Shi Liang Liu

The modified glasgow prognostic score is an independent prognostic factor in patients with inoperable thoracic esophageal squamous cell carcinoma undergoing chemoradiotherapy.

Background and purpose: There is increasing evidence that the presence of an inflammation-based prognostic score (modified Glasgow prognostic score, mGPS) is associated with survival in patients with advanced cancer. This study aimed to assess whether the mGPS has prognostic value in patients with thoracic esophageal squamous cell carcinoma undergoing chemoradiotherapy. Materials and methods: A total of 212 patients undergoing chemoradiotherapy for newly-diagnosed esophageal squamous cell carcinoma between October, 2006 and December, 2011 were retrospectively analyzed. Serum C-reactive protein (CRP) and albumin were measured before initiation of treatment. The relationships between the mGPS and other relevant variables including white blood cell count, neutrophilic granulocyte count, platelet count, hemoglobin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated. Significant prognostic factors were identified using univariate and multivariate analyses. Results: Three-year OS for all patients was 24.6%; 3-year PFS was 21.3%. Patients with a mGPS of 0, 1 and 2 were 90, 78, 44, respectively. Higher mGPS was related to higher white blood cell, neutrophilic granulocyte and platelet counts, and lower total bilirubin. T stage, M stage and mGPS were independent prognostic indicators for OS; T stage, M stage, mGPS and platelet count were independent prognostic indicators for PFS. Conclusions: Pretreatment mGPS is an easily measurable significant prognostic factor and can be used in combination with conventional TNM staging to predict survival in patients with squamous cell carcinoma undergoing chemoradiotherapy.

Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients with inoperable thoracic esophageal squamous cell carcinoma

Background and purpose The benefit of concurrent chemoradiotherapy (CCRT) in elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients. Methods and materials Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73). Results No treatment-related deaths occurred and no patients experienced any acute grade 4 non-hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS) rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008). Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients ≤ 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years. Conclusion Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit.

Concurrent cisplatin and 5-fluorouracil versus concurrent cisplatin and docetaxel with radiotherapy for esophageal squamous cell carcinoma: a propensity score-matched analysis.

The optimal concurrent chemotherapy regimen with radiotherapy for esophageal cancer is unknown. Here, we compared the survival outcomes and toxicity of definitive chemoradiotherapy with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin (DP) in patients with unresectable esophageal squamous cell carcinoma (ESCC). In this study, we identified 317 patients with ESCC who received PF or DP concurrently with definitive radiotherapy. PF group patients received two cycles of cisplatin (60 mg/m2) and 5-fluorouracil (300 mg/m2) at 4-week intervals during radiotherapy. DP group patients received a concurrent three-weekly schedule of docetaxel (60 mg/m2) and cisplatin (80 mg/m2) or cisplatin (25 mg/m2) and docetaxel (25 mg/m2) weekly. The overall survival (OS) and progression-free survival (PFS) were compared using propensity score (−adjusted, −weighted, −stratified, and −matched) analyses. A sensitivity analysis was performed to examine the impact of unmeasured confounders. Inverse probability of treatment weighting for propensity score demonstrated an improvement in OS and PFS with DP group in comparison with PF group (hazard ratio, 0.700; 95% CI, 0.577-0.851) and similar results were achieved with propensity score matching and stratification. Grade 3-4 esophagitis was more common (16/102 vs. 4/102) and grade 3-4 thrombopenia and skin toxicity were less common (3/102 vs. 10/102; 7/102 vs. 19/102; respectively) in the PF group than the DP group. In conclusion, concurrent chemoradiotherapy with the DP regimen resulted in better OS and PFS compared to concurrent PF regimen with tolerable toxicities in ESCC patients. Prospective randomized trials are required to confirm the efficacy of the DP regimen.

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.

Polymorphisms of insulin-like growth factor binding protein-3 as a predictor for risk and patient survival in esophageal squamous cell carcinoma

BACKGROUND AND PURPOSE Genetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 (IGFBP-3) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT). MATERIALS AND METHODS We undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A>C and rs2854746 G>C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing. RESULTS The obtained results indicated that overall, no statistically significant association was observed in rs2854746 G>C. However, rs2854744 A>C genotype was at increased risk of ESCCs (P=0.032; odds ratio (OR)=1.201, CI 95%:1.014-1.423). Moreover, rs2854744 A>C genotype ESCCs were more significantly common in patients with tumor size of >6cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG+GC genotype ESCC. CONCLUSIONS In conclusion, polymorphism in IGFBP-3 rs2854744 A>C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results.

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.

Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma.

Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC.

Comparative outcomes of induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma

Purpose: To compare the clinical outcomes of induction chemotherapy (IC) followed by chemoradiotherapy (CRT) versus chemoradiotherapy alone in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Patients and methods: Between 2002 and 2015, 267 ESCC patients who received definitive CRT with docetaxel and cisplatin were enrolled in this study. Through a matched case-control study, 85 patients receiving IC before CRT were matched 1:1 to patients who received CRT alone, according to age, gender, performance status, tumor location, tumor length, and pretreatment TNM stage. Results: The median overall survival (OS) in the IC group was significantly better than that in the CRT group (26.0 vs. 22.0 months), with 3-year OS rates of 30.6% vs. 25.9%, respectively (P = 0.028). However, IC plus CRT was associated with a significantly higher rate of grade 3-4 leukopenia than CRT alone (P = 0.048). The overall clinical response rate was 50.6% after IC in the IC group. The IC responder group showed significantly more favorable OS (P=0.002) and progression-free survival (P=0.001) compared with the IC non-responder group and the CRT group. Multivariate analysis revealed that age ≥ 60 (P = 0.003) and the addition of IC (P=0.016) were independent prognostic factors that affected survival positively. Conclusions: The addition of IC before CRT yielded satisfactory clinical outcomes and manageable toxicities. The combination of IC with CRT might be a promising treatment strategy to further improve systemic control and survival in ESCC. Prospective randomized trials are required to confirm the role of IC.

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.