Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer.

OBJECTIVE: To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation. METHODS: Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed. RESULTS: Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups. CONCLUSION: Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy.

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESOwhole); ESOwhole within the treatment field (ESOinfield); ESOinfield, excluding the tumor (ESOinfield-tumor) and ESOwhole, excluding the tumor (ESOwhole-tumor). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESOwhole, ESOinfield, ESOinfield-tumor and ESOwhole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10-2% and 1.5 × 10-3%. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.

A Dosimetric Study of Using Fixed-Jaw Volumetric Modulated Arc Therapy for the Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastasis.

PURPOSE: To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT) and large-field volumetric modulated radiotherapy (LF-VMAT) for nasopharyngeal carcinoma (NPC) with cervical lymph node metastasis. METHODS: Computed tomography (CT) datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV) coverage, conformity index (CI), homogeneity index (HI), organ-at-risk sparing, monitor units (MUs) and treatment time (TT). RESULTS: The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes), PTV1 (high-risk PTV) and PTV2 (low-risk PTV) than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor). The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR) volumes (PRVs) of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87) were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62). In terms of the TT, no significant difference was found between the two kinds of plans. CONCLUSIONS: FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs.

Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy.

This study aimed to determine the optimal fraction scheme (FS) in patients with small peripheral non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT) with the 4 × 12 Gy scheme as the reference. CT simulation data for sixteen patients diagnosed with primary NSCLC or metastatic tumor with a single peripheral lesion ≤3 cm were used in this study. Volumetric modulated arc therapy (VMAT) plans were designed based on ten different FS of 1 × 25 Gy, 1 × 30 Gy, 1 × 34 Gy, 3 × 15 Gy, 3 × 18 Gy, 3 × 20 Gy, 4 × 12 Gy, 5 × 12 Gy, 6 × 10 Gy and 10 × 7 Gy. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three other models were utilized to estimate the normal tissue complication probability (NTCP) value to the lung and the modified equivalent uniform dose (mEUD) value to the chest wall (CW). The 1 × 30 Gy regimen is recommended to achieve 4.2% higher TCP and slightly higher NTCP and mEUD values to the lung and CW compared with the 4 × 12 Gy schedule, respectively. This regimen also greatly shortens the treatment duration. However, the 3 × 15 Gy schedule is suggested in patients where the lung-to-tumor volume ratio is small or where the tumor is adjacent to the CW.

Volumetric modulated arc therapy vs. c-IMRT for the treatment of upper thoracic esophageal cancer.

OBJECTIVE: To compare plans using volumetric-modulated arc therapy (VMAT) with conventional sliding window intensity-modulated radiation therapy (c-IMRT) to treat upper thoracic esophageal cancer (EC). METHODS: CT datasets of 11 patients with upper thoracic EC were identified. Four plans were generated for each patient: c-IMRT with 5 fields (5F) and VMAT with a single arc (1A), two arcs (2A), or three arcs (3A). The prescribed doses were 64 Gy/32 F for the primary tumor (PTV64). The dose-volume histogram data, the number of monitoring units (MUs) and the treatment time (TT) for the different plans were compared. RESULTS: All of the plans generated similar dose distributions for PTVs and organs at risk (OARs), except that the 2A- and 3A-VMAT plans yielded a significantly higher conformity index (CI) than the c-IMRT plan. The CI of the PTV64 was improved by increasing the number of arcs in the VMAT plans. The maximum spinal cord dose and the planning risk volume of the spinal cord dose for the two techniques were similar. The 2A- and 3A-VMAT plans yielded lower mean lung doses and heart V50 values than the c-IMRT. The V20 and V30 for the lungs in all of the VMAT plans were lower than those in the c-IMRT plan, at the expense of increasing V5, V10 and V13. The VMAT plan resulted in significant reductions in MUs and TT. CONCLUSION: The 2A-VMAT plan appeared to spare the lungs from moderate-dose irradiation most effectively of all plans, at the expense of increasing the low-dose irradiation volume, and also significantly reduced the number of required MUs and the TT. The CI of the PTVs and the OARs was improved by increasing the arc-number from 1 to 2; however, no significant improvement was observed using the 3A-VMAT, except for an increase in the TT.

Improving target coverage and organ-at-risk sparing in intensity-modulated radiotherapy for cervical oesophageal cancer using a simple optimisation method.

