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.

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.

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.

[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.

[Clinical features and prognosis of nasal type NK/T cell lymphoma].

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.

[Effect of hypoxic radiosensitizer sodium glycididazole on long-term result of radiotherapy for nasopharyngeal carcinoma].

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.

Neoadjuvant chemotherapy followed by late-course accelerated hyperfractionated radiation therapy for locally advanced non-small-cell lung cancer: long-term results of a phase I/II clinical trial.

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.

[Prognostic factors and treatment of 74 patients with dermatofibro-sarcoma protuberans].

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.

[Retrospective analysis of 934 nasopharyngeal carcinoma patients treated with conventional external beam radiotherapy alone].

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.

Comparison of Epstein-Barr virus DNA level in plasma, peripheral blood cell and tumor tissue in nasopharyngeal carcinoma.

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.

[Intensity modulated radiation therapy for 49 patients with recurrent nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the feasibility, toxicity and tumor control of intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma. METHODS: Fourty-nine patients (Karnofsky performance status (KPS) >or= 80) with local-regional recurrence in the nasopharynx were treated with full course IMRT. Three patients with cervical lymph node metastasis (N1 2 and N3 1) were further supplemented with 5 to 6 courses of chemotherapy (Cisplatin + 5-Fu) after IMRT. RESULTS: The results of treatment plan showed that the mean dose of covering gross tumor volume (GTV) (D(95)) in the nasopharynx was 68.09 Gy and the mean volume of GTV (V(95)) receiving the 95% dose was 98.46%. The mean dose of GTV, clinical target volume CTV1 and CTV2 in the targets were 71.40 Gy, 63.63 Gy and 59.81 Gy. The median follow-up time was 9 months (range 3 to 16 months). The local-regional progression-free survival was 100% with local-regional residual disease in 3 (6.1%) cases but was complicated with nasopharyngeal mucosa necrosis in 14 (28.6%) cases after IMRT. CONCLUSION: Intensity modulated radiation therapy, as a re-treatment option for recurrent nasopharyngeal carcinoma, is able to improve the tumor target coverage and spare the adjacent critical structures. As high dose IMRT can result in radio-necrosis of nasopharyngeal mucosa, the prescription dose of GTV should be suitably decreased to 60 - 65 Gy.

[Quantitative analysis of Epstein-Barr virus DNA in plasma and peripheral blood cells in patients with nasopharyngeal carcinoma].

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.

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.

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.

[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.

[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.

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.

[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.