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Purpose: Emerging evidence shows that immune checkpoint inhibitors lead to durable responses in a variety of cancers, including nasopharyngeal carcinoma (NPC), however, combination approaches (i.e., stereotactic body radiation therapy, SBRT) are required to extend this benefit beyond a subset of patients. This study retrospectively evaluated eight recurrent/metastatic NPC patients, to investigate how radiation could potentiate PD-1 checkpoint inhibition therapy.Methods: Between September 2016 and July 2017, eight consecutive cases with histologically confirmed PDL1-positive status, for which prior standard therapy had been ineffective (five patients), were treated at our institution and Macao Clinics and two patients had disease progression within 6 months of completion of definitive chemoradiation, or one patient refused to receive chemoradiotherapy. All received PD-1 inhibitors first, seven of them accepted SBRT with an unmodified PD-1 inhibitors regimen after first evaluation as they were unresponsive to PD-1 inhibitors alone. Treatment was discontinued as long as patients were experiencing a clinical benefit in the opinion of the physicians and at least five cycles were given before stoppage.Results: Median follow-up time was 56.7 months. The confirmed objective response rate based on RECIST-v1.1 at first evaluation was 12.5% (1/8). For the seven cases who received SBRT, six of them experience an objective response (6/7, 85.7%) after SBRT. Only one patient showed rapid progress and die within 95 days after the initiation of SBRT intervention. Three patients who did not have all lesions exposed to irradiation were available to evaluate the incidence of an abscopal effect, however, it did not occur as expected. Median PFS and OS for the seven patients were 8.0 and 30.8 months after SBRT intervention, respectively. Two-year OS as indicated was 71.0%.Conclusions: PD-1 inhibitors combined with SBRT demonstrated promising antitumor activity in patients with PD-L1 positive RM-NPC. Patients may benefit from continue immunotherapy beyond disease progression when SBRT was introduced. [ABSTRACT FROM AUTHOR]

Background: The impact of radiotherapy interruption due to the Spring Festival holidays in China on the survival of patients with nasopharyngeal carcinoma (NPC) is unclear.Methods: Nontrial patients with locoregionally advanced NPC receiving radiotherapy plus induction chemotherapy (IC) and/or concurrent chemotherapy (CC) were included (N = 5035) and divided into two groups based on the Spring Festival-induced radiotherapy interruption. Kaplan-Meier curves for overall survival (OS) and failure-free survival (FFS) were compared between rival groups. Impact of the timing of radiotherapy interruption (during or outside the Spring Festival) on survival was investigated in a propensity score-matched dataset. We adopted ordination correspondence analysis to determine the cut-off of radiotherapy prolongation for prognostic prediction, and accordingly performed subgroup analysis based on delayed days and chemotherapy details. Individual patient data of three phase III NPC trials (NCT00677118, NCT01245959, NCT01872962) were used for validation (N = 1465).Results: Radiotherapy interruption was most frequently observed between December to January of the following year. Significantly lower OS and FFS were associated with the Spring Festival-induced interruption of radiotherapy (P = 0.009 and 0.033, respectively), but not that interruption of IC. In two matched comparison groups, the timing of radiotherapy interruption during the Spring Festival was more likely to lead to a decrease in FFS than outside the Spring Festival (P = 0.046), which was not observed in the validation using clinical trial data or in the subgroup analysis based on the 5-day delayed time. The absence of CC and the accumulated dose of cisplatin < 200 mg were related to the negative influences of the Spring Festival-induced radiotherapy interruption on FFS (P = 0.002) and OS (P = 0.010), respectively.Conclusions: The poor survival of patients with NPC is associated with the Spring Festival-induced interruption of radiotherapy. We recommend that these patients receive adequate doses of cisplatin concurrently with radiotherapy. [ABSTRACT FROM AUTHOR]