PURPOSE: To assess the performance of a simple optimisation method for improving target coverage and organ-at-risk (OAR) sparing in intensity-modulated radiotherapy (IMRT) for cervical oesophageal cancer. METHODS: For 20 selected patients, clinically acceptable original IMRT plans (Original plans) were created, and two optimisation methods were adopted to improve the plans: 1) a base dose function (BDF)-based method, in which the treatment plans were re-optimised based on the original plans, and 2) a dose-controlling structure (DCS)-based method, in which the original plans were re-optimised by assigning additional constraints for hot and cold spots. The Original, BDF-based and DCS-based plans were compared with regard to target dose homogeneity, conformity, OAR sparing, planning time and monitor units (MUs). Dosimetric verifications were performed and delivery times were recorded for the BDF-based and DCS-based plans. RESULTS: The BDF-based plans provided significantly superior dose homogeneity and conformity compared with both the DCS-based and Original plans. The BDF-based method further reduced the doses delivered to the OARs by approximately 1-3%. The re-optimisation time was reduced by approximately 28%, but the MUs and delivery time were slightly increased. All verification tests were passed and no significant differences were found. CONCLUSION: The BDF-based method for the optimisation of IMRT for cervical oesophageal cancer can achieve significantly better dose distributions with better planning efficiency at the expense of slightly more MUs.

More accurate definition of clinical target volume based on the measurement of microscopic extensions of the primary tumor toward the uterus body in international federation of gynecology and obstetrics Ib-IIa squamous cell carcinoma of the cervix.

PURPOSE: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. RESULTS: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. CONCLUSION: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: a feasibility study.

AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). METHODS: Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. RESULTS: Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. CONCLUSION: SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Mitochondrial DNA haplogroup confers genetic susceptibility to nasopharyngeal carcinoma in Chaoshanese from Guangdong, China.

Recent studies have shown association of mtDNA background with cancer development. We analyzed mitochondrial DNA (mtDNA) control region variation of 201 patients with nasopharyngeal carcinoma (NPC) and of 201 normal controls from Chaoshan Han Chinese to discern mtDNA haplogroup effect on the disease onset. Binary logistic regression analysis with adjustment for gender and age revealed that the haplogroup R9 (P = 0.011, OR = 1.91, 95% CI = 1.16-3.16), particularly its sub-haplogroup F1 (P = 0.015, OR = 2.43, 95% CI = 1.18-5.00), were associated significantly with increased NPC risk. These haplogroups were further confirmed to confer high NPC risk in males and/or individuals ≥ 40 years of age, but not in females or in subjects <40 years old. Our results indicated that mtDNA background confers genetic susceptibility to NPC in Chaoshan Han Chinese, and R9, particularly its sub-haplogroup F1, is a risk factor for NPC.

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy.

AIM: To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. CONCLUSION: The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter.

Long term outcomes and prognostic factors of n0 stage nasopharyngeal carcinoma: a single institutional experience with 610 patients.

Treatment responses of N0 stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with N0 NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with N0 NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with N0 NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

[Dosimetric comparison between intensity-modulated radiotherapy and conformal radiotherapy for upper thoracic esophageal carcinoma].

BACKGROUND AND OBJECTIVE: Treatment planning for radiotherapy of upper thoracic esophageal carcinoma is challenging due to the anatomical features. The difficulty may be resolved by intensity-modulated radiotherapy (IMRT). This study was to compare the dosimetric advantages of IMRT to that of conformal radiotherapy (CRT) for upper thoracic esophageal carcinoma, and to explore the clinical application of IMRT. METHODS: Eleven patients with upper thoracic esophageal carcinoma were enrolled. In addition to the actually used CRT plan, a five-field IMRT plan was generated for each case. The parameters of dose volume histogram for targets and organs at risk were compared between two techniques. RESULTS: For the planning target volume (PTV) of tumor and para-tumor tissues, the mean dose, maximal dose, doses covering 99% and 95% volume were similar in IMRT and CRT plans (P>0.05). However, IMRT plan had a higher conformity index than CRT plan (0.68+/-0.04 vs. 0.46+/-0.11, P<0.01). For the PTV of supraclavicular region, IMRT plan showed a better dose heterogeneity index than CRT plan (1.17+/-0.05 vs. 1.33+/-0.15, P=0.01). IMRT plan had lower maximal dose to the planning risk volume of the spinal cord (44.4 Gy vs. 52.5 Gy, P<0.05) and lower lung volume received dose of 10 Gy or higher [(32+/-6)% vs. (35+/-9)%, P<0.05] than CRT plan. CONCLUSION: For the upper thoracic esophageal carcinoma, IMRT has more conformal distribution of dose and better spinal cord sparing than CRT, and can reduce the volume of lung that received dose of 10 Gy or higher.

