C. Han

Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trail

BACKGROUND AND PURPOSE This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400mg/m(2) loading dose on day 1; and on day 1 of the 2nd-7th weeks: cetuximab 250mg/m(2), paclitaxel 45mg/m(2), and cisplatin 20mg/m(2), concurrent with 59.4Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status. RESULTS Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples. CONCLUSIONS Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate.

Investigation of Using Diffusion-Weighted Magnetic Resonance Imaging to Evaluate the Therapeutic Effect of Esophageal Carcinoma Treatment

Aim: To explore the associations of diffusion-weighted magnetic resonance imaging (DWI) measurements with the therapeutic effect (TE) on and survival of esophageal carcinoma patients treated with chemoradiotherapy (CRT). Methods: From March 2010 to December 2011, 77 patients were prospectively enrolled into a cohort study. DWI was performed at the beginning and 1-3 months after CRT. The immediate post-CRT TE was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). The associations between the disappearance status of hyperintense expression (HE) in DWI and the apparent diffusion coefficient (ADC) of DWI with the complete response (CR) as TE and survival were analyzed. Results: 3 patients were excluded due to the absence of HE in DWI. Analysis of the remaining 74 patients indicated that their ADC values were significantly improved from 1.64 ± 0.48 to 2.65 ± 0.58 mm2/s from pre-CRT to post-CRT (p = 0.000). Both univariate and multivariate Cox model analyses showed that high post-CRT ADC values and the disappearance status of HE associated significantly with the TE (CR rate) and survival. Conclusions: DWI examination could afford useful markers to predict the treatment response as well as the survival of patients with esophageal squamous cell carcinoma. The non-disappearance of HE in DWI and low ADC values after CRT were risk factors.

The diffusion-weighted magnetic resonance imaging (DWI) predicts the early response of esophageal squamous cell carcinoma to concurrent chemoradiotherapy

PURPOSE To investigate the predictive value of serial diffusion-weighted MRI (DWI) on tumor response of the concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma (ESCC) and to determine the optimal time point of DWI measurements. METHODS AND MATERIALS From June 2010 to October 2011, 38 ESCC patients were consecutively enrolled into this prospective cohort study. During their treatment, the longitudinal DWIs were acquired at beginning and every week during the course of CCRT. ADC maps were generated from there DWIs. The tumor responses were evaluated according to the RECIST. RESULTS (1) At completion of CCRT, 20 (52.6%) and 18 (47.4%) patients were evaluated as CR and PR, respectively. Over the time points of measures, the series of ADC values (10-3mm2/s) in whole GTV were consistently characterized with higher (all p<0.05) for these CR patients as their means (std) were 2.24 (0.49), 2.23 (0.51), 2.44 (0.57), 2.54 (0.52), 2.70 (0.46), 2.80 (0.55), 2.92 (0.62), compared with these PR patients as 1.83 (0.31), 1.79 (0.21), 1.87 (0.30), 1.97 (0.37), 2.15 (0.44), 2.26 (0.46), 2.32 (0.51), respectively. However, the ADC change rates (ΔADC) of two groups were found to be similar. These results were also supported by the multivariate ANOVA analyses. The same analysis results of DWI based GTV volumes were also found. (2) The comparisons of logistic regression analysis indicated that only the ADC values at Week 3 (15 fractions) were an independent prognostic factor of tumor response (OR=0.303, p=0.003). ROC curve analysis showed that Area Under Curve for ADC values of the end of 2nd and 3rd weeks were biggest (0.822) and the prediction efficacy was comparatively optimized. The corresponding cut-off values were 2.11 and 2.14 (10-3mm2/s), respectively. (3) Additional analyses on those eight patients with tumor local recurrence within 1year demonstrated the level-off after the continuously increased ADC values till Week 4. CONCLUSIONS DWI can be used as a biomarker to predict TE of esophageal cancers in early time during CCRT. The treatment-induced change in ADC of whole GTV during the first 2-3weeks can be highly predictive to TE. The unchanged ADC value in late period may indicate the high tendency of tumor recurrence after 1year.

Retrospective analysis of safety profile of high-dose concurrent chemoradiotherapy for patients with oesophageal squamous cell carcinoma

BACKGROUND AND PURPOSE To evaluate the safety profile and efficacy of high-dose (60 Gy) concurrent chemoradiotherapy (CCRT) compared with standard-dose (50.4-54 Gy) CCRT. MATERIALS AND METHODS Patients with oesophageal squamous cell carcinoma (OSCC) undergoing CCRT were eligible for a propensity score matched cohort (1:1 for high dose versus standard dose). Adverse events, local control (LC) and overall survival (OS) were assessed. RESULTS A total of 380 patients with good balance in observed co-variables were enrolled. OS and LC rates of patients receiving high-dose CCRT were significantly higher than those receiving standard-dose CCRT, with the 10-year OS at 24% versus 13.3%, respectively. In contrast, there was a trend towards increased grades 2-3 acute oesophagitis toxicity among patients receiving high-dose versus standard-dose CCRT (37.4% versus 27.9%, respectively). None experienced grade 5 acute oesophagitis and grade 4 acute toxicities were rare. Similar rates of late radiation oesophagitis, radiation pneumonitis, gastrointestinal reactions and haematological toxicities were observed between patients receiving high-dose versus standard-dose CCRT. Six patients (3.2%) receiving high-dose CCRT experienced >grade 3 leucocytopaenia, and two (1.1%) received standard-dose CCRT, whereas none experienced >grade 3 thrombocytopaenia or anaemia. Three patients (2.3%) receiving high-dose CCRT died of infections caused by myelosuppression. Multivariate analysis showed that anaemia is a significant independent predictor of poor prognosis. CONCLUSIONS Compared with standard-dose CCRT, high-dose CCRT yielded more favourable local control and survival outcomes for patients with OSCC. Grades 2-3 acute oesophagitis toxicity in patients undergoing high-dose CCRT increased, whereas severe, life-threatening toxicities (>grade 3) did not.