Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary.

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.

Results of a phase 2 study examining the effects of omitting elective neck irradiation to nodal levels IV and Vb in patients with N(0-1) nasopharyngeal carcinoma.

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.

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results of a phase 2 study.

BACKGROUND: The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. METHODS: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m(2) /d on Days 1 and 22) was administered. RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.

A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma.

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.

CT-guided needle biopsy through mandibular area for the diagnosis of nasopharyngeal carcinoma in the parapharyngeal space.

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.

Studies on pentoxifylline and tocopherol combination for radiation-induced heart disease in rats.

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.

[Phase II clinical trial of sodium glyci-didazole (CM-Na) combined with concurrent radiochemotherapy for advanced esophageal carcinoma].

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.

[Correlation of TGF-beta1 mRNA expression to irradiation-induced heart damage in rats].

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.

Defining internal target volume (ITV) for hepatocellular carcinoma using four-dimensional CT.

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.

[The values of MRI, CT, and PET-CT in detecting retropharyngeal lymph node metastasis of nasopharyngeal carcinoma].

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.

[Design planning target volumes (PTVs) in intensity-modulated radiotherapy for nasopharyngeal carcinoma].

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).

[Prospective study on long-term efficacy of external plus intracavitary radiotherapy on stage I-II nasopharyngeal carcinoma].

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.

[Internal target volume definition using four-dimensional CT and dosimetric evaluation for hepatocellular carcinoma].

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.

[Radiation-induced temporomandibular joint damage in nasopharyngeal carcinoma patients after intensity-modulated radiotherapy].

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.

Quality of life of nasopharyngeal carcinoma survivors in Mainland China.

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.

[Changes of hypoxia in primary lesion of nasopharyngeal carcinoma during the treatment course and the clinical value thereof].

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.

[Effect of concurrent chemoradiotherapy on serum vascular endothelial growth factor in esophageal squamous cell carcinoma patients--a report of 43 cases].

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.

[Initial outcome of induction chemotherapy with weekly paclitaxel followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer].

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.

[Treatment outcome and prognosis of 112 patients with nasal and nasopharyngeal peripheral T cell lymphomas].

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.

[Clinical value of barium swallow in observing esophageal tumor regression during radiotherapy].

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.