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Purpose: To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT)., Methods: Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation., Results: There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis., Conclusion: Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the patterns of nodal failure and toxicity in clinically negative necks of N0-1 nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT) but did not receive elective neck irradiation (ENI) to level IV and Vb nodes., Methods and Materials: We conducted a phase 2 prospective study in N0-1 NPC patients treated with IMRT. ENI included the retropharyngeal nodes and levels II to Va but omitted levels IV and Vb in clinically negative necks. Patterns of nodal failure, regional control (RC), and late toxicity were evaluated., Results: Between 2001 and 2008, a total of 212 patients (128 N0 and 84 N1) were enrolled in the study. Seven patients (4 in-field and 3 out-of-field) developed nodal failure. One patient (0.5%) developed nodal failure at level Vb, but no patients developed nodal failure at level IV. The 5-year RC rates of the entire group, N0 patients and N1 patients were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed distant metastases. The 5-year distant failure-free survival (DFFS) and overall survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%, and 17.9%, respectively., Conclusions: The rate of out-of-field nodal failure when omitting ENI to levels IV and Vb in clinically negative necks of patients with N0-1 NPC was extremely low; therefore, a further phase 3 study is warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: A multi-center prospective randomized trial was conducted to evaluate the efficacy and safety of Actovegin in the prevention and treatment of chemoradiotherapy-induced acute oral mucositis., Methods and Materials: Between February 2006 and May 2007, 156 evaluable patients with nasopharyngeal carcinoma were randomized to Group 1 (n=53) for prevention, Group 2 (n=51) for treatment, and Group 3 (n=52) for control. All patients received concomitant chemoradiotherapy ± induction chemotherapy. Radiation technique and dose were similar among 3 groups. Intravenous Actovegin of 30 ml daily (5 days/week) was administrated from day 1 of the radiotherapy for Group 1 and from the onset of grade 2 mucositis for Group 2, until the end of the radiotherapy., Results: The incidence of grade 3 mucositis was lower in Group 1 compared with Group 3 (26.4% vs. 55.8%, P=0.002). Group 2 had a lower progression rate of mucositis from grade 2 to 3 compared with Group 3 (39.2% vs. 60.4%, P=0.035). There was no difference in the onset time of grade 3 mucositis among 3 groups. Actovegin was well tolerated and no treatment-related adverse events were observed., Conclusions: Actovegin is effective in the prevention and treatment of chemoradiotherapy-induced oral mucositis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Objective: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC., Methods: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus., Results: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment., Conclusions: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.

Objective: To explore the relationship between the genesis of Pi-Wei damp-heat syndrome (PDS) and the Helicobacter pylori (HP) infection in patients with chronic gastritis (CG) by observing the levels of nuclear factor kappaB (NF-kappaB) mRNA and heat shock protein 70 (HSP70) expressions., Methods: Gastric mucous membrane tissues collected through gastroscopy from gastric antrum of 51 CG patients, 36 of PDS type (CG-PDS) and 15 of Pi-qi deficiency syndrome (CG-non-PDS) type, and 8 healthy persons (as control) were examined to diagnose the inflammation level with HE stain and to detect the existence of HP infection by rapid urease test and methylthioninium chloride stain. The mRNA expressions of NF-kappaB and HSP70 in the tissues were determined quantitatively with FQ-PCR as well., Results: Patients of CG-PDS showed higher level of HSP70 mRNA expression than in the control; and level of NF-kappaB mRNA expression was higher than that in the control and CG-non-PDS (all P<0.05); but both expressions were insignificantly different in CG-PDS patients with positive or negative HP infection (P>0.05). Positive correlation of the two expressions was shown in CG-PDS with negative HP infection., Conclusion: NF-kappaB and HSP70 may partially embody, in some extent, the power of vital qi and evil qi in the organism; the over-expressed NF-kappaB and HSP70 may indicate the severe fighting between evil qi and vital qi, and both would be influenced to a certain degree in the fighting process.

It has been proved in recent studies that the chronic gastric disease (CGD) of Pi-Wei damp-heat syndrome type (CGD-PWDH) is closely related with heat shock protein 70 (HSP70) and nuclear factor-kappa B (NF-kappaB). HSP70 can protect the auto-stability of cells and elevate the immune function in organism against tumor or multiple exogenous pathogens. Increasing of NF-kappaB expression presents in case of Helicobacter pylori (Hp) stimulation, it could induce inflammatory reaction, while inflammation factors could act inversely to enhance the expression of NF-kappaB, thus to cause and expand the damage of gastric mucosa. In addition, HSP shows blocking effect on the activation and expression of NF-kappaB. So, the author considered that in patients of Hp associated CGD-PEDH, HSP 70 exhibits the effect as that of "vital energy" and NF-kappaB play a role as the "evil qi" in Chinese medicine, the expressions of the two may embody the vital-evil combating manner of Pi-Wei damp-heat syndrome.

Purpose: To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-beta1mRNA in rats., Methods and Materials: A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-beta1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction., Results: Compared with the irradiated group, levels of TGF-beta1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-beta1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1., Conclusion: PTX and Vit. E downregulated the expression of TGF-beta1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.

Background & Objective: Although concurrent radiochemotherapy is popularly accepted as a standard treatment for advanced esophageal carcinoma, there is still great room to improve the clinical efficacy. This phase II clinical trial was to further verify the efficacy of sodium glyci-didazole (CM-Na), as a valid sensitizer, combined with concurrent radiochemotherapy on advanced esophageal carcinoma, and observe adverse events., Methods: A total of 37 patients with esophageal carcinoma received radiotherapy at a dose of 54-60 Gy to the gross tumor volume (GTV) and a course of PF regimen [continuous intravenous drip of cisplatin 20 mg x (m(2) x d) g(-1) and 5-fluorouracil (5-FU) 500 mg x (m(2) x d) g(-1) on Days 1-5] every 3 weeks. All patients were given intravenous drip of CM-Na 700 mg/m(2) at 1 h before irradiation or chemotherapy three times weekly., Results: All patients completed the treatment. Three months after treatment, 16 (43.2%) patients achieved complete remission (CR) and 17 (46.0%) achieved partial remission (PR); the overall response rate was 89.2%. The 1-and 2-year survival rates were 78.6% and 48.7%. The median survival time was 23.2 months. The occurrence rate of grade III adverse events was 21.6%; no neurotoxicity was observed., Conclusion: Concurrent chemoradiotherapy combined with CM-Na could enhance the response rate and prolong survival of the patients with advanced esophageal carcinoma.

Background & Objective: Radiation-induced heart damage is one of the prognostic factors of the patients who had received radiation to the mediastinum. This study was to investigate the correlation of transforming growth factor-beta1 (TGF-beta1) mRNA expression to the radiation response of the heart in rats, in order to provide references for further study on irradiation-induced heart damage., Methods: Sixty Sprague-Dawley rats were divided into 2 groups: the 30 rats in irradiation group were irradiated with 20 Gy on the heart; the 30 rats in control group received no irradiation. At each time point of the 1st day, the 2nd, 4th, 8th 12th, and 24th week after irradiation, 5 rats in each group were killed. The serum levels of cardiac troponin and isoenzyme of creatine kinase (CK-MB) were detected. The expression of TGF-beta1 mRNA was detected by polymerase chain reaction (PCR). Heart damage was observed with Masson staining under microscope., Results: The serum level of cardiac troponin was elevated at 24 h after irradiation, and reached the peak at 2 weeks after irradiation, which was significantly higher than that in control group [(0.73+/-0.11) ng/mL vs. (0.11+/-0.04) ng/mL, P<0.05]. There was no significant difference in the serum level of CK-MB between two groups (P>0.05). The expression of TGF-beta1 mRNA was elevated at the 1st day after irradiation, and reached peaks at 2 and 12 weeks after irradiation, which were significantly higher than those in control group [(8.55+/-1.19)x10(-8) microg/mL vs. (1.27+/-0.11)x10(-8) microg/mL, (4.63+/-0.41)x10(-8) microg/mL vs. (1.35+/-0.15)x10(-8) microg/mL, P<0.05]. The proportion of collagen fibers was increased since 2 weeks after irradiation, which was significantly higher than that in control group [(2.87+/-0.37)% vs. (1.14+/-0.55)%, P<0.05]. The expression of TGF-beta1 mRNA was positively correlated to the proportion of collagen fibers in the rat hearts after irradiation (r=0.48, P<0.05)., Conclusions: TGF-beta1 is involved not only in the onset but also in the development of radiation fibrosis. Inhibiting the peak expression of TGF-beta1 mRNA may reduce the radiation-induced damage to the heart.