Radiation-induced temporal lobe necrosis (TLN) is one of the late post-radiotherapy complications in nasopharyngeal cancer (NPC) patients. Since NPC is common to have skull base infiltration, irradiation of the temporal lobes is inevitable despite the use of the more advanced intensity-modulated radiotherapy (IMRT). Moreover, the diagnosis and treatment of TLN remain challenging. In this review, we discuss the diagnosis of TLN with conventional and advanced imaging modalities, onset and predictive parameters of TLN development, the impact of IMRT on TLN in terms of incidence and dosimetric analyzes, and the recent advancements in the treatment of TLN. [ABSTRACT FROM AUTHOR]

Background: Radiation for Graves' ophthalmopathy (GO) has traditionally utilized lateral opposing fields (LOF) or three-dimensional conformal radiotherapy (3DCRT) technique. The current study was conducted to report clinical outcomes and therapeutic effects of intensity modulated radiation therapy (IMRT) in treating GO patients.Methods: One hundred sixteen patients with GO were treated with IMRT as initial local therapy between July 2010 and August 2013, with a median follow-up of 62 months (range 45-81 months). Radiotherapy dose was 20 Gy in 10 fractions within two to three weeks. The immediate and long-term response to IMRT was evaluated in GO severity score and in each category of symptoms. Acute and long-term complications were recorded to assess its safety.Results: Symptom severity score significantly fell from the start of treatment to 4- or 6- month post-IMRT (P < 0.01). In total, 85 patients (73.3%) experienced improvement of GO symptoms in the first half-year, and only 4 of them (4.7%) suffered recurrence of the GO symptoms during the subsequent follow-ups. Orbital pain, tearing and extraocular muscle dysfunction had the best treatment reaction to IMRT, while proptosis and blurred vision were the most refractory symptoms. Acute complications were slight and self-limited, mainly including intermittent eye redness in 9 patients (7.8%), sideburns hair loss in 19 patients (16.4%), increased milphosis or madarosis in 23 patients (19.8%) and pseudo-progression of GO symptoms in 15 patients (12.9%). For long-term complications, chronic xerophthalmias occurred in 7 patients (6.03%), cataract developed in 2 patients (1.72%), and all were well-managed by medical interventions. Radiation retinopathy and secondary malignancy was not presented in the cohort.Conclusion: The study demonstrated that IMRT could serve as a viable option in treating GO patients, with a satisfactory symptom control ability, and relatively slight and acceptable post-radiotherapeutic complications. [ABSTRACT FROM AUTHOR]

Objective: Today intensity modulated radiation therapy (IMRT) can be considered the standard of care in patients with head and neck tumors. IMRT treatment plans are proven to reduce acute treatment related side effects by optimal sparing of organs at risk (OAR). At the same time, areas that were out of the former 3D fields now receive low radiation doses. Amongst those areas the brainstem (BS) and the vestibular system (VS) are known to be physiologically connected to nausea and vomiting (NV). In our study we tried to find out, if doses to these areas are linked to NV.Material& Methods: NV were assessed at different time points during treatment in 26 patients leading to 98 documented toxicity scores that were later correlated to dose deposition in the described areas. Patients were either treated with normo-fractionated or simultaneously integrated boost IMRT plans in a curative approach. Subareas of the BS as well as the VS were delineated. Toxicity was rated based on the common toxicity criteria (CTCAE Version 4.0). Other factors such as age, gender, chemotherapy, location of the tumor, irradiated volume and unilateral dose to the VS were taken into account and analyzed also.Results: The majority (65.4%) of our patients experienced an episode of NV at least once during treatment. NV was more frequent when treating the oropharyngeal region compared to the hypopharyngeal region, as well as when patients were female and/ or of a younger age. Nevertheless, upon statistical analysis (ROC analysis, 'within/ between analysis') no significant association between delivered doses to subareas and toxicity could be demonstrated.Conclusion: In our analysis, no significant correlation between radiation dose to the BS or the VS and the occurrence of NV could be found. Therefore, until conclusive data are available, we recommend to rely on the published data regarding OAR tolerance within the BS and not to compromise on dose coverage. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is most common in Southeast Asia. The purpose of this study is to investigate the correlation between wait time and length of radiotherapy and overall survival (OS) of NPC patients in Taiwan.Methods: From Taiwan's National Health Insurance Research Database, this nationwide population-based cohort study identified 3605 NPC patients who received radiotherapy between 2008 and 2011. The impact of time factors on NPC survival rates was estimated with Kaplan-Meier survival curves. A multivariable Cox hazards regression model tested the significance of results after adjustment for other covariables.Results: In all, 317 patients had wait times >4 weeks, 1404 patients had longer duration of radiotherapy (i.e., >10 weeks) and 499 died. Patients with wait times > 4 weeks and length of radiotherapy ≤ 10 weeks didn't have significantly inferior survival. Patients with wait times >4 weeks and length of radiotherapy >10 weeks had significantly lower OS than other groups, with an adjusted hazard ratio of 1.7 (95 % CI, 1.10-2.60).Conclusion: Time was a significant prognostic factor for NPC patients who had both >4 weeks wait times and length of radiotherapy >10 weeks. Patients with wait time > 4 weeks and length of radiotherapy ≤ 10 weeks had a trend toward an inferior survival. [ABSTRACT FROM AUTHOR]

