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Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC).One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019.In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p = 0.03). There was no difference in overall survival and the adverse events were tolerable.The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.

Purpose To evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors. Methods A total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed. Results The median follow-up time for the whole group was 31.5 months (range 5–138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/μl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS. Conclusion Taxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

The aim of the study was to report long-term results of intensity-modulated radiotherapy for patients with T4 classification nasopharyngeal carcinoma (NPC). From September 2007 to January 2013, 155 patients were retrospectively analyzed. The estimated 10-year local recurrent-free survival (LRFS), regional recurrent-free survival (RRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 79.4%, 93.2%, 69.0%, and 54.2%, respectively. Cycle number of chemotherapy was a significant predictor of LRFS, OS, and progression-free survival. There was no significant difference in survival rates between patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and patients with IC plus IMRT and adjuvant chemotherapy (AC).

The purpose of this study was to compare the efficacy and toxicity of induction chemotherapy (IC) plus radiotherapy (RT) and IC plus concurrent or adjuvant chemoradiotherapy (CCRT/AC) in nasopharyngeal carcinoma (NPC) patients with negative Epstein–Barr virus DNA (EBV DNA) after IC. A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC + RT group and the IC + CCRT/AC group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan–Meier method. Propensity score matching (PSM) was performed to balance the variables. The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC + RT and the IC + CCRT/AC groups, both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that the treatment schedule was not an independent predictor for survival rates. Patients in the IC + RT group had fewer treatment-related acute toxicities and better tolerance. IC + RT displayed similar survival outcomes as IC + CCRT/AC for NPC patients with negative post-IC EBV DNA.

To improve the radiation therapy outcomes by inducing more toxicity for tumors and less for normal tissue and switch microenvironment immunosuppressive caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles (AuNPs) and superparamagnetic iron oxide nanoparticles (SPIOs)( antiPD-L1-SPIOs@PLGA@Au). AntiPD-L1-SPIOs@PLGA@Au targeted on the B16F10 cell membrane and in cytoplasm, and the association could be reduced by the antibody blocking. In vivo T2-weight image, the best enhancement effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au. Compared with radiation alone, the Do sensitization ratios of antiPD-L1-SPIOs@PLGA@Au was 1.34. The inhibition effect of irradiation combined with antiPD-L1-SPIOs@PLGA@Au was higher than that of radiotherapy alone in the B16F10 subcutaneous tumor model. During the entire observation period, all mice in the antiPD-L1-SPIOs@PLGA@Au group lived longer than 3 weeks. AntiPD-L1-SPIOs@PLGA@Au enhancing radiosensitivity was achieved by increasing ROS production and attenuating DNA damage repair. In vitro and in vivo experiments showed that antiPD-L1-SPIOs@PLGA@Au could promote the polarization of tumor-associated macrophages (TAMs) to M1 and reverse the immunosuppressive regulation induced by TAMs. antiPD-L1-SPIOs@PLGA@Au could increase the expression of CRT in tumor, block the PD-L1/PD pathway, activate CD8+T cells, promote the increase of IFN-γ, TNF-α and IL-12 release, and finally activate the anti-tumor immune response. In conclusion, antiPD-L1-SPIOs@PLGA@Au was proved to have the ability to form targeted imaging and enhance radiosensitivity, block the PD-L1/PD-1 immune checkpoint pathway, reverse the immunosuppressive regulation caused by TAMs, successfully realizing the synergistic effect of radiotherapy combined with immunotherapy.

Background The aim of the study is to identify clinical and dosimetric factors that could predict the risk of hypothyroidism in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT). Methods A total of 404 non-metastatic NPC patients were included in our study. All patients were treated with IMRT. The thyroid function were performed for all patients before and after radiation at regular intervals. The time onset for developing hypothyroidism was defined as the time interval between the completion of RT and the first recorded abnormal thyroid hormone test. The cumulative incidence rates of hypothyroidism were estimated using Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to detect the most promising factors that were associated with hypothyroidism. Results Median follow up was 60.6 months. The 3-, 5- and 7- year cumulative incidence rate of hypothyroidism was 39.4%, 49.1% and 54.7%, respectively. The median time to primary hypothyroidism and central hypothyroidism were 15.4 months (range 2.9–83.8 months) and 29.9 months (range 19.8–93.6 months), respectively. Univariate and multivariate analyses revealed that younger age, female gender and small thyroid volume were the most important factors in predicting the risk of hypothyroidism. Dtmean (mean dose of thyroid), V30-V50 (percentage of thyroid volume receiving a certain dose level) and VS45-VS60 (the absolute volumes of thyroid spared from various dose levels) remained statistically significant in multivariate analyses. Cutoff points of 45 Gy (Dtmean), 80% (Vt40) and 5 cm3 (VS45Gy) were identified to classify patients as high-risk or low-risk group. Conclusion Thyroid Vt40 highly predicted the risk of hypothyroidism after IMRT for NPC patients. We recommended plan optimization objectives to reduce thyroid Vt40 to 80%. Trial registration: Retrospectively registered.