Objective: To investigate the hypoxia status in the primary lesion of nasopharyngeal carcinoma (NPC) during the treatment and the clinical value thereof., Methods: Sixty-two patients with untreated NPC were examined by 99m Tc-4, 9-diaza-3, 3, 10, 10-tetramethy ldodecan-2, 11-dione dioxime (99 Tcm-HL91) SPECT imaging and CT-simulation (CT-Sim) scan before the treatment, in the mid-treatment (after receiving about 40 Gy) and at the end of treatment respectively. (1) All hypoxia images obtained at the 3 time pints were analyzed by visual analysis and semi-quantitative analysis, the radioactivity ratio of the high density region in the nasopharyngeal lesion to the normal nasopharyngeal tissue (T+/N) was calculated with the technique of region of interesting (ROI). Then the changes of hypoxia status during the treatment were evaluated according to the changes of the visual results and the ratios of T+/N. (2) The tumor volumes in different time points were measured by relevant CT-Sim images in the CT-Sim working station (Exomio 2.0, Medintec), and the percentage of tumor shrinkage in the mid-treatment and at the end of treatment were calculated to evaluate the tumor's response to treatment. The relationships between the hypoxia status before treatment, hypoxic changes during the treatment, and the tumor's response to treatment were analyzed finally., Results: Fifty-six of the 62 NPC cases were hypoxia-positive before the treatment, the hypoxic location in the same patient remained in the same site in different time points, and no new hypoxic area was found during the treatment. Eight cases changed to negative in the mid- treatment and 19 changed to negative at the end of treatment. The ratio of T+/N decreased gradually in the same case (F = 109.073, P = 0.000). The tumor shrinkage rates in the mid-treatment and at the end of treatment of those with high-grade hypoxia (T+/N >or= 1.52) were all both significantly lower than those of the cases with low-grade hypoxia (T+/N < 1.52) (P = 0.019 and 0.000) and those of the hypoxia-negative group (P = 0.038 and 0.000). The ratios of T+/N variation in the mid-treatment and at the end of treatment were both positively correlated with the percentages of tumor shrinkage in the mid-treatment and at the end of treatment (r = 0.587, P = 0.003 and r = 0.655, P = 0.001)., Conclusion: The hypoxia of the primary lesion of NPC alleviates gradually or disappears along with the treatment course. Hypoxia has some negative effects on the tumor response to treatment.

Background and Purpose: To define individualized internal target volume (ITV) for hepatocellular carcinoma using four-dimensional computed tomography (4DCT)., Materials and Methods: Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory phases of 4DCT scans in 10 patients with hepatocellular carcinoma. The 3D and 4D treatment plans were performed for each patient using two different planning target volumes (PTVs): (1) PTV(3D) was derived from a single CTV plus conventional margins; (2) PTV(4D) was derived from ITV(4D), which encompassed all 10 CTVs plus setup margins (SMs). The volumes of PTVs and dose distribution were compared between the two plans., Results: The average PTV volume of the 4D plans (328.4+/-152.2cm(3)) was less than 3D plans (407.0+/-165.6cm(3)). The 4D plans spared more surrounding normal tissues than 3D plans, especially normal liver. Compared with 3D plans, the mean dose to normal liver (MDTNL) decreased from 22.7 to 20.3Gy. Without increasing the normal tissue complication probability (NTCP), the 4D plans allowed for increasing the calculated dose from 50.4+/-1.3 to 54.2+/-2.6Gy, an average increase of 7.5% (range 4.0-16.0%)., Conclusions: The conventional 3D plans can result in geometric miss and include excess normal tissues. The 4DCT-based plans can reduce the target volumes to spare more normal tissues and allow dose escalation compared with 3D plans.

Background & Objective: Three-dimensional conformal and intensity-modulated radiotherapy is the direction of developing radiotherapy for nasopharyngeal carcinoma (NPC). The accuracy of target area outlines is especially important. This study was to explore the clinical diagnostic values of magnetic resonance imaging (MRI), computed tomography (CT), and 18-F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT in detecting retropharyngeal lymph node metastasis of NPC, and to provide references to the plan of radiotherapy., Methods: MRI, enhanced spiral CT, and PET-CT reports of the nasopharynx and whole neck of 87 naive NPC patients, histologically diagnosed and treated in Cancer Center of Sun Yat-sen University between Jan. 2003 and Apr. 2005, were analyzed. The detection rates of retropharyngeal lymph node metastasis were compared among MRI, CT and PET-CT using Chi-square test., Results: Among the 174 parapharyngeal spaces of the 87 patients, the detection rates of retropharyngeal lymph node metastasis by MRI and CT were significantly higher than that by PET-CT (44.8% and 33.9% vs. 24.1%, P < 0.001 and P = 0.002). As compared with CT, MRI played an advantage in detecting retropharyngeal lymph node metastasis of NPC (P = 0.037). The minimal axial diameter of retropharyngeal lymph node was positively correlated to the standard uptake value (SUV) of PET-CT (r = 0.832, P <0.001)., Conclusions: MRI are better than CT and PET-CT in detecting retropharyngeal lymph node metastasis of NPC. The combination of MRI, CT, and PET-CT is useful for delineating targets accurately in 3-dimensional conformal intensity-modulated radiotherapy for NPC.

The aim of this study is to evaluate the quality of life (QoL) of nasopharyngeal carcinoma (NPC) survivors. 192 NPC survivors treated in 1999 and 2000 were enrolled in this study. Median follow up was 3.6 years (range 2.4-4.6 years). The Chinese SF-36 questionnaire and a self-reported symptom checklist consisting of 14 items were completed at clinics. Sociodemographic factors and clinical information were also collected. Most functional domains of the Chinese SF-36 were significantly worse in NPC survivors compared to the normal population. Xerostomia, hearing loss, hypomnesia, dysphagia, and trismus were frequently reported symptoms. Sociodemographic variables including gender, age, dialect, educational level, monthly income, economic status, and number of comorbidities were univariate predictors of different SF-36 domains and symptoms. Patients with earlier T and N stage, irradiated by linear accelerator, with lower dose and weekly dose to nasopharynx and neck, and those who had anterior nasal radiation field reported better QoL. Multiple stepwise regression analysis showed that the number of comorbidities, monthly income, age, and T stage were independent factors affecting global QoL. We concluded that NPC survivors had worse QoL than the normal population and improving radiotherapy might increase physical and functional domain of QoL.

Background & Objective: Intensity-modulated radiotherapy (IMRT) may help to diminish radiation-induced normal tissue damage and improve quality of life of nasopharyngeal carcinoma (NPC) patients. However, highly conformal treatment techniques commonly establish steep dose gradients between tumor and normal tissues, therefore, daily setup variations can significantly compromise the ultimate precision of idealized IMRT delivery. This study was to investigate the setup accuracy of thermoplastic masks used for immobilizing NPC patients treated by simultaneous integrated boost IMRT, and to determine adequate margins to account for those uncertainties., Methods: Nineteen patients with early stage (T1-2N0M0) NPC received CT scan weekly during their 6-week treatment course of fractionated IMRT. A total of 85 scanning parameters were obtained. The differences in anatomic landmark coordinates in 3-dimensional directions between daily setup and the first day setup were calculated through comparing the CT images with Osiris software., Results: Mean target isocenter translation was (0.89+/-0.69) mm in x-direction, (0.82+/-0.79) mm in y-direction, and (0.95+/-1.24) mm in z-direction. The systematic errors were 0.94 mm, 1.00 mm, and 1.32 mm. The random errors were 0.87 mm, 0.80 mm, and 1.04 mm. The mean total magnitude vector of isocenter motion was 1.87 mm; the 95% confidence interval (CI) was 2.03-7.24 mm., Conclusion: During IMRT for early stage nasopharyngeal carcinoma, setting appropriate margin of planning target volume (PTV) by widening 3 mm from clinical target volume (CTV) in x, y, z directions will be sufficient to compensate for the dosimetric uncertainty of target areas due to patient setup error. The measured data in the present study should enable the user of this kind of thermoplastic mask to assign appropriate margins for the generation of planning target volumes (PTVs).