Objectives: This retrospective study reassessed nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), to determine the significance how magnetic resonance imaging (MRI)-derived masticator space involvement (MSI) affected patients' prognosis.Methods: One thousand one hundred ninety seven NPC patients who had complete set of MRI and medical records were enrolled. Basing on their MRI findings, the T-categories of tumors were identified according to the seventh edition of American Joint Committee on Cancer staging system, which considers MSI a prognostic indicator for NPCs. Rates of overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant metastasis-free survival (DMFS) were analyzed by the Kaplan-Meier method, and the Log-Rank test compared their differences. Cox regression analysis was employed to evaluate various prognostic factors systematically. Statistical analyses were conducted with SPSS 18.0 software, P value < 0.05 was considered statistically significant.Results: Medial pterygoid muscle (MPM) was involved in 283 (23.64 %) cases, of which lateral pterygoid muscle (LPM) was concurrently affected in 181 (15.12 %) and infratemporal fossa (ITF) in 19 (1.59 %). Generally, MSI correlated with an OS, LRFS, and DMFS consistent with a T4-stage diagnosis (P > 0.05). Although different degrees of MSI presented a similar OS and DMFS (P > 0.1), tumors involving LPM had a relatively poorer LRFS than those affected the MPM only (P = 0.027), even for subgroup of patients composed of T3 and T4 classifications (P = 0.035). A tumor involving MPM brought an LRFS consistent with a T2 or T3-stage disease (P > 0.1). If the tumor affected LPM or ITF concurrently, the survival outcomes were more consistent with a T4-stage disease (P > 0.1). Nevertheless, compared to tumor infiltrating MPM, those invading LPM or ITF more frequently spread into other concurrent sites that earned higher T-staging categories. Moreover, multivariate analyses indicated the degree of MSI was a significant prognostic factor for the OS of NPCs (P = 0.036).Conclusions: Degree of MSI is a significant prognosticator for the OS of IMRT-treated NPCs, and the prognosis of patients with lateral MSI extension (LPM and ITF) were shown to be significantly worse than those affected only MPM or the T3-stage disease. Thus, it is highly recommended that lateral MSI extension be a higher T-staging category. [ABSTRACT FROM AUTHOR]

Background: Previous studies report body-mass index (BMI) and percent weight loss (WL) to have prognostic significance when treating patients with nasopharyngeal carcinoma (NPC). However, most of these investigations studied patients treated using different radiotherapeutic techniques. We evaluated the predictive effect of these two nutrition-related measurements on therapeutic outcome in NPC patients who only received intensity-modulated radiation therapy (IMRT) as part of their total treatment program. Methods: We retrospectively studied NPC patients treated with IMRT from January 2006 to February 2012. Cox proportional hazards was used to test the association of pretreatment BMI (<23 kg/m² vs. ≥23 kg/m²) and percent weight loss (≥5 % vs. <5 %) during therapy and related survival rates while controlling for various potential confounders. Results: Eighty-one (34 %) of the 238 patients had BMIs ≥23 kg/m² at pretreatment and 150 (63 %) had significant (≥5 %) weight loss. Median follow-up time was 41.71 months; median radiotherapy was 7.46 ± 0.77 weeks. Those with BMIs ≥23 kg/m² did not have a better 3-year overall survival (p = 0.672), 3-year disease specific survival (p = 0.341), 3-year locoregional free survival (p = 0.281), or 3-year distant metastatic free survival (p = 0.134). Those with significant WL (≥5 %) did not have worse 3-year clinical endpoints, even after stratifying magnitude of weight loss by BMI category. In sensitivity test, the adjusted hazard ratio remained statistically insignificant using different cutoffs for BMIs and percent weight loss. Conclusions: This study found no significant relationship between BMI and percent weight loss on survival of NPC patients receiving IMRT based therapy. Further studies might want to consider other nutrition related factors as prognostic indicators when studying the correlate between malnutrition and survival in this population. [ABSTRACT FROM AUTHOR]

Background: To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. Methods: Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). Results: Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). Conclusion: With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain. Methods: The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS). Results: We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment. Conclusions: Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent. [ABSTRACT FROM AUTHOR]

Objective To compare the treatment outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) alone to concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). Methods From November 2001 to December 2009, 333 patients with pathologically diagnosed, locoregionally advanced NPC were treated by IMRT-SIB with or without weekly cisplatin concurrent chemotherapy at our institute. Among them, 62 patients received neo- or adjuvant chemotherapy or molecular target drugs were excluded from this analysis. There were 129 patients received IMRT-SIB alone, and 142 patients received IMRT-SIB with weekly cisplatin 30 mg/m2 for 7 weeks. The radiotherapy protocol was identical for each group. Results There were no significant differences in survival between CCRT and IMRT-SIB group in terms of gender, T/N classifications and concurrent chemoradiotherapy. The 5-year local control (LC), overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) for the entire group were 87.0%, 79.4%, 69.7 and 83.3%, respectively. The LC, OS, DFS and DMFS for CCRT and IMRT-SIB alone groups were 80.6% vs. 90.8% (P = 0.10), 71.7% vs. 83.2% (P = 0.201), 63.9% vs. 74.6% (P = 0.07), and 79.6% vs. 86.0% (P = 0.27), respectively. Conclusion Compared to CCRT, IMRT-SIB alone had demonstrated similar disease LC, OS, DFS and DMFS in locoregionally advanced NPC. Careful radiation target volume design and simultaneous integrated boost may play a role that overrides the benefit from concurrent chemotherapy. Further investigation with randomized study is necessary to determine whether IMRT-SIB alone can achieve similar outcomes of concurrent chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). Methods From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT) + CCRT to 82 patients and CCRT + adjuvant chemotherapy (AC) to 11 patients. Results The 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (p = 0.004), 49.2% and 68.5% (p = 0.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACT + CCRT and CCRT + AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (p = 0.107) when compared with RT alone group, and NACT + CCRT could significantly improve distant metastasis-free survival (p = 0.017). Conclusions For advanced N-stage NPC patients, NACT + CCRT might be a reasonable treatment strategy. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to analyze the feasibility of omitting irradiation to the contralateral lower neck in stage N1 nasopharyngeal carcinoma (NPC) patients.Materials and Methods: From July 2008 to January 2012, 52 patients with stage N1 NPC were analyzed. All patients were treated with intensity-modulated radiation therapy (IMRT) and received bilateral upper neck irradiation to levels II, III and VA and ipsilateral lower neck irradiation to levels IV and VB. The contralateral lower neck irradiation was omitted.Results: The median follow-up was 29 months (range, 12-52 months). The 3-year overall survival (OS) rate, progress-free survival (PFS), local failure-free (LFS), nodal recurrence-free survival (NFS) and distant metastasis-free survival (DMFS) rates were 92.2%, 94.1%, 94.3%, 98% and 94.1%, respectively. Only one patient developed a neck recurrence in the irradiation field, while no patients experienced out-of-field nodal recurrence. Univariate analysis suggested that T classification was the only significant prognostic factor for overall survival, and age was significantly associated with PFS. Multivariate analyses indicated that age was also a predictor for overall survival. The elective neck irradiation procedure was not a significant predictor for all of the treatment results.Conclusion: Selective irradiation to bilateral levels of II, III and VA and unilateral levels of IV and VB, omitted the contralateral lower neck in a proportion of patients with N1 stage NPC was safe and practicable. [ABSTRACT FROM AUTHOR]