To explore the effect of evidence-based nursing on the application of ultrasonic emulsification operation for cataract and the postoperative rehabilitation indicators. 110 cataract patients were included. All of them received ultrasonic emulsification operation for cataract and were divided into the control group(n=55) and the observation group(n=55) by random number method. The control group received routine nursing. The visual acuity, intraocular pressure, quality of life and adverse reactions of patients in both groups after discharge were compared and evaluated. The clinical effective rate(92.73%), postoperative visual acuity(0.68 ± 0.05) and SF-36 score(82.37 ± 4.13) in the observation group were higher than those in the control group(76.36%), (0.55 ± 0.02) and(74.06 ± 3.42), Conclusion: Evidence-based nursing can effectively improve the curative effect and postoperative vision, and improve the quality of life. The intraocular pressure in the observation group(9.95 ± 2.46) mmHg and the incidence of adverse reactions(29.09%) were lower than those in the control group(11.03 ± 3.11) mmHg and 10.91%(P

This study aimed to develop prognosis signatures through a radiomics analysis for patients with nasopharyngeal carcinoma (NPC) by their pretreatment diagnosis magnetic resonance imaging (MRI). A total of 208 radiomics features were extracted for each patient from a database of 303 patients. The patients were split into the training and validation cohorts according to their pretreatment diagnosis date. The radiomics feature analysis consisted of cluster analysis and prognosis model analysis for disease free-survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Additionally, two prognosis models using clinical features only and combined radiomics and clinical features were generated to estimate the incremental prognostic value of radiomics features. Patients were clustered by non-negative matrix factorization (NMF) into two groups. It showed high correspondence with patients’ T stage (p

Background The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity‐modulated radiotherapy (IMRT). Methods A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109/L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). Results Sixty‐nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high‐grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. Conclusions HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

e18069 Background: De-intensification in chemoradiation provides a strategy to optimize the trade-off between treatment efficacy and toxicities in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). However, the failure of RTOG 1016 and De-ESCALaTE indicated the pitfall of de-escalation in an unselective population and the importance of patient selection for future study design. Induction chemotherapy (IC), as a potential biomarker, has been adopted in several trials to screen candidates for de-intensified treatment based on its tumor response. In present trial, we investigated the feasibility of selectively de-intensified chemoradiotherapy by reducing radiation dose and omitting concurrent chemotherapy guided by response to IC. Methods: From Jan 2019 to July 2021, 48 patients with p16 positive OPSCC, T1-2/N1-3M0 (excluding T1N1M0 patients with single and≤3cm lymph node) or T3-4N0-3M0 according to the UICC/AJCC 8th staging system were enrolled. All of them received two cycles of IC with cisplatin and docetaxel. Those with major response to IC (defined as cCR or ≥50% cPR of both primary site and lymph nodes) received de-intensified treatment with intensity modulated radiation therapy (IMRT) alone with 60Gy to high-risk and 54Gy to low-risk regions (Di cohort). Those with less than major response were given standard chemoradiotherapy with 70Gy to both primary tumor and positive lymph nodes, 63Gy to high-risk and 56Gy to low-risk regions, concurrently with two cycles of cisplatin (St cohort). The primary endpoint was 2-year progression-free survival (PFS). Results: 26/48 (54.2%) patients entered Di cohort while other 22/48 (45.8%) patients entered St cohort. With a median follow-up time of 20.5 months (2.8-36.7months), 3 deaths (1 in Di cohort and 2 in St cohort), 5 loco-regional recurrence (1 in Di cohort and 4 in St cohort) and 6 distant metastases (1 in Di cohort and 5 in St cohort) were documented. The 2-year PFS rates for Di and St cohort were 100% and 60.0% (P = 0.002) with overall survival (OS) rates of 100% and 83.1% (P = 0.062), loco-regional recurrence-free survival (LRFS) rates of 100% and 77.0% (P = 0.035), metastasis-free survival (MFS) rates of 100% and 66.8% (P = 0.011), respectively. Conclusions: For major responders to IC, reduced-dose radiation with omitted concurrent chemotherapy yielded good survival results. In comparison, patients resistant to IC showed poor prognosis even under standard-dose chemoradiotherapy, calling for treatment intensification or development of novel therapeutic agents. Selective de-intensification of chemoradiation guided by response to IC is promising in HPV-associated OPSCC and warrants further evaluation in future studies. Clinical trial information: NCT04012502.

