Yuan-Hong Gao

Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis

BackgroundTissue factor (TF) is emphasized as the promising target in the future targeted therapy strategy for colorectal cancer (CRC). Recent evidence showed that TF expression is under the control of K-ras and p53. However, a comprehensive evaluation of TF expression, K-ras status, and p53 mutation has not been systematically analyzed. The aims of this study were to identify the percentages of positive TF in CRC patients; analyze the associations of TF expression, K-ras status, and p53 mutation; and evaluate the prognostic value of TF in CRC patients.MethodsNinety-six CRC samples were tested for TF expression, p53 mutation, and K-ras status by semiquantitative immunohistochemistry, Western blotting analysis, direct sequencing, and real-time quantitative PCR. Associations were sought with TF expression and clinical outcomes.ResultsTF expression was related to clinical stages, tumor differentiation, and tumor size. The positive proportions of TF expression on tumor cells and tumor vascular endothelial cells were 70% and 53% respectively in CRC patients. The positive proportion of TF co-expression on both cancer cells and tumor vascular endothelial cells was 40%, compared to an 83% total TF positive proportion in CRC patients. TF expression on CRC appeared to be increased with K-ras and/or p53 mutation(s). Disease-free survival and overall survival were significantly reduced in CRC patients with high TF expression.ConclusionsTF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis and could be considered as a prognostic indicator for patients CRC.

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.

Is long interval from neoadjuvant chemoradiotherapy to surgery optimal for rectal cancer in the era of intensity-modulated radiotherapy?: a prospective observational study

Objectives To evaluate the impact of interval between neoadjuvant chemoradiotherapy (NACRT) and surgery on therapeutic and adverse effects of surgery, and long-term outcome of patients with locally advanced rectal cancer (RC), in the era of intensity-modulated radiotherapy (IMRT). Patients and methods Patients diagnosed with stage II–III RC and treated with IMRT-based NACRT followed by radical surgery were enrolled consecutively from April 2011 to March 2014. The data of all the patients were collected prospectively and grouped according to their NACRT-to-surgery interval. The therapeutic and adverse effects of surgery, and survivals were compared between the patients with interval ≤7 weeks and those with interval ≥8 weeks. Results A total of 231 patients were eligible for analysis, including 106 cases with interval ≤7 weeks and 125 cases with interval ≥8 weeks. The therapeutic and adverse effects of surgery were similar between these two groups of patients. However, interval ≥8 weeks appeared to lead to poorer overall, distant-metastasis-free and disease-free survivals, compared with interval ≤7 weeks. The HRs were 1.805, 1.714, and 1.796 (P-values were 0.045, 0.049, and 0.028), respectively. Conclusion For patients with locally advanced RC, a long NACRT-to-surgery interval might bring a potential risk of increased distant metastasis rather than a better tumor regression in the era of IMRT.

The total number of lymph nodes harvested from pathological T3N0 rectal cancer patients: Prognostic significance and potential indication for postoperative radiotherapy

Background: Lymph node status is important in staging colorectal cancer. The use of combination treatment for pathological T3N0 (pT3N0) rectal cancer patients has been controversial. We aimed to explore the prognostic significance of the total number of lymph nodes harvested from pT3N0 rectal cancer patients. Methods: Between June 2004 and November 2011, 289 pT3N0 rectal cancer patients who received total mesorectal excision (TME) with or without postoperative chemotherapy were retrospectively reviewed. The main independent variable was the total number of harvested lymph nodes, and the endpoints included local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). Results: The patients had a median of 13 lymph nodes harvested. When compared with patients who had < 12 lymph nodes harvested, patients who had ≥12 lymph nodes harvested had higher 5-year LRFS (84.7% vs. 98.0%, P < 0.001), DFS (71.4% vs. 86.8%, P < 0.001), and OS (77.6% vs. 94.9%, P < 0.001) rates. Multivariate analysis demonstrated that the patients who had ≥12 lymph nodes harvested had a significantly lower risks of local relapse (hazard ratio [HR], 0.099; P < 0.001), treatment failure (HR: 0.291; P < 0.001), and death (HR: 0.231; P < 0.001) when compared with patients who had <12 lymph nodes harvested. Conclusions: The number of lymph nodes harvested was independently associated with local relapse, treatment failure, and OS rates in pT3N0 rectal cancer patients who received initial TME with or without postoperative chemotherapy. Postoperative radiotherapy should not be omitted for pT3N0 rectal cancer patients who had <12 lymph nodes harvested.

