. The overall response rate was 77.8% (14/18). The median progression-free survival (PFS) was 12 months, and the 1-year PFS was 37.6%. Our results support both the feasibility of incorporating 3D-CRT with concurrent vinorelbine and carboplatin and a dose escalation to 70 Gy for Chinese patients with NSCLC, based on the acceptable toxicity and encouraging overall response and survival rates. A further evaluation of this regimen in a prospective Phase II trial is ongoing.

BackgroundPatients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer.MethodsPatients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT).ResultsFrom March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups.ConclusionCompared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial.

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