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.

Characterization of the complete mitochondrial genome of short-tailed field vole, Microtus agrestis.

In this study, the complete mitochondrial genome of short-tailed field vole, Microtus agrestis, was determined through sequencing of PCR fragments. The complete mitochondrial genome of M. agrestis was 16,538 bp in length and encoded 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and two ribosomal RNA genes. The overall nucleotide composition is: 15.7% A, 27.5% T, 25.5% C, and 31.4% G, with a total G + C content of 56.9%. By phylogenetic analysis using Bayesian method, M. agrestisa showed the closest relationship with the southern vole (Microtus rossiaemeridionalis).

Targeted therapy of multiple liver metastases after resected solitary gastric metastasis and primary pulmonary adenocarcinoma.

Gastric metastases from lung adenocarcinoma are rare and usually asymptomatic. A 61-year-old woman was referred to our department because of a right lower pulmonary mass found on a chest X-ray film in August 2012. Right lower lobectomy was performed for pulmonary adenocarcinoma. Four months later, she developed epigastric discomfort. A fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) scan showed a malignancy at the cardias of the stomach. A biopsy diagnosed poorly differentiated carcinoma and a gastric carcinoma was suspected. She underwent a subtotal gastrectomy and part of esophagectomy. The histologic diagnosis was metastasis from the pulmonary adenocarcinoma. She visited us again for her increasing level of carcinoembryonic antigen (CEA) after two months. FDG-PET/CT showed multiple malignant lesions in her liver, considering metastases from pulmonary origin. As she harbored activating epidermal growth factor receptor (EGFR) mutation, she received erlotinib from April, 2013. She survives 4 years after the lung resection and is still on erotinib treatment with complete response. Although gastric metastasis from lung cancer is considered a late stage of the disease, a radical resection might provide survival in solitary metastasis. Moreover, systemic therapy was emphasized after local treatment in some late stage cases.

Sustained improvement of quality of life for nasopharyngeal carcinoma treated by intensity modulated radiation therapy in long-term survivors.

UNLABELLED: IMRT has achieved an excellent survival and less radiation-induced sequelae with improvement of QoL within 2 years compared to conventional radiotherapy for NPC. Whether IMRT could sustained decrease incidence of late sequelae and improve QoL further for long-term survivors remained unknown. 176 patients from Aug. 2002 to Jun. 2009 were retrospectively analyzed. Radiation-related toxicities were graded according to both the Acute and the Late Radiation Morbidity Scoring Criteria of the EORTC/RTOG; QoL was assessed by the EORTC QLQ-C30 and H&N35 questionnaires at 5 and 8 years. The 5-year overall survival rate was 68.2% with a median follow-up time of 86 months. The most common radiation-related acute and late toxicity was xerostomia, the incidence of Grade ≥ 1 xerostomia was 90.3%, 84.1%, 75.9% and 59.2%, respectively at acute, 6 months, 2 years and 5 years. Statistical analysis indicated a close relationship between 5 years with 6 months and 2 years for patients who had ≥ 3 xerostomia at acute phase (r = 0.538 for late xerostomia at 6 months with 5 years, r = 0.732 for 2 years with 5 years); Sustained amelioration of other sequelae was also observed; QoL questionnaires at 5 years showed a significant improvement of most items and got stable between 5 to 8 years. IN CONCLUSION: IMRT could sustain reduce late radiation sequelae and improve QoL for long-term survivors over time; Patients with severe acute xerostomia (≥ grade 3) would have a significant correlation of mitigatory xerostomia during the late follow-up time.

A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.

INTRODUCTION: The aim of this study was to compare the efficacy and toxicity of dicycloplatin plus paclitaxel with those of carboplatin plus paclitaxel as first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: In this study, 240 NSCLC patients with stage IIIB (with pleural effusion) and stage IV disease were randomly assigned (1: 1) to receive dicycloplatin 450 mg/m(2) or carboplatin AUC = 5, in combination with paclitaxel 175 mg/m(2) (D + P or C + P) every 3 weeks for up to 4 to 6 cycles. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: The response rates for the D + P and C + P arm were 36.44% and 30.51%, respectively (p = 0.33). The median PFS was 5.6 months in the D + P arm and 4.7 months in the C + P arm (p = 0.31). The median OS was 14.9 months for D + P and 12.9 months for C + P (p = 0.37). Adverse events in the two arms were well balanced. The most common grade 3/4 adverse event was hematologic toxicity. CONCLUSIONS: Patients treated with D + P had similar response and survival rates to those treated with C + P, and toxicities of both treatments were generally tolerable.

Subsequent treatment choices for patients with acquired resistance to EGFR-TKIs in non-small cell lung cancer: restore after a drug holiday or switch to another EGFR-TKI?

The outcomes of first-generation EGFR-TKIs (Gefitnib and Erlotinib) have shown great advantages over traditional treatment strategies in patients with non-small cell lung cancer (NSCLC), but unfortunately we have to face the situation that most patients still fail to respond in the long term despite initially good control. Up to now, the mechanism of acquired resistance to EGFR-TKIs has not been fully clarified. Herein, we sought to compile the available clinical reports in the hope to better understanding the subsequent treatment choices, particularly on whether restoring after a drug holiday or switching to another EGFR-TKI is the better option after failure of one kind of EGFR-TKI.

The effect of palonosetron hydrochloride in the prevention of chemotherapy-induced moderate and severe nausea and vomiting.

The current study aimed to evaluate the efficacy and safety of palonosetron hydrochloride injection for preventing chemotherapy-induced moderate and severe nausea and vomiting. A multi-centered, randomly stratified, double-blind, double-dummy, parallel-group and positive-controlled trial was performed. A total of 240 patients who underwent chemotherapy treatment which induced moderate or severe vomiting were divided into the experimental and control groups. Half an hour before chemotherapy, the experimental group received a 0.25-mg palonosetron hydrochloride injection, whereas the control group received a 3-mg granisetron injection. The acute vomiting complete remission rate (CRR) of the experimental group was not significantly different compared with that of the control group (P=0.35). The delayed vomiting CRR of the experimental group was significantly higher compared with that of the control group (P=0.002). No difference in full course vomiting CRR, vomiting control time, treatment failure time or acute nausea CRR was identified between the two groups. No significant differences in adverse events were observed between the experimental group and the control group. No significant differences in adverse reactions occurred between the experimental group and the control group (12.50%). Palonosetron hydrochloride injection had a better effect on delayed vomiting CRR than granisetron hydrochloride injection. The two injections exhibited similar effects on acute vomiting CRR, full course vomiting CRR, vomiting control time, treatment failure time (days), acute nausea CRR and adverse events.

[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.

Development of a class-specific polyclonal antibody-based indirect competitive ELISA for detecting fluoroquinolone residues in milk.

Modified 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) method was employed to synthesize the artificial antigen of norfloxacin (NOR), and New Zealand rabbits were used to produce anti-NOR polyclonal antibody (pAb). Based on the checkerboard titration, an indirect competitive enzyme-linked immunosorbent assay (icELISA) standard curve was established. This assay was sensitive and had a working range from 0.12 to 68.40 ng/ml, with the half maximal inhibitory concentration (IC(50)) and limit of detection (LOD) values of 2.7 ng/ml and 0.06 ng/ml, respectively. The produced pAb exhibited high cross-reactivity to fluoroquinolones (FQs) tested, and the IC(50) values to enoxacin, ciprofloxacin, and pefloxacin were 3.1, 3.4, and 4.1 ng/ml, respectively. It also indicated that the concentrations of NaOH and methanol in assay buffer should not be higher than 10% and 30%. When spiked in milk at 5, 20, and 50 ng/ml, the recoveries for NOR, enoxacin, ciprofloxacin, and pefloxacin ranged 90.5%-98.0%, 84.0%-95.2%, 94.0%-106.0%, and 89.5%-100.0%, respectively. The results suggest that this class-specific pAb-based icELISA could be utilized for the primary screening of FQ residues in animal-original products.

Identification and characterization of a small inhibitory peptide that can target DNA-PKcs autophosphorylation and increase tumor radiosensitivity.

PURPOSE: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. METHODS AND MATERIALS: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. RESULTS: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged γ-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. CONCLUSIONS: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

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.

[Expression profiles of microRNAs in radioresistant esophageal cell line].

