Anaplastic thyroid cancer (ATC) is the most aggressive thyroid tumor, with lower morbidity and higher mortality rates. Radical surgery could improve local control and survival rates. Conformal radiotherapy is superior to conventional radiotherapy, which could improve the patients’ quality of life. There are a few chemotherapeutic drugs against ATC, and the outcome of chemotherapy alone is modest. Concurrent chemoradiotherapy can prolong the survival. Targeted therapy brings new hope for refractory patients. Many cancer centers are exploring surgery, radiotherapy, chemotherapy, targeted therapy and other biological treatment of comprehensive application, in order to enhance the curative effect. This article reviewed the foregoing treatments for ATC.

Salivary gland damage with subsequent xerostomia has been an unavoidable complication in most head and neck cancer patients after radiotherapy.However,there were many shortcomings of each current detecting technique.Magnetic resonance sialography(MRS) and diffusion-weighted magnetic resonance imaging(DW MRI) ,as two of the most important progresses in the latest MRI techniques,with the virtue of non-invasion and non-ionizing radiation,has been rapidly developed in salivary function assessment in recent years,and it has kept on improving technically.This article mainly reviewed the clinical applications and research advances of these two MRI technologies in post-radiotherapy salivary function assessment in patients with head and neck cancers,so as to provide reference for further study.

ObjectiveTo evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP)chemotherapy combined with intensity-modulated radiation therapy (IMRT)in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods71 patients (Stage Ⅲ:41,Stage ⅣA:30) with locoregionally advanced NPC were entered this study.Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m2 intravenously on d1-3 and gemcitabine 1000 mg/m2 in 30 minutes intravenous infusion on days 1 and 8,every 3 weeks for 2 cycles.Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy.The prescription doses was 66.0-70.4 Gy to the gross tumor volume,66 Gy to positive neck nodes,60 Gy to the high-risk clinical target volume,54 Gy to the low-risk clinical target volume.ResultsThe overall response rate to neoadjuvant chemotherapy was 91.2％,acute toxicity was mainly grade 1-2 myleosuppression.All patients completed IMRT.The median follow-up duration was 38 months.The 3-year nasopharyngeal local control,regional control,distant metastasis-free survival rate and overall survival rate were 93％,99％,91％,90％,respectively.Severe late toxicities included grade 3 trismus in 1 patient,grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients,respectively.No grade 4 late toxicities were observed.Conclusions The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated,convenient,effective,and warrants further studies of more proper cycles of GP regimen.

