Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Clinical Characteristics and Long-Term Outcomes following Surgery Combined with Adjuvant Radiotherapy for Patients with Frontal Sinus Malignancies.

Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage II-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline.

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC). METHODS: The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options. RECOMMENDATIONS: Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Variations of Clinical Target Volume Delineation for Primary Site of Nasopharyngeal Cancer Among Five Centers in China.

PURPOSE: The purpose of this study is to investigate the current status of clinical target volume (CTV) delineation for primary site of nasopharyngeal cancer (NPC) among five large tertiary cancer centers in China. MATERIALS AND METHODS: The simulation CT and MR images of a patient with T3N2M0 NPC were sent to the centers participating. Fourteen experienced physicians contoured the targets independently, and the outlined structures were compared. The consistency and differences among these 14 CTVs are discussed. RESULTS: Two different CTV designs were used in the centers. "One-CTV" design defines one CTV with a dose of 60 Gy, whereas "two-CTV" design has a high-risk CTV with dose of 60 Gy and a medium risk CTV with dose of 54 Gy. We found that the coverage of prophylactic area is very consistent between these two designs. The variances on the coverage of some sites were also significant among physicians, including covering cavernous sinus at un-involved side, posterior space of styloid process, and caudal border on posterior pharyngeal wall. CONCLUSIONS: Standardization is the main requirement for personalization of care; our study shows that among the 14 physicians in the five centers the coverage of prophylactic areas is in excellent agreement. Two distinct strategies on CTV design are currently being used, and multiple controversies were found, suggesting further optimization of CTV for primary site of NPC is needed.

Post-Procedural Anticoagulation After Primary Percutaneous Coronary Intervention for Anterior Acute Myocardial Infarction With Severe Left Ventricular Dysfunction.

BACKGROUND: Patients with anterior acute myocardial infarction (AMI) and left ventricular (LV) dysfunction have an increased risk of LV thrombus (LVT). In the thrombolytic era, short-term anticoagulation using low-molecular-weight heparin during hospitalization proved to significantly reduce LVT formation, but, the effect of this prophylactic approach remains unclear in the current era. Therefore, we conducted a study to evaluate the effects of post-procedural anticoagulation (PPAC) using enoxaparin in addition to dual antiplatelet therapy (DAPT) after primary percutaneous coronary intervention (PCI) in such patients.Methods and Results:A total of 426 anterior AMI patients with LV ejection fraction ≤40% were retrospectively enrolled and classified into 2 groups based on whether they received PPAC (enoxaparin SC for at least 7 days). All patients received primary PCI and DAPT. The primary endpoint was definite LVT at 30 days diagnosed by echocardiography. The secondary endpoints were 30-day mortality, embolic events, and major bleeding events. PPAC was independently associated with a lower incidence of LVT (odds ratio 0.139, 95% confidence interval 0.032-0.606, P=0.009). The 30-day mortality, embolic events, and major bleeding events were not statistically different between groups. CONCLUSIONS: Short-term PPAC using enoxaparin after primary PCI may be an effective and safe way to prevent LVT in patients with anterior AMI and LV dysfunction.

Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 is a worldwide health emergency. The immense damage done to public health and economies has prompted a global race for cures and vaccines. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein by adding two proline substitutions at the top of the central helix (S-2P). To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. The neutralizing abilities in pseudotyped lentivirus reporter or live wild-type SARS-CoV-2 were measured with reciprocal inhibiting dilution (ID50) titers of 5120 and 2560, respectively. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th-1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens with up to 50 g of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018/alum as a candidate vaccine to prevent COVID-19 disease.

Prognostic value of admission electrocardiographic findings in non-ST-segment elevation myocardial infarction.