Background & Objective: The dose distribution of brachytherapy is different from that of external radiotherapy. Combining these 2 modalities can enhance the conform degree of dose distribution. This study was to evaluate long-term efficacy of external plus intracavitary irradiation on stage I-II nasopharyngeal carcinoma (NPC)., Methods: A total of 321 patients were randomized into 2 groups: 223 in simplex group were given conventional irradiation in total doses of 66-74 Gy with lead block fitful fields; 98 in combination group were given the same external irradiation in total doses of 58-62 Gy and 15-20 Gy intracavitary irradiation., Results: Within 5-year follow-up, in simplex group, 16 patients had tumor relapsed at the nasopharynx and 35 died, with 5-year overall survival rates of 90.63% for stage I patients and 80.82% for stage II patients (P=0.018)û in combination group, 1 patient had tumor relapsed at the nasopharynx and 6 died, with 5-year overall survival rates of 95.24% for stage I patients and 93.36% for stage II patients (P=0.025). There were fewer adverse events in combination group., Conclusion: The long-term efficacy of external plus intracavitary radiotherapy on stage I-II NPC is better than that of conventional external radiotherapy alone with fewer adverse events.

Background & Objective: Radiation-induced temporomandibular joint damage is a kind of common complication after radiotherapy for nasopharyngeal carcinoma (NPC) patients. Trimus is the main symptom of this damage, and severely affects the quality of life of the patients. This study was to evaluate radiation-induced temporomandibular joint damage in NPC patients treated with intensity-modulated radiotherapy (IMRT), and analyze its affecting factors., Methods: From Feb. 2001 to Feb. 2003, 148 naive NPC patients were treated with IMRT by 2.27-2.80 Gy per fraction at a total dose of 63-77 Gy within 31-86 days. The distance between 2 dens incisivus medialis (DDIM) was measured before radiotherapy, and 6 months, 1 year, 2 years, and 3 years after radiotherapy, respectively., Results: The overall 1-, 2-, and 3-year survival rates were 97.26%, 94.83%, and 92.04%. The irradiation dose to temporomandibular joint was 17.9-51.36 Gy. Seven (4.73%) patients suffered from grade I-II temporomandibular joint damage after IMRT; no patient had grade III-IV temporomandibular joint damage., Conclusions: IMRT can spare the temporomandibular joint from high dose irradiation. The risk of radiation-induced severe temporomandibular joint damage in NPC patients after IMRT is low.

Background & Objective: Accurate definition of target volume is difficult in three-dimensional conformal radiotherapy (3D CRT) for liver tumors because of the wide moving extent of tumors with respiration. This study was to define individualized internal target volume (ITV) using four-dimensional computed tomography (4D-CT), and compare planning target volumes (PTVs) and dose distribution of 3D planning with 4D planning for hepatocellular carcinoma (HCC)., Methods: Seven primary HCC patients received 4D-CT scanning. Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory phases of CT images. The 3D and 4D treatment plans were made for each patient using different PTVs, namely, PTV-3D derived from a single CTV plus conventional margins; PTV-4D derived from ITV-4D which encompassing all 10 CTVs plus setup margins (SM). The two plans were designed at the 20% respiratory phase CT images using 3D treatment planning system and compared with respect to PTVs, dose distribution to normal tissues, normal tissue complication probability. The prescription dose and design of irradiating fields were identical for both plans., Results: The average PTV was (417.6+/-197.7) cm(3) in 3D plan and (331.9+/-183.1) cm(3) in 4D plan, decreased by 20.50% (12.60%-34.40%). PTV coverage and dose uniformity were similar in the 2 plans. 4D plans spared more normal liver, kidney, stomach, and small intestine than 3D plans, especially for the liver. The V30 and V40 of the liver were lower in 4D plans than in 3D plans (33.59% vs. 38.77%, 22.62% vs. 27.32%); the mean dose to normal liver was decreased from 24.13 Gy to 21.5 Gy; liver complication probability was decreased from 21.57% to 15.86%. Without increasing the normal tissue complication probability, the prescription dose was higher in 4D plans than in 3D plans [(54.86+/-2.79) Gy vs. (50.57+/-1.51) Gy], increased by 9.72% (4%-16%)., Conclusions: The 3D plans have pitfalls of geometric miss or over coverage of target volume. The 4D plans can accurately definite target volume to spare more normal tissues and make dose escalation as compared with 3D CRT.

Objective: To evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma., Methods: Between May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis., Results: The clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy., Conclusion: Sodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.

Background & Objective: The prognosis of esophageal cancer is not only affected by TNM stage but also by the level of serum vascular endothelial growth factor (S-VEGF). This study was to investigate the effect of concurrent chemoradiotherapy on S-VEGF in esophageal squamous cell carcinoma (ESCC), and to explore the correlation of S-VEGF to the prognosis of ESCC., Methods: Serum samples were obtained from ESCC patients, treated with concurrent chemoradiotherapy in Cancer Center of Sun Yat-sen University from Dec. 2002 to May 2004, before treatment and 1 month after treatment. The serum samples from sex- and age-matched healthy donors were used as controls. Two courses of chemotherapy, comprised of cisplatin and 5-fluorouracil, were given during radiotherapy at 4-week intervals. S-VEGF level was measured by ELISA. The changes of S-VEGF level before and after treatment were observed, and its correlation to progress-freely survival rate of ESCC patients was analyzed., Results: S-VEGF level was significantly higher in ESCC patients before and 1 month after treatment than in healthy controls [(516.27+/-67.89) ng/L and (347.19+/-35.42) ng/L vs. (294.20+/-23.40) ng/L, P<0.01, P=0.002]; concurrent chemoradiotherapy significantly reduced S-VEGF level (P<0.01). S-VEGF level before treatment was significantly lower in the patients achieved complete remission than in those achieved partial remission or had progressive disease [(345.82+/-76.29) ng/L vs. (669.37+/-99.04) ng/L, P =0.020]. The 1-year progress-freely survival rate was 0 in the patients with S-VEGF level of > 516.27 ng/L before treatment and >347.19 ng/L after treatment, 17% in the patients with S-VEGF level of > 516.27 ng/L and <347.19 ng/L, respectively, 57% in the patients with S-VEGF level of < 516.27 ng/L and >347.19 ng/L, respectively, and 72% in the patients with S-VEGF level of < 516.27 ng/L and <347.19 ng/L, respectively (P= 0.005)., Conclusions: S-VEGF level is higher in ESCC patients than in healthy control. Concurrent chemoradiotherapy could reduce S-VEGF level in ESCC. The changes of S-VEGF level before and after treatment may provide prognostic information for ESCC patients.

Background & Objective: The efficacy of radiotherapy alone on locally advanced non-small cell lung cancer (NSCLC) is poor. Although the combined modality of chemoradiotherapy and dose-escalation of radiotherapy have been the main trends, the optimal modality still remains unknown. This study was to evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3D CRT) and concurrent weekly paclitaxel on unresectable NSCLC., Methods: Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC=5-6, d1) combined with paclitaxel (175 mg/m(2), d1), then followed by weekly paclitaxel (40 mg/m(2)) and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 < or =31% and spinal cord dose < or =50 Gy., Results: Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild (16/31): all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious (29/31, grade 3 in 21). Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grade 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grade 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months., Conclusions: The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Background & Objective: Barium swallow is widely used to observe the treatment response of esophageal squamous cell carcinoma (ESCC) and as a routine examination for long-term follow-up in China because of its convenience and inexpensiveness. This study was to observe esophageal tumor regression by barium swallow during radiotherapy, analyze the correlations of tumor regression speed to short-term response and long-term survival, and evaluate the clinical value of barium swallow during radiotherapy for ESCC., Methods: Clinical data from 94 patients with ESCC, treated with radiotherapy (39 patients) or chemoradiotherapy (55 patients) from Jan. 2001 to Jun. 2003 at Cancer Center of Sun Yat-sen University, were retrospectively reviewed. Of the 94 patients, 18 (19.1%) were at stage II, 36 (36.3%) at stage III, and 42 (44.6%) at stage IV. Barium swallow was performed at the radiation dose of 40 Gy and the radiation end, and the X-ray appearance was classified according to Zhengzhou Meeting criteria. The patients were divided into 3 groups according to their tumor regression speed: Group A had rapid regression, with the X-ray appearance classified as grade I or II at 40 Gy, Group B had slow regression, with the X-ray appearance classified as grade III or IV at 40 Gy, but as grade I or II at the radiation end, Group C had obvious residual tumors, with the X-ray appearance kept being classified as grade III or IV till radiation end. The correlations of tumor regression speed to short-term response and long-term survival were analyzed., Results: The complete response (CR) rates were 100.0% in Group A, 65.2% in Group B, and 28.3% in Group C (P<0.001), the 3-year survival rates were 44.0%, 24.2%, and 17.3%, respectively (P<0.001). Multivariate Cox regression analysis showed that short-term response and M stage were independent prognostic factors. The 3-year survival rates of CR patients were 44.0% in Group A, 32.6% in Group B, and 42.2% in Group C (P=0.814). The locoregional failure rates were 50% in Group A, 88% in Group B, and 81% in Group C, and the occurrence rates of severe radiation-related complications were 19%, 0%, and 6%, respectively., Conclusions: Barium swallow during radiotherapy for ESCC could be used to judge tumor regression speed, which is closely related to short-term response. Short-term response is an important prognostic factor of ESCC.

