SummaryRadiotherapy (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). (J Histochem Cytochem 62:499-509, 2014)

SummaryRadiotherapy 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). (J Histochem Cytochem 63:88-98, 2015)

BackgroundGross target volume of primary tumor (GTV-P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity-modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to find a suitable cut-off value of GTV-P for prognosis prediction.MethodsClinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver operating characteristic (ROC) curves were used to identify the cut-off values of GTV-P for the prediction of different endpoints [overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS)] and to test the prognostic value of GTV-P when compared with that of the American Joint Committee on Cancer T staging system.ResultsThe 358 patients with locally advanced NPC were divided into two groups by the cut-off value of GTV-P as determined using ROC curves: 219 (61.2%) patients with GTV-P ≤46.4 mL and 139 (38.8%) with GTV-P >46.4 mL. The 3-year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV-P ≤46.4 mL than in those with GTV-P > 46.4 mL (all P < 0.05). Multivariate analysis indicated that GTV-P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve verified that the predictive ability of GTV-P was superior to that of T category (P < 0.001). The cut-off values of GTV-P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively.ConclusionIn patients with locally advanced NPC, GTV-P >46.4 mL is an independent unfavorable prognostic indicator for survival after IMRT, with a prognostic value superior to that of T category.

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.

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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 Deek's 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.

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. Begger's and Egger's 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.

BackgroundThe potential benefits and possible risks associated with combined nimotuzumab and concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma (NPC) have yet to be determined.MethodsThe 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).ResultsNine 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.ConclusionNimotuzumab 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.