BACKGROUND: Admission electrocardiographic (ECG) findings of non-ST-segment elevation myocardial infarction (NSTEMI) include transient ST-segment elevation (TSTE), ST-segment depression (STD), T-wave inversion (TWI), and no ischemic changes (NIC). HYPOTHESIS: This study aimed to assess the prognostic value of qualitative ECG findings at presentation and to clarify the influence of invasive treatment on the prognostic value of admission ECG findings. METHODS: We analyzed the Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) study post hoc. NSTEMI patients were included and classified into four groups per ECG findings. Study endpoints were in-hospital and 30-day mortality rates and major adverse events (MAE). We performed multivariate logistic regression, adjusting for covariates in the Global Registry of Acute Coronary Events risk model, with subset analyses of patients treated with or without invasive management. RESULTS: STD patients had significantly higher in-hospital and 30-day mortality rates/MAE than TWI patients, which had lower in-hospital mortality rate/MAE than the NIC group. TSTE patients had intermediate outcomes. In multivariate logistic regression using the TWI group as the reference, STD and NIC remained independently associated with worse outcomes. Subset analysis showed prognostic value of admission ECG in non-invasively managed but not in invasively managed patients. CONCLUSIONS: STD was associated with adverse outcomes, TWI with benign prognoses. NIC should not be taken to indicate low risk. Qualitative analysis of admission ECG is suitable for rapid risk stratification of NSTMI patients at presentation. However, it may not be predictive of short-term outcomes of NSTEMI patients after invasive management.

Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas.

INTRODUCTION: We aimed to analyze the relationship between the changed status of vocal cord mobility and survival outcomes. METHODS: Seventy-eight patients with dysfunctional vocal cords and hypopharyngeal carcinomas accepted non-surgical treatment as the initial therapy between May 2009 and December 2016. Vocal cord mobility was assessed before and after the initial non-surgical treatment. The cord mobility status was classified as normal, impaired, and fixed. Patients with improved mobility (IM) (n =56) were retrospectively analyzed for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) and compared with 22 patients with non-improved mobility (non-IM). RESULTS: Fifty-six (71.8%) patients had improved cord mobility after the initial non-surgical treatment. The non-improved cord mobility was significantly associated with shortened DFS (P=0.005), RFS (P=0.002), and OS (P<0.001). If non-improved cord mobility was regarded as an indicator for local-regional recurrence within 1 year, the sensitivity and the specificity were 60.9%, 87.5% respectively. The multivariate analysis showed that improved cord mobility (P=0.006) and salvage surgery (P=0.015) were both independent protective factors for OS. CONCLUSION: Changes in cord mobility are a key marker for predicting prognosis. Non-improved cord mobility may indicate a high possibility of a residual tumor, therefore, patients whose cord mobility remains dysfunctional or worsens after non-surgical treatment might need an aggressive salvage strategy.

The prognostic effect of left ventricular thrombus formation after acute myocardial infarction in the contemporary era of primary percutaneous coronary intervention: A meta-analysis.

BACKGROUNDS: The prognosis and management of left ventricular thrombus (LVT) following acute myocardial infarction (AMI) have not been well evaluated since the advent of primary percutaneous coronary intervention (PCI). We therefore conducted a meta-analysis to assess the prognostic effect of LVT after AMI in primary PCI era and investigate the impact of triple therapy on outcomes. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library for studies conducted in primary PCI era up to 29 March 2019, compering the incidence of embolic events and mortality after AMI between LVT patients and Non-LVT patients. Random-effect models were used. Subgroup analysis was done by comparing triple therapy treated LVT group with Non-LVT group. RESULT: A total of 12 studies were included. LVT was associated with increased risk of embolic events and long-term mortality (RR 3.97, 95%CI 2.68-5.89, P < 0.0001; RR 2.34, 95%CI 1.38-3.96, P = 0.002). Subgroup analysis was also done by comparing triple therapy treated LVT group with Non-LVT group. Despite a downward tendency was observed, the embolic risk of triple therapy subgroup was higher than non-LVT group (RR 2.79, 95%CI 1.32-5.91, P = 0.007). Triple therapy subgroup had a similar mortality rate compared with non-LVT group (RR 0.93, 95%CI 0.34-2.52, P = 0.88). CONCLUSION: In primary PCI era, LVT formation after AMI indicated a fourfold increased embolic risk and twofold long-term mortality rate. Triple therapy may be a safe way to improve the outcomes, but still need to be confirmed by future trials.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. METHODS: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. RESULTS: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim). CONCLUSIONS: Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Failure patterns and prognostic factors of patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses.