e18060 Background: Target volume delineation in nasopharyngeal carcinoma (NPC) remains a challenge because of the narrow therapeutic margin. There are no-well established guidelines for clinical target volume (CTV) delineation with long-term follow-up. Current consensus continues to rely heavily on bony structure and experience from conventional two and three- dimensional radiation. The aim of our study, is to clarify different anatomic distribution of local recurrence of NPC based on various T stages and spread patterns, provide a high-risk map of local recurrence of NPC, and thus provide suggestion for modification of CTV delineation based on T stages and spread patterns. Methods: We retrospectively enrolled 869 patients with newly diagnosed nonmetastatic NPC treated with definitive IMRT in our institution. With a median follow-up of 54.4 months, 72 patients developed local failure. All the cases of local failure were reviewed and those of local residual disease were excluded. After that, 52 cases with tracaeble primary radiotherapy plans and MR imaging of local recurrence were included in this study. Gross tumor volume of local recurrence (GTVr) and normal structures were delineated in each recurrent patient on primary CT of radiotherapy. The overlap of normal structures with GTVr were analyzed, as well as the stepwise patterns of tumor spread in NPC, based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%, etc). Results: The anatomic distributions of local recurrence of various primary T stages were compared between early and late stages of NPC. Of note, these structures were significantly highly involved in T3/4 cases, compared with T1/2 cases, including lateral pterygoid muscle, inferior orbital fissure，posterior ethmoid sinus，cavernous sinus as well as hypoglossal canal. As for tumor spread patterns of local relapse, most cases relapsed in the nasopharynx and retropharyngeal lymph node (38.5%), followed by anterior-lateral tumor extension (via nasal cavity-pterygoid process-pterygopalatine fossa, 17.31%), posterior tumor extension (via prevertebral muscle-clivus, 13.46%), anterior-superior extension (via nasal cavity-ethmoid sinus-sphenoidal sinus,13.46%), superior extension(via foramen lacerum-cavernous sinus, 11.54%), etc. Finally, we depicted a map of high-risk area based on different T stages and relapsed risk (≥5%, ≥10%, ≥20%). Conclusions: Comprehensive analysis of local recurrence distributions and tumor spread patterns in real-world IMRT provides important reference for modification of CTV delineation for primary NPC. Certain structures such as cavernous sinus and lateral pterygoid muscle are not routinely recommended in the delineation of high-risk CTV for T1-2 disease. Future individualized delineations should be based on relapsed risk and tumor spread patterns.

To investigate the impact of training sample size on the performance of deep learning-based organ auto-segmentation for head-and-neck cancer patients, a total of 1160 patients with head-and-neck cancer who received radiotherapy were enrolled in this study. Patient planning CT images and regions of interest (ROIs) delineation, including the brainstem, spinal cord, eyes, lenses, optic nerves, temporal lobes, parotids, larynx and body, were collected. An evaluation dataset with 200 patients were randomly selected and combined with Dice similarity index to evaluate the model performances. Eleven training datasets with different sample sizes were randomly selected from the remaining 960 patients to form auto-segmentation models. All models used the same data augmentation methods, network structures and training hyperparameters. A performance estimation model of the training sample size based on the inverse power law function was established. Different performance change patterns were found for different organs. Six organs had the best performance with 800 training samples and others achieved their best performance with 600 training samples or 400 samples. The benefit of increasing the size of the training dataset gradually decreased. Compared to the best performance, optic nerves and lenses reached 95% of their best effect at 200, and the other organs reached 95% of their best effect at 40. For the fitting effect of the inverse power law function, the fitted root mean square errors of all ROIs were less than 0.03 (left eye: 0.024, others: R square of all ROIs except for the body was greater than 0.5. The sample size has a significant impact on the performance of deep learning-based auto-segmentation. The relationship between sample size and performance depends on the inherent characteristics of the organ. In some cases, relatively small samples can achieve satisfactory performance.

Objective: To evaluate clinical outcomes of cervical node recurrence/residual tumor of nasopharyngeal carcinoma (NPC) with treatment decisions made by a multidisciplinary treatment (MDT) team. Methods: Between March 2010 and July 2019, patients who had previously undergone definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma and presented with residual or recurrent cervical lymph nodes were enrolled in our study. Clinical features and treatment modalities were retrospectively reviewed, and survival outcomes were analyzed. Results: A total of 183 patients were enrolled in the study, among whom 139 underwent neck dissection, and the remaining 44 were either considered not eligible for surgery or refused surgery. For the two groups of patients, the 3-year overall survival (OS) was 73.4% vs 36.8% (p=0.000), and the progression-free survival (PFS) was 57.1% vs 32.3% (p=0.004), respectively. Patients who underwent neck dissection had a significantly better clinical outcome and shorter latency between the prior treatment and detection of neck recurrence/residual tumor than those who did not. Conclusion: For regional failure cases that have no contradictions for surgery and are predicted to benefit from surgery by the MDT team, neck dissection could be the best choice. It is important for an experienced MDT team to choose the optimum treatment modalities for patients for the cervical failure of NPC. Regular follow-up after prior treatment contributes to the early detection of regional failure and provides a chance for surgery.

