The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

PURPOSE We evaluate whether the change of heat shock protein 90a (HSP90a) level before and after definitive chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC) affects tumor response and overall survival (OS). This study aimed to investigate the role of HSP90a reduction ratio after CRT. METHODS Correlations between pre-CRT HSP90a levels and the tumor response to CRT were analysed. Patients were divided into three groups (Group 1: Serum HSP90a levels pretreatment CRT less than 124 ng/mL; Group 2: pre-CRT HSP90a of 124 ng/mL or more with HSP90a reduction ratio of 65% or more; Group 3: pre-CRT HSP90a of 124 ng/mL or more with HSP90a reduction ratio less than 65%), and their oncologic outcomes were compared. RESULTS The rates of good response in HSP90a low (pre-CRT HSP90a ≤ 124 ng/mL) and high groups (pre-CRT HSP90a ≤ 124 ng/mL) were 67.3% (68/101) and 37.78% (20/79), respectively (P= 0.004). The rates of good response were significantly higher in Group 1 than in Groups 2 and 3 (58.5% vs. 46.0% and 27.8%, respectively; P= 0.013). The results from statistical analysis indicated that the tumor response was significantly associated with the serum levels of pre-CRT HSP90a and HSP90a Group (P< 0.05). The OS rate was not different between Groups 1 and 2 but was significantly lower in Group 3. HSP90a Group were independent prognostic factors for OS. CONCLUSIONS HSP90a levels could be of clinical value as a predictor of response to CRT HSP90a reduction ratio might be an independent prognostic factor for in ESCC patients treated with definitive CRT.

Background: Peripheral blood lymphocytes play an important role in antitumour immunity. We examined the relationship between the minimum absolute lymphocyte counts (Min ALCs) during radiotherapy (RT) and clinical outcomes in patients with hepatocellular carcinoma (HCC). Methods: Data from a total of 69 HCC patients who had received RT were retrospectively analysed. Peripheral blood lymphocytes were measured before RT, weekly during RT and after RT. Regression and mixed-effect models were used to assess the relationships with and potential predictors of overall survival (OS). Receiver-operating characteristic (ROC) curve analysis was used to define optimal cut-off points of continuous variables for outcomes. Results: The median follow up was 30 months (range, 4–68 months). The median survival time (MST), 1-year OS rate and 2-year OS rate of the whole group were 25 months, 51% and 39%, respectively. The average circulating lymphocyte counts declined during RT (1493.19 versus 503.48 cells/µl, p < 0.001). A lower Min ALC was associated with worse OS ( p = 0.001), with a cut-off value of 450 cells/µl (sensitivity and specificity, 50% and 70.6%, respectively). The MSTs, 1-year OS rates and 2-year OS rates were 15 months versus 47 months, 27% versus 78% and 4% versus 71% for patients with relatively lower (⩽450 cells/µl) and higher Min ALCs (>450 cells/µl), respectively ( p < 0.001). After adjusting for potential confounders, multivariate Cox regression analysis demonstrated that Min ALC independently predicted patients’ OS (HR, 0.32; 95% CI, 0.15–0.69). Conclusions: Lower Min ALCs during RT may act as a worse prognostic factor for HCC after RT.

Aberrant microRNA (miRNA) expression in cancer affects the transcription of target genes, and profoundly influences cancer‑associated signaling pathways. Radiation resistance is a major problem encountered in the treatment of cancer. The present study aimed to investigate the role of miRNA (miR)‑21 in the development of radiation resistance in non‑small cell lung cancer cells. A radiation‑resistant cell line was generated from A549 cells. Significant upregulation of miR‑21 was detected in the radioresistant cancer cells, as compared with the radiosensitive cells, and overexpression of miR‑21 rendered A549 parental cells resistant to radiation. In addition, glycolysis was increased in the radioresistant cells, as compared with the sensitive cells. Furthermore, hypoxia‑inducible factor‑1α (HIF1α) was upregulated by miR‑21 in radioresistant cells, resulting in promotion of the key enzymes of glycolysis. Inhibition of HIF1α by small interfering RNA suppressed glycolysis and resensitized the cancer cells to radiation, whereas the recovery of HIF1α in miR‑21‑inhibited radioresistant cells resulted in recovery of radioresistance. In conclusion, the present study suggested that miR‑21 may modulate radioresistance through the upregulation of HIF1α. These results may provide a novel perspective on miRNA for the development of anti-radioresistance drugs.