Background: To retrospectively analyze whether primary tumor volume and primary nodal volume could be considered independent prognostic factors for nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.Methods: Three hundred sixty-three consecutive nasopharyngeal carcinoma (NPC) patients who were stage I-IVa+b and treated with intensity-modulated radiotherapy (IMRT) in our center from October 2003 to October 2005 were analyzed retrospectively. The predictive ability of gender, age, T and N stage, combined chemotherapy, primary tumor and nodal volume for the 5-year local control (LC), distant-metastasis free survival (DMFS) and overall survival (OS) rate were investigated. Primary tumor and nodal volume were measured based on registration of magnetic resonance imaging (MRI) with contrast-enhanced computed tomography (CT) images. The Kaplan-Meier method was used for survival analysis, the log-rank test was used for univariate analyses and the Cox proportional hazard model was used for multivariate prognostic analyses.Results: The mean value of primary tumor and nodal volume were 31.5 ml and 9.7 ml. The primary tumor and nodal volume were respectively divided into four groups for analysis (primary tumor volume: TV1≤20 ml, 2040 ml; primay nodal volume: NV1≤5 ml, 520 ml). In univariate analysis, the 5-year LC and DMFS rate for TV4 was significantly decreased compared to the other groups (LC: p<0.001, DMFS: p=0.001), the 5-year OS rate for TV3 and TV4 were significantly decreased compared to other two subgroups (p=0.002) and the 5-year regional control (RC), DMFS and OS rate for NV3 and NV4 were significantly less than NV1 and NV2 (RC: p=0.002, DMFS: p=0.01, OS: p=0.014). Multivariate analysis showed that TV>40 ml was an adverse prognostic factor for the 5-year local regional control (LRC) rate (RR 2.454, p=0.002). Primary nodal volume had no statistical significance in predicting 5-year LRC, DMFS and OS rate in multivariate analysis.Conclusions: Primary tumor volume could predict LRC rate of NPC patients, and the primary tumor volume of 40 ml may be the cut-off. Primary nodal volume may have predictive significance, but more data are needed. These factors should be considered in the TNM staging system of NPC for better estimates of prognosis. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. Results: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. Conclusion: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications. [ABSTRACT FROM AUTHOR]

Background: MiRNA-21 was previously reported to be up-regulated in many kinds of cancer. In the present study, we want to investigate the potential role of miRNA-21 in non-small cell lung cancer. Materials and methods: Expression of miRNA-21 was detected in 60 non-small cell lung cancer (NSCLC) samples and adjacent histologically normal tissue using RT-qPCR, Correlation between miRNA-21 expression and clinicopathological features of NSCLC was analyzed using statistical software. The effect of miRNA-21 expression on the growth and apoptosis of A549 cells induced by irradiation was examined. Results: miRNA-21 expression increased in non-small cell lung cancer. Expression of miRNA-21 was positively associated with lymph node metastasis, clinical stage and poor prognosis. Multivariate Cox regression analysis showed that miRNA-21 was an independent prognostic factor for patients. Down-regulation of miRNA-21 inhibited proliferation and cell cycle progress of A549 cells and sensitized cells to radiation. Decreased miRNA-21 expression promoted the apoptosis of A549 cells induced by irradiation. Conclusions: miRNA-21 may be considered as a potential novel target for future development of specific therapeutic interventions in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain injury (RI). Treatment for RI remains a challenge. We conducted this study to investigate the indications of neurosurgery, operation time and prognosis of patients with RI after NPC radiotherapy who underwent neurosurgical management. Methods: This was a follow-up study between January 2005 and July 2011. Fifteen NPC cases of RI who underwent neurosurgery were collected. Brain Magnetic resonance imaging (MRI), surgery and histology were studied. The outcome was assessed by LENT/SOMA scales and modified Rankin scale. Results: Brain lesion resection (86.7%) was more common than decompressive craniotomy (13.3%). According to LENT/SOMA scale before and six months after surgery, 13 of 15, 12 of 15, 14 of 15, and 14 of 15 cases showed improvement at subjective, objective, management and analytic domains, respectively. 12 of 15 patients showed improvement of modified Rankin scale after surgery. Three patients who underwent emergency surgery showed significant improvement (average score increment of 2, 2.7, 2.7, 3 and 2 at LENT/SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively), as compared with 12 cases underwent elective surgery (average score increment of 1, 1, 1.4, 1.8 and 1 at LENT SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively). Conclusions: Neurosurgery, including brain necrotic tissue resection and decompressive craniotomy, improves the prognosis for RI patients, especially for those with indications of emergency surgery. [ABSTRACT FROM AUTHOR]

