Radiomics combined with clinical characteristics predicted the progression-free survival time in first-line targeted therapy for advanced non-small cell lung cancer with EGFR mutation.

OBJECTIVE: This study was to explore the most appropriate radiomics modeling method to predict the progression-free survival of EGFR-TKI treatment in advanced non-small cell lung cancer with EGFR mutations. Different machine learning methods may vary considerably and the selection of a proper model is essential for accurate treatment outcome prediction. Our study were established 176 discrimination models constructed with 22 feature selection methods and 8 classifiers. The predictive performance of each model were evaluated using the AUC, ACC, sensitivity and specificity, where the optimal model was identified. RESULTS: There were totally 107 radiomics features and 7 clinical features obtained from each patient. After feature selection, the top-ten most relevant features were fed to train 176 models. Significant performance variations were observed in the established models, with the best performance achieved by the logistic regression model using gini-index feature selection (AUC = 0.797, ACC = 0.722, sensitivity = 0.758, specificity = 0.693). The median R-score was 0.518 (IQR, 0.023-0.987), and the patients were divided into high-risk and low-risk groups based on this cut-off value. The KM survival curves of the two groups demonstrated evident stratification results (p = 0.000).

Tumor location as an indication for adjuvant radiotherapy in pT3N0 rectal cancer after surgery.

BACKGROUND: The optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer. METHODS: We performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: For patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients. CONCLUSION: Tumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.

Elevated circulating tumor cells and squamous cell carcinoma antigen levels predict poor survival for patients with locally advanced cervical cancer treated with radiotherapy.

OBJECTIVE: To evaluate the prognostic effects of combining serum circulating tumor cells (CTCs) and squamous cell carcinoma antigen (SCC-Ag) levels on patients with locally advanced cervical cancer treated with radiotherapy. METHODS: Ninety-nine patients with locally advanced cervical cancer ([FIGO] stage IIB-IVA) undergoing radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) were identified. The association between serum CTC level and clinicopathological parameters was examined. Univariate and multivariate survival analyses were performed by using Cox's proportional hazards regression model. RESULTS: Elevated CTC and SCC-Ag levels were significantly associated with poor disease-free survival (DFS). Multivariate analysis suggest that serum CTC level, FIGO stage and serum SCC-Ag level were independent prognostic factors for two-year DFS. When CTC and SCC-Ag levels were combined into a new risk model to predict disease progression of cervical cancer patients, it performed a significantly better predictive efficiency compared with either biomarker alone. CONCLUSION: Serum CTC and SCC-Ag levels are potentially useful biomarkers for prediction of prognosis in locally advanced cervical cancer patients and their combination significantly improves predictive ability for survival in locally advanced cervical cancer patients.

Extraskeletal osteosarcoma in right neck subcutaneous tissue: A case report of an extremely rare tumour.

Extraskeletal osteosarcoma (ESOS) is a rare soft-tissue sarcoma that is treated with surgical resection, chemotherapy and radiotherapy; however, as it is now considered to be radiation resistance, it is associated with conflicting management principles and poor outcomes. A multimodality approach is currently used to treat ESOS, which entails the incorporation of multidrug chemotherapy and/or radiotherapy coupled with surgery to obtain the best outcome; however, there are many factors that influence the treatment effects and clinical outcomes of ESOS. In the present study, a case of an 81-year-old man who suffered from primary ESOS in the subcutaneous tissue of the right-hand side of the neck was reported. The patient was treated several times with partial resection and once with radiotherapy, and was still living following 3 years of follow-up. Thus, the present case report demonstrated that surgical resection and postoperative radiotherapy regimens may be favourable in the short term with a disease-free survival of ~15 months; however, patients are prone to relapse.

P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line.

A previous study demonstrated that p300 is overexpressed in nasopharyngeal carcinoma (NPC), and that its expression is an independent prognostic factor. The aim of the present study is to investigate the role of p300 in human NPC development. A small hairpin (sh) RNA lentiviral expression vector targeting the p300 gene was constructed to suppress the expression of p300 in NPC cells. Knockdown of p300 was verified by reverse transcription-quantitative polymerase chain reaction and western blotting. Wound-healing, invasion, immunofluorescence and immunoprecipitation assays were performed to assess the influence of p300 on nasopharyngeal tumorigenesis and metastasis in vitro. The expression of p300 was upregulated in NPC cell lines. After knockdown of p300, the migration and invasion ability of shp300 cells were significantly inhibited (P<0.05). Furthermore, the depletion of p300 expression in NPC cell lines resulted in the upregulation of epithelial phenotype marker E-cadherin and α-catenin, and downregulation of mesenchymal phenotype markers N-cadherin and vimentin. p300 promotes epithelial-mesenchymal transition (EMT) through the acetylation of Smad2 and Smad3 in the tumor growth factor-ß signaling pathway. In conclusion, p300 may be involved in the invasion and metastasis of NPC through the induction of EMT.

Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. METHODS: Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical-pathological parameters was examined. Univariate and multivariate survival analyses were performed. FINDINGS: The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. CONCLUSION: The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant metastasis-free survival in patients with NPC.

ShRNA-mediated silencing of the ubiquitin-specific protease 22 gene restrained cell progression and affected the Akt pathway in nasopharyngeal carcinoma.

Ubiquitin-specific protease 22 (USP22) is closely related with poor prognosis of cancer patients. However, the role of USP22 expression in nasopharyngeal carcinoma (NPC) has not been determined. The main aim of this study was to determine the role of USP22 in the pathologic processes of NPC. Immunohistochemistry (IHC), western blot (WB), and real-time polymerase chain reaction (RT-PCR) were used to measure the expression of USP22 in cell lines and tissues of NPC in comparison with expression in non-cancerous cells and tissues. USP22-specific short hairpin RNA (shRNA) was used to knock down USP22 expression in the NPC cell line CNE-1 and CNE-2. Furthermore, the impact of USP22 in cellular proliferation, growth, and cell cycle were detected respectively. WB was used to determine the role of USP22 in the AKT/GSK-3/Cyclin signaling pathway. The expression levels of USP22 were remarkably higher in NPC cell lines and tissues. With cell counting and the MTS assay, cellular growth and proliferation progression of USP22 knockdown cell line was shown to be effectively restrained. The USP22 silencing both in CNE-1 and CNE-2 cells caused them to accumulate in the G0/G1 phase of the cell cycle. USP22 knockdown was also found to modulate the AKT/GSK-3/Cyclin pathway, resulting in downregulation of p-AKT, p-GSK-3ß, and cyclinD1. This study suggests that USP22 plays a critical regulatory role in the pathologic processes of NPC, and that it may be a potential biological treatment target in the future.

High expression of p300 is linked to aggressive features and poor prognosis of nasopharyngeal carcinoma.

BACKGROUND: Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood. METHODS: In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model. RESULTS: Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036). CONCLUSIONS: Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.

[Intensity-modulated or 3-D conformal radiotherapy combined with chemotherapy with docetaxel and cisplatin for locally advanced esophageal carcinoma].

OBJECTIVE: To evaluate the therapeutic effect and toxicity of intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy combined with chemotherapy (3-DCRT) with docetaxel and cisplatin in the treatment of locally advanced esophageal carcinoma. METHODS: Sixty patients with locally advanced esophageal carcinoma were randomly assigned in two equal groups to receive IMRT or 3-DCRT, both combined with the chemotherapy with docetaxel and cisplatin. The total dose of radiotherapy was 64 Gy, administered in 30 fractions in 6 weeks. RESULTS: The complete response rate (complete and partial remissions) of IMRT group was 90.0%, significantly higher than the rate of 80.0% in 3-DCRT group (P>0.05). The 1-, 2-, and 3-year survival rates of IMRT group were 86.7%, 70.0%, and 66.7%, as compared to 70.0%, 63.3%, and 63.3% in 3-DCRT group, respectively, showing no significant differences between the two groups (P>0.05). IMRT showed advantages over 3-DCRT in terms of the V20 and V30 parameters of the lung (P<0.05), and the incidences of radiation-induced esophagitis were comparable between the two groups (P>0.05). CONCLUSION: When combined with the chemotherapy with docetaxel and cisplatin, IMRT appears to be a more effective treatment than 3-DCRT for locally advanced esophageal cancer.

[In vitro induced and expanded Epstein Barr virus-specific cytotoxic T lymphocytes can specifically kill nasopharyngeal carcinoma cells].