Purpose: Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods: PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results: Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07-5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57-0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67-2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478-13.56; P, 0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06-13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion: Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment.

BACKGROUND AND PURPOSE:To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. PATIENTS AND METHODS:Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. RESULTS:The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V 50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower D mean (mean dose) and V 20 (V n, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). D mean of nontarget normal liver and V 30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. CONCLUSION:HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy.

BACKGROUND: At present no useful factors to predict the sensitivity to neoadjuvant chemoradiotherapy (nCRT) have been established in patients with locally advanced rectal cancer (LARC).OBJECTIVE: The objective of this study was to explore the prognostic role of T cell factor 4 (TCF4) expression in predicting tumor response to nCRT and tumor outcomes for patients with LARC.METHODS: The study enrolled 96 patients who underwent nCRT followed by total mesorectal excision (TME). The TCF4 expression of all patients' biopsies before nCRT was evaluated by Immunohistochemical staining method.RESULTS: After completion of nCRT, 5 cases (5.2%) achieved clinical complete response (cCR) thus the remaining 91 patients underwent a standardized total mesorectal excision (TME) procedure. There were 44 patients (45.8%) achieved good tumor response (including TRG 3-4 and 5 cCR patients) while poor response (TRG 0- 2) was achieved in 52 patients (54.2%). Our results demonstrated that patients with low expression of TCF4 were more sensitive to nCRT than those with high TCF4 expression (P = 0.031). Low TCF4 expression before nCRT and good response were significantly associated with improved 5-year diseasefree survival and 5-year overall survival (P < 0.05). Multivariate analysis confirmed that the pretreatment TCF4 expression was an independent prognostic factor.CONCLUSIONs: Our data revealed that low TCF4 protein expression was a useful predictive factor of good tumor response to nCRT and good outcomes in patients with LARC.

Locally advanced rectal cancer is currently treated with preoperative radiochemotherapy, but the response is not uniform. Most patients benefit from preoperative CRT, however, a small proportion of a patient population is less likely to respond to the treatment. The purpose of this study was to measure neoadjuvant therapy combined with Ki-67 and VEGF expression in pretreatment biopsies and postoperative specimens，serum carcinoembryonic antigen (CEA) and CA19-9 level from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome.Â

Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been implemented as a standard treatment strategy in locally advanced rectal cancer (LARC). However, there is a wide spectrum of response to nCRT. The aim of this study was to determine whether enhancer of zeste homologue 2 (EZH2) expression could predict response to nCRT and outcomes for patients in LARC.Method: The study examined the EZH2 expression in 112 biopsies by immohistochemistry. The associations between EZH2 and clinical characters were analyzed.Results: EZH2 expression in biopsy tissue was significantly related to increased tumor cell proliferation, as assessed by Ki-67 expression with a cutoff value of 37% (p < 0.001). High EZH2 expression was correlated closely with low differentiation (p = 0.029), high CEA level (p = 0.041), T4 status (p = 0.011) and node metastasis (p = 0.045). By univariate and multivariate analysis, we observed low EZH2 expression could reliably and independently predict the good response to nCRT (p = 0.026 and p = 0.023) and down-staging (p = 0.021 and p = 0.027). In univariate analysis, high EZH2 expression was significantly associated with poor 5-year disease-free survival (p = 0.025) and 5-year overall survival (p = 0.032). In multivariate analysis, EZH2 was a prognostic factor for 5-year DFS (HR = 2.287; 95% CI 1.137-4.602, p = 0.020) but not for 5-year OS (HR = 2.182; 95% CI 0.940-5.364, p = 0.069).Conclusion: Our study revealed that low EZH2 expression in biopsy tissue might be a useful predictive factor of good tumor response to nCRT and longer 5-year DFS in patients with LARC. However this is a relatively small retrospective study, to further validate the role of EZH2 in rectal cancer, large consistent cohort studies are needed.

