Xinqiong Huang

High Expression of SOX2 and OCT4 Indicates Radiation Resistance and an Independent Negative Prognosis in Cervical Squamous Cell Carcinoma

Radiotherapy (RT) as a preoperative or postoperative adjuvant or primary treatment is the most common management modality for locally advanced cervical cancer. Radioresistance of tumor cells remains a major therapeutic problem. Consequently, we aimed to explore if the stem cell biomarkers SOX2 and OCT4 protein could be used to predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). These 132 patients were divided into two groups (radiation-resistant and radiation-sensitive groups) according to progress-free survival (PFS). Using pretreatment paraffin-embedded tissues, we evaluated SOX2 and OCT4 expression using immunohistochemical staining. The percentage of overexpression of SOX2 and OCT4 in the radiation-resistant group was much higher than that in the radiation-sensitive group (p<0.001 and p <0.001, respectively). The patients with high expression of SOX2 and OCT4 showed a shorter PFS than those with low expression. Our study suggests that the expression of SOX2 and OCT4 in tumor cells indicates resistance to radiotherapy and that these two factors were important predictors of poor survival in patients with LACSCC (hazard ratio [95% CI], 2.294 [1.013, 5.195] and 2.300 [1.050, 5.037], respectively; p=0.046 and p=0.037, respectively).

Aberrant Expression of Osteopontin and E-Cadherin Indicates Radiation Resistance and Poor Prognosis for Patients with Cervical Carcinoma

Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group (p<0.001). These patients also had a lower 5-year PFS rate (p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001).

Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis

The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Beggers and Eggers tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency.

Mean cerebral blood volume is an effective diagnostic index of recurrent and radiation injury in glioma patients: A meta-analysis of diagnostic test

We conducted a meta-analysis to evaluate the diagnostic values of mean cerebral blood volume for recurrent and radiation injury in glioma patients. We performed systematic electronic searches for eligible study up to August 8, 2016. Bivariate mixed effects models were used to estimate the combined sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and their 95% confidence intervals (CIs). Fifteen studies with a total number of 576 participants were enrolled. The pooled sensitivity and specificity of diagnostic were 0.88 (95%CI: 0.82-0.92) and 0.85 (95%CI: 0.68-0.93). The pooled positive likelihood ratio is 5.73 (95%CI: 2.56-12.81), negative likelihood ratio is 0.15 (95%CI: 0.10-0.22), and the diagnostic odds ratio is 39.34 (95%CI:13.96-110.84). The summary receiver operator characteristic is 0.91 (95%CI: 0.88-0.93). However, the Deeks plot suggested publication bias may exist (t=2.30, P=0.039). Mean cerebral blood volume measurement methods seems to be very sensitive and highly specific to differentiate recurrent and radiation injury in glioma patients. The results should be interpreted with caution because of the potential bias.

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy

The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

Dosimetric Comparisons of Volumetric Modulated Arc Therapy and Tomotherapy for Early T-Stage Nasopharyngeal Carcinoma

Purpose To compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in treating early T-stage nasopharyngeal carcinoma (NPC). Method Ten patients with early T-stage NPC who received tomotherapy using simultaneously integrated boost (SIB) strategies were replanned with VMAT (RapidArc of Varian, dual-arc). Dosimetric comparisons between the RapidArc plan and the HT plan included the following: (1) D98, homogeneity, and conformity of PTVs; (2) sparing of organs at risk (OARs); (3) delivery time and monitor units (MUs). Results (1) Compared with RapidArc, HT achieved better dose conformity (CI of PGTVnx + nd: 0.861 versus 0.818, P = 0.004). (2) In terms of OAR protection, RapidArc exhibited significant superiority in sparing ipsilateral optic nerve (Dmax: 27.5Gy versus 49.1Gy, P < 0.001; D2: 23.5Gy versus 48.2Gy, P < 0.001), contralateral optic nerve (Dmax: 30.4Gy versus 49.2Gy, P < 0.001; D2: 26.2Gy versus 48.1Gy, P < 0.001), and optic chiasm (Dmax: 32.8Gy versus 48.3Gy, P < 0.001; D2: 30Gy versus 47.6Gy, P < 0.001). HT demonstrated a superior ability to protect the brain stem (D1cc: 43.0Gy versus 45.2Gy, P = 0.012), ipsilateral temporal lobe (Dmax 64.5Gy versus 66.4 Gy, P = 0.015), contralateral temporal lobe (Dmax: 62.8Gy versus 65.1Gy, P = 0.001), ipsilateral lens (Dmax: 4.27Gy versus 5.24Gy, P = 0.009; D2: 4.00Gy versus 5.05Gy, P = 0.002; Dmean: 2.99Gy versus 4.31Gy, P < 0.001), contralateral lens (Dmax: 4.25Gy versus 5.09Gy, P = 0.047; D2: 3.91Gy versus 4.92Gy, P = 0.005; Dmean: 2.91Gy versus 4.18Gy, P < 0.001), ipsilateral parotid (Dmean: 36.4Gy versus 41.1Gy, P = 0.002; V30Gy: 54.8% versus 70.4%, P = 0.009), and contralateral parotid (Dmean: 33.4Gy versus 39.1Gy, P < 0.001; V30Gy: 48.2% versus 67.3%, P = 0.005). There were no statistically significant differences in spinal cord or pituitary protection between the RapidArc plan and the HT plan. (3) RapidArc achieved a much shorter delivery time (3.8 min versus 7.5 min, P < 0.001) and a lower MU (618MUs versus 5646MUs, P < 0.001). Conclusion Our results show that RapidArc and HT are comparable in D98, dose homogeneity, and protection of the spinal cord and pituitary gland. RapidArc performs better in shortening delivery time, lowering MUs, and sparing the optic nerve and optic chiasm. HT is superior in dose conformity and protection of the brain stem, temporal lobe, lens, and parotid.

Nimotuzumab combined with concurrent chemoradiotherapy benefits patients with advanced nasopharyngeal carcinoma

Background The potential benefits and possible risks associated with combined nimotuzumab and concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma (NPC) have yet to be determined. Methods The databases PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang were systematically searched through February 2017 for studies comparing combined nimotuzumab and chemoradiotherapy versus chemoradiotherapy alone in the treatment of NPC. Primary outcomes were complete and partial responses, and the secondary outcome was adverse reactions. The random-effect model was used to pool relative risks (RRs) and 95% confidence intervals (CIs). Results Nine randomized control trials and six cohort studies were included in the final analysis (n=1,015 patients). Compared with chemoradiotherapy alone, chemoradiotherapy combined with nimotuzumab was associated with an increased response rate (RR =1.11, 95% CI: 1.01–1.22). Combined treatment further reduced the occurrence rate of erythropenia (RR =0.11, 95% CI: 0.05–0.28) and neutropenia (RR =0.12, 95% CI: 0.05–0.27). The differences in the rates of other complications were not significant. Conclusion Nimotuzumab combined with concurrent chemoradiotherapy is more effective in patients with advanced NPC than chemoradiotherapy alone. Patients receiving combination therapy did not have a higher rate of adverse reactions. Nimotuzumab can thus be recommended as an adjunct therapy in patients with advanced NPC.