Purpose To evaluate the clinical characteristics and prognosis of elderly nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). Methods From June 2008 to October 2014, 148 newly diagnosed non-metastatic elderly NPC patients (aged ≥ 70 years) receiving IMRT were recruited. Comorbid condition was evaluated using the age-adjusted Charlson Comorbidity Index (ACCI). Kaplan–Meier method was used to estimate survival rates and the differences were compared using log-rank test. Hazard ratio (HR) and the associated 95% confidence interval (CI) were calculated using Cox proportional hazard model by means of multivariate analysis. Results The median follow-up time was 66.35 months. Estimated OS rate at 5 years for the entire group was 61.8% (95% confidence interval [CI] 0.542–0.703). The 5-year OS rate of RT alone group was 58.4% (95% [CI] 0.490–0.696) compared with 65.2% (95% [CI] 0.534–0.796) in CRT group (p = 0.45). In patients receiving IMRT only, ACCI score equal to 3 was correlated with superior 5-year OS rate in comparison with higher ACCI score 62.1% (95% [CI] 0.510–0.766) to 48.5% (95% [CI] 0.341–0.689), respectively; p = 0.024). A 5-year OS rate of 63.1% (95% [CI] 0.537–0.741) was observed in patients younger than 75 years old compared with 57.5% (95% [CI] 0.457–0.723) in patients older (p = 0.026). Patients with early-stage disease (I–II) showed better prognosis than patients with advanced-stage (III–IV) disease (5-year OS, 72.3–55.4%, respectively; p = 0.0073). The Cox proportional hazards model suggested that age independently predicted poorer OS (HR, 1.07; 95%CI 1.00–1.15, p = 0.04). Conclusion The survival outcome of patients aged ≥ 70 years receiving IMRT only was similar to chemoradiotherapy with significantly less acute toxicities. Among the population, age is significantly prognostic for survival outcomes.

Lu Di,1–3,* Kai Qian,2,4,* Chengrun Du,1,2 Chunying Shen,1,2 Ruiping Zhai,1,2 Xiayun He,1,2 Xiaoshen Wang,1,2 Tingting Xu,1,2 Chaosu Hu,1,2 Hongmei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 3Department of Oncology, Liyang People’s Hospital, Changzhou, Jiangsu 213000, China; 4Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China *These authors contributed equally to this work Background: Salivary duct carcinoma (SDC) is an extremely rare and highly malignant carcinoma, and surgical radical resection is the most effective therapy. However, there were quite a proportion of patients receiving non-radical resections, and how to treat them remained controversial. Thus, the aim of this study is to evaluate whether postoperative radiotherapy could be a salvage treatment of SDC in major salivary glands without radical operations.Patients and methods: We identified 40 pathologically diagnosed SDC patients who came to our hospital and did not receive radical operations. Thirty-three patients received at least one treatment (remedial operation, postoperative radiotherapy and chemotherapy), and seven patients only chose observation and received no further treatment. The prognostic indicators of the local–regional control (LRC) and distant disease-free survival were analyzed using the Kaplan–Meier methods and the Cox proportional hazards regression models.Results: Thirteen patients experienced local–regional recurrence or local progression, and distant metastases were observed in 15 patients. Through multivariate analysis, we found that postoperative radiotherapy was associated with better LRC, but this kind of treatment did not show significant efficacy in the prevention of distant metastasis.Conclusion: SDC is a rare, aggressive malignancy, and a substantial proportion of these patients experienced inadequate initial treatments. Although postoperative radiotherapy could not decrease distant metastases, it might help to improve LRC in patients with SDC. Keywords: salivary duct carcinoma, prognosis, non-radical resection, postoperative radiotherapy

Chemical information is essential in understanding the characteristics of airborne particles, and effectively controlling airborne particulate matter pollution, but it remains unclear in some regions due to the scarcity of measurement data. In the present study, 92 daily PM 2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) samples as well as historical observation data of air pollutants were collected in urban Ningbo, one of important industrial cities in the coastal area of the Yangtze River Delta, China in autumn and winter (from Nov. 2014 to Feb. 2015). Various chemical species in PM 2.5 were determined including water soluble ions, organic and elemental carbon and elements. Positive matrix factorization model, cluster analysis of back trajectories, potential source contribution function (PSCF) model and concentration-weighted trajectory (CWT) model were used for identifying sources, apportioning contributions from each source and tracking potential areas of sources. The results showed the PM 2.5 concentration has been reducing; nonetheless, the concentrations of PM 2.5 are still much higher than the World Health Organization guideline with high PM 2.5 concentrations observed in autumn and winter for the past few years. During the sampling period, the average PM 2.5 mass concentration was 77 μg/m 3 with the major components of OC, NO 3 − , SO 4 2 − , NH 4 + and EC, accounting for 24.7, 18.8, 14.5, 11.8 and 6.4% in the total mass concentration, respectively. When the aerosol pollution got worse during the sampling period, the NO 3 − , SO 4 2 − and NH 4 + concentrations increased accordingly and NO 3 − appeared to increase at fastest rate. SO 4 2 − transported from industrial areas led to slight difference in spatial distribution of SO 4 2 − in Ningbo. More secondary organic carbon was formed and the enrichment factor values of Cu, Ag, Cd, Sn and Pb increased with the degradation of air quality. Ten types of sources were identified for PM 2.5 in the autumn and winter of Ningbo, which are metallurgical industry, biomass burning and waste incineration, manufacturing related with Mo, chlor-alkli chemical industry, oil combustion, vehicular emission, secondary source, soil dust, road dust and manufacturing related with Cr, accounting for 9.4, 4.8, 9.4, 7.6, 8.1, 18.7, 27.6, 2, 7.1 and 5.2% of the total sources, respectively. There were five groups of air parcels arriving in Ningbo, of which inland air masses originating from Shandong province were associated with the highest PM 2.5 concentrations. Despite the slight differences, it was obvious that the north of Jiangxi, east of Anhui, west of Jiangsu, south of Shandong were identified as major potential sources-areas of SO 4 2 − , NO 3 − , NH 4 + , Cl − , OC and EC by both PSCF and CWT models.

Purpose In this study, we evaluated the prognostic values of hematological biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving definitive intensity-modulated radiotherapy (IMRT). Methods There were 427 NPC patients enrolled between January 2010 and March 2013 at Fudan University Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The Kaplan–Meier method and log-rank test were utilized to calculate progression-free survival (PFS) and overall survival (OS). The Cox proportional hazard models were applied to assess variables. Results ANC, APC and ALC were declined, while NLR and PLR were elevated significantly after therapy (P

Objective: To analyze the prognostic value of pre-treatment serum lactate dehydrogenase (SLDH) level in patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Methods: From January 2010 to March 2013, 427 eligible patients were reviewed. Pre-treatment SLDH level was measured within 2 weeks prior to treatment. Receiver operating characteristic (ROC) curve analysis was performed to select the optimal cutoff point. The impact of pre-treatment SLDH on overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. Further propensity score matching was carried out to adjust bias. Results: The optimal cutoff point of 168.5 IU/L was selected based on ROC curve analysis. Multivariate analysis showed that high pre-treatment SLDH level was an independent prognostic factor for OS (P=0.001), PFS (P=0.004) and DMFS (P=0.001). After propensity score matching was performed, it remained to be significantly associated with poor OS (P=0.009), PFS (P=0.015) and DMFS (P=0.008) in the adjusted model. Conclusion: High pre-treatment SLDH level predicts poor survival in patients with NPC treated with IMRT-based therapy. As a routinely performed biomarker, pre-treatment SLDH can be utilized in combination with current Tumor-Node-Metastasis staging to predict survival and to plan a personalized treatment in these patients.

Background: The Cox proportional hazards (CPH) model is the most commonly used statistical method for nasopharyngeal carcinoma (NPC) prognostication. Recently, machine learning (ML) models are increasingly adopted for this purpose. However, only a few studies have compared the performances between CPH and ML models. This study aimed at comparing CPH with two state-of-the-art ML algorithms, namely, conditional survival forest (CSF) and DeepSurv for disease progression prediction in NPC. Methods: From January 2010 to March 2013, 412 eligible NPC patients were reviewed. The entire dataset was split into training cohort and testing cohort in a ratio of 90%:10%. Ten features from patient-related, disease-related, and treatment-related data were used to train the models for progression-free survival (PFS) prediction. The model performance was compared using the concordance index (c-index), Brier score, and log-rank test based on the risk stratification results. Results: DeepSurv (c-index = 0.68, Brier score = 0.13, log-rank test p = 0.02) achieved the best performance compared to CSF (c-index = 0.63, Brier score = 0.14, log-rank test p = 0.38) and CPH (c-index = 0.57, Brier score = 0.15, log-rank test p = 0.81). Conclusions: Both CSF and DeepSurv outperformed CPH in our relatively small dataset. ML-based survival prediction may guide physicians in choosing the most suitable treatment strategy for NPC patients.

