Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma

AIM To evaluate the long-term effectiveness and late toxicities of paclitaxel(PTX) plus cisplatin(DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer.METHODS Between 2008 and 2011, 76 patients were enrolled in a phase Ⅱ study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy(68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP(25 mg/m^2 per day for 3 d) and PTX(175 mg/m^2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern.RESULTS A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient(heart failure). In log-rank analysis, the pretreatment stage(stage Ⅱ + Ⅲ: 36.1 mo vs stage Ⅳ: 14.9 mo) and the completed cycle(1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors(P = 0.037 < 0.05 and P = 0.013 < 0.05).CONCLUSION Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

Objective： In recent years, the combination of cetuximab and chemoradiotherapy （CRT） has been used to treat stage III non-small cell lung cancer （NSCLC）; however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT （CCRT） in Chinese patients with stage III NSCLC. Methods： Eligibility criteria were Zubrod performance status （PS） 0-1, forced expiratory volume in 1 second （FEV1） 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab （initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT） with cisplatin/vinorelbine （NP） chemotherapy （every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy （TRT） （60-66 Gy/2 Gy）. The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography （PET-CT） scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis （TNM） stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results： Seventeen patients were enrolled and 16 completed the full regime. The overall response rate （ORR） was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval （CI）： 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% （95% CI, 60.6-96.9%） and 58.8% （95% CI, 60.6-77.8%）, respectively. Three patients remain progression-free to date, and the median progression-free survival （PFS） was 13.5 months （95% CI, 6.8-20.2 months）. No treatment-related death occurred; however, 76% of the patients experienced grade 3＋ adverse events （AEs）, including nansea/vomiting, intestinal obstruction, and esophagitis （〈6%）, while other AEs were mostly of hematological nature （71%）. The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL （P=0.027）, SUV-T （P=0.025）, and PS （P=0.006） as potential survival predictors, with a hazard ratio （HR） of 3.4, 3.7, and 9.9, respectively. Conclusions： The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Genome-wide Scan for Seed Composition Provides Insights into Soybean Quality Improvement and the Impacts of Domestication and Breeding

The complex genetic architecture of quality traits has hindered efforts to modify seed nutrients in soybean. Genome-wide association studies were conducted for seed composition, including protein, oil, fatty acids, and amino acids, using 313 diverse soybean germplasm accessions genotyped with a high-density SNP array. A total of 87 chromosomal regions were identified to be associated with seed composition, explain- ing 8%-89% of genetic variances. The candidate genes GmSAT1, AK-HSDH, SACPD-C, and FAD3A of known function, and putative MtN21 nodulin, FATB, and steroid-5-^-reductase involved in N2 fixation, amino acid biosynthesis, and fatty acid metabolism were found at the major-effect loci. Further analysis of additional germplasm accessions indicated that these major-effect loci had been subjected to domes- tication or modern breeding selection, and the allelic variants and distributions were relevant to geographic regions. We also revealed that amino acid concentrations related to seed weight and to total protein had a different genetic basis. This helps uncover the in-depth genetic mechanism of the intricate relationships among the seed compounds. Thus, our study not only provides valuable genes and markers for soybean nutrient improvement, both quantitatively and qualitatively, but also offers insights into the alteration of soybean quality during domestication and breeding.

Particle therapy for cancers:a new weapon in radiation therapy

Particle irradiation started to draw attention in the past decade and has now become a hotspot in the radiation oncology community.This article reviews the most advanced developments in particle irradiation,focusing on the characteristics of proton and carbon ions in radiation physics and radiobiology.The Bragg peak of physical dose distribution causes proton and carbon beams to optimally meet the requirement for cancer irradiation because the Bragg peak permits the accurate concentration of the dose on the tumor,thus sparing the adjacent normal tissues.Moreover,carbon ion has more radiobiological benefits than photon and proton beams.These benefits include stronger sterilization effects on intrinsic radio-resistant tumors and more effective killing of hypoxic,G0,and S phase cells.Compared with the most advanced radiation techniques using photon,such as three-dimensional conformal radiation therapy and intensity-modulated radiation therapy,proton therapy has yielded more promising outcomes in local control and survival for head and neck cancers,prostate carcinoma,and pediatric cancers.Carbon therapy in Japan showed even more promising results than proton therapy.The local controls and overall survivals were as good as that treated by surgery in early stages of non-small cell lung cancer,hepatocellular carcinoma,prostate carcinoma,and head and neck cancers,especially for such highly resistant tumors as melanoma.The non-invasive nature of particle therapy affords more patients with chances to receive and benefit from treatment.Particle therapy is gradually getting attention from the oncology community.However,the cost of particle therapy facilities has limited the worldwide use of this technology.