Background: The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system. Methods: Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis. Results: Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 - 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis. Conclusion: Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system. [ABSTRACT FROM AUTHOR]

Background: To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age=65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. Results: CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade=3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score≥2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score≥2. Conclusions: CRT is feasible and effective in elderly patients with locoregionally advanced NPC without severe comorbidities. CRT should be used under serious consideration and be further tested in elderly patients with severe comorbidities. As such, it is essential to perform a comprehensive evaluation of pretreatment comorbidity status for all elderly NPC patients. [ABSTRACT FROM AUTHOR]

Purpose: To analyze of survival curve and toxicity outcomes for patients treated for nasopharyngeal carcinoma (NPC) by intensity-modulated radiotherapy (IMRT) delivered by helical TomoTherapy (HT). Materials and methods: Since May 2006, 72 patients with primary NPC were treated. In 67 cases PET-CT was used to help delineate the gross tumor volume (GTV); in 4 of these cases distant metastases in bone, mediastinal lymph nodes and unexpected small neck nodes were detected by high SUV uptake. 3, 22, 19, and 27 patients, respectively, had AJCC stage I to IV disease. Patients received a median total dose of 72 Gy to the GTV, 64.8 Gy to the elective PTV, and 54 Gy to the clinically negative neck region. Results: At a median follow-up of 41 months (range 0.2 to 67 months), no patient has recurred locally. Two patients with stage IIb disease, both of whom received chemotherapy, recurred regionally. Ten patients developed distant metastases. One died from progressive disease with initial proved bony metastasis. Two patients with stage IIb disease, both of whom received chemotherapy, experienced neck node recurrence. 5-year locoregional control rate was 97%; freedom from distant metastases was 84.6% at 5 years. No evidence of disease was detected in 13 early stage (I/IIa/IIb) patients who did not receive chemotherapy. Acute grade 3 toxicity occurred in four patients and grade 4 in two patients. Late toxicities were low, with no grade 3+ xerostomia, grade 2 xerostomia in two patients (3%), and grade 3 hearing loss in two patients (3%). Conclusions: HT resulted in excellent long-term disease control and survival in heterogeneous NPC patients. Generally mild acute and late toxicity, with low rates of xerostomia, were obtained. Image-guided HT offers the ability to deliver conformal, OAR-sparing dose distributions to a wide variety of NPC patients with good long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). Methods: The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66-70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54-59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. Results: The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity = grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). Conclusion: Concurrent chemoradiation without the addition of adjuvant chemotherapy cycles using IMRT with an integrated boost concept yielded good disease control and overall survival in patients suffering from primary nasopharyngeal cancer with acceptable acute side effects and limited rates of late toxicity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcomes and patterns of failure in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy (IMRT) in Northwest China. Methods and materials: From January 2006 to December 2009, 138 NPC patients were treated at Xijing Hospital. Of them, 25 cases with stage I-II received IMRT only, 113 cases with stage III-IVb received IMRT plus accomplished platinum-based chemotherapy. The IMRT prescribed dose was PTV 68-74 Gy to gross disease in nasopharynx and 66-72 Gy to positive lymph nodes in 30-33 fractions, and high risk and low risk region PTV was 60-63 Gy and 50.4~56 Gy in 30~33 and 28 fractions respectively. Plasma Epstein Barr virus (EBV) DNA load was measured before treatment. The clinical toxicities, outcomes and patterns of failure were observed. Results: The median follow up time was 23 months (range 2 to 53 months). EBV infection positive was only 15.9%. Overall disease failure developed in 36 patients, 99% belonged to stage III/IV disease. Among these, there were 26 distant metastases, 6 local recurrence, and 4 regional recurrence. The 3-year local control rate(LCR), distant metastasis-free survival (MFS), disease-free survival (DFS) and the overall survival (OS) was 93.9%, 79.5%, 70% and 83.1% respectively. Multivariate analyses revealed that age and anemia pre-radiotherapy were independent predictors for OS. Conclusion: IMRT with or without chemotherapy can improve the long term survival of NPC patients in Northwest China. Distant metastasis becomes the main cause of treatment failure. Age and anemia before radiotherapy were the main prognosis factors of NPC patients [ABSTRACT FROM AUTHOR]