[Long-term efficacy of prophylactic upper neck irradiation for stage N0 nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Whether prophylactic irradiation should cover the whole neck or just the upper neck for nasopharyngeal carcinoma (NPC) patients, without neck lymph node metastasis (N0), remains controversial. This study was to assess the rationality of prophylactic upper neck irradiation for stage N0 NPC patients. METHODS: Clinical data of 432 stage N0 NPC patients were analyzed. All patients were treated with radical radiotherapy alone. The extent of prophylactic irradiation was limited to the upper neck of the patients. Median radiation doses were 70 Gy for the primary tumors, and 50 Gy for the upper necks. Kaplan-Meier method was used to analyze survival rates and neck recurrence rates. Log-rank test was used to compare neck recurrence rates in patients with or without nasopharyngeal recurrence. Cox proportional hazards model was used to evaluate the prognostic factors for neck control. RESULTS: Seventeen out of 432 patients had neck recurrence. The 5-year control rate of the neck was 96.06%. Among the 17 patients with neck recurrence, 6 had concurrent nasopharyngeal relapse. The occurrence rates of neck recurrence alone were 0.93%(4/432) in the upper necks and 1.62% (7/432) in the lower necks (P=0.937). The neck recurrence rates were 9.52% (6/63) and 2.98% (11/369) in patients with and without nasopharyngeal recurrence, respectively (P=0.002). Nasopharyngeal recurrence was the only independent prognostic factor for neck control. CONCLUSION: The overall neck recurrence rate is low for stage N0 NPC patients after receiving irradiation. Prophylactic upper neck irradiation is reasonable for stage N0 NPC patients.

[Relationship between radiotherapy enhancing effect of arsenic trioxide and the proliferation and apoptosis of related protein in nasopharyngeal carcinoma patients].

OBJECTIVE: To explore the mechanism of arsenic trioxide (ATO) in enhancing radiotherapy in nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy-four patients with NPC of T(1-4) N(0-1)M0 were randomized into two groups: 35 patients in Group A were treated with conventional radiotherapy alone, and the 39 in Group B received radiotherapy and additional administering of ATO. The regressions of nasopharyngeal lesions and cervical lymph nodes were compared between the two groups at 40 Gy of radiation was given. And biopsy of the tissue from NPC was taken before treatment and 24 h after radiation of 20 Gy to determine the-expressions of proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and p53 protein by immunohistochemistry. RESULTS: When irradiation for 40 Gy, the completely regression rates of nasopharyngeal lesion were 20.0% (7/35) in Group A and 43.6% (17/39) in Group B, showing significant difference between them (chi2 = 4.684, P = 0.003), but no significant difference was shown between the two groups in regression rate of cervical lymph node. Expression of PCNA, Bax, Bcl-2 and p53 protein was reduced in both groups, but significant difference only showed between pre- and post-treatment in PCNA (Z = -2.449, P = 0.014) and Bax protein (Z = -3.031, P = 0.002) in Group B. Significantly reduction of PCNA (Z = -2.656, P = 0.008), Bax (Z = -2.359, P = 0.018) and p53 protein (Z = -1.999, P = 0.046) in patients with complete tumor regression at radiation for 20 Gy, while in those with no complete tumor regression only PCNA showed significant reduction (Z = -32.815, P = 0.015). CONCLUSION: ATO shows effect in enhancing radiotherapy on NPC patients, its mechanism might be associated with the down-regulation of PCNA and apoptosis related protein and the inhibition on tumor proliferation and apoptosis inducing.

[Analysis of differences on delineation of the gross tumor volume (GTV) of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Accurate delineation of tumor target volume and organ at risk based on CT simulation, is essential in modern radiotherapy planning. It is also the basic requirement to improve the treatment outcome and quality of life in nasopharyngeal carcinoma (NPC). In this study, the impact factors on delineation of the gross tumor volume (GTV) of NPC were analysis. by comparing difference among various doctors' contours. METHODS: Thirty cases of NPC treatment planning with contrast enhanced CT scan were reviewed. Primary GTV delineated by in-charged physician was defined as GTV1. Another GTV delineated by author and a radiologist was defined as GTV2, while GTV1 was concealed by the functions of the treatment planning system, the longest diameters of each axis of GTV were measured and recorded respectively as X(1), Y(1), Z(1), and X(2), Y(2), Z(2). The volumes of GTV were calculated as V1 and V2. Maximum permitted error (MPE) was 2 mm on X and Y axes and 3 mm on Z axis. Margin of each axis was compared to Coparable MPEs by matching t-test. RESULTS: The differences on axes of X, Y, Z between GTV1 and GTV2 were 2.95+/-4.33, 6.24+/-7.52, 6.25+/-9.35, respectively (P

Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma.

