Impact of glucocorticoids on the efficacy of neoadjuvant chemoradiotherapy and survival of patients with locally advanced rectal cancer: a retrospective study.

BACKGROUND: Preclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it's essential to assess the effect of GCs on clinical outcomes. METHODS: LARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan-Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS. RESULTS: This retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8-16) and low-NAR (< 8) (odds ratio [OR], 0.615; 95% CI, 0.420-0.901; P = 0.013), and the high-NAR (> 16) and low-NAR (0.563; 0.352-0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%-84.37%) vs. 85.30% (82.06%-88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%-78.82%) vs. 78.7% (75.14%-82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001-1.014], 0.036) and DFS (1.010 [1.004-1.017], 0.001). CONCLUSIONS AND RELEVANCE: Our study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.

Preoperative chemoradiotherapy with capecitabine and triweekly oxaliplatin versus capecitabine monotherapy for locally advanced rectal cancer: a propensity-score matched study.

BACKGROUND: Distant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine. METHODS: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared. RESULTS: A total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared. CONCLUSIONS: Triweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway.

An elevated level of S100A6 is associated with poor outcomes of many tumor types, but, how S100A6 contributes to nasopharyngeal carcinoma (NPC) progression remains unknown. Here, we investigated the expression and prognostic significance of S100A6 in NPC and explored the molecular mechanisms under-lying the role of S100A6 in NPC development. The results showed that S100A6 was markedly up-regulated in NPC tissues and cell lines compared to paired peritumoral normal tissues and a normal nasopharyngeal epithelial cell line, respectively. In tissues from 92 NPC patients, high S100A6 expression was associated with advanced N stage, locoregional failure and disease progression and was predictive of poor locoregional recurrence-free survival (LRRFS, P = 0.001) and progression-free survival (PFS, P = 0.001). Multivariate analysis showed that S100A6 is an independent prognostic factor for LRRFS and PFS. Silencing S100A6 using siRNA or shRNA significantly suppressed NPC cell proliferation, colony formation and p38/mitogen-activated protein kinase (MAPK) activity in vitro and inhibited tumor growth in a xenograft mouse model of NPC. In contrast, overexpressing S100A6 via plasmid transfection resulted in increased NPC cell proliferation and p38/MAPK activation. S100A6-induced proliferation was abolished by a p38 inhibitor. In summary, S100A6 may be a new prognostic marker of NPC and may promote NPC development via the activation of p38/MAPK signaling pathways. These findings suggest S100A6/p38/MAPK signaling as a potential therapeutic target for NPC. © 2016 Wiley Periodicals, Inc.

Risk factors and prediction-score model for distant metastasis in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1%. N2-3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm(3), haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0-2), intermediate risk (3-4) and high risk (5-8). The 5-year DM rates were 4.6, 21.8 and 50.8%, respectively (P < 0.001). The areas under the curve for DM in the prediction-score model and the UICC/AJCC staging system seventh edition were 0.748 and 0.627, respectively (P < 0.001). The scoring model is useful in evaluating the risk of DM in IMRT-treated NPC patients and guiding future therapeutic trials. Further prospective study is needed.

Comparison of the efficacy among different interventions for radiodermatitis: A Bayesian network meta­analysis of randomized controlled trials.