Background & Objective: At present, the detection of retropharyngeal lymph node (RLN) metastasis in nasopharyngeal carcinoma (NPC) mainly depends on imaging, but the diagnosis criteria are controversial. Recently, the 18F-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET-CT) has been widely applied in diagnosing cancer. This study was to evaluate CT, MRI, and (18)FDG-PET-CT in detecting RLN metastasis of NPC, and explore the imaging diagnosis criteria., Methods: From Dec. 2003 to Aug. 2005, 53 consecutive patients with NPC treated in Cancer Center of Sun Yat-sen University were enrolled. Contrast enhanced CT, MRI, and (18)FDG-PET-CT were performed on bilateral RLNs of the patients within 10 days before treatment. The diagnosis criteria of RLN metastasis for CT and MRI included single node with maximum diameter of > or =4 mm, and the presence of central necrosis or ringed enhancement; the criteria for (18)FDG-PET-CT included abnormal accumulation of irradiation in the RLN with the standard uptake value (SUV) of > or =2.5. Considering the response of RLN to clinical treatment, the differences of CT, MRI, and PET-CT in detecting RLN metastasis were compared., Results: Among the 106 intropharyngeal spaces of the 53 patients, the positive rate of RLN metastasis was significantly higher detected by CT and MRI than by PET-CT (39.6% and 45.3% vs. 20.8%, P<0.01), but the difference between CT and MRI was not significant (P>0.05). CT detected 27 cases of RLN metastasis with the maximum diameter of 0.4-0.9 cm, MRI detected 31 cases, and PET-CT only detected 5 cases. Especially, MRI detected 7 cases of RLN metastasis with the maximum diameter of < or =0.5 cm, CT detected 4 cases, but PET-CT detected none. CT detected 12 cases of RLN metastasis with the maximum diameter of > or =1.0 cm, MRI detected 14 cases, and PET-CT detected 13 cases. All patients were followed-up after treatment. One case of RLN metastasis with necrosis and the maximum diameter of 1.0 cm, and 1 case with the maximum diameter of 1.5 cm were eliminated within 6 months after treatment; the rest were eliminated within 3 months., Conclusions: In detecting RLN metastasis in NPC, MRI has no obvious advantage over CT, while PET-CT is markedly inferior to CT and MRI, especially in detecting the cases with the maximum diameter of <1.0 cm. Furthermore, the metastatic RLNs with necrosis or the maximum diameter of < or =5 mm can't be detected by PET-CT. Setting the maximum diameter of > or =4 mm as a diagnosis criterion of RLN metastasis for CT or MRI is reasonable and feasible.

Objective: To retrospectively analyze the treatment outcomes and prognostic factors of nasal and nasopharyngeal peripheral T cell lymphomas (PTCL) patients., Methods: One hundred and twelve patients with pathologically confirmed nasal and nasopharyngeal PTCL were included, among which 39 were CD56(+) NK/T cell lymphomas. The median pre-treatment disease course was 4 months. 84 were males and 28 females median age was 46 years. The tumors mainly involved nasal cavity (88 cases) and/or nasopharynx (50 cases) and adjacent structures, and 83 cases with extra-cavity diseases. 91.1% of the patients had Ann Arbor I(E)/II(E) diseases. The International Prognostic Indices (IPI) were less than 2 scores in 78.8% of the patients. Seventy two patients received combined chemo-radiotherapy, 32 chemotherapy only, 3 radiotherapy only and 5 no any treatment., Results: Median follow-up duration was 42 months. Chemotherapy achieved a complete remission (CR) rate of 34.4% for initial treatment, and of 65.1% after primary treatment. The local tumor controlled rate was 50.5%, and the median time to tumor progression (TTP) was 11 months. There were evidences of systemic relapse in more than 30% of the patients. The extra-cavity tumors usually had a shorter TTP (r(s) = -0.191, P = 0.024). The progress-free survival and overall survival rates were 38.8% and 52.4% at 3 years, and 34.9% and 44.8% at 5 years respectively. Univariate analysis showed that favorable prognostic factors for survival were pre-treatment course > 3 months, earlier clinical stage, non NK/T lymphoma, no skin involvement, lower IPI, CR after initial chemotherapy, radiotherapy, CR after primary treatment and local tumor controlled. Multivariate analysis showed that, pre-treatment course > 3 months (P = 0.011), non NK/T lymphoma (P = 0.007), CR after initial chemotherapy (P = 0.008) and radiotherapy (P = 0.000) were favorable prognostic factors for survival., Conclusions: Although most nasal and nasopharyngeal peripheral T-cell lymphomas were diagnosed at early stage diseases, some of them were highly aggressive with poor prognosis, particularly CD56(+) NK/T cell lymphomas. Combination chemo/radiotherapy, though remained principal treatments, more effective therapeutic modalities are expected.

Background & Objective: On the basis of our previous research, this study was to validate the rationality of AJCC/UICC staging system (1997) of nasopharyngeal carcinoma (NPC), and to provide some suggestions., Methods: Survival data of 915 NPC patients, received radical radiotherapy alone in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998, were analyzed with Life table, Cox regression, Kaplan-Meier, and log-rank methods., Results: Cox regression analysis showed that the 5-year survival rate of the 915 patients was significantly correlated to their age and tumor stage classified according to AJCC/UICC (1997) staging system; while that of the 803 patients no more than 60 years old was only significantly correlated to tumor stage. Life table analysis validated that the tumor stage classified according to AJCC/UICC staging system can roughly predict the prognosis, but the differences between stage I and IIa, or IVa and IVb were not significant. Kaplan-Meier analysis showed no significant differences of survival rate between stage T1 and T2a, or T3 and T4 when adjusted by N classification, and between stage N2 and N3a, or N3a and N3b when adjusted by T classification. Therefore, we adjusted stage T2a to T1, stage N1 with inferior cervical nodes metastasis to N2, combined stage N3a and N3b to N3, adjusted stage IIa to I, stage IIb to II, and stage IVb to IVa. After the modifications, the differences among stages I-IVa, T1-T4 (adjusted by N classification) and N0-N3 (adjusted by T classification) were significant., Conclusion: Taking the impact of age on the prognosis and the interaction between T stage and N stage into consideration, the above modifications should be included when renewing the AJCC/UICC staging system (1997).

Background & Objective: Tumor hypoxia is an important biologic feature of malignancies, which affects their response to radiotherapy and chemotherapy. There is still no reliable and convenient way in clinic to detect the hypoxia of nasopharyngeal carcinoma (NPC). This study was to explore the clinical application value of (99m)Tc-HL91 hypoxia imaging in NPC., Methods: A total of 38 NPC patients were included. Single photon emission computed tomography (SPECT) scan of the head and neck was performed 3.5 h after intravenous injection of 925 MBq (99m)Tc-HL91. The images were qualified visually and processed with semi-quantitative analysis. The nasopharynx (NP) lesions with radioactivity higher than that of normal NP tissue background (N) were identified as hypoxia positive. Region of interesting (ROI) technique was used to determine the positive imaging interested region (T+) and the negative imaging interested region (T-) in the same NP lesion for all positive cases. T+ -to-normal NP tissue background (T+/N) ratio and T- -to-normal NP tissue background (T-/N) ratio were measured. The correlation of T+/N ratio to tumor volume was analyzed., Results: Of the 38 NPC patients, 32 (84.21%) were hypoxia-positive, with the T+/N ratio significantly higher than the T-/N ratio (1.54+/-0.44 vs. 1.08+/-0.19, P <0.001). The T+/N ratio was positively correlated to tumor volumes (r=0.788, P <0.001)., Conclusion: (99m)Tc-HL91 is a convenient hypoxia imaging agent, and has potential clinical value in NPC hypoxia imaging and confirming target area for radiotherapy.