OBJECTIVE: To establish a method for efficient induction and expansion of Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) in vitro and evaluate the possibility of using this strategy for treatment of nasopharyngeal carcinoma (NPC). METHODS: EBV-transformed B lymphoblastoid cells (BLCLs) were used as the antigen stimuli and antigen-presenting cells. EBV-specific CTL was induced by co-culture of the autologous peripheral blood mononuclear cells (PBMCs) and the irradiated BLCLs, and expanded with a cocktail method consisting of OKT-3, irradiated homologous PBMC, and IL-2. The specific activity of the CTL against the NPC cells was measured with MTT assay. RESULTS: EBV-specific CTL was successfully induced and expanded by 600 folds. The killing efficiency of the CTL was 76% for autologous BLCLs, 13% for homologous BLCLs, 51% for autologous NPC cells, and 27% for homologous CNE cell line, and after expansion, the corresponding killing efficiencies were 63%, 25%, 49%, and 33%, respectively. The non-specific killing only slightly increased after the expansion. CONCLUSION: EBV-specific CTL can be successfully induced and expanded in vitro for specific killing of autologous NPC cells, suggesting the potential of this strategy in the treatment of NPC.

[Effect of Selaginella combined with radiotherapy on nasopharyngeal carcinoma].

OBJECTIVE: To observe the Chinese herbal medicine Selaginella-induced radiosensitization of terminal nasopharyngeal carcinoma (NPC). METHODS: Totally 180 patients with NPC were divided equally into 3 groups with the same radiotherapeutic protocols. The patients in group A received radiotherapy alone, those in group B were given daily Selaginella (30 g) prepared into 50 ml decoction during the entire course of radiotherapy, and those in group C had Selaginella 30 g daily in the late course of radiotherapy. RESULTS: The complete remission rate of nasopharyngeal primary lesions in groups B and C was significantly higher than that in group A, with also significantly higher complete remission rates of the cervical lymph nodes. The acute toxicity of the skin and mucous membrane was milder in the latter two groups, but the differences were not significant. CONCLUSION: Selaginella may induce radiosensitization for terminal NPC and does not increase the acute toxicity of radiotherapy.

[Hyperfractionated radiation therapy combined with concomitant chemotherapy for inoperable stage III non-small cell lung cancer: clinical analysis of 70 cases].

OBJECTIVE: To evaluate the effect of hyperfractionated radiation therapy and concomitant chemotherapy for inoperable stage III non-small cell lung cancer (NSCLC). METHODS: Seventy patients were randomized equally into two group. The therapy group received radiotherapy with hyperfractionated radiation therapy combined with concomitant chemotherapy, and the control group was treated with chemotherapy only. RESULT: The overall response rate, including the rate of both complete (CR) and partial responses (PR), in the therapy group was 60.0% with a CR rate of 8.6%. The overall response rate in the control group was 40.0% with a CR rate of 5.7%. The difference in overall response rate was statistically significant between the two groups (P<0.05). The median survival time, 1- and 2-years survival rate were 12.8 months, 48.6%, and 25.7%, respectively, in the hyperfractionated radiotherapy group, and 9.4 months, 34.3%, and 17.1%, respectively, in the chemotherapeutic group (P 0.031). The major toxic effects of the chemotherapy were myelosuppression and radiation esophagitis. CONCLUSION: Hyperfractionated radiation therapy plus concomitant chemotherapy with paclitaxel for inoperable stage III NSCLC improves the short-term response of the patients, but fail to raise the survival rate.

Clinical evaluation of combined-modality therapy for bone metastasis of non-small-cell lung cancer.

OBJECTIVE: To compare the therapeutic effects of single- and combined-modality therapy on bone metastasis of non-small-cell lung cancer. METHODS: Seventy patients with bone metastasis of non-small-cell lung cancer were treated with one of the therapeutic modalities of radiotherapy, radioisotope, chemotherapy or medication with Bonefos respectively, while another 71 cases received combined-modality therapy through different combinations of the already listed modalities. RESULTS: The single modality of radiotherapy, radioisotope, chemotherapy and Bonefos had similar efficacy in treating the bone metastasis cases, which were 55.0%, 56.2%, 42.1% and 53.3% respectively, with a total efficacy rate of 51.4%. Combined-modality therapy proved to be much superior in terms of the total efficacy rate (76.0%, P <0.05), but the blood and the gastrointestinal toxicity was not significantly reduced as compared with that in single-modality group (P >0.05). CONCLUSION: The combined- modality therapy is more effective for treating bone metastasis of non-small-cell lung cancer than single-modality therapy.