AIM: To investigate the expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS: The reduced expression rate of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression rate was 56.5%. Expression of gamma-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (chi(2) = 4.183 and chi(2) = 5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (chi(2) = 5.769, P<0.05). Reduced expression of E-cadherin and gamma-catenin was associated with poor differentiation of tumor, reduced expression of gamma-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and gamma-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and in reduced expression one and were 78% and 48% in gamma-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of alpha-catenin correlated with that of E-cadherin and beta-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and gamma-catenin, but not alpha-catenin, beta-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.

Clinicopathologic analysis of esophageal and cardiac cancers and survey of molecular expression on tissue arrays in Chaoshan littoral of China.

AIM: To investigate clinical and pathologic data of esophageal carcinoma (EC) and cardiac carcinoma (CC) among residents in Chaoshan region of China. METHODS: Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC in the Chaoshan population were collected and analyzed. Moreover, Chaoshan esophageal carcinoma tissue arrays were made for high-throughput study. RESULTS: Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average age of the occurrence of EC was 54.6 years, and of CC was 58.1 years. For both EC and CC, age at diagnosis was a little younger in Chaoshan region than in most other areas. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%); the second was the lower third (15.3%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type was the second (39.6%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer (96.4%); adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal carcinoma tissue arrays were easily for high-throughput study, and tissue cores with a diameter of 1.5 mm could better keep more structure for molecular expression study. CONCLUSION: Both EC and CC are common in males. The average occurrence age of EC and CC is younger in Chaoshan than in most other regions of China. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer; adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma. Tissue arrays technology is applicable for rapid molecular profiling of large numbers of cancers in a single experiment.

[Arsenic trioxide induces differentiation of human nasopharyngeal carcinoma in BALB/C nude mice xenograft model].

BACKGROUND & OBJECTIVE: There is evidence that arsenic trioxide (AS2O3) induce differentiation of leukemia cells; however, little is known about its effect on solid tumors. The aim of this study was to investigate whether AS2O3 can induce cell differentiation and its association with growth inhibition in human nasopharyngeal carcinoma using BALB/C nude mice xenograft model. METHODS: Poorly differentiated human nasopharyngeal squamous carcinoma cells from CSNE-1 cell strain were transplanted subcutaneously to BALB/C nude mice to produce tumors. AS2O3 at a dose of 5 mg.(kg.d)-1 was given intraperitoneally for 10 consecutive days, and then 3 times a week for the following 3 weeks. The xenograft tumor growth in mice was observed after drug administration. The morphological changes of the tumors were examined under light and electron microscopy. Proliferating cell nuclear antigen (PCNA) expression was determined by immunohistochemistry. RESULTS: AS2O3 at dose of 5 mg.(kg.d)-1 significantly inhibited the tumor growth in vivo, with a inhibitory rate of 75.4%. Remarkable cell differentiation induced by AS2O3 was observed under light microscope and transmission electron microscope, which was characterized by keratinization of tumor cells, decreased nuclear/cytoplasm ratio, increased cytoplasmic organelles and rich tonofibrils in cytoplasm. Desmosomes and micro-processes were much more frequently observed in tumors treated with AS2O3. Significantly decreased PCNA expression was observed in AS2O3-treated tumor cells. The PCNA-positive cell index (PI) was 53.6 +/- 7.0% in AS2O3-treated mice, and 95.2 +/- 5.0% in control, respectively (P < 0.001). CONCLUSION: The growth of human nasopharyngeal carcinoma xenograft in BALB/C nude mice can be significantly inhibited by AS2O3, which might be related to the cell differentiation induced by AS2O3.

[Comparison of effects of three chemotherapy regimens for advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: The platinum-combination chemotherapy has been proved to be benefit to the patients with advanced non-small cell lung cancer (NSCLC), but the suitable regimen of chemotherapy has been much debated during the last decade. This study was designed to compare MIP regimen [mitomycin + ifosfamid + cisplatin], TP regimen [Taxol + cisplatin], and DP regimen [docetaxel + cisplatin] and to evaluate the efficacy of the three regimens in patients with advanced NSCLC. METHODS: Ninety-two patients were enrolled in this study, 32 for MIP, 30 for TP, and 30 for DP. The characteristics of patients were comparable except there were more stage IV patients and second chemotherapy patients in DP group. RESULTS: For MIP, TP, and DP groups, the objective response rates were 43.8%, 40%, and 46.7%, respectively; the median duration of survival were 11, 10, and 12 months respectively; the 1 year survival rate were 46%, 40%, and 50%, respectively. The major toxicities were bone marrow suppression, nausea, vomiting, and alopecia. CONCLUSIONS: MIP, TP, and DP regimens are effective and safe chemotherapy protocols for the treatment of advanced NSCLC patients.