PURPOSE:The analysis was designed to compare dosimetric parameters among 3-D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and RapidArc (RA) to identify which can achieve the lowest risk of radiation-induced liver disease (RILD) for hepatocellular carcinoma (HCC). METHODS:Twenty patients with HCC were enrolled in this study. Dosimetric values for 3DCRT, IMRT, and RA were calculated for total dose of 50 Gy/25 f. The percentage of the normal liver volume receiving >40, >30, >20, >10, and >5 Gy (V(40), V(30), V(20), V(10) and V(5)) were evaluated to determine liver toxicity. V5, V(10), V(20), V(30) and D(mean) of liver were compared as predicting parameters for RILD. Other parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V(110%)) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (D(mean)) for the organs at risk (OARs) and the maximal dose at 1% volume (D1%) for the spinal cord. RESULTS:The D(mean) of IMRT was higher than 3DCRT (p = 0.045). For V5, there was a significant difference: RA > IMRT >3DCRT (p <0.05). 3DCRT had a lower V(10) and higher V(20), V(30) values for liver than RA (p <0.05). RA and IMRT achieved significantly better CI and lower V(110%) values than 3DCRT (p <0.05). RA had better HI, lower MUs and shorter delivery time than 3DCRT or IMRT (p <0.05). CONCLUSION:For right lobe tumors, RapidArc may have the lowest risk of RILD with the lowest V(20) and V(30) compared with 3DCRT or IMRT. For diameters of tumors >8 cm in our study, the value of Dmean for 3DCRT was lower than IMRT or RapidArc. This may indicate that 3DCRT is more suitable for larger tumors.

Objective: The purpose of this study was to examine the role of programmed cell death 4 (PDCD4) expression in predicting tumor response to neoadjuvant chemoradiotherapy and outcomes for patients with locally advanced rectal cancer. Methods: Clinicopathological factors and expression of PDCD4 were evaluated in 92 patients with LARC treated with nCRT. After the completion of therapy, 4 cases achieved clinical complete response (cCR), and thus the remaining 88 patients underwent a standardized total mesorectal excision procedure. There were 38 patients (41.3%) with a good response (TRG 3-4) and 54 (58.7%) with a poor one (TRG 0-2). Results: Immunohistochemical staining analyses showed that patients with high expression of PDCD4 were more sensitive to nCRT than those with low PDCD4 expression (P=0.02). High PDCD4 expression before nCRT and good response (TRG3-4) were significantly associated with improved 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis demonstrated that the pretreatment PDCD4 expression was an independent prognostic factor. Conclusion: Our study demonstrated that high expression of PDCD4 protein is a useful predictive factor for good tumor response to nCRT and good outcomes in patients with LARC.

The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.

OBJECTIVE:The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).METHODS:All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system.RESULTS:There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors.CONCLUSION:Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS.

Patients with esophageal small cell carcinoma undergoing definitive chemoradiotherapy (CRT) seem to have disparity in tumor response. The identification of CRT sensitivity-related tumor markers would be helpful for selecting patients most likely to benefit from CRT. The aim of this study was to examine the predictive value of biological markers in small cell carcinoma of the esophagus (SCEC) patients treated with definitive CRT. Pretreatment serum levels of neurone-specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and carcinoembryonic antigen (CEA) were measured by immunoradiometric assays, while the tumor responses were evaluated according to the World Health Organization response criteria. The relationships between pretreatment expression of NSE, CYFRA21-1, CEA, and the tumor response to CRT were analyzed. The effective rates (complete response + partial response) in NSE high and low groups were 10.80 % (9/82) and 37.98 % (31/82), respectively (P = 0.003).The results from statistical analysis indicated that the effectiveness of CRT was significantly associated with the serum levels of NSE before treatment (P = 0.002). The overall survival (OS) of the patients with high NSE levels was worse than that of those with low NSE levels (P = 0.004). In multivariate analysis, low level of NSE was the most significant independent predictor of good OS (P = 0.003). The result showed a promising predictive value of NSE regarding to the sensitivity of tumors to CRT. NSE may be a reliable surrogate marker of CRT efficacy in patients with SCEC.

Neoadjuvant chemoradiotherapy followed by radical resection has been the standard treatment for patients with LARC, showing to reduce postoperative locoregional recurrence and improve postoperative survival. However, the response of individual tumor to nCRT is not uniform and the complete pathologic response rate varies from 8% to 31% (Kim et al., 2002; Sauer et al., 2004; Bosset et al., 2006). It means some patients could benefit from the current therapeutic regimen whereas others could not. How to identify the patients who show poor pathological response to nCRT is very important owning nCRT is timeconsuming, costly, and potentially harmful, especially for patients in whom nCRT has little therapeutic effectiveness. Recently, some authors have found that the occurrence and development of tumor is not only related to the biological characteristics of tumor cells, but also to the tumor microenvironment (Coussens and Werb, 2002), which participates in the neoplastic process, fostering proliferation, survival and migration of the tumor cells. The blood cell counts in peripheral blood, which partially reflect the immune function in rectal cancer patients, are considered part of the internal environment. Many

