Jian Hua Fu

High expression of the transcriptional co-activator p300 predicts poor survival in resectable non-small cell lung cancers

PURPOSE To investigate the correlation between p300 (a transcriptional co-activator) expression and clinical/prognostic characteristics in surgically resected NSCLC patients for the purpose of identifying patients with increased risk of cancer recurrence and providing them with tailored therapy. METHODS One hundred and sixty-nine completely resected NSCLC patients were included in this study. Paraffin-embedded primary tumour tissues of patients were supplied to produce a tissue microarray, and immunohistochemistry was used for the evaluation of p300 expression. The clinical/prognostic significance of p300 expression was analysed for statistical significance. Survival was calculated by the Kaplan-Meier method, and the log-rank test was used to assess differences in survival between the groups. The prognostic impact of clinicopathologic variables and p300 expression was evaluated using a Cox proportional hazards model. RESULTS High expression of p300 was associated with poor disease-free survival (p = 0.027) and overall survival (p = 0.006) in NSCLC patients. Further analysis suggested that this difference in overall survival also existed in patients with T2 (p = 0.040), positive lymph nodes (p = 0.023), stage IIIA (p = 0.003), adenocarcinoma (p = 0.021), and a well-differentiated histological grade score (p = 0.011). The multivariate Cox regression analysis showed that low p300 expression is an independent marker of better disease-free survival (relative risk = 0.628, p = 0.047) and overall survival (relative risk = 0.545, p = 0.024) in operable NSCLC patients. CONCLUSIONS Low p300 expression is an independent prognostic marker of better survival in operable NSCLC patients. The combination of clinicopathological TNM staging classification with p300 expression may be useful in identifying patients with increased risk of cancer recurrence to provide them with tailored therapy.

Neoadjuvant chemoradiotherapy with cisplatin plus vinorelbine versus cisplatin plus fluorouracil for esophageal squamous cell carcinoma: A matched case-control study

BACKGROUND To compare the clinical outcomes of neoadjuvant chemoradiotherapy (CRT) with cisplatin/vinorelbine versus cisplatin/fluorouracil in patients with locally advanced esophageal cancer. METHODS Between 2000 and 2012, 279 patients with thoracic esophageal squamous cell carcinoma (SCC) undergoing neoadjuvant CRT followed by surgery were reviewed. Through a matched case-control study, 57 patients treated with cisplatin/vinorelbine were matched 1:1 to patients who received cisplatin/fluorouracil according to age, sex, performance status, tumor location, tumor length, and pretreatment TNM stage. RESULTS Patient and disease-related characteristics were comparable between the two groups. The pathologic complete response (pCR) rate was 47.4% for the cisplatin/vinorelbine group and 28.1% for the cisplatin/fluorouracil group (P=0.034). Median overall survival (OS) in the cisplatin/vinorelbine group was significantly better compared with the cisplatin/fluorouracil group (52.8 vs. 25.2 months), with 3-year OS rates of 64.3% vs. 31.3%, respectively (P=0.001). However, cisplatin/vinorelbine was associated with a significantly higher rate of grade 3-4 leukopenia than cisplatin/fluorouracil (P=0.03). Multivariate analysis showed that being female, age ⩾55 years, pCR after CRT, and chemotherapy with cisplatin/vinorelbine were independent positive prognostic factors for survival. CONCLUSIONS Cisplatin/vinorelbine might lead to a higher pCR rate and better survival outcomes than cisplatin/fluorouracil in esophageal SCC. The incidence of hematologic toxicity is increased with cisplatin/vinorelbine, but is tolerable and manageable. Prospective controlled studies are required to confirm the efficacy of this regimen.

TNM staging matched-pair comparison of surgery after neoadjuvant chemoradiotherapy, surgery alone and definitive chemoradiotherapy for thoracic esophageal squamous cell carcinoma

Introduction: We used the TNM staging matched-pair approach to compare the efficacies of surgery after neoadjuvant chemoradiotherapy (NCT), surgery alone and definitive chemoradiotherapy (CCRT) in patients with localized advanced thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 642 patients with ESCC from previous studies were studied. Patients whose treatment involved NCT + surgery and surgery alone were compared with patients receiving CCRT. Prospensity score matched-pair comparison based on pre-treatment TNM staging was developed to assess the efficacies of these treatment options. Results: Prospensity score matched-pair comparison to control for bias generated a cohort of 274 patients who were eligible for comparison. The 3-year OS rate was 70.0% in the NCT + surgery group, compared to 51.7% in the surgery group (p=0.000) and 61.9% in the CCRT group (p=0.082). With the TNM staging matched-pair approach, the CCRT group had more upper thoracic ESCC patients (43/92, 46.7%), while the surgery group had more lower thoracic ESCC patients (37/92, 40.2%). The 3-year OS rates were comparable between the surgery alone group and CCRT group (p=0.109). Conclusions: NCT plus surgery was superior in OS to surgery alone or CCRT. The 3-year OS rates were comparable between the surgery alone group and CCRT group with TNM staging matched-pair approach. Further investigation is warranted to confirm these findings.