The article reports on the analysis of the diagnosis and treatment of temporal lobe necrosis (TLN), a late stage complication after radiation therapy in patients with nasopharyngeal cancer (NPC). It states the analysis has revealed that prevention is better than treatment in managing TLN. It states conventional treatment including steroids and anticoagulants fails to reverse the pathogenesis of TLN and in some cases TLN is difficult to make according to conventional radiological modalities.

Background: Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC.Methods: A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves.Results: The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%.Conclusions: In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports. [ABSTRACT FROM AUTHOR]

Reirradiation is a feasible option for patients who do not otherwise have treatment options available. Depending on the location and extent of the tumor, reirradiation may be accomplished with external beam radiotherapy, brachytherapy, radiosurgery, or intensity modulated radiation therapy (IMRT). Although there has been limited experience with hypofractionated stereotactic radiotherapy (hSRT), it may have the potential for curative or palliative treatment due to its advanced precision technology, particularly for limited small lesion. On the other hand, severe late adverse reactions are anticipated with reirradiation than with initial radiation therapy. The risk of severe late complications has been reported to be 20- 40% and is related to prior radiotherapy dose, primary site, retreatment radiotherapy dose, treatment volume, and technique. Early researchers have observed lethal bleeding in such patients up to a rate of 14%. Recently, similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT like in case of carotid blowout syndrome. To determine the feasibility and efficacy of reirradiation using modern technology, we reviewed the pertinent literature. The potentially lethal side effects should be kept in mind when reirradiation by hSRT is considered for treatment, and efforts should be made to minimize the risk in any future investigations. [ABSTRACT FROM AUTHOR]

Background: To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).Methods: Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.Results: After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.Conclusion: HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Radiation recall pneumonitis (RRP) describes a rare reaction in previously irradiated area of pulmonary tissue after application of triggering agents. RRP remains loosely characterized and poorly understood since it has so far only been depicted in 8 cases in the literature. The objective of the study is to disclose the general characteristics of RRP induced by chemotherapy after thoracic irradiation for lung cancer, and to draw attention to the potential toxicity even after a long time interval from the previous irradiation. Methods: Medical records were reviewed. RRP induced by chemotherapy was diagnosed by the history of chemotherapy after radiotherapy, clinical presentation and radiographic abnormalities including ground-glass opacity, attenuation, or consolidation changes within the radiation field, plus that radiographic examination of the thorax before showed no radiation pneumonitis. RRP was graded according to Common Terminology Criteria for Adverse Events version 3.0. The characteristics of the 12 RRP cases were analyzed. Results: Twelve patients were diagnosed of RRP, of who 8 received taxanes. The median time interval between end of radiotherapy and RRP, between end of radiotherapy and beginning of chemotherapy, and between beginning of chemotherapy and RRP was 95 days, 42 days and 47 days, respectively. Marked symptomatic and radiographic improvement was observed in the 12 patients after withdrawal of chemotherapy and application of systemic corticosteroids. Seven patients were rechallenged with chemotherapy, of whom four with the same kind of agents, and showed no recurrence with steroid cover. Conclusions: Doctors should pay attention to RRP even after a long time from the previous radiotherapy or after several cycles of consolidation chemotherapy. Taxanes are likely to be associated with radiation recall more frequently. Withdrawal of causative agent and application of steroids are the treatment of choice. Patients may be rechallenged safely with steroid cover and careful observation, which needs to be validated. [ABSTRACT FROM AUTHOR]