OBJECTIVES: To analyse the failure patterns and prognostic factors influencing survival in patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses. MATERIALS AND METHODS: Fifty-one patients were analysed retrospectively. Forty-eight, 33, 10, and 13 patients underwent surgery, radiotherapy, chemotherapy, and immunotherapy, respectively. Failure events, including local recurrence, regional relapse, distant metastases, and death, were examined. RESULTS: During follow-up (median: 59.0 months), 36 patients experienced failure after treatment, including local (n = 17), regional (n = 8), and distant organ (n = 23) metastases. The median failure times for local, regional, and distant metastases were 13.0, 14.0, and 8.0 months, respectively. The median survival times from local, regional, and distant failure to death were 10.5, 8.0, and 4.0 months, respectively. The 5-year overall survival rates of patients with and without distant organ metastases were 14.4% and 72.6%, respectively (p < .001). Multivariate analyses showed that radiotherapy increased local recurrence-free and regional relapse-free survival. Patients with stage IV tumours had reduced distant metastasis-free and overall survival compared to patients with stage I-III tumours. CONCLUSIONS: Distant metastasis was mainly owing to failure. Radiotherapy and the disease stage were prognostic factors for survival.

High-risk factors of parotid lymph node metastasis in nasopharyngeal carcinoma: a case-control study.

BACKGROUND: Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma. METHODS: This was a 1:2 case-control study. All patients in this study were newly diagnosed NPC with N2-3 classification from January 2005 to December 2012. Cases were 22 sides with ipsilateral PLNM. Controls were 44 patients who were randomly selected from N2-3 disease in database. RESULTS: 20/1096 (1.82 %) NPC patients were found PLNM. Sum of the longest diameter for multiple lymph nodes (SLD) in level II was larger in case group than that in control group (6.0 cm vs. 3.6 cm, p = 0.003). Level II lymph node necrosis, level Va/b involvement, and rare neck areas involvement were more common in case group (p = 0.016, p = 0.034, and p < 0.001, respectively). RPN, level III, and level IV metastases showed no significant difference between the two groups. Multivariate analysis in logistic regression showed that only SLD ≥5 cm in II area (OR = 4.11, p = 0.030) and rare neck areas involvement (OR = 3.95, p = 0.045) were associated with PLNM in NPC patients. CONCLUSIONS: PLNM was an uncommon event in NPC patients. SLD ≥5 cm in level II and involvement in rare-neck areas may be potentially high-risk factors for PLNM. Sparing parotid in IMRT was not recommended for NPC patients with high risks of PLNM.

Long-term outcomes of patients with esthesioneuroblastomas: A cohort from a single institution.

OBJECTIVE: Esthesioneuroblastoma is a rare cancer. The purpose of this study was to review the long-term outcomes of patients with esthesioneuroblastomas (ENBs) who were treated at a single institution. MATERIALS AND METHODS: One hundred thirteen patients with biopsy-proven ENBs between June of 1979 and November of 2014 were retrospectively reviewed. There was 1 patient at stage A, 23 stage B and 89 stage C according to Kadish classifications. The initial treatments included pre-operative radiotherapy (RT) followed by surgery in 11 patients, surgery followed by post-operative RT in 51, primary RT in 47, and surgery in 3, and only a single patient was treated with palliative chemotherapy alone. RESULTS: The median follow-up was 75months, 5-year overall survival (OS), loco-regional control rate (LRC) and distant metastasis-free survival were 65%, 73% and 67%, respectively. The OSs at 5years were 91% in the pre-operative RT group, 82% in the post-operative RT group, and 50% in the primary RT group (p<0.001). Regarding the patients in early disease stages (Kadish A/B), no survival differences were observed between primary RT and combination treatment. Regarding the node-negative Kadish C disease patients, combination of surgery and RT elicited superior survival, and pre-operative RT yielded the best prognoses. Distant failure rate is over 60% for N-positive disease, chemotherapy may play a more important role. CONCLUSIONS: The optimal treatment policy for ENBs remains the combination of surgery and radiotherapy. When choosing the most adequate therapy for ENBs, disease stage, age and lymph nodes status should be taken into consideration.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure.