Purpose: Our previous study demonstrated the benefit of cumulative dose of cisplatin during the whole treatment on locally advanced nasopharyngeal carcinoma (NPC) treated with various chemotherapy strategies. The purpose of this study is to identify the subgroup of locally advanced NPC who benefits from higher dose of cisplatin, and to clarify whether cumulative dose of cisplatin during the whole treatment brings survival benefit to those treated with concurrent chemoradiotherapy (CCRT). Materials and methods: This retrospective study enrolled 527 patients with locally advanced NPC treated with intensity-modulated radiation therapy (IMRT) and chemotherapy in our institution from 2009 to 2010. The median cumulative dose of cisplatin of 300mg/m2 was chose to be the cutoff value of low and high dose subgroups. Survival curves were estimated using the Kaplan-Meier method. Univariate analysis was conducted using the log-rank test. Multivariate analyses (MVA) were performed using Cox proportional hazards regression model. Results: With a median follow-up of 54.5 (1-76.7) months, high-dose subgroup had a significant higher distant metastasis-free survival (DMFS) (82.0% vs. 76.5%, p=0.029) and overall survival (OS) (84.1% vs. 74.0%, p=0.028). Cumulative dose of cisplatin were demonstrated an independent prognostic factors for DMFS (HR=0.524, 95% CI 0.340-0.806) and OS (HR=0.577, 95% CI 0.373-0.893) for the entire cohort upon MVA. As for T1-2N2-3, high-dose subgroup had a trend of better DMFS (85.7% vs. 76.3%, p=0.069) and a significant improvement in OS (87.8% vs. 76.3%, p=0.041). Similarly, in the subgroup of T3-4N2-3, higher dose of cisplatin was associated with higher OS (80.3% vs. 52.3%, p=0.032). Cumulative dose of cisplatin was an independent prognostic factor for DMFS (HR=0.483, 95%CI 0.292-0.798) and OS (HR=0.429, 95%CI 0.258-0.715) for patients with T1-4N2-3 disease upon MVA. However, the benefit of higher dose of cisplatin was not observed in the subgroup of T3-4N0-1. For patients receiving CCRT (n=278), those treated with higher dose of cisplatin had a significantly higher DMFS (87.7% vs. 75.4%, p=0.004). The benefit mainly derived from T3-4N2-3 patients treated with CCRT (5y DMFS: 87.9% vs. 58.2%, p=0.034). Cumulative dose of cisplatin was associated with a lower risk of distant metastasis (HR=0.427, 95% CI 0.228-0.801) for patients treated with CCRT upon MVA. Conclusions: Our study identified that patients with N2-3 disease were those benefited from higher cumulative dose. The benefit of higher cumulative dose maintained in those treated with CCRT. The intensity of chemotherapy may be tailored based on various stage subgroups in locally advanced NPC.

// Chengrun Du 1 , Hongmei Ying 1 , Youwang Zhang 1 , Yafang Huang 2 , Ruiping Zhai 1 and Chaosu Hu 1 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 2 Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, P.R. China Correspondence to: Hongmei Ying, email: yinghongmei2011@sina.com Keywords: retropharyngeal nodes, undifferentiated squamous cell carcinoma, transoral sonography-guided fine-needle aspiration, primary unknown, radiotherapy Received: September 18, 2016 Accepted: February 21, 2017 Published: March 18, 2017 ABSTRACT Background and Objective: To evaluate treatment outcomes for patients with retropharyngeal metastatic undifferentiated squamous cell carcinoma (SCC) from an unknown primary site. Methods: From January 2005 to January 2015, patients who presented with enlarged retropharyngeal nodes underwent transoral sonography-guided fine-needle aspiration to confirm histology. Those with metastatic undifferentiated SCC with unknown primary tumors were treated with radical radiotherapy to nasopharyngeal mucosa plus bilateral neck. Chemotherapy was administered for patients staged N2-3. Endpoints included metastatic nodes control, the appearance of primary tumor, overall survival and treatment-related toxicities. Results: A total of 49 patients were recruited into this study. Retropharyngeal and cervical nodal disease was controlled in 96% of all patients. The incidence of occult primary cancer appearance was 8%. No primary cancer other than of the nasopharynx was detected during the course of follow-up. Ten patients developed distant metastases. The 5-year overall survival, progression-free survival, regional relapse free survival, distant metastasis free survival were 79.6%, 61.1%, 83.4%, 73.8%, respectively. Common late adverse effects included xerostomia (57%) and hearing impairment (35%). Conclusion: Radical radiotherapy to both the nasopharynx and bilateral neck can achieve excellent outcome with mild toxicities for patients with retropharyngeal metastatic undifferentiated squamous cell carcinoma from an unknown primary site.