Purpose: To report our experience with intensity-modulated or stereotactic reirradiation in patients suffering from recurrent nasopharyngeal carcinoma. Patients and Methods: The records of 17 patients with recurrent nasopharygeal carcinoma treated by intensitymodulated (n = 14) or stereotactic (n = 3) reirradiation in our institution were reviewed. Median age was 53 years and most patients (n = 14) were male. The majority of tumors showed undifferentiated histology (n = 14) and infiltration of intracranial structures (n = 12). Simultaneous systemic therapy was applied in 8 patients. Initial treatment covered the gross tumor volume with a median dose of 66 Gy (50-72 Gy) and the cervical nodal regions with a median dose of 56 Gy (50-60 Gy). Reirradiation was confined to the local relapse region with a median dose of 50.4 Gy (36-64Gy), resulting in a median cumulative dose of 112 Gy (91-134 Gy). The median time interval between initial and subsequent treatment was 52 months (6-132). Results: The median follow up for the entire cohort was 20 months and 31 months for survivors (10-84). Five patients (29%) developed isolated local recurrences and three patients (18%) suffered from isolated nodal recurrences. The actuarial 1- and 2-year rates of local/locoregional control were 76%/59% and 69%/52%, respectively. Six patients developed distant metastasis during the follow up period. The median actuarial overall survival for the entire cohort was 23 months, transferring into 1-, 2-, and 3-year overall survival rates of 82%, 44% and 37%. Univariate subset analyses showed significantly increased overall survival and local control for patients with less advanced rT stage, retreatment doses > 50 Gy, concurrent systemic treatment and complete response. Severe late toxicity (Grad III) attributable to reirradiation occurred in five patients (29%), particularly as hearing loss, alterations of taste/smell, cranial neuropathy, trismus and xerostomia. Conclusion: Reirradiation with intensity-modulated or stereotactic techniques in recurrent nasopharyngeal carcinoma is feasible and yields encouraging results in terms of local control and overall survival in patients with acceptable toxicity in patients with less advanced recurrences. However, the achievable outcome is limited in patients with involvement of intracranial structures, emphasising the need for close monitoring after primary therapy. [ABSTRACT FROM AUTHOR]

Background: To compare the results of external beam radiotherapy in combination with 3D- computed tomography (CT)-implanted interstitial high dose rate brachytherapy (ERT/3D-HDR-BT) versus conventional external beam radiotherapy (ERT) for the treatment of stage T2b nasopharyngeal carcinoma (NPC). Methods: Forty NPC patients diagnosed with stage T2b NPC were treated with ERT/3D-HDR-BT under local anesthesia. These patients received a mean dose of 60 Gy, followed by 12-20 Gy administered by 3D-HDR-BT. Another 101 patients diagnosed with non-metastatic T2b NPC received a mean dose of 68 Gy by ERT alone during the same period. Results: Patients treated with ERT/3D-HDR-BT versus ERT alone exhibited an improvement in their 5-y local failurefree survival rate (97.5% vs. 80.2%, P = 0.012) and disease-free survival rate (92.5% vs. 73.3%, P = 0.014). Using multivariate analysis, administration of 3D-HDR-BT was found to be favorable for local control (P = 0.046) and was statistically significant for disease-free survival (P = 0.021). The incidence rate of acute and chronic complications between the two groups was also compared. Conclusions: It is possible that the treatment modality enhances local control due to improved conformal dose distributions and the escalated radiation dose applied. [ABSTRACT FROM AUTHOR]

Background: Current staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC. Methods: A retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome. Results: GTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (≧13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn ≧ 13 ml, overall survival was better after ≧4 cycles of chemotherapy than after less than 4 cycles. Conclusions: The incorporation of GTVprn can provide more information to adjust treatment strategy. [ABSTRACT FROM AUTHOR]