Mengzhong Liu

Cervical nodal metastases of unresectable thoracic esophageal squamous cell carcinoma: Characteristics of long-term survivors after concurrent chemoradiotherapy

PURPOSE To analyze the clinical implications of metastatic cervical lymph nodes in unresectable thoracic esophageal squamous cell carcinoma (SCC) after concurrent chemoradiotherapy (CRT). METHODS AND MATERIALS 208 thoracic esophageal SCC patients treated with concurrent CRT were analyzed retrospectively. Patients were divided into 3 groups according to different status of metastatic cervical lymph nodes: 1. CLN(-), no evidence of metastatic cervical lymph nodes; 2. CPLN(+), evidence of enlarged cervical paraesophageal lymph node without any other metastatic cervical lymph nodes; 3. OCLN(+), any other situations of enlarged cervical lymph nodes. The prognostic factors were examined univariately, then selected for inclusion in a multivariate Cox regression model. RESULTS Three-year OS of CLN(-),CPLN(+), and OCLN(+) groups were 39%, 33%, and 15% (logrank p=0.001). On univariate analysis, variables significantly associated with OS included sex, primary esophageal tumor location, length and cervical nodal disease. On multivariate analysis, primary tumor location (HR1.5, 95%CI 1.1-1.9, p=0.005), tumor length (HR1.5, 95%CI 1.1-2.0, p=0.010) and cervical nodal disease (HR1.2, 95%CI 1.0-1.5, p=0.014) were prognostic factors on OS. CONCLUSIONS (1) Primary tumor location, tumor length, and cervical nodal disease were significant prognostic factors on OS in esophageal SCC patients. (2) Patients with CPLN(+) disease tended to have a potential better long-term survival than those with OCLN(+) disease, and metastatic CPLN could be considered as local disease. The survival benefit in CPLN(+) subgroup might be contributed by the patients who presented with upper third thoracic tumors and shorter tumor length. Further investigation is needed.

Sorafenib modulates the radio sensitivity of hepatocellular carcinoma cells in vitro in a schedule-dependent manner

BackgroundHepatocellular carcinoma (HCC) has a high incidence and mortality. Radiotherapy and sorafenib have proven effective for HCC. Here, we investigated whether sorafenib modulated the response of HCC cells to irradiation in vitro, effect of timing of sorafenib, and the underlying mechanisms.MethodsCell viability of the HCC cell lines, SMMC-7721 and Bel-7402, was examined by the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2 H-terazolium (MTT) assays. Clonogenic growth assays of SMMC-7721 and Bel-7402 were determined by colony formation assays. DNA damage was assessed by monitoring γ-HAX foci in irradiated cells with immunofluorescence microscopy, and cell cycle distribution changes were examined by flow cytometry. Effects of sorafenib (15 μM) added 30 min prior to radiation (pre-irradiation sorafenib) of SMMC-7721 and BEL-7402 or 24 h post-irradiation (post-irradiation sorafenib) on irradiated SMMC-7721 and BEL-7402 cells were compared to those of radiation alone or no treatment.ResultsThe effect of sorafenib was dependent on its time of addition in relationship to irradiation of cells. Pre-irradiation sorafenib did not significantly affect the viability of SMMC-7221 and BEL-7402 cells compared with irradiation treatment alone. In contrast, post-irradiation sorafenib increased the sensitivity of irradiated SMMC-7221 and BEL-7402 cells significantly in a time-dependent manner. Pre-irradiation sorafenib significantly increased the surviving fraction of SMMC-7221 and BEL-7402 cells in clonogenic assays whereas post-irradiation sorafenib significantly reduced the surviving fractions of SMMC-7221 and BEL-7402 cells. SMMC-7721 cells treated with sorafenib 30 min before irradiation had significantly fewer cells with γ-H2AX foci (23.8 ± 2.9%) than SMMC-7721 cells receiving radiation alone (59.9 ± 2.4; P < 0.001). Similarly, BEL-7402 cells receiving sorafenib prior to irradiation had significantly fewer cells with γ-H2AX foci (46.4 ± 3.8%) than those receiving radiation alone (25.0 ± 3.0%; P < 0.001). In addition, irradiation (6 Gy) caused a significant increase in the percentage of both SMMC-7721 and BEL-7402 cells in G2/M at 12 to 16 h post irradiation, which was markedly delayed by pre-irradiation sorafenib.ConclusionsSorafenib combined with irradiation exerted a schedule-dependent effect in HCC cells in vitro, which has significant implications for the combined use of sorafenib and radiotherapy for HCC patients.