Objective: The prevalence of retropharyngeal lymph node (RLN) metastasis in nasopharyngeal carcinoma (NPC) is high, but its role in '92 Fuzhou staging system for NPC is uncertain. This study was to identify the prognostic value of RLN metastasis in NPC, and to evaluate its role in the staging system., Methods: Clinical data of 749 untreated patients with histologically diagnosed NPC, without metastasis, presented between Jan. 1999 and Dec. 1999 at the Department of Radiation Oncology of Cancer Center of Sun Yat-sen University, were reviewed. All patients received enhanced spiral CT scan on the nasopharynx and whole neck before treatment. Cox regression model was used to investigate the prognostic value of RLN metastasis. According to the principle of the staging system, the indices of hazard consistency, hazard discrimination, and distribution were evaluated to identify the role of RLN metastasis in the staging system for NPC., Results: The occurrence rate of RLN metastasis was 51.5%; the occurrence rates were significantly higher in the patients in advanced T stage, N stage, and clinical stage than in the patients in early stages (57.8% vs. 45.2%, P=0.001; 60.3% vs. 47.6%, P=0.001; 57.9% vs. 38.9%, P<0.001). The 5-year overall survival rate and 5-year distant metastasis-freely survival rate were significantly lower in the patients with RLN metastasis than in the patients without RLN metastasis (58.7% vs. 72.2%, P<0.001; 74.5% vs. 84.9%, P<0.001). In multivariate analysis, RLN metastasis was not a prognostic factor for overall survival, but borderline significant difference was observed for distant metastasis-freely survival (P=0.053). The hazard ratios of death and distant metastasis for N0 stage with RLN metastasis were 0.540 and 0.411, respectively, which was similar to those for N1 stage (0.601 and 0.555, respectively). Classifying RLN metastasis to N1 stage improved the hazard consistency in the N classification, but the distribution was unsatisfactory, and the proportion of N1 stage patients was 50.2%. Classifying RLN metastasis to T2 stage improved the hazard discrimination, with good balances of distribution found in T classification, N classification, and clinical staging., Conclusions: Based on the enhanced CT image, RLN metastasis tends to affect distant metastasis-freely survival of NPC patients. According to the principle of '92 Fuzhou staging system and present patterns of radiotherapy for the primary tumor, classifying RLN metastasis to T2 stage is more reasonable.

Objective: To investigate the clinical features, treatment modalities and the prognosis of nasal type NK/T cell lymphoma., Methods: The data of 39 such patients treated from June 2000 to December 2003 were retrospectively reviewed. Twenty three patients were treated by combined chemoradiotherapy, basing on anthracycline-containing CHOP or similar regimens (median 5 cycles). Eleven patients by chemotherapy alone, 2 by radiotherapy alone and 2 aged patients by palliative chemotherapy or radiotherapy. Radiotherapy was given by high energy photon ray combined with electron beam with a median curative dose of 56 Gy in conventional fractionation. Bivariate correlations and univariate prognostic factors were analyzed., Results: Median follow-up time for the 21 patients who were still alive was 22.5 months. The overall remission rate (RR) after initial treatment was 66.7% (21 CR, 3 PR). Chemotherapy alone got a CR rate of only 37.5%. The overall local control rate was 59.4%. Local relapse rate after curative radiotherapy was 25.0%. Radiotherapy was positively correlated with local control (P = 0.000) and time to disease progression (TTP, P = 0.002). Skin and intestine were among the extranodal relapse sites. Fifteen patients had highly aggressive tumors with a median survival time of only 5 months. Univariate analysis showed that significant favorable survival prognostic factors were: radiotherapy (P = 0.001); lower risk International Prognostic Index (IPI, P = 0.001); complete remission after primary treatment (P = 0.000); pre-diagnostic history > 2 months (P = 0.024); and free of skin involvement (P = 0.034)., Conclusion: Most of nasal type NK/T cell lymphoma are in early stage when diagnosed. Radiotherapy remains to be the mainstay of treatment. Combined chemoradiotherapy needs further improvement for the progressive disease type. Some patients may have highly aggressive tumors with poor prognosis. Optimal prognostic factors and individualized treatment regimens need to be investigated.

Background & Objective: With the elevation of survival rate of nasopharyngeal carcinoma (NPC) patients after treatment, their quality of life (QOL) is more and more emphasized. This study was designed to evaluate the QOL of disease-freely survival NPC patients after treatment, and to investigate the factors correlated with their QOL., Methods: From Jul. to Aug. 2003, disease-freely survival NPC patients who had been treated from 1999 to 2000 in Cancer Center of Sun Yat-sen University were enrolled. The Chinese SF-36 questionnaire and a checklist consists of 14 items about self-rating symptoms were self-reported by all participants at clinic. Sociodemographic and clinical data of the patients were also collected, and their relationships with SF-36 data and symptoms were analyzed., Results: A total of 192 patients were enrolled in the study. The median survival time was 3.6 years (ranged 2.4-4.6 years). Xerostomia was the first common symptom, followed by hypoacusis, hypomnesia, dysphagia, and trismus. Univariate analysis showed that gender, age, educational level, monthly income, economic status, religion, and the number of complications had influences on QOL; the patients in earlier T and N stages, irradiated by linear accelerator, with lower total dose and weekly dosage to the nasopharynx and neck, and those who had anterior nasal field radiation reported better QOL. Multiple stepwise regression analysis showed that the number of complications, monthly income, age, and T stage were independent factors affecting total QOL., Conclusions: Improving radiotherapy might enhance physical functions of NPC patients. The prevention and control of chronic diseases, the development of economy, and the increase of income may promote NPC patients' QOL.

Background & Objective: Along with the development of treatments, different tumor staging systems are coexisted and have been modified. This study was to validate the rationality of the Fuzhou staging system (1992) of nasopharyngeal carcinoma (NPC), and to provide some suggestions., Methods: A total of 915 NPC patients received radical radiotherapy alone in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998. The 1-, 3-, and 5-year follow-up rates were 98.7%, 95.2%, and 91.7%, respectively. The survival data were analyzed with Life table, Cox regression, Kaplan-Meier, and log-rank methods., Results: The 1-, 3-, and 5-year overall survival rates of the 915 patients were 87.69%, 72.73%, and 64.44%; the 1-, 3-, and 5-year disease-freely survival rates were 86.87%, 69.72%, and 58.33%, respectively. Cox regression analysis showed that the 5-year survival statuses of the 915 patients were significantly correlated with their age and the tumor stage classified by the Fuzhou staging system (1992); the 5-year survival statuses of the 803 patients no more than 60 years old were only significantly correlated with tumor stage, and had no correlation with their age. Life table analysis validated that the tumor stage classified by Fuzhou staging system (1992) can roughly predict the prognosis, but the difference between the 5-year survival rates of stage I and II patients was not significant. Kaplan-Meier analysis showed no significant difference between survival statuses of stage T1 and T2 patients when adjusted by N classification. Therefore, we adjusted stage T2 without parapharyngeal space invasion to stage T1, stage T3 with carotid vagina invasion to stage T2, stage T4 with paranasal sinus involvement to stage T3, stage T3 with cranial nerve injury to stage T4, and stage N1 with bilateral lymph nodes involvement to stage N2. After the modifications, the differences among stage I to IVa, stage T1 to T4 (adjusted by N stage), or stage N0 to N3 (adjusted by T stage) were significant., Conclusion: Taking the impact of age on the prognosis and the interaction between T stage and N stage into consideration, the above modifications of should be included when renewing the Fuzhou staging system (1992).

Objective: To analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone., Methods: 34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node., Results: The 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months., Conclusion: It may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.

Background & Objective: Concurrent chemoradiotherapy is recommended as standard treatment for unresectable esophageal carcinoma now. This study was to analyze the prognostic factors of unresectable esophageal carcinoma after concurrent chemoradiotherapy., Methods: A total of 132 unresectable esophageal carcinoma patients received concurrent chemoradiotherapy from Jan. 1996 to Dec. 2003 in our hospital. All patients received chemotherapy at the beginning of radiotherapy, and when the radiation dose escalated to 40 Gy. Total dose of irradiation was 60-70 Gy. Gender, age, disease course, focus location, swallow embarrassment, weight loss, Karnofsky's performance status (KPS) score, family history, hemoglobin (HB) before therapy, X-ray type, pathologic grade, focus length, TNM stage, irradiation method and technology, irradiation dose, radiotherapy interval, short-term effect, esophagus perforation, esophagus haemorrhage, and retreatment methods were used as analysis factors for Cox regression univariate and multivariate analyses., Results: Univariate analysis showed that diseases course, focus location, weight loss, M stage, short-term effect, esophagus perforation, esophagus haemorrhage, and retreatment methods were prognostic factors of these patients. Multivariate analysis showed that M stage [P=0.014, odds ratio (OR)=2.515], short-term effect (P < 0.001, OR=2.181), esophagus perforation (P=0.022, OR=3.266), and retreatment methods (P=0.026, OR=1.142) were independent prognostic factors., Conclusion: The main prognostic factors of the patients with unresectable esophageal carcinoma treated with concurrent chemoradiotherapy are M stage, short-term effect, esophagus perforation, and retreatment methods.