Analysis of Clinical characteristics to predict pathologic complete response for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

To explore clinical characteristics which could be applied to predict pathologic complete response (pCR) for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision (TME). 297 patients with locally advanced rectal cancer (cT3-4 or cN+) who were treated with neo-CRT followed by TME were retrospectively reviewed. Clinical characteristics including age, gender, tumor distance from anus, serum CEA, hemoglobin levels before treatment and clinical TN stage were used to investigate the association with pCR after neo-CRT. Seventy-nine (26.6%) patients achieved pCR after neo-CRT. pCR were achieved in 42 (34.4%) patients in cT1-3 stage and 37 (21.1%) in cT4 stage. pCR rate was 36.4% and 16.4% for patients with pre-treatment serum CEA ≤5.33ng/ml and >5.33ng/ml, respectively. Uni- and multi-variate analyses revealed that pre-treatment serum CEA level ≤5.33ng/ml and clinical T stage, (i.e., cT1-3 versus cT4) were highly correlated with pCR (p < 0.05). Clinical T stage and pre-treatment serum CEA level were strongly associated with pCR for patients with locally advanced rectal cancer treated with neo-CRT followed by TME which could be applied as clinical predictors for pCR.

Long-term outcome of oxaliplatin and capecitabine (XELOX) concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer

Purpose: This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC). Methods: From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery. Disease-free survival (DFS) time and overall survival (OS) time were analyzed. Results: The median follow-up was 51 months. Twelve (26.7%) patients developed local recurrence or distant metastasis, including 10 (22.2%) patients developing distant metastasis only, 1 (2.2%) patient local recurrence only, and 1 (2.2%) patient both local recurrence and distant metastasis. The estimated 3-year DFS and OS was 75.5% (95% CI, 63.0%-88.0%) and 88.6% (95% CI, 98.0%-79.2%), respectively. Receiving adjuvant chemotherapy was a significant predictor for DFS, with hazard ratio 0.24 (95% CI: 0.08-0.74). Conclusion: This intensified strategy with oxaliplatin and capecitabine (XELOX) administered concomitantly with neoadjuvant radiotherapy and then extended to the resting period in high-risk LARC patients is efficient. The long-term outcome is promising. Further study of this strategy is warranted.

Apolipoprotein A-I Is a Prognosticator of Nasopharyngeal Carcinoma in the Era of Intensity-modulated Radiotherapy

Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid). Hazard ratio (HR) and 95% confidence interval (CI) were calculated for each independent prognosticator. After univariate and multivariate survival analysis, low apoAI level (< 1.125 mmol/L) appeared to predict poor 5-year overall survival (OS), disease-free survival (DFS) and distant-metastasis-free survival (DMFS).The HRs were 1.549 (95% CI, 1.137-2.109), 1.293 (95% CI, 1.047-1.597) and 1.288 (95% CI, 1.022-1.623), respectively. Subgroup survival analysis showed that the apoAI maintained predicting independence for OS, DFS and DMFS in patients with locally advanced NPC, even in those treated with concurrent chemoradiotherapy. Conclusions / Significance: NPC patient with low serum level of pretreatment apoAI might be at risk of distant metastasis. Treatment aiming to eradicate distant metastasis might improve survival of these patients.