Purpose To develop and validate a quantitative complication model of temporal lobe necrosis (TLN). To analyze the effect of clinical and dosimetric factors on TLN. Patients and methods In this study the prediction model was developed in a training cohort that consisted of 256 nasopharyngeal carcinoma (NPC) patients from January 2009 to December 2009. Dosimetric and clinical factors were extracted for model building. Dosimetric factors including the maximum dose, minimum dose, mean dose, dose covering specific volume and dose of percentage volume. Clinical factors include age, gender, T/N-stage, overall stage, diabetes and hypertension. LASSO (least absolute shrinkage and selection operator) regression model was used for feature selection, and prediction model building. A testing cohort containing 493 consecutive patients from January 2010 to December 2010 was used for model validation. The performance of the prediction model was assessed with respect to its calibration, discrimination. Results The prediction model, which consisted of two dosimetric features (D0.5cc and D10), is significantly associated with LN status (P

Supplement A. The detail of the model building. Supplement B. Data splitting bias evaluation, method and results. Supplement C. Univariate analysis for dosimetric factors and correlation analysis. Supplement D. Support material for the prediction power. (DOCX 1997 kb)

// Fangfang Kong 1,2 , Hongmei Ying 1,2 , Ruiping Zhai 1,2 , Chengrun Du 1,2 , Shuang Huang 1,2,3 , Junjun Zhou 1,2 , Xiayun He 1,2 , Chaosu Hu 1,2 , Zhuoying Wang 2,4 , Tuanqi Sun 2,4 and Qinghai Ji 2,4 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China 3 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, P. R. China 4 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China Correspondence to: Hongmei Ying, email: // Keywords : intensity-modulated radiotherapy; IMRT; radiotherapy; carcinoma showing thymus-like differentiation; CASTLE Received : March 15, 2016 Accepted : September 02, 2016 Published : September 08, 2016 Abstract Purpose: To evaluate the efficacy and toxicity of adjuvant intensity-modulated radiotherapy (IMRT) after surgery for carcinoma showing thymus-like differentiation (CASTLE). Methods: Between September 2008 and June 2015, 14 CASTLE patients were retrospectively enrolled. The clinical features, treatment procedure and clinical outcomes were reviewed. All patients received postoperative IMRT. The radiation doses ranged from 56Gy/28 fractions to 66Gy/33 fractions. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Results:After a median follow-up period of 42 months, only one patient suffered local recurrence and distant metastasis. The most frequently seen acute toxicities were mucositis and dermatitis (grade 1-2). No grade 3-4 toxicities were observed. Conclusions: Although based upon a small series of consecutively treated patients, our study showed that adjuvant IMRT provides satisfactory local-regional control for CASTLE, with acceptable toxicities. Further studies are still warranted to clarify our findings.

Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation.

Background To evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods One hundred and eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy. Results The median survival time was 33 months. The 3-year actuarial rates of local recurrence–free survival (LRFS), distant metastases–free survival (DMFS), and overall survival (OS) rates were 85.1, 91.1, and 46.0%, respectively. About 53% of the patients experienced Grade 3–4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS. Conclusion IMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Ronald Wihal Oei,1,2,* Lulu Ye,1,2,* Fangfang Kong,1,2 Chengrun Du,1,2 Ruiping Zhai,1,2 Tingting Xu,1,2 Chunying Shen,1,2 Xiaoshen Wang,1,2 Xiayun He,1,2 Lin Kong,1,2 Chaosu Hu,1,2 Hongmei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this article is to investigate the significance of pretreatment prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and their combination in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT).Materials and methods: A total of 585 patients were included. PNI and SII were calculated within 2 weeks prior to treatment. The optimal cutoff points were determined based on receiver operating characteristics curve analysis. The correlation between variables was analyzed. Kaplan–Meier method and Cox proportional hazards model were performed to evaluate the impact of both indices on overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Further propensity score matching (PSM) was carried out to minimize the effects of confounders. Results: The optimal cutoff point of 53.0 for PNI and 527.20 for SII were selected. Pearson correlation coefficient showed an inverse correlation between PNI and SII (r = –0.232, P < 0.001). Multivariate analysis demonstrated that pretreatment PNI was an independent prognostic factor for OS (P = 0.047) and DMFS (P = 0.002) while pretreatment SII was an independent prognostic factor for OS (P = 0.003), PFS (P = 0.002), and DMFS (P = 0.002). After PSM, both parameters remained as independent prognosticators of survival. Additional prognostic value was observed in the combined use of PNI and SII.Conclusion: Pretreatment PNI and SII are promising indicators of survival in NPC patients undergoing IMRT. They can be utilized to refine current TNM staging system in predicting prognosis and developing an individualized treatment in these patients. Keywords: prognostic nutritional index, systemic immune-inflammation index, nasopharyngeal carcinoma, intensity-modulated radiotherapy, prognostic factor, survival