Background & Objective: Although concurrent radiochemotherapy is recommended as the standard treatment for advanced esophageal carcinoma, the local failure still reaches up to 44%-54%. This study aimed to explore maximum tolerance dose (MTD) of sodium glycididazole(CM-Na) in the combined planning as the recommended dose for phase II study., Methods: Twenty-two patients with pathologically confirmed esophageal squamous carcinoma of stage III-IV were recruited according to the inclusion criteria. All patients were divided into 4 groups (at least 3 patients in a group) by turn as the dose of CM-Na escalated from 400 to 600, 700, and 800 mg x (m(2) x d)(-1) by Fibonacci's method, and treated according to the plan. All patients underwent the same concurrent radiochemotherapy. Conventional radiotherapy was performed with total dose of 60 Gy within 6 weeks. CM-Na was given 1 h before radiotherapy at Monday, Wednesday, and Friday every week, combined with 2 circles of continuous 5-day chemotherapy of 500 mg x (m(2) x d)(-1) of 5-fluoruracil (5-FU) and 20 mg x (m(2) x d)(-1) of cisplatin (DDP) at the first and the fifth week., Results: Low-grade gastrointestinal adverse reactions were observed in the 4 groups during the period of chemotherapy, but no adverse reactions of nervous system, kidney, or heart were observed. Severe adverse reactions occurred in 800 mg x (m(2) x d) (-1) group, included 3 cases of grade III radioactive esophagitis, 2 cases of grade IV aminopherase risen, and 1 case of grade III thrombocytopenia. All the 19 patients in the rest 3 groups suffered grade I-II thrombocytopenia. The rates of complete remission and partial remission were 27% (6/22) and 68% (15/22) at the end of treating, and 46% (10/22) and 54% (12/22) 1 month after treating., Conclusion: Liver disfunction is the main dose-limited toxicity of the treatment schemeu 700 mg x (m(2) x d) (-1) of CM-Na is recommended to phase II clinical study.

Background & Objective: Xerostomia, an ubiquitous sequelae in nasopharyngeal carcinoma (NPC) patients after radiotherapy, seriously affects life quality of the patients. This study was to investigate clinical value of submandibular salivary gland transfer in preventing radiation-induced xerostomia of NPC patients., Methods: A total of 70 eligible patients with NPC were recruited, and divided into test group (36 patients) and control group (34 patients). In test group, the submandibular glands were transferred to the submental spaces before conventional radiotherapy. The submental spaces were shielded during radiotherapy. Oral cavity mucous membrane reaction during radiotherapy, submandibular gland function and salivary fluid before and after radiotherapy, and questionnaire of xerostomia 3 months after radiotherapy were compared between test group and control group., Results: Acute oral cavity mucous membrane reaction was severer in control group than in test group; the incidence of stage III reaction was significantly higher in control group than in test group ( 8/34 vs. 3/36, P = 0.007). Three months after radiotherapy, trapping and excretion functions of the transferred submandibular glands were significantly better than those of the untransferred submandibular glands in test group (P = 0.001 and P = 0.000); trapping and excretion functions of the submandibular glands were significantly better in test group than in control group (P = 0.004 and P = 0.000). The mean weight of salivary fluid after radiotherapy was heavier in test group than in control group (1.41 g vs. 0.71 g). Incidence of moderate to severe degree of xerostomia was significantly higher in test group than in control group (76.5% vs. 13.9%, P = 0.000)., Conclusion: Submandibular gland transfer may be used to prevent radiation-induced xerostomia of NPC patients, and may improve life quality of the patients.

Background & Objective: Concurrent chemoradiotherapy is the standard treatment for unresectable esophageal carcinoma. Local failure and recurrence are main reasons of treatment failure. This study was to discuss the factors related with local failure and recurrence of unresectable esophageal carcinoma after concurrent chemoradiotherapy., Methods: Records of 132 patients with esophageal carcinoma, treated with concurrent chemotherapy in our hospital from Jan. 1996 to Dec. 2003, were reviewed. The patients received the first cycle of chemotherapy at the beginning of radiotherapy, and the second cycle of chemotherapy when radiation dose escalated to 40 Gy. Local failure-related factors were analyzed by binary logistic regression., Results: To the terminal of follow-up, of the 132 patients, 54 had local failure or in-fields recurrence, 20 had in-fields recurrence and lymph nodes or distant metastasis, 5 had out-fields recurrence. Logistic regression analysis showed that short-term effect and irradiation dose were correlated with local failure and recurrence. Local failure and recurrence rate was lower in patients with complete remission (CR) than in patients with partial remission (PR) after chemoradiotherapy (44.9% vs. 79.6%, P < 0.001); and the mean time to recurrence was longer in CR patients than in PR patients (12.9 months vs. 6.1 months, P=0.002). When irradiated with 50-60 Gy,60.1-69.9 Gy, >/=70 Gy of x-ray, the local failure rates of the patients were 69%, 61%, and 52% (P=0.027), respectively, the mean time to recurrence were 5.3, 9.1, and 10.3 months, respectively., Conclusion: Radiation dose and short-term effect may influence local control of unresectable esophageal carcinoma.

Toxicity, response, and long-term results of a definitive chemotherapy/radiation therapy (RT) protocol in patients with unresectable stage III non-small-cell lung cancer (NSCLC) were evaluated. Two cycles of cisplatin-based chemotherapy were delivered before RT, and another 2 cycles were added for patients who responded to the first 2 cycles of chemotherapy. The first course of radiation covered the primary lesion and elective nodal regions, given in 2 Gy per fraction, 5 days a week for a dose of 40 Gy. Late-course hyperfractionated accelerated RT was delivered to the gross tumor twice a day for an additional 27 Gy within 2 weeks, using 1.5 Gy per fraction. Fifty-three patients with unresectable stage IIIA (N2) and IIIB NSCLC were eligible for analysis. Twelve patients developed grade 3 neutropenia, and 3 patients developed grade 4 neutropenia. Grade 2 or 3 esophagitis was observed in 14 and 2 patients, respectively, and grade 2 or 3 pneumonitis was observed in 9 and 1 patient, respectively. Six patients developed grade 2 and 1 patient developed grade 3 late lung toxicity. The median survival time was 15.5 months. Twenty-six of 53 patients (49%) have died of locoregional progression inside the thorax. The distant metastasis rate was 59.5% (22 of 37 patients) for those who did not respond to chemotherapy and 18.8% (3 of 16 patients) for those who responded to chemotherapy (P = 0.006). Late-course hyperfractionated accelerated RT combined with induction chemotherapy was well tolerated and yielded long-term results that compare favorably with those of studies using 2 cycles of induction chemotherapy and conventional fractionated RT. However, local control was still discouraging.

Objective: To analyze treatment and prognostic factors of 74 patients with dermatofibro-sarcoma protuberans (DFSP)., Methods: From August 1990 to November 1999, 74 patients with DFSP confirmed pathologically were treated. There were 52 males and 22 females with a median age of 37 years (range 4 to 80 years) on diagnosis. Seventeen patients were treated by extensive excision and 2 by limited excision. Fifty-two patients had surgical resection alone (S), and 22 postoperative radiotherapy (S + R) of 50-70 Gy. The multivariate parameters were analyzed using Cox model. Kaplan-Meier and Log-Rank test were used to evaluate the results of the recurrence-free survival., Results: The rate of recurrence was 28.4% for all patients. The 5-year recurrence-free survival rate (RFSR) was 66.6% and the 10-year RFSR was 52.5%. The 5-year and 10-year in the S group were 58.4% and 41.2%, compared with 90.0% and 83.3% in the S + R group (P < 0.05). The 5-year and 10-year RFSR in the pathologically positive margin group were 57.5% and 41.4% respectively, compared with the 75.0% and 56.6% in the pathologically negative group (P < 0.05). Multivariate analysis suggested radiotherapy and negative pathological margins were favorable prognostic factors., Conclusion: Post-operation radiotherapy and pathological margin are the independent prognostic factors.