Prognostic Value of the Cycle Number of Perioperative Chemotherapy in Locoregionally Advanced Rectal Cancer: a Propensity Score Matching Analysis

Background: Appropriate cycle number of perioperative chemotherapy for patients with locoregionally advanced rectal cancer (LARC) remains unknown. This study aimed to evaluate how cycle number of perioperative chemotherapy influenced the prognosis of LARC patients. Methodology / Principal Findings: In this study, a total of 388 consecutive patients were enrolled and retrospectively reviewed if they were diagnosed with untreated stage cII-III LARC and treated with neoadjuvant chemoradiotherapy plus radical surgery followed by adjuvant chemotherapy or not. After grouping by the postoperative pathologic stage (yp0-I vs. ypII-III), propensity score matching was performed in each group to balance baseline characteristics between the patients treated with chemotherapy cycle ≤ 7 and those treated with chemotherapy cycle ≥ 8. The chemotherapy cycle was analyzed for its association with the survivals of the matched patients in the 2 groups, respectively. And the incidence of treatment-related complications was also compared. Through analysis, chemotherapy cycle ≥ 8 appeared to predict better overall, disease-free and distant-metastasis-free survivals in the whole cohort of matched patients (P values were 0.003, 0.002 and 0.004, respectively) and the ypII-III group (P values were 0.006, 0.005 and 0.014, respectively). But in the yp0-I group, chemotherapy of 8 cycles or more brought no improvement of survivals but only more acute toxicities (83.5% vs. 57.0%, P < 0.001). Conclusions / Significance: Chemotherapy cycle ≥ 8 was proven associated with improved prognosis of LARC patients, especially those with ypII-III disease. But prolonged chemotherapy should be performed with caution in patients with yp0-I stage.

A pilot study of neoadjuvant chemoradiotherapy for unresectable locally advanced adherent colon cancer: Assessing local tumor response.

727 Background: To analyze the outcomes of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC). Methods: 40 unresectable LAACC patients were identified from Sun Yat-Sen university cancer-center Database from October 2010 to December 2014. Unresectability was determined by multidisciplinary consultation (MDT) according to image examination or confirmed by exploratory laparotomy. NeoCRT followed by surgery and postoperative chemotherapy were given to these patients. There were 27 males and 13 females. Median age was 56 years old. The location of primary tumors were as sigmoid 31, descending colon 3, ascending colon 5, and cecum1, respectively. All the patients were treated with 45-50Gy/25F using 3D-CRT or IMRT, and concomitantly with capecitabine-based chemotherapy every 3 weeks. Surgery was scheduled 6-8 weeks after completion of radiotherapy. Results: A total of 40 patients completed neoCRT and 33 patients (82.5%) received radical resecti...

Preoperative radiotherapy combined with simultaneous chemotherapy with capecitabine plus oxaliplatin versus surgery alone: A single-centered, phase II study in patients with mid/low rectal cancer.

609 Background: Though total mesorectal excision (TME) has proved to effectively decrease local recurrence rate of mid/low rectal cancer, the efficacy of preoperative radiotherapy in Asian patients remains unclear. The present study aimed to compare the efficacy of TME alone versus TME after preoperative radiotherapy and simultaneous chemotherapy with capecitabine plus oxaliplatin in Chinese patients with stage II and III mid/low rectal adenocarcinoma. Methods: Patients (n=192) aged between 18 and 70 years enrolled from March 23, 2008 to August 2, 2012 were randomly divided into two groups. Group A (n=97) received preoperative radiotherapy and simultaneous chemotherapy [46-50 GY/23-25 with oxaliplatin 100 mg/m2 (D1) and capecitabine 1,000 mg/m2 (bid, D1-15), repeated since D22], which was followed by TME; while patients in group B (n=95) underwent TME alone. While disease free survival (DFS) was the primary endpoint; the following were evaluated as secondary endpoints: pathological response rate, patholog...