BACKGROUND: Radiation dermatitis (RD) is a prevalent and difficult-to-manage consequence of radiation therapy (RT). A variety of interventions have been proven effective in preventing and treating RD. However, the optimal approach remains unclear. This network meta-analysis (NMA) conducted a comparison and ranking of the effectiveness and patient-reported outcomes (PROs) of the interventions currently utilized in RD. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were searched to identify pertinent randomized controlled trials (RCTs) focused on the prevention and treatment of RD. The primary outcome measures included the incidence of grade≥2 RD (i.e., percentage of moist desquamation) and RD score. The secondary outcome measures encompassed patients' subjective assessment scores of pains, itching and burning sensations. RESULTS: Our meta-analysis encompassed 42 studies and 4884 participants. Regarding the primary outcomes, photobiomodulation treatment (PBMT) ranked first in surface under curve cumulative ranking area (SUCRA:0.92) for reducing the incidence of grade≥2 RD. It demonstrated a significant difference when compared to Trolamine (OR 0.18,95%CrI 0.09-0.33) and Xonrid® (OR 0.28,95%CrI 0.12-0.66). Mepitelfilm (SUCRA: 0.98) achieved the highest rank in reducing the RD score, demonstrating superiority over StrataXRT® (MD -0.89, 95% CrI -1.49, -0.29). Henna (SUCRA: 0.89) demonstrated the highest effectiveness in providing pain relief, with a significant difference compared to Hydrofilm (MD -0.44, 95% CrI -0.84, -0.04) and Mepitelfilm (MD -0.55, 95% CrI -0.91, -0.19). Hydrofilm (SUCRA: 0.84) exhibited the fewest itching sensations, demonstrating superiority over Mepitelfilm (MD -0.50, 95% CrI -0.84, -0.17). No statistically significant difference was observed among various interventions in the assessment of burning sensations. CONCLUSION: PBMT and Mepitelfilm demonstrated better efficacy in reducing the incidence of grade≥2 RD and RD score, respectively. In terms of PROs, Henna and Hydrofilm had fewer complaints in pain and itching sensations, respectively. However, studies with larger sample size on different interventions are warranted in the future. TRIAL REGISTRATION: PROSPERO registration number CRD42023428598.

Excluding external iliac node irradiation during neoadjuvant radiotherapy decreases lower intestinal toxicity without compromising efficacy in T4b rectal cancer patients with tumours involving the anterior structures.

PURPOSE: To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. METHODS: We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. RESULTS: The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3-4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. CONCLUSIONS: Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis.

BACKGROUND: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. METHODS: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. RESULTS: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%). CONCLUSIONS: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

The Effect of Lymph Node Harvest on Prognosis in Locally Advanced Middle-Low Rectal Cancer After Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The purpose of this study was to investigate the relationship between lymph node harvest and the prognosis in locally advanced rectal cancer (LARC) patients after neoadjuvant chemoradiotherapy (nCRT). METHODS: Patients who were diagnosed with clinical LARC and treated with nCRT and radical surgery between June 2008 and July 2017 were included in this study. The relationship between lymph node retrieval and prognosis was analyzed. Other lymph node-related indicators were explored. RESULTS: A total of 837 patients with a median follow-up of 61 (7-139) months were included in the study. The five-year DFS and OS rates of all patients were 74.9% and 82.3%, respectively. Multivariate survival analysis suggested that dissection of ≥ 12 lymph nodes did not improve OS or DFS. 7 was selected as the best cutoff value for the total number of lymph nodes retrieved by Cox multivariate analysis (χ2 = 10.072, HR: 0.503, P=0.002). Dissection of ≥ 5 positive lymph nodes (PLNs) was an independent prognostic factor for poorer DFS (HR: 2.104, P=0.004) and OS (HR: 3.471, p<0.001). A positive lymph node ratio (LNR) of more than 0.29 was also an independent prognostic factor for poorer DFS (HR: 1.951, P=0.002) and OS (HR: 2.434, p<0.001). CONCLUSION: The recommends that at least 7 harvested lymph nodes may be more appropriate for LARC patients with nCRT. PLN and LNR may be prognostic factors for LARC patients with ypN+ after nCRT.

Clinical predictors of pathological good response in locally advanced rectal cancer.

PURPOSE: The aim of this study was to identify the clinical predictors of pathological good response (PGR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) to clarify the indications for local excision. METHODS AND MATERIALS: A total of 173 patients with LARC (cT3-4/N +) who were treated with nCRT followed by surgery were enrolled in our retrospective study. Patients were categorized into two groups according to the different tumor responses of surgical pathology. Stage ypT0-1N0 was defined as the group with PGR, and stage ypT2-4N0/ypTanyN + was the defined as the pathological poor response (PPR) group, and the potential predictors were compared. RESULTS: Of 173 patients, PGR was achieved in 57 patients (32.95%). The distance from the inferior margin of the tumor to the anal verge, cT classification, pretreatment carcinoembryonic antigen (CEA) and the interval from the end of radiation to surgery were correlated with pathological response. In the multivariate analysis, the distance from anal verge < 5 cm (OR = 0.443, p = 0.019), pretreatment CEA < 5 ng/mL (OR = 0.412, p = 0.015) and the interval from the end of radiation to surgery ≥ 84 days (OR = 2.652, p = 0.005) were independent predictors of PGR. CONCLUSIONS: The distance from the inferior margin of the tumor to the anal verge, pretreatment CEA and the interval from the end of radiation to surgery were significant predictors of PGR in LARC. A prospective study is needed to further validate these results in the future.

The benefit of adjuvant radiotherapy on overall survival in resected stage I to II pancreatic cancer: A propensity-adjusted analysis.

BACKGROUND: The survival time of patients with early pancreatic cancer (PC) is still disappointing, even after surgical resection. PC has an extremely poor prognosis. Herein, we aimed to investigate the survival effect of postoperative radiotherapy (PORT) on resected stage I to II PC. MATERIAL AND METHODS: A large eligible sample of patients was identified from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) registry. Survival analysis was conducted to evaluate the efficiency of PORT. Propensity score matching (PSM) analysis was used to reduce selection bias and to make the groups comparable. RESULTS: A total of 3219 patients with resected stage I to II PC was included after rigid screening. The median overall survival (OS) was 26 months with PORT (n = 1055) versus 21 months with non-PORT (n = 2164) before matching (p<0.001). By multivariable analysis, PORT remained a favorable prognostic predictor for OS. In PSM analysis, receiving PORT was associated with improved OS (median, 26 months vs. 23 months; at 2 years, 51.7% vs. 46.7%; at 5 years, 23.3% vs. 17.4% (P = 0.006). After further meticulous exploration, only the stage IIB subgroup benefited from PORT (p<0.001). This result was due to the positive lymph node state (N+), whose mortality risk was cut by 23.4% (p<0.001) by PORT. CONCLUSION: Addition of PORT to the treatment of patients with resected stage I to II PC conveys a survival benefit, particularly among those with N-positive or stage IIB disease.

A Pilot Study: N-Staging Assessment of Shear Wave Elastrography in Small Cervical Lymph Nodes for Nasopharyngeal Carcinoma.

Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients. Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05. Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively. Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.

Predictive value of carcinoembryonic antigen and carbohydrate antigen 19-9 related to downstaging to stage 0-I after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVE: To explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0-I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer. MATERIALS AND METHODS: We respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre-post-CA19-9 ratio, and pre-post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients' thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0-I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system. RESULTS: Multivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre-post-CEA ratio, and pre-post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone. CONCLUSION: The 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre- post-CEA ratio, and pre-post-CA19-9 ratio is of more value in predicting downstaging to stage 0-I patients with locally advanced rectal cancer after nCRT than using the parameters alone.

Pathologic study of tumour extension for clinically localized unilateral nasopharyngeal carcinoma: Should the contralateral side be included in the clinical target volume?

INTRODUCTION: The clinical target volume (CTV) delineation is crucial for tumour control and normal tissue protection. This study investigated the contralateral extension of nasopharyngeal carcinoma (NPC) in patients with a clinically diagnosed unilateral tumour to pursue the possibility of CTV reduction. METHODS: Twenty NPC patients with localized tumours confined to only one side of the nasopharynx as shown by magnetic resonance imaging and fibreoptic endoscopy were selected for biopsy. The tissues of the contralateral pharyngeal recess (CPR) and the contralateral posterosuperior wall (CPSW) of the nasopharynx were obtained in each case and prepared for pathological examination. The factors associated with contralateral tumour infiltration were analysed. RESULTS: Five of 20 (25.0%) patients were pathologically confirmed to have carcinoma cell infiltration in the CPSW, including 2 (10.0%) that had carcinoma cell infiltration in the CPR. The T classification (P = 0.014) and primary tumour volume (P = 0.033) were positively associated with the infiltration of the CPSW, but none of the primary tumour factors affected the involvement of the CPR. The contralateral retropharyngeal lymph node (LN) metastasis (P = 0.016), but not the contralateral cervical LN, was significantly associated with the infiltration of the CPR. Positive Epstein-Barr virus DNA (EBV-DNA) was another factor that increased the probability of CPR invasion (P = 0.044). CONCLUSIONS: Contralateral pharyngeal recess infiltration is rare in patients with clinically diagnosed unilateral primary NPC. Reduced CTV coverage, including the CPSW but not CRP, is feasible for patients with unilateral cancer of the nasopharynx without contralateral LN metastasis or positive EBV-DNA. Further large-sample studies are needed.