Purpose: To evaluate the prognostic value of serum CYFRA21-1, CEA and hemoglobin levels regarding long-term survival of patients with esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). Methods: Age, gender, Karnofsky Performance Status (KPS), tumor location, tumor length, T stage, N stage and serum hemoglobin, and CYFRA21-1 and CEA levels before concurrent CRT were retrospectively investigated and related to outcome in 113 patients receiving 5-fluorouracil and cisplatin combined with radiotherapy for ESCC. The Kaplan-Meier method was used to analyze prognosis, the log-rank to compare groups, the Cox proportional hazards model for multivariate analysis, and ROC curve analysis for assessment of predictive performance of biologic markers. Results: The median survival time was 20.1 months and the 1-, 2-, 3-, 5- year overall survival rates were 66.4%, 43.4%, 31.9% and 15.0%, respectively. Univariate analysis showed that factors associated with prognosis were KPS, tumor length, T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level. Multivariate analysis showed T-stage, N-stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis. By ROC curve, CYFRA21-1 and hemoglobin showed better predictive performance for OS than CEA (AUC= 0.791, 0.704, 0.545; P=0.000, 0.000, 0.409). Conclusions: Of all clinicopathological and molecular factors, T stage, N stage, hemoglobin, CYFRA21-1 and CEA level were independent predictors of prognosis for patients with ESCC treated with concurrent CRT. Among biomarkers, CYFRA21-1 and hemoglobin may have a better predictive potential than CEA for long-term outcomes.

BACKGROUND:Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT.METHODS:Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis.RESULTS:The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P = 0.001 and P = 0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P = 0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P = 0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P = 0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P = 0.007).CONCLUSIONS:CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.

Objectives The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. Methods Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. Results The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). Conclusions Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.

AIMS:A prospective study was undertaken to reduce bladder volume variation and the irradiated small bowel injury by irrigating the bladder during postoperative pelvic IMRT in rectal cancer patients.METHODS:12 consecutive patients underwent three sets of computed tomography scans during the treatment course: Group I, a distended (not empty) bladder before the radiation course; Group II, a distended bladder at the end of the fourth week; Group III, an irrigated bladder at the end of the fourth week. A seven-field coplanar intensity- modulated radiotherapy plan of 50.4 Gy was made to the clinical target volume. The total volume of regions of interest and volume within every isodose level, their maximum dose and mean dose were analysed.RESULTS:Compared with group I, the median reduction of bladder volume was 147.7 cm3 (24.3%), and the median increment of small bowel was 122.4 cm3 in group II. The volume of small bowel within every isodose level was increased (P<0.05). Statistical analysis showed a correlation between the volume change of bladder and small bowel. The mean radiation dose (Dmean) of small bowel and bladder was increased in group II compared to groups I and III (P<0.05).CONCLUSIONS:Bladder volume declines significantly during the course of radiotherapy, leading to an increment in irradiated small bowel volume. Bladder irrigation is a feasible method to guarantee a consistent bladder volume and reduce small bowel radiation exposure.

The objective was to evaluate expression of second mitochondria-derived activator of caspase (Smac) expression before and after treatment in patients treated with preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer and to correlate the clinicopathological characteristics and level of Smac expression with pathologic response and outcome. Expression of biomarker was evaluated by immunohistochemistry in tumor samples from 98 patients with clinical Stage II and III rectal cancer treated with preoperative pelvic radiotherapy plus concurrent chemotherapy. All patients received a standardized total mesorectal excision procedure after a long interval of 4-6 weeks. For Smac, patients with a good response to neoadjuvant CRT tended to have higher pre-therapy levels (P = 0.007). The level of Smac expression decreased after neoadjuvant therapy (P = 0.016). High expression of Smac before CRT, and high Dworak's tumor regression grade (TRG) were significantly associated with improved 5-year disease-free survival (P < 0.05). Pretreatment nodal status also was significantly associated with 5-year disease-free survival and 5-year local relapse-free survival (P < 0.05). Multivariate analysis confirmed that the pretreatment expression of Smac and Lymph nodal status were independent prognostic factors. Our study suggests that high expression of Smac before neoadjuvant CRT could predict good outcome in locally advanced rectal cancer patients.