Background Retninal neovascular diseases caused by hypoxia has become a major blinding disease,which is lack of effective chemical treatment currently,it's important to study the molecuar mechanism of the disease,so as to guide the clinical medication.Objective This study was to explore the effect of 15 (S)-hydroxyeicosate traenoic acid (15-HETE) on the proliferation of hypoxic retinal microvascular endothelial cells (RMVECs) and its probable mechanism.Methods RMVECs were isolated from C57BL/6J mice and incubated and then identified with anti-Ⅷ factor antibody by immunochemistry and immunofluorescence.The cells were divided into the normoxia group and the hypoxia group.The hypoxia cell models were established by treated with 125 μmol/L CoCl2.The cells were cultured with serum-free DMEM containing endothelial cell growth supplement (ECGS)and high glucose for 48 hours,and then different concentrations of 15-HETE (0.0,0.1,1.0,5.0 μmol/L) were added in the medium for 48 hours respectively to subgroup the groups.The proliferation of the cells (absorbance,A) was detected using MTT.The relative expression levels of protein and mRNA of hypoxia inducible factor-1α (HIF-1α),bcl-2 and caspase-3 were assayed by reverse transcription PCR (RT-RCR)and Western blot.Results The cells showed the positive response for anti-Ⅷ factor antibody with the positive rate of (94.38 ±4.25)％.No significant difference was found in the cell proliferation of various groups under the normoxia condition (F =0.283,P =0.837),but under the hypoxia condition,the proliferation values were significantly different among various groups (F =702.582,P＜0.001).The cell proliferation value in the 1.0 μmol/L 15-HETE group and 5.0 μmol/L 15-HETE group was lower than that of the simple hypoxia group respectively(both at P＜0.05).The inhibitory rates in the 0.1,1.0,5.0 μ mol/L 15-HETE groups were (1.09±0.31) ％,(21.09± 3.53) ％ and (49.86 ±4.15) ％,showing a dosedependent manner.No significant difference was seen in the expression levels of bcl-2,caspase-3 and HIF-1α mRNA in various groups under the normoxia conditions.However,compared with the simple normoxia group,the relative expressions of bcl-2 mRNA and HIF-1α mRNA in the cells were increased by 1.53 folds and 1.7 folds in the simple hypoxia group respectively,and caspasse-3 mRNA expression decreased by 70％ (all at P ＜ 0.05).Under the normoxia condition,the expression of bcl-2 and pro-caspase-3 protein in the cells were not significantly different among the various groups (P＞0.05),however,the expressions of bcl-2 and pro-caspase-3 proteins were elevated by 1.6 folds and 1.9 folds in the hypoxia group in compared with the normoxia group (P＜0.05).Compared with the simple hypoxia group,the expressions of bcl-2 and pro-caspase-3 were lowed by 40.4％ and 42.5％ in the 5.0 μmol/L 15-HETE group (P＜0.05).Conclusions 15-HETE inhibits the proliferation of RMVECs and therefore suppresses neovascularization by down-regulating the expressions of HIF-1α and bcl-2 and the activation of caspase-3 in a dose-dependent manner.

Purpose:To study treatment and prognostic factors in 74 patients with maxillary sinus carcinoma to improve methods of treatment. Methods:From January 1985 to December 1995,74 patients with maxillary sinus carcinoma were treated in our hospital.There were 46 males and 28 females,with a median age at diagnosis of 55 years(25-76 years),the tumor histology included squamous cell carcinoma ,adenocarcinoma,undifferentiated carcinoma (found in 55,8,11 patients).Using the AJCC method of classication,T 2 4 cases,T 3 32 cases and T 4 38 cases.Twenty of 74 patients had cervical lymphadenopathy at initial presentation,fifteen of 20 patients were in ipsilateral upper neck.Total dose was 50 Gy/28 f/41 d-78 Gy/39 f/55 d.Forty three patients had radiotherapy alone,thirty one had surgical resection and radiotherapy. Kaplan Meier and Log Rank test were used for evaluating the results of the local control and survival rates in this series,the multivariate parameters were analyzed by Cox model. Results:The 5 year survival rates were 33.9% for all patients.The 5 year loss of control rates of primary site were 56.2%,the 5 year neck failurs rates were 20.0%,the 5 year metastatic rates were 19.7%.The 5 year survival rates for radiothery alone, combined therapy were 16.4% and 56.1% respectively( P =0.0003).Of the 54 patients with N 0 disease,7 had neck recurrence,of the 7 neck failure,5 were in ipsilateral upper neck.The 5 year survival rates for patients who remained N 0 were 41.9% and for those [N(+) group] with initial cervical involvement or recurred in the neck were 20%( P =0.0076). Conclusions:Primary local failure is the most cause of therapeutic failure, the neck failure is in ipsilateral upper neck in many patients whose prognosis is poor,combined treatment is beneficial in maxillary sinus carcinoma.

Objective To compare the efficacy after conventional radiotherapy and late course accelerated fractionation radiotherapy for nasopharyngeal carcinoma (NPC).Methods A total of 200 NPC patients were enrolled and randomly assigned to conventional radiotherapy (CF) group with 99 cases or late course accelerated fractionation radiotherapy (LCAF) group with 101 cases,who received irradiation to 60Co γ or 6 MV X-rays.In the CF group,the total dose of nasopharynx was 70 Gy/35 fractions at 2 Gy daily.In the LCAF group,for the first two-thirds of the treatment,two daily fractions of 1.2 Gy were given to the primary lesion and the total dose was 48 Gy/40 fractions.For the last one third of the treatment,the dose per fraction was increased to 1.5 Gy and the total dose was 30 Gy/20 fractions.Results There were 25,16,25 in CF group and 16,13,18 patients in LCAF group who had recurrence of nasophaynx,cervical lymph nodes,and distant metastasis,respectively.The 5-year nasopharyngeal control and overall survival rates was 75.9％ and 87.6％ in CFgroup (x2 =4.066,P＜0.05),58.0％ and 74.1％(x2 =5.076,P ＜ 0.05) in LCAF group,respectively.Cervical lymph nodes local rates and distant metastasesfree rates at 5 years were 8 1.5％ and 90.0％ in CF group (P ＞ 0.05),74.1％ and 83.3％ (P ＞ 0.05) in LCAF group,respectively.Conclusions Compared with CF,LCAF can improve nasopharyngeal control and overall survival rates,but there are no significant difference in the recurrence rates of cervical lymph nodes and distant metastasis.

ObjectiveTo evaluate the function of the salivary glands with gustatory stimulation by using MR DWI.MethodsA prospective study was conducted in 30 patients with nasopharyngeal carcinoma who had normal salivary function.A DWI sequence was performed on the salivary glands at resting state,and continually repeated on the parotid immediately after oral ascorbic acid stimulation over a period of 21 minutes (once every 18 seconds).The multiple b-values (0,400,600,800,1000 s/mm2) were used.ADC maps were evaluated with a manually placed region of interest including the entire salivary gland.The ADC of each gland was obtained by taking the mean of values on three contiguous sections containing the largest areas of the gland.The paired two-tailed Student t test was used to compare the ADC values of the parotid and the submandibular glands at rest,and of the parotid before and after stimulation.ResultsThe mean ADC value at rest was significantly lower in the parotid [ (1.23 ±0.12) × 10-3 mm2/s] than in the submandibular glands [(1.34 ± 0.07 ) × 10 -3 mm2/s,t =4.545,P ＜ 0.01 ].After acid stimulation,the ADC value increased from the baseline to (1.41 ±0.19) × 10-3 mm2/s firstly and then fluctuated at the following time,with a peak value of ( 1.49 ± 0.20 )× 10 -3 mm2/s and the average value of ( 1.36 ±0.17) × 10-3 mm2/s.The average value was significantly different from the baseline value (t =15.127,t =11.905,P ＜ 0.01 ).The minimum value [ ( 1.24 ± 0.14) × 10-3 mm2/s] was not significantly different compared to the baseline value (t =1.329,P ＞ 0.05 ).ConclusionMR DW1 can noninvasively evaluate the physiologic changes of salivary glands before and after acid stimulation.

Objective Nasopharyngeal carcinoma patients with stage N3 disease are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy(CRT).The aim of this study is to compare the ettlcacy of difierent chemotherapy sequences in these patients.Methotis All patients with histologically proven,carcinoma of the nasopharynx treated between July 1999 and November 2003 were restaged according to the AJCC 2002 stage classification system.A total of 114 patients had AJCC N3 diseases were analyzed retrospectively.Patients were treated by conventional RT technique using 6 MV photons or 60 Coγ-ray with 1.8-2.0 Gy per fraction,5 fractions a week,to a planned dose of 70 Gy.The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The prophylactic irradiation dose of the neck wss 54-60 Gy.Any positive lymph node was boosted to a total dose of 60-68 Gy.All patients received cisplatin-based chemotherapy of difierent sequences but 9 patients received RT alone.CRT regimen was delivered in 37 patients,neoadjuvant chemotherapy(NACT)+CRT regimen in 53 patients and CRT+adjuvant chemotherapy(AC)regimen in 15 patients.Results The median follow up time was 54 months(3-117months).The 5-year overall survival rate was 59.1%in whole groups,and with 17%,51%,68%and 71%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=15.44,P=0.001).The 5-year relapse-free survival rates were 83%,77%,88%and 93%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=2.34,P=0.505).The 5-year metastasis-free survival rates were 17%,54%,72%and 80%in RT,CRT,NACT+CRT and CRT+AC group,respectively(X2=19.28,P=0.000).Conclusions The NACT+CRT and CRT+AC regimens were more effective than CRT alone for N3 disease in the current study.Large prospective,randomized clinieal studies are warranted.

OBJECTIVE: To investigate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) as a noninvasive tool to assess salivary gland function for follow-up of patients with radiation-induced xerostomia. MATERIALS AND METHODS: This study included 23 patients with nasopharyngeal carcinoma who had been treated with parotid-sparing radiotherapy (RT). Salivary function was assessed by DW-MRI pre-treatment and one week and one year post-RT, respectively. The maximum apparent diffusion coefficient (ADC) of parotid glands (pADCmax) and the time to peak ADC of parotid glands (pTmax) during stimulation were obtained. Multivariate analysis was used to analyze factors correlated with the severity of radiation-induced xerostomia. RESULTS: The ADCs of parotid and submandibular glands (1.26 ± 0.10 × 10−3 mm2/s and 1.32 ± 0.07 × 10−3 mm2/s pre-RT, respectively) both showed an increase in all patients at one week post-RT (1.75 ± 0.16 × 10−3 mm2/s, p < 0.001 and 1.70 ± 0.16 × 10−3 mm2/s, p < 0.001, respectively), followed by a decrease in parotid glands at one year post-RT(1.57 ± 0.15 × 10−3 mm2/s, p < 0.001) but not in submandibular glands (1.69 ± 0.18 × 10−3 mm2/s, p = 0.581). An improvement in xerostomia was found in 13 patients at one year post-RT. Multivariate analysis revealed 4 significant predictors for the improvement of xerostomia, including dose to parotid glands (p = 0.009, odds ratio [OR] = 0.639), the ADC of submandibular glands (p = 0.013, OR = 3.295), pADCmax (p = 0.024, OR = 0.474), and pTmax (p = 0.017, OR = 0.729) at one week post-RT. CONCLUSION: The ADC value is a sensitive indicator for salivary gland dysfunction. DW-MRI is potentially useful for noninvasively predicting the severity of radiation-induced xerostomia.
Diffusion ; Follow-Up Studies* ; Head and Neck Neoplasms ; Humans ; Magnetic Resonance Imaging* ; Multivariate Analysis ; Odds Ratio ; Parotid Gland ; Radiotherapy ; Salivary Glands* ; Submandibular Gland ; Xerostomia*

Objective To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool in evaluating major salivary gland function before and after radiotherapy (RT) for nasopharyngeal carcinoma patients.Methods From August 2009 to June 2010,patients with stage Ⅰ and Ⅱa (AJCC/UICC 2002) nasopharyngeal carcinoma were enrolled.All the patients were treated with intensity modulated radiation therapy alone.MRS with salivary stimulation was performed in patients before and after RT on a 3.0T MR scanner.An MRS categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT.The relationship between MRS score and EORTC Core QOL and EORTC Head and Neck QOL was analyzed.Spearman rank correlation test was performed to analyze the non-stimulated and stimulated MRS findings and the clinical severity of xerostomia.Results All 10 enrolled patients completed planned treatment.The mean dose of the parotid glands and submandibular glands were (37.99 + 3.70) Gy and (55.65 + 2.99) Gy,respectively.Good-quality MRS images were obtained.The visibility scores of both the parotid and submandibular ducts were increased after secretion stimulation.Irradiation decreased the visualization of the salivary ducts and attenuated the response to secretion stimulation.There were specific correlations between post-RT secretion response of the parotid gland and EORTC QLQ scales ( global QOL scale in QLQ-C30 ( rs =0.636,P =0.048 ) and xerostomia scale in QLQ H&N35 ( rs =- 0.694,P =0.026) ).Conclusions MRS can be used as a non-invasive way to evaluated of the functional changes of major salivary glands before and after RT and as a promising approach for investigating radiation-induced xerostomia.