Background & Objective: Transcatheter arterial chemoembolization (TACE) is the routine treatment for unresectable primary liver cancer, but 3-year survival rate of patients received TACE alone is only about 20%. This research was to evaluate efficacy of external radiotherapy (RT) combined with TACE on unresectable primary live cancer., Methods: From Jun. 1994 to Apr. 2002, 114 patients with unresectable primary liver cancer were non-randomized to receive TACE plus RT (54 patients), or TACE alone (60 patients) as control. For TACE, after skiagram confirmed catheterization, suspension of 300 mg of carboplatin, 50-60 mg of epirubicin, 14-20 mg of mitomycin, and 10-30 ml of iodized oil was perfused into hepatic arteries, 1-2 mm of Gelfoam particles was given to embolize hepatic arteries according to blood supply conditions of tumors, this process was repeated every 4-8 weeks. Either group was treated with 1-4 sessions of TACE. In TACE+RT group, patients received radiation on tumor and generous margin 21-28 days after TACE. The radiation dose was 46-60 Gy in daily 2 Gy fractions., Results: In TACE+RT group, response rate (AFP titer decrease of >50%) was 61.1%, and 1-, 2-, 3-year survival rates of TACE+RT group were significantly higher than those of TACE group (66.5% vs. 53.9%, 48.4% vs. 37.2%, and 37.4% vs. 17.8%, P<0.05). Three-year survival rate correlated with tumor size, liver function grade, and portal vein embolus., Conclusion: TACE combined with RT may prolong survival time of patients with unresectable primary live cancer.

Background & Objective: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis. This study was to analyze long-term results, and prognostic factors of patients with MPM., Methods: Records of 24 patients with MPM, proved by pathology or cytology, treated in our hospital from Jan. 1988 to Dec. 2001 were analyzed retrospectively. Of the 24 patients, 12 received chemotherapy alone (1-6 cycles of cisplatin-based regimens), 7 received surgery plus postoperative chemotherapy (1-6 cycles of cisplatin-based regimens), and 5 received surgery plus postoperative radiotherapy. Kaplan-Meier method and log-rank test were used to evaluate the survival rates. Cox regression model was used to explore prognostic factors of MPM., Results: Of the 24 patients, 1-, 3-, and 5-year survival rates were 37.5%, 20.8%, and 4.2%, respectively,with a median survival time of 9 months; those in chemotherapy group were 16.7%, 0, and 0, respectively, with a median survival time of 5 months; in surgery plus chemotherapy group were 28.6%, 14.3%, and 0, respectively, with a median survival time of 10 months; in surgery plus radiotherapy group were 100.0%, 80.0%, and 20.0%, respectively, with a median survival time of 42 months. There were significant differences among 3 groups (Chi(2)=11.93, P =0.002). Multivariate analysis showed that clinical classification (P=0.038), and mode of treatment (P=0.005) were independent prognostic factors of MPM., Conclusion: Mode of treatment, and clinical classification are independent prognostic factors for patients with MPM.

Background & Objective: Local-regional uncontrolled is an important reason of treatment failure for advanced nasopharyngeal carcinoma (NPC) after radiotherapy. Local-regional control rate increased with dose to tumor target volumes. Because of the complex anatomy features, dose escalation using conventional two-dimensional radiotherapy planning is limited by the tolerance of adjacent critical organs. In order to enhance doses to target volumes and local-regional control rates, this study explored application of intensity modulated radiation therapy (IMRT) in local-regional advanced NPC., Methods: Sixty patients with naive primary NPC, 49 in stage III, and 11 in stage IVa, received IMRT alone with an inverse planning system (CORVUS 3.0, Peacock plan). Treatment was delivered with the Multi-leaf Intensity Modulating Collimator (MIMiC) using a slice-by-slice arc rotation approach. The prescription dose was 68 Gy to nasopharynx gross tumor volume (GTVnx), 60-64 Gy to positive neck lymph nodes (GTVnd), 60 Gy to clinical target volume I (Target I), and 54 Gy to clinical target volume II (Target II), delivered by 30 fractions. Acute normal tissue effects were graded according to RTOG/EORTC radiation morbidity scoring criteria. Local control rate, regional control rate, distant metastasis-free rate, and overall survival rate were calculated using Kaplan-Meier method., Results: Analysis of dose-volume histograms (DVH) showed that the average mean dose delivered were 71.21 Gy to GTVnx, 65.85 Gy to GTVnd(L), 66.26 Gy to GTVnd(R), 67.59 Gy to Target I, and 61.42 Gy to Target II. The mean fractional dosage delivered were 2.37 Gy to GTVnx, 2.20 Gy to GTVnd(L), and 2.21 Gy to GTVnd(R). The average volumes of all target volumes covered by 95% isodose were more than 99%, and the average volume of GTVnx covered by 105% isodose was 43.87%; 5% of brainstem volume, and 1cc of spinal cord volume received average dosage were 46.96 Gy, and 39.99 Gy; 33% of volume of bilateral parotids, and T-M Joints received average dose was less than 38 Gy. There was no Grade 4 acute toxicity in all patients, and incidences of acute grade 3 toxicity of skin, mucous membrane, and salivary glands were 1.7%, 15.0%, and 1.7%, respectively. With the median follow-up of 15.5 months (6-37 months), no patient failed at the primary site, 2 patients relapsed at neck, 7 patients developed distant metastases, 9 patients died. The 3-year local control rate, regional control rate, and distant metastasis-free rate were 96.67%, 94.06%, and 84.98% respectively, 3-year overall survival rate was 74.97%., Conclusions: IMRT could escalate the total dose and fractional dosage to target volumes, and decrease the irradiation dose of surrounding critical organs. The acute toxicities were slight and tolerable. The local-regional control rates were satisfied. Distant metastasis is the main cause of failure.

Background & Objective: Surgery is the major treatment for glioma, and radiotherapy is often needed after operation. This study was to evaluate prognostic factors of patients with cerebral glioma treated with radiotherapy., Methods: Records of 158 patients with cerebral glioma, including 123 patients with astrocytoma (AC), 12 patients with oligodendroglioma (OD) or mixed oligoastrocytoma (OA), and 23 patients with glioblastoma multiforme (GBM), received radiotherapy in our center were analyzed. Eighty patients received total resection, 77 received subtotal resection, and 1 received biopsy before radiotherapy. Median radiation dose was 58 Gy (36-75 Gy). Median waiting time from operation to radiotherapy was 29 days (12-261 days). Sixty-eight patients received chemotherapy before or after radiotherapy. Cox model was used for univariate and multivariate analysis., Results: Median follow-up was 23 months (2-62 months), 27 patients relapsed, and 57 patients died. The 2- and 4-year overall survival rate were 66.5% and 45.7%. Univariate analysis showed that histologic grade (I/II vs. II/IV), histologic type (AC/OD vs. GBM), Karnofsky performance state (KPS) before radiotherapy (>/=80 vs.< 80), extent of resection (total vs non-total), and age(40 years) were significant predictors in association with overall survival rate of patients with glioma. Multivariate analysis showed that histologic grade (P=0.001), age (P=0.006), KPS before radiotherapy (P=0.009), and extent of resection (P=0.037) were independent prognostic factors of glioma., Conclusion: Low grade (I/II), age /=80 before radiotherapy, and total resection are independent factors for predicting better survival of glioma patients.

Background: The plasma Epstein-Barr virus DNA (EBV-DNA) level has been found to be an indicator for staging and prognosis of nasopharyngeal carcinoma (NPC)., Materials and Methods: The EBV-DNA level in plasma, peripheral blood cells (PBC) and neoplastic tissues was quantitatively analyzed and potential associations with clinical parameters of NPC were investigated., Results: The plasma EBV-DNA detecting rate and level in NPC (92%, 82,500 copies/ml) was significantly higher than that in NPC after treatment (19%, 0 copy/ml) and in controls (12%, 0 copy/ml) (p < 0.001); while there was no significance of the PBC EBV-DNA detecting rate and EBV-DNA load in NPC before (24%, 0 copy/actin) and after treatment (14%, 0 copy/actin), and in controls (16%, 0 copy/actin). The plasma EBV-DNA level was not correlated to the PBC EBV-DNA load in NPC before (p = 0.92) and after treatment (p = 0.267), and in controls (p = 0.735). The EBV-DNA level in NPC tumor (27.8 copies/actin) was significantly higher than that in nasopharyngitis and was positively correlated to the ratio of EBER1-positive cells on the NPC section (p = 0.001). The plasma EBV-DNA level was significantly increased in TNM stages I, II, III and IV NPC, whereas there was no significant difference of PBC EBV-DNA load in different stage NPC., Conclusion: Our results indicate that plasma EBV-DNA is a more sensitive and reliable biomarker than PBC EBV-DNA for diagnosis, staging and therapeutic effect evaluation at a molecular level in NPC clinical practice. Plasma EBV-DNA may derive from the cancer cells and PBC EBV-DNA from circulating mononuclear cells in NPC patients.