Effectiveness of Three-dimensional Conformal Radiotherapy for Treating Early Primary Nasopharyngeal Carcinoma

Objective:In 2-dimensional radiotherapy, the irradiating portal is defined mainly by soft tissues and bony structures, so the exact location of nasopharyngeal tumors and many spatial relationships are unknown, resulting in high local-regional relapse rates and radiation toxicities. Three-dimensional conformal radiotherapy (3D CRT) provides more precise targeting of radiation. We studied whether 3D CRT could maintain survival and increase local-regional tumor control whereas reducing the morbidity and severity of radiation toxicity in patients with early primary nasopharyngeal carcinoma (NPC). Methods:Patients with histologically proven keratinizing or nonkeratinizing undifferentiated NPC (T1–2N0–1M0 stage) received a prescribed 3D CRT dose of 70 Gy to the gross tumor volume (GTVnx), 60 Gy to the GTVnx with an additional 5- to 10-mm margin (CTVnx60), 60 to 70 Gy to the region involved by the metastatic lymph nodes (GTVnd), and 50 Gy to the prophylactic irradiating region (CTVnd50). Results:Of 58 patients enrolled between August 2001 and December 2006, (48 men; median age, 46 years; range, 29–69 years), 15 had stage I and 43 had stage II disease. At 5 years, overall survival was 95% and disease-free survival was 91%; 93% of patients were free of local-regional recurrence and 98% were free of distant metastases. Grade 2 or 3 xerostomia occurred in 7 patients and trismus occurred in 5. Mean standard deviation (SD) dental gap was 37.4 (6.9) mm. Four patients had recurrent lesions, mainly in-field. Conclusions:The survival and morbidity provided by 3D CRT were excellent in these patients with early NPC.

A phase II randomized controlled trial: Definitive concurrent chemoradiotherapy with docetaxel plus cisplatin versus 5-fluorouracil plus cisplatin in patients with oesophageal squamous cell carcinoma

Purpose: To evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (CCRT) with docetaxel plus cisplatin (DP regimen) versus 5-fluorouracil plus cisplatin (PF regimen) in patients with oesophageal squamous cell carcinoma (ESCC). Patients and Methods: In this phase II randomized controlled trial, eighty-six patients with clinical stage II - IVa ESCC were randomized to receive radiotherapy concurrently with two cycles of the PF or DP regimen at 3-week intervals. The primary endpoint was overall survival (OS). The secondary end points included the overall response rate (ORR), progression-free survival (PFS) and treatment-related toxicities. Results: The ORRs were 84.4% in the DP group and 87.3% in the PF group (P = 0.653). After a median follow-up time of 25.1 months, the 1- and 2-year OS rates were 93.7% and 86.2% for the PF group and 87.3% and 69.1% for the DP group, respectively (P = 0.364). The 1- and 2-year PFS rates were 77.4% and 55.0% for the PF group and 78.8% and 69.4% for the DP group, respectively (P = 0.845). Grade 3/4 leukocytopenia/neutropenia (68.9% vs. 19.5%, P < 0.001) was significantly more common in the DP group. Conclusion: The treatment response, OS and PFS associated with using CCRT with the DP regimen were not superior to those associated with using CCRT with the PF regimen as a first-line treatment in patients with ESCC. Additionally, the DP regimen was associated with more severe haematological toxicities. This trial has been registered with the US National Institute of Health (clinicaltrials.gov, Identifier NCT 02969473).