OBJECTIVE: To identify the differential microRNA expression profiles of acquired radioresistant esophageal cell line established by fractionated ionizing radiation (FIR) versus parental cell line. METHODS: MicroRNA microarray was employed for detection. Bioinformatic software tools were used to predict the target genes of identified microRNAs. For an understanding of miRNA functions, the GO analysis of abundantly differentially expressed targets of miRNAs was performed by GeneOntology Browser. RESULTS: Compared with parental cell line, 10 microRNAs (hsa-miR-1539, hsa-miR-1237, hsa-miR-92b, etc.) were up-regulated over 2-fold and 25 microRNAs (hsa-miR-185, hsa-miR-18b, hsa-miR-17, etc.) down-regulated in KYSE-150R. Eighteen miRNAs had their target genes, 10 of them had the potential to individually target up to 200 mRNAs. Hsa-let-7a, hsa-miR-185, hsa-miR-141, hsa-miR-92b, hsa-miR-22 and hsa-miR-301a were known as important genes associated with radioresistance. CONCLUSION: These results confirm the involvement of miRNA in radiation resistance. It may potentially help to explain the mechanisms of gene regulation in cellular response to radioresistance.

[Aberrant methylation of T-cadherin gene in human esophageal carcinoma cells].

OBJECTIVE: To explore the methylation status of T-cadherin promoter region in human esophageal carcinoma cell lines EC1 and EC109 and elucidate the effects of 5-azacytidine-2'-deoxycytidine (5-Aza-CdR) on their abilities of proliferation and invasion, the methylation status and the expression of T-cadherin. METHODS: The expression level of T-cadherin was measured by Western blot. And the methylation status of T-cadherin promoter region was analyzed by methylation-specific PCR (polymerase chain reaction), separately before and after a treatment of demethylating agent 5-Aza-CdR. RESULTS: The T-cadherin gene was hypermethylated in EC109 cells but semi-methylated in EC1 cells. After a treatment of 5-Aza-CdR, T-cadherin gene methylation was reversed. And the gene expression was strongly up-regulated in both cells. 5-Aza-CdR could decrease the proliferation and effectively inhibit the ability of cell invasion (P < 0.01). CONCLUSION: The aberrant methylation in promoter region is an important mechanism of T-cadherin gene inactivation in human esophageal carcinoma cells. 5-Aza-CdR can increase the expression of T-cadherin by a reversal of hypermethylation and effectively inhibit the proliferation and invasion of tumor cells.

[Protein microarray analysis on changes in protein phosphorylation in recurrent nasopharyngeal carcinoma].

OBJECTIVE: To compare the differential phosphorylation level of proteins between relapsed nasopharyngeal carcinoma (rNPC) and primary nasopharyngeal carcinoma (pNPC). METHODS: Total protein was extracted from 4 pNPC tissue and 4 rNPC tissue samples from January 2003 to September 2005. Then it was analyzed by antibody microarray with 656 antibodies. The differential phosphorylation level of proteins was screened and clustering analysis conducted. The phosphorylation status of the protein sites and its functional pathways were analyzed via an online database of PhosphoSite Plus. The protein expressions were detected by immunohistochemistry. RESULTS: Relapsed and primary nasopharyngeal carcinomas had differential phosphorylation level of proteins. And 6 differentially expressed proteins were identified. The phosphorylation levels of KIT, ATP1A1, Synapsin, SEK1 and histone H2AX were up-regulated in rNPC (P = 0.007 - 0.048) while c-Jun was down-regulated (P = 0.030). The expression of P-H2AX in rNPC was significantly higher than that in pNPC [0.390 (0.175) vs 0.290 (0.155)], but p-c-Jun was significantly lower in rNPC than that in pNPC [0.625 (0.145) vs 0.725 (0.178)] (both P < 0.05). Among them, the changes in the phosphorylation levels of c-Jun, histone H2AX, SEK1 and KIT might play important roles in the relapse of NPC through improving DNA damage repair ability, inhibiting apoptosis and promoting tumorigenesis. CONCLUSION: The changes of protein phosphorylation may help to explain the recurrent mechanisms of NPC and provide new therapeutic anti-recurrence targets.

[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.

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.

[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.

[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.

[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.

[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.