ABSTRACT
OBJECTIVES: Long-term locoregional control following intensity-modulated radiotherapy (IMRT) for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN) remains challenging. This study aimed to assess the efficacy and toxicity of IMRT with and without chemotherapy or surgery in locally advanced SCCHN. MATERIALS AND METHODS: Between January 2007 and January 2011, 61 patients with locally advanced SCCHN were treated with curative IMRT in the Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 28% underwent definitive IMRT and 72% postoperative IMRT, combined with simultaneous cisplatin-based chemotherapy in 58%. The mean doses of definitive and postoperative IMRT were 70.8 Gy (range, 66-74 Gy). Outcomes were analyzed using Kaplan-Meier curves. Acute and late toxicities were graded according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer radiation morbidity scoring criteria. RESULTS: At a median follow-up of 35 months, 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 83.8%, 86.1%, 82.4%, 53.2%, and 62%, respectively. Postoperative IMRT (n = 44, 72%) had significantly higher LRFS/OS/DMFS than definitive IMRT (n = 17, 28%; P < 0.05). IMRT combined with chemotherapy (n = 35, 58%) had significantly higher LRFS/OS/DMFS than IMRT alone (n = 26, 42%; P < 0.05). One year after radiotherapy, the incidence of xerostomia of grade 1, 2, or 3 was 13.1%, 19.7%, and 1.6%, respectively. No grade 4 acute or late toxicity was observed. CONCLUSION: IMRT combined with surgery or chemotherapy achieved excellent long-term locoregional control and OS in locally advanced SCCHN, with acceptable early toxicity and late side-effects.
ABSTRACT
BACKGROUND: Eukaryotic initiation factor eIF4E, an important regulator of translation, plays a crucial role in the malignant transformation, progression and radioresistance of many human solid tumors. The overexpression of this gene has been associated with tumor formation in a wide range of human malignancies, including breast cancer. In the present study, we attempted to explore the use of eIF4E as a therapeutic target to enhance radiosensitivity for breast carcinomas in a xenograft BALB/C mice model. MATERIALS AND METHODS: Ninety female BALB/C mice transfected with EMT-6 cells were randomly divided into six groups: control, irradiation (IR), pSecX-t4EBP1, pSecX-t4EBP1+irradiation, pSecX and pSecX+irradiation. At the end of the experiments, all mice were sacrificed, the xenografts were harvested to measure the tumor volume and mass, and the tumor inhibition rates were calculated. Apoptosis was detected with a flow cytometric assay. Immunohistochemistry was used to detect the expression of HIF-1α. RESULTS: The xenografts in pSecX-t4EBP1 mice showed a significantly delayed growth and smaller tumor volume, with a higher tumor inhibition rate compared with the control and pSecX groups. A similar result was obtained in the pSecX-t4EBP1+IR group compared with IR alone and pSecX+irradiation. The expression of HIF-1α in the tumor cells was significantly decreased, while the apoptosis index was much higher. CONCLUSIONS: pSecX-t4EBP1 can significantly inhibit tumor growth and enhance the radiosensitivity of breast carcinoma xenografts in BALB/C mice. This is possibly associated with the downregulation of HIF-1α expression, which suggests that pSecX-t4EBP1 may serve as an ideal molecular target for the radiosensitization of breast carcinoma.