Adjuvant chemotherapy does not benefit patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

BACKGROUND: The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). METHODS: The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically. RESULTS: A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups. CONCLUSIONS: The short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.

Long Noncoding RNA FAM201A Mediates the Radiosensitivity of Esophageal Squamous Cell Cancer by Regulating ATM and mTOR Expression via miR-101.

Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC. Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR. Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC. Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.

The Feasibility Study of a Hybrid Coplanar Arc Technique Versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost.

This study demonstrated the feasibility and advantages of a hybrid, volumetric arc therapy technique that used two 90° coplanar arcs and two three-dimensional conformal tangential beams in the simultaneous-integrated boost radiotherapy of left-sided breast cancer after breast-conserving surgery. A total of nine patients with stage I, left-sided breast cancer who underwent breast-conserving surgery were selected for this retrospective study. For each patient, a hybrid arc plan was generated and then compared with two hybrid intensity-modulated radiotherapy plans. All plans were optimized using the same objectives and dose constraints. The prescription dose was 50.4 Gy to the planning target volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28 fractions. The differences among these hybrid plans were analyzed by the Kolmogorov-Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans achieved the clinical requirements of target dose coverage and normal tissue (NT) dose constraints. It was found that the hybrid arc plans showed advantages in the conformity index of the expanded gross target volume, the V5 of the heart, the D2 of the left ventricle, and the D2 and V50.4 of NTs. The average beam-on time and monitor units of the hybrid arc plans were significantly lower (P < 0.001).

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment.

BACKGROUND: The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments. METHODS: We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index). RESULTS: We identified and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63). CONCLUSION: We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.

Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway.

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.

The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the short-term efficacy and safety of recombinant human endostatin (Endostar) combined with chemoradiotherapy for the treatment of advanced, locally recurrent nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Between March 2010 and October 2013, a total of 22 patients with stage rIII-IVb locally recurrent NPC underwent salvage radiotherapy with Endostar in Sun Yat-Sen University Cancer Center. Intensity-modulated radiotherapy (IMRT) was delivered. Platinum-based chemotherapy was used in a neoadjuvant protocol. Endostar was continuously administered intravenously (105 mg/m2) for 14 days (Days 1-14) from the first day of treatment during a 21-day cycle. Tumor response and treatment toxicities were observed. RESULTS: Until January 2014, the median follow-up time was 13 months (range, 4-41 months). All patients completed the planned radiotherapy. A complete response was achieved in 20 patients, and a partial response was achieved in 2 patients. The incidence of grade 3-5 late radiation injury in this study was 50% (11/22) and that of nasopharyngeal mucosal necrosis was 31.8% (7/22). CONCLUSIONS: Endostar combined with chemoradiotherapy may be effective in decreasing both the incidence of nasopharyngeal mucosal necrosis. Studies with a larger sample size and longer follow-up are warranted.

Distant metastasis risk and patterns of nasopharyngeal carcinoma in the era of IMRT: long-term results and benefits of chemotherapy.

PURPOSE: To report the distant metastasis (DM) risk and patterns for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to analyze the benefits of chemotherapy based on DM risk. MATERIALS AND METHODS: 576 NPC patients were analyzed. The DM rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences. The patients were divided into different risk subclassifications according to DM hazard ratios. RESULTS: 91 patients developed DM after treatment, with bone as the most common metastatic sites. 82.4% of DMs occurred within 3 years of treatment. Patients were classified as low-risk, intermediate-risk and high-risk, and the corresponding 5-year DM rates were 5.1%, 13.1% and 32.4%, respectively (P < 0.001). Chemotherapy failed to decrease the DM rate in the low-risk subclassification, but decreased the DM risk in the intermediate-risk subclassification (P = 0.025). In the high-risk subclassification, the DM rate was 31.9% though chemotherapy was used, which was significantly higher than that of other two subclassifications. CONCLUSIONS: DM is the dominant treatment failure in NPC treated by IMRT, with similar occurrence times and distributions to those that occurred in the era of conventional radiotherapy. Further studies on treatment optimization are needed in high-risk patients.