Combined modalities of magnetic resonance imaging, endoscopy and computed tomography in the evaluation of tumor responses to definitive chemoradiotherapy in esophageal squamous cell carcinoma

PURPOSE To explore the value of combined modalities, including anatomical and functional magnetic resonance imaging (MRI), endoscopy and computed tomography (CT), for the assessment of tumor responses to definitive chemoradiotherapy (dCRT) in esophageal squamous cell carcinoma (ESCC). METHODS Sixty-seven patients with locally advanced ESCC were enrolled. Tumor response (TR) was assessed two months after the completion of dCRT. Evaluation criteria according to combined modalities, including MRI, endoscopy and CT, were established and compared with traditional criteria based on CT and endoscopy. Progression-free survival (PFS)⩾12months was used as the reference standard, and the accuracy of the two criteria in response assessment was analyzed. RESULTS Thirty-seven (55.2%) and 10 (14.9%) patients were considered to exhibit CR, as assessed by combined modalities and the traditional criteria, respectively. Using PFS⩾12months as a surrogate for CR, the sensitivity and specificity of the combined modalities were 82.4% and 88.9%, respectively, compared with 20.6% and 92.6% for the traditional criteria. TR assessed by combined modalities (CR vs. non-CR) was prognostic of PFS in univariate and multivariate analyses (Log-rank, P<0.0001; Cox regression, HR=0.114, 95% CI 0.048-0.272). CONCLUSIONS Tumor responses assessed by the combined modalities of MR, endoscopy and CT seemed highly predictive of prognosis after dCRT in ESCC patients.

Adjuvant therapy for a microscopically incomplete resection margin after an esophagectomy for esophageal squamous cell carcinoma

Purpose: To investigate the prognosis of esophageal squamous cell carcinoma with a microscopically incomplete (R1) resection margin following an esophagectomy, as well as the impact of adjuvant treatment on survival. Methods: Data obtained from 124 patients with R1-resected ESCC were reviewed. The impact of clinicopathological factors and adjuvant treatment on the overall survival, locoregional recurrence, and distant recurrence were explored. Results: For a median follow-up time of 16.8 months, the median overall survival of 124 patients was 25.6 months. The 1, 3, and 5-year overall survival rates were 75.6%±4.0%, 35.9%±5.1%, and 23.2%±5.0%, respectively. Adjuvant therapy was administered in 78 patients. In the univariate analyses, patients with a pN0 stage (log rank, p=0.028) and adjuvant chemotherapy (log rank, p=0.032) exhibited more favorable overall survival. In the multivariate analyses, the pN stage (HR=2.192, p=0.004) and adjuvant chemotherapy (HR=0.032, p=0.004) were independent prognostic factors for overall survival. Locoregional recurrence was the main failure pattern after R1 resection. The pN stage (HR=2.567, p=0.009) and adjuvant radiotherapy (HR=0.278, p=0.000) were independent prognostic factors for locoregional recurrence. Conclusion: In R1-resected esophageal squamous cell carcinoma, adjuvant radiotherapy reduced locoregional recurrence; however, it did not improve overall survival. Adjuvant chemotherapy demonstrated benefits for overall survival. The pN stage was an independent prognostic factor for locoregional recurrence and overall survival.

Comparing docetaxel plus cisplatin versus fluorouracil plus cisplatin in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy

Objective The optimal neoadjuvant chemoradiotherapy (CRT) regimen in esophageal cancer has not yet been defined. This study was aimed to compare the differences in pathologic response and survival between docetaxel/cisplatin and fluorouracil/cisplatin as neoadjuvant CRT in locally advanced esophageal squamous cell carcinoma (SCC). Methods We retrospectively analyzed patients with thoracic esophageal SCC who received neoadjuvant CRT followed by esophagectomy from 2000 to 2014. After adjusting for sex, age, performance status, tumor length, tumor location and clinical TNM stage, 32 docetaxel/cisplatin-treated patients were matched to 62 patients who received fluorouracil/cisplatin at a ratio of 1:2. Treatment toxicity, pathologic complete response (pCR) and survival outcomes were compared between groups. Results Baseline characteristics were well balanced between groups. The pCR rate in the docetaxel/cisplatin group was higher than that in the fluorouracil/cisplatin group but without significant difference (40.6% vs. 30.6%, P = 0.333). The 3-year overall survival rate in the docetaxel/cisplatin group was 64.9% versus 46.0% in the fluorouracil/cisplatin group (P = 0.039). There were no significant differences in incidence of treatment toxicity during CRT or surgical complications between groups, with the exception of Grade 3-4 hematologic toxicity (37.5% vs. 17.7%, P = 0.035), which was more frequent in the docetaxel/cisplatin group. Conclusions Docetaxel/cisplatin might be associated with more favorable survival than fluorouracil/cisplatin in esophageal SCC treated with neoadjuvant CRT. Prospective validation is warranted.