Purpose: The purpose of this study was to define the maximum tolerated dose (MTD) by describing the dose-limiting toxicity (DLT) of paclitaxel given as a 3-hour intravenous infusion concurrently with conventional radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC)., Materials and Methods: Patients with locoregionally advanced NPC were enrolled into a dose-escalating study. Toxicity was graded according to Common Toxicity Criteria 2.0. MTD was defined when 2 of 6 patients developed DLT. The starting dose of paclitaxel was 20 mg/m2 once weekly, with a subsequent dose escalation of 10 mg/m2 in cohorts of 3 new patients. Radiation therapy was administered in a conventional technique over 7 weeks in 2.0-Gy/daily fractions for 5 days/wk up to total doses of 68-70 Gy., Results: From November 2000 to June 2001, 16 patients completed chemoradiotherapy. On the first-dose level (20 mg/m2), no patient experienced DLT. On the next dose level with 30 mg/m2, 1 patient experienced DLT with grade 3 mucositis, which lasted for 5 weeks, and among the additional 3 patients, no one developed DLT. On the third dose level with 40 mg/m2, 1 patient developed grade 3 mucositis and another grade 3 dermatitis, and both of them lasted more than 3 weeks. To make the trial more credible, another 4 patients were added to the 30-mg/m2 level, and no DLT occurred. Thus, the accrual of patients stopped., Conclusion: Combined modality with paclitaxel given weekly, as a 3-hour infusion concomitant to conventional radiotherapy, is feasible for locoregionally advanced NPC. The dose recommended for a phase II trial is 30 mg/m2 with mucositis and dermatitis as DLT, and other toxicity is mild.

Objective: To quantitative analysis of Epstein-Barr virus (EBV) DNA levels in plasma, peripheral blood cells (PBCs) and tumor tissue in nasopharyngeal carcinoma (NPC), to investigate the relationship between EBV-DNA levels and clinical parameters., Methods: Blood of 150 primary NPC and 49 corresponding tumor tissues, 47 nasopharyngitis tissues and blood of 75 controls were entered this investigation. Plasma and PBCs were isolated for quantitative detection of EBV-DNA by using real-time quantitative PCR (RQ-PCR). The paraffin-embedded tissue sections were conducted to quantitative detection of EBV-DNA, and EBER1 in situ hybridization (ISH) for calculating the percentage of positive cells on the tissue section., Results: Plasma EBV-DNA levels and detecting rate in NPC before treatment (median 82 500 copies/ml, 92%) were significantly higher than that in NPC after treatment (median 0 copy/ml, 19%) and in controls (median 0 copy/ml, 12%) (P < 0.05), whereas there was no significant difference between NPC after treatment and controls (P > 0.05). There was no significant difference of PBCs EBV-DNA load and detecting rate in NPC before (0 copy/actin, 24%) and after treatment (0 copy/actin, 14%), as well as in controls (0 copy/actin, 16%) (P > 0.05). Plasma EBV-DNA level was not correlated to PBCs EBV-DNA load in NPC before (P = 0.92) and after treatment (P = 0.27), and controls (P = 0.74). EBV-DNA level (27.8 copies/actin) in NPC tumor tissues was significantly higher than that in nasopharyngitis (0 copy/actin) (P < 0.05), and was positively correlated to the ratio of EBER1 positive cells to total cells on the NPC section. In NPC patients, plasma EBV-DNA level was significantly increased in TNM stage I (2500 copies/ml), II (32 590 copies/ml), III (86 000 copies/ml) and IV (166 200 copies/ml), whereas there was no significantly difference of PBCs EBV-DNA loads in difference stages of NPC., Conclusion: Plasma EBV-DNA level is a more sensitive and reliable biomarker than PBCs EBV-DNA loads for reflection the tumor volumes in NPC patients. Plasma EBV-DNA detection will improve TNM staging in NPC clinical practice on molecular level.

Background & Objective: There is few report on the xerostomia of the patients with nasopharyngeal carcinoma after conventional radiation therapy. Xerostomia is a serious, permanent, and ubiquitous sequelae in the patients with nasopharyngeal carcinoma after conventional radiation therapy. It has a significant impact on the patient's quality of life. This study was designed to investigate the severity of xerostomia and its impact on the quality of life in patients with nasopharyngeal carcinoma after conventional radiation therapy., Methods: One hundred and thirty-six patients with nasopharyngeal carcinoma, treated by conventional radiation therapy in Cancer Center, Sun Yat-sen University, were surveyed by interview at the outpatient. A questionnaire and a visual analog scale (VAS) were used in analysis of xerostomia and xerostomia-related problems., Results: Of 136 patents, 73.5% of the patients experienced a moderate to severe degree of xerostomia. 82.4% of the patients had to sip water to facilitate speech; 92.6% of the patients had to sip water to facilitate chewing and swallowing; 91.2% of the patients changed their feeding pattern (can eat only mashed food); 61.3% of the patients had to wake up to drink water because of dry mouth; 75.0% of the patients had teeth deteriorated., Conclusion: 73.5% of the patients with nasopharyngeal carcinoma after conventional radiation therapy experienced a moderate to severe degree of xerostomia. Xerostomia has a significant impact on the patient's speech, deglutition, sleep, and increases the morbidity rate of the tooth.

Background: Serologic measurement of antibodies to Epstein-Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group., Methods: Real-time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme-linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non-NPC tumors, and in 47 control individuals., Results: The median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non-NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers > or = 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers < or = 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC., Conclusions: The results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor., (Copyright 2004 American Cancer Society.)

Purpose: To report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC)., Methods and Materials: A total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9-78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68-70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT., Results: The treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V(95-GTV)) was 98.5%, and the dose encompassing 95% of GTV (D(95-GTV)) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3-13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%)., Conclusion: The improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome.

Background & Objective: Keratinocyte growth factor (KGF) causes the proliferation of type II pneumocytes in the lungs and confers protection against many external stimulation in the lung. Historically, the kinetic parameters, especially of slowly proliferating normal tissues, such as the lung, were difficult to measure. However, recently developed techniques made it possible to measure accurately the cellular kinetics in normal tissues. Flow cytometric techniques following bromodeoxyuridine (BrdUrd) incorporation into DNA of cells allow the accurate measurement of cellular proliferation. The purpose of this study was to measure the changes of the dynamic kinetics of normal lung tissue after treatment with KGF so as to build up the basis to prevent the occurrence of radiation-induced pneumonitis., Methods: C3Hf/Kam mice were treated intratracheally (i.t.) with KGF (5 mg/kg) or the control (saline) and were sacrificed at 0, 1, 2, 3, 4, 5, and 7 days. The mice were labeled intraperitoneally (i.p.) with BrdUrd (60 mg/kg) at 20 minutes or 6 hours before sacrifice. Lungs were excised, fixed in 60% ethanol, digested to produce nuclei; and BrdUrd as well the total DNA content were labeled for flow cytometric analysis. The kinetic parameters including the labeling index (LI), duration of S-phase (T(S)), and potential doubling time (T(pot)) were measured by novel analytical methodology. Immunofluorescence staining was used to identify the specific cell type that was proliferating., Results: (1)An optimum route for the administration (i.t.), dose (5 mg/kg), and time course of KGF to stimulate proliferation of type II pneumocytes in the lungs was established. (2)Lung LI control values (0.5%) rose to a maximum (5.5%) at 3 days after KGF treatment and returned to normal level on the 7(th) day. (3)Of the lung tissue, there is a dramatic reduction in T(pot) from 75.5 days to 4.7 days in the KGF-treated mice, while the saline-treated control mice exhibited no change in proliferative parameter values., Conclusion: KGF caused the proliferation of type II pneumocytes, followed with the elevated LI and reduced T(pot). This proliferative effect was transient and levels returned to normal level by the 7(th) day. The data obtained from this study would lay the groundwork for future investigation of KGF as a possible radioprotector of the lung in the field of radiation oncology.