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.

Nasopharyngeal carcinoma with intracranial extension in the era of intensity-modulated radiotherapy: case-control study using propensity score matching method.

The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.

Spread patterns of lymph nodes and the value of elective neck irradiation for esthesioneuroblastoma.

OBJECTIVES: This study was aimed to characterize patterns of lymphatic spread and assess the value of prophylactic elective neck irradiation (ENI) for esthesioneuroblastoma (ENB). METHODS: A retrospectively analysis of 116 patients with newly diagnosed ENB at our institution over 35-year period was undertaken. RESULTS: 32 patients (28%) presented lymph node metastasis at initial diagnosis, the common sites involved were level II, Ib, level III and VIIa. Among 80 N-negative patients staged in Modified Kadish B/C, 50 patients were delivered with ENI, 30 patients were not. The 5-year regional failure-free survival was 98% in patients treated with ENI and 75% in patients without ENI (p=0.005), regional failure rate decreased significantly from 23% (7/30) to 2% (1/50) after ENI (p=0.002). Multivariate analysis also suggested that ENI was an independent favorable predictor for regional controlling (HR, 0.102; 95% CI: 0.012-0.848; p=0.035). CONCLUSIONS: This is the largest cohort of ENB so far in a single institute, and also the first detailed description of nodal spread patterns of N-positive ENB. Elective neck irradiation reduced the regional failure significantly and should be recommended as a part of initial treatment strategy for patients staged with Modified Kadish B/C.

Multi-subject atlas-based auto-segmentation reduces interobserver variation and improves dosimetric parameter consistency for organs at risk in nasopharyngeal carcinoma: A multi-institution clinical study.

BACKGROUND AND PURPOSE: To assess whether consensus guideline-based atlas-based auto-segmentation (ABAS) reduces interobserver variation and improves dosimetric parameter consistency for organs at risk (OARs) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Eight radiation oncologists from 8 institutes contoured 20 OARs on planning CT images of 16 patients via manual contouring and manually-edited ABAS contouring. Interobserver variation [volume coefficient of variation (CV), Dice similarity coefficient (DSC), three-dimensional isocenter difference (3D-ICD)] and dosimetric parameters were compared between the two methods of contouring for each OAR. RESULTS: Interobserver variation was significant for all OARs in manual contouring, resulting in significant dosimetric parameter variation (P<0.05). Edited ABAS significantly improved multiple metrics and reduced dosimetric parameter variation for most OARs; brainstem, spinal cord, cochleae, temporomandibular joint (TMJ), larynx and pharyngeal constrictor muscle (PCM) obtained most benefit (range of mean DSC, volume CV and main ICD values was 0.36-0.83, 12.1-84.3%, 2.2-5.0mm for manual contouring and 0.42-0.86, 7.2-70.6%, 1.2-3.5mm for edited ABAS contouring, respectively; range of dose CV reduction: 1.0-3.0%). CONCLUSION: Substantial objective interobserver differences occur during manual contouring, resulting in significant dosimetric parameter variation. Edited ABAS reduced interobserver variation and improved dosimetric parameter consistency, particularly for brainstem, spinal cord, cochleae, TMJ, larynx and PCM.

Concurrent chemotherapy for T4 classification nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy.

OBJECTIVE: To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). METHODS: From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone. RESULTS: The median follow-up time was 58.97 months (range, 2.79-114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group. CONCLUSION: IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.

Update report of T4 classification nasopharyngeal carcinoma after intensity-modulated radiotherapy: an analysis of survival and treatment toxicities.

OBJECTIVE: To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. CONCLUSION: The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT.