Nasopharyngeal carcinoma (NPC) is a malignant carcinoma that is closely associated with Epstein Barr virus (EBV) infection. After the comprehensive treatment based on modern intensity-modulated radiation therapy, the oncological outcomes can be further improved. The main target of treatment is to increase the efficacy of patients with high risk and recurrent/metastatic (R/M) NPC. Recently, continuous progress has been made in the application of immunotherapy in the field of cancer treatment. Based on the accumulated knowledge on EBV antigen and immune checkpoint inhibitors, significant progress has been made in use of immunotherapy in treating R/M-NPC. Immunotherapy combined with radiotherapy or chemoradiotherapy will become the hot spot in the clinical management of patients with newly-diagnosed high-risk NPC.

Mucosal melanoma of the head and neck (MMHN) is a rare malignancy.The sinonasal cavity and oral cavity are the most common primary sites.MMHN is a very aggressive malignant tumor,with the 5-year overall survival (OS) rate less than 30％.Currently,the optimal treatment modality remains unclear.In the najority of available retrospective studies,postoperative radiotherapy improves the local control of MMHN,but without significant effect on OS.This article aims to improve our understanding of the clinical features,diagnosis,staging,treatment modalities,and outcomes of this malignancy.

Objective To observe the clinical manifestation and pathological immunohistochemical features of intraspinal extramedullary peripheral primitive neuroeetodermal tumour (PNET). Methods From Apr. 1996 to Aug. 2007, totally 5 patients with intraspinal extramedullary peripheral PNET were treated, including 3 male and 2 female, aging from 11 to 48 years. The primary site was cervical vertebral in 2 (C5-C7 and C5-T1 ) and thoracic vertebral in 4( T4-T6, T6-T8 ,T4-T5 and C5-T1 ). The clinical manifestation was paresis of limbs in 5 and incontinence in 4. All the patients were pathologically diagnosed Results All of the three patients who had CD99 staining expressed CD99 ( + ). All the 5 patients received surgery followed by radiotherapy and 4 received postoperative chemotherapy. The most common treatment failure was local recurrence. The overall survival time of the 5 patients was 4.8year,2.5year,2. 1ycar, 1.6year and 0.8 year respectively. Conclusions Intraspinal extramedullary peripheral PNET is highly malignant tumor.Patients have very poor survival and local control New treatment protocol should be studied to improve the local disease control and increase remission rate. To distinguish central PNET from peripheral PNET has crucial significance since different entities have different treatment protocol and prognosis.

Objective To detect the clinical features and prognostic factors of nasal cavity malignancy with breast metastasis.Methods 846 Patients with nasal cavity malignancy from January 1999 to December 2011 were enrolled,the clinical and pathological features,clinical diagnostic methods and prognostic factors for breast metastasis patients were analyzed.Results Six female cases (median age 25) were diagnosed with breast metastasis,including 3 rhabdomyosarcoma and 3 olfactory neuroblastoma; consisting 0.7％ of the total 846 cases of primary nasal malignancy group.The metastasis were more likely to be multiple breast lesions with/without metastasis in other site.For the primary tumor,five patients received 66-72 Gy/30-33f of radical radiotherapy,one patient with rest rhabdomyosarcoma received 58 Gy of palliative radiation since breast metastasis was found after 14 Gy of radiation and breast mass resection were performed right after.For the breast metastasis,five of 6 patients received breast surgery,one patients with olfactory neuroblastoma received 6 cycles cyclophosphamide + adriamycin + vincristine chemotherapy.Median survival was 12.7 months.Conclusions For nasal cavity malignancy,breast metastasis more likely occur in younger female patients.Ultrasound may provide useful information in evaluating breast metastasis.Cases combined with metastasis except breast have unfavorable prognosis.

Objective To evaluate the outcome of Stage Ⅱ nasopharyngeal carcinoma(NPC) trea-ted by conventional fractionation radiotherapy. Methods From January 1990 to May 1999,216 patients with untreated stage Ⅱ NPC were irradiated by 6 MV photons and 9-12 MeV electrons with linear accelera-tor. Of 26 patients with residual lesions after 70 Gy irradiation, 18 received intracavitary brachytherapy and 8 received stereotactic irradiation boost. Results The 10-year overall survival (OS) of patients with T2 N0 M0, T1N1M0 and T2N1M0 disease were 90%, 80% and 75.2% (χ2 = 3.26, P =0. 200), respectively. The corresponding disease-free survival(DFS) and distant metastasis-free survival(DMFS) were 79% ,60% and 62.6% (χ2 = 5.87, P = 0.053) ;90% ,74% and 68.0% (χ2 = 7.09, P = 0. 030), respectively. In uni-variate analysis, T stage had no impact on OS, DFS or DMFS (χ2 = 0.44, P = 0. 500 ; χ2 = 0.44, P = 0.500 ; χ2 = 0.25, P = 0. 610), while N stage significantly influenced DFS and DM FS (χ2 = 5.86, P = 0. 015 ; χ2 = 5.31 ,P = 0. 021). Multivariate analysis showed that N stage was an independent prognostic factor for DFS and DMFS(χ2=5.03,P=0.025;χ2=6.47,P=0.01). Conclusions Stage Ⅱ NPCwithposifivelymph node treated by radiotherapy alone is inadequate. In order to improve DFS and DMS, combined chemo-radio-therapy should be considered.

Objective To investigate the clinical features,treatment outcome and prognosis of pa tients with nasopharyngeal adenoid cystic carcinoma(ACC).Methods From March 1963 to August 2002, 33 patients with ACC were retrospectively reviewed.Among them,13 received multimedality therapy(S + R in 9 and R +S in 4) and the remaining 20 received radiotherapy alone.The interval between the first visit and clinical diagnosis was 12 months(1.0-36.4 months).The misdiagnosis rate was 55% (18/33),with the most common error of otitis media.The clinical symptoms of ACC were similar to those of squamous carcino ma in nasopharynx,though the cervical lymph node metastasis was rare(12%) and cranial nerve invasion was common (58%). ResultsAfter a median follow-up of 60.8 months (5.0-245.2 months),the 5-and 10-year overall survival rates,free-disease survival rates,local regional control rates and metastasis-free sur vival rates were 66% and 29% ,41% and 27% ,61% and 40% ,62% and 62% ,respectively.Among the 20 patients(61%) with recurrence,15 had local regional failure(13 in situ and 2 in cervical lymph node) ,and 9 had distant metastasis(5 in the lung,2 in the lung and bone,1 in the liver and I in the bone).Univariate analysis showed that clinical stage was a prognostic factor(Ⅰ + II vs Ⅲ + Ⅳ,P = 0.009),while treatment modality(radiotherapy alone vs multimodality therapy) was not. ConclusionsNasopharyngeal ACC is a locally aggressive disease with a long course.Either radiotherapy alone or muhimodality therapy(S + R/R + S) is effective in the treatment.

Objective To evaluate the efficacy of intensity-madulated radiotherapy(IMRT) as the primary treatment in nasopharyngeal carcinoma (NPC). Methods Between November 2001 and March 2006,147 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 3 patients, Stage Ⅱ in 35,Stage Ⅲ in 67 and Stage Ⅳ in 42. For T1-2 disease,the prescription dose was 70 Gy to the gross tumor volume( GTVnx) and positive neck nodes ,60 Gy to the planning target volume I, and 50-56 Gy to the clinically negative neck. For T3-4 disease,the prescription dose was 74-78 Gy to GTVnx. The local control rate(LC),overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) were estimated by Kaplan-Meier method. Results The 3-year LC, OS, DFS and DMFS of the whole group were 93.2% ,93.5% ,72.6% and 74.4% ,respectively. T stage was a significant predictor of LC and OS. For patients with T1-2 and T3-4 disease,the LC was 100% and 86.9% (P=0.007) and OS was 95.5% and 91.3% (P=0.030), respectively. N stage was a significant predictor of OS, DFS and DMFS(P=0.03,0.004 and 0.0004,respectively). The grade Ⅰ+ Ⅱ and Ⅲ acute toxieities of parotid were 96.6% and 1.4%. The rate of grade Ⅱ xerostomia at 3-month, 6-month, 1-year and 2-year after radiotherapy were 43.0%, 12.0% ,4.9% and 3.2%. Conclusions The treatment results are promising according to our target definition and dose prescription protocol for nasopharyngeal carcinoma.

Objective To study the dynamic change of anatomy and dosimetry distribution and its influence during intensity modulated radiation therapy(IMRT) for nasopharyngeal carcinoma(NPC). Methods From June 2006 to August 2007,12 patients with stage Ⅲ-Ⅳ NPC receiving initial IMRT concurrently combined with chemotherapy were included in the study. The target volumes and,involving organs were contoured on the first set of spiral CT images. When IMRT planning was finished,a second CT scans was acquired to rectify the treatment center. Weekly spiral CT images acquired during the treatment period according to the same treatment center were fused with the first CT images. In order to determine the best time of replanning, modified plan target volume( PTV1 ) and normal organs( parotids and outline) were contoured on the fusion interface by a single physician. Changes of each structure throughout treatment period were measured by a system software. Then the dose distributions were computed and evaluated for replanning CT using the same beams arrangement in the original plan. Cumulative dose was estimated compared with the original plan. Results The volume of outlines and parotids decreased gradually, and the change came to peak in the fifth week. So the fifth and first week CT scans were selected as research objectives. No significant changes in maximal and mean dose was observed in the brainstem, spinal cord or mandible. Despite volume changes,D99 and D95 of the PTV1 did not change siguificantly(P＞0.05). D95 of the bilateral parotids increased significantly ( PL = 0.03,PR = 0.01 ). Conclusions During IMRT for NPC, the volume of PTV1, the outlines and parotids decrease,and the change come to peak in the fifth week. Comparing to the first treatment plan, the dose parameters of the parotids increase significantly in the second plan based on the fifth week CT,but those of the brainstem,cord,mandible and PTV1 change slightly.

Objective To evaluate the impact of the hypoxia induced by bevacizumab on the antitumor effect in combining with irradiation in CNI-H441 xenografts in mice. Methods Bevacizumab of 5 mg/kg mouse for groups of control, bevacizumab alone, irradiation alone, earlier combination (EC), and later combination (LC) were initially injected peritoneally. Single irradiation of 14 Gy (122Sc γ-ray) was given at the 4th hour for the group of irradiation alone, 24th hour for EC group, and 72nd hour for LC group after the initial injection. Tumor hypoxia, micro vessels density and permeability of tumor vasculature,pathological responses, apoptosis, and tumor growth delay curve were evaluated after using bevacizumab and/or irradiation. Results Although it was lower than the control at the 24 hr after using bevacizumab (3. 1 × 106: 6.1 × 106 ;t = - 1.73 ,P > 0. 05), the HIF-1α rapidly increased to 3 - 4 times and 2 - 3 times of the control at day 3 (7.4 × 106: 20. 4 × 106; t = 2. 36, P < 0. 05) and lasted until day 10, which was consistent with the changes of tumor function vessels count. The count of residual micro vessel density count in LC group was higher than that in groups of EC and irradiation at day 3 after irradiation (9. 33: 3. 17;t =- 2. 43, P < 0. 05). The apoptotic count of tumor cells was lower in LC group than that in EC group (23.33: 43.83; t= 2.54, P< 0.05, at day 3 after radiation). Tumor growth delay time of LC groupwas shorter than that of EC groups (10. 5 days vs. 23. 0 days , t = 2. 67 , P < 0. 05) . Conclusions Hypoxia level induced by bevacizumab decreases the antitumor effect in later combination of bevacizumab and irradiaion. It shows a time window that determines whether the combination of bevacizumab and irradiation will be benefit or diverse.

Objective To evaluate the dose distribution of the target volume and the cranial base in nasopharyngeal carcinoma ( NPC ) treated with facial-cervical fields, and to analyze the differences of dose distribution using different isoeenters with the CT-simulator and treatment planning system (TPS). Methods Eleven patients with nasopharyngeal carcinoma were treated by conventional radiotherapy as their primary treatment. All patients were simulated by the conventional simulator and the field borders were marked with thin lead wires on the mask. Then the patients were scanned by the CT-sim with the same immobilization. The planning CT images were transferred to the TPS and the field borders were copied on the DRR, and then GTV and the cranial base were contoured on the coronal CT slices. Two isoeenters were chosen, including one in front of the 1 st cervical vertebra to measeure the depth of the nasopharynx and the other in front of the 3rd cervical vertebra to measure the depth of the upper neck. The prescription dose of 36 Gy was given in 18 fractions. Dose distributions of GTV and the cranial base were calculated with TPS. Results The actual dose of 95% volume of GTV was 33.31 -35.54 Gy (median 34.83 Gy) and 31.43 -33.36 Gy (median 32.44 Gy) when the isoeenters were set in the nasopharynx and the superior neck, respectively. The corre-sponding actual dose of 95% volume of the cranial base was 17.76 - 34.60 Gy ( median 30.28 Gy ) and 16.52 -32.60 Gy (median 28.52 Gy), respectively. Conclusions For NPC patients treated with conven-tional radiotherapy using facial-cervical fields, the actual dose of GTV and the cranial base is lower than the prescribed dose whenever the isocenter is set in the nasopharynx or the upper neck,which is more significant in the latter. The isocenter should be set in the nasopharynx when the conventional radiotherapy is applied and a boost of 4- 8 Gy should be given when the cranial base is involved.