A retrospective dosimetry study of intensity-modulated radiotherapy for nasopharyngeal carcinoma: radiation-induced brainstem injury and dose-volume analysis.

BACKGROUND: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. METHODS: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141 months), and six with T4 and two with T3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T4 stage, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.

Serum BMP-2 up-regulation as an indicator of poor survival in advanced non-small cell lung cancer patients.

PURPOSE: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). METHODS: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. RESULTS: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. CONCLUSION: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.

Clinical observations on safety of fixed dose rate gemcitabine chemotherapy by intravenous infusion.

PURPOSE: To observe the safety of fixed dose rate gemcitabine by intravenous infusion (iv-FDR) for cancers. METHODS: From January 1, 2007 to December 31, 2009, four patients who were pathologically diagnosed with advanced pancreatic or breast cancer were recruited into this study. They were treated by gemcitabine 10mg/m2/min iv-FDR on days 1 and 8, and combined with other chemotherapeutics, repeated every four weeks. Toxicity was determined in line with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). RESULTS: The main toxicity was reversible myelosuppression; other side effects included gastrointestinal toxicity and liver impairment. Cardiac or renal toxicity was not detected. CONCLUSION: The toxicity of iv-FDR gemcitabine combination chemotherapy was well tolerated, so that iv-FDR gemcitabine deserves to be further studied as a treatment option.

Lack of influence of XRCC1 and XPD gene polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancers.

PURPOSE: Genetic polymorphisms of DNA repair genes are associated with differential enzyme activity and may help explain interindividual differences in response rates after platinum-based chemotherapy for non small cell lung cancers (NSCLCs). This study was conducted to assess relationships between X-ray repair cross complementing group1 (XRCC1) and xeroderma pigmentosum group D (XPD) genetic polymorphisms and outcome in NSCLC patients. METHODS: From March 1, 2005 to December 31, 2008, the polymerase chain reaction-restriction fragment length polymorphism method was applied to evaluate genetic polymorphisms of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) DNA repair genes in 108 patients with stage IIIB and IV NSCLCs treated with platinum-based chemotherapy in the Department of Chemotherapy of Jiangsu Cancer Hospital and Research Institute. RESULTS: Among the assessed NSCLC patients, the overall response rate of chemotherapy was 21.6%. No association was found with either of the genetic polymorphisms, although the XRCC1 399Arg/Arg genotype was associated with a non-significant higher median survival time (29 months versus 21 months for the Arg/Gln genotype and 15 months for the Gln/Gln genotype, P= 0.09). CONCLUSION: Our results suggested no influence of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) genetic polymorphisms on treatment response and survival in advanced NSCLC patients with platinum-based chemotherapy.