Ronald Wihal Oei,1,2,* Lulu Ye,1,2,* Juan Huang,1,2 Fangfang Kong,1,2 Tingting Xu,1,2 Chunying Shen,1,2 Xiaoshen Wang,1,2 Xiayun He,1,2 Lin Kong,1,2 Chaosu Hu,1,2 Hongmei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China *These authors contributed equally tothis work Purpose: To investigate the prognostic value of nutritional markers for survival in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT), with or without chemotherapy. Patients and methods: This retrospective study included 412 NPC patients who received IMRT-based treatment. Weight loss (WL) during treatment, hemoglobin level (Hb) and serum albumin level (Alb) before treatment were measured. The prognostic values of these markers for overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were analyzed using Kaplan–Meier method and Cox proportional hazards regression analysis. Propensity score matching was performed to reduce the effect of confounders. Results: WL, Hb and Alb were significantly correlated with each other and inflammatory markers. Adjusted Cox regression analysis showed that critical weight loss (CWL) (WL≥5%) was an independent prognostic factor for OS (HR: 2.399, 95% CI: 1.267–4.540, P=0.007) and LRFS (HR: 2.041, 95% CI: 1.052–3.960, P=0.035), while low pretreatment Hb was independently associated with poor DMFS (HR: 2.031, 95% CI: 1.144–3.606, P=0.016). However, no significant correlation was found between Alb and survival in our study cohort. The prognostic value of these markers was further confirmed in the propensity-matched analysis. Conclusion: CWL, Hb and Alb have a significant impact on survival in NPC patients undergoing IMRT. They can be utilized in combination with conventional staging system to predict the prognosis of NPC patients treated with IMRT. Keywords: weight loss, hemoglobin, albumin, nasopharyngeal carcinoma, intensity-modulated radiotherapy, survival

Purpose Manual contouring of gross tumor volumes (GTV) is a crucial and time-consuming process in rectum cancer radiotherapy. This study aims to develop a simple deep learning-based autosegmentation algorithm to segment rectal tumors on T2-weighted MR images. Material and methods MRI scans (3T, T2-weighted) of 93 patients with locally advanced (cT3-4 and/or cN1-2) rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were enrolled in this study. A 2D U-net similar network was established as a training model. The model was trained in two phases to increase efficiency. These phases were tumor recognition and tumor segmentation. An opening (erosion and dilation) process was implemented to smooth contours after segmentation. Data were randomly separated into training (90%) and validation (10%) datasets for a 10-folder cross-validation. Additionally, 20 patients were double contoured for performance evaluation. Four indices were calculated to evaluate the similarity of automated and manual segmentation, including Hausdorff distance (HD), average surface distance (ASD), Dice index (DSC), and Jaccard index (JSC). Results The DSC, JSC, HD, and ASD (mean ± SD) were 0.74 ± 0.14, 0.60 ± 0.16, 20.44 ± 13.35, and 3.25 ± 1.69 mm for validation dataset; and these indices were 0.71 ± 0.13, 0.57 ± 0.15, 14.91 ± 7.62, and 2.67 ± 1.46 mm between two human radiation oncologists, respectively. No significant difference has been observed between automated segmentation and manual segmentation considering DSC (P = 0.42), JSC (P = 0.35), HD (P = 0.079), and ASD (P = 0.16). However, significant difference was found for HD (P = 0.0027) without opening process. Conclusion This study showed that a simple deep learning neural network can perform segmentation for rectum cancer based on MRI T2 images with results comparable to a human.

// Kai Qian 1, 2, * , Kai Guo 1, 2, * , Lu Di 2, 3 , Tuanqi Sun 1, 2 , Xiaoke Zheng 1, 2 , Yi Wu 1, 2 , Qinghai Ji 1, 2 , Hongmei Ying 2, 3 and Zhuoying Wang 1, 2 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China 3 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China * These authors contributed equally to this work Correspondence to: Zhuoying Wang, email: zhuoyingwang@hotmail.com Keywords: papillary thyroid carcinoma; radiation exposure; radiotherapy; clinic pathological characteristics; second primary tumor Received: March 29, 2017 Accepted: December 27, 2017 Published: January 02, 2018 ABSTRACT Purpose: To explore clinical characteristics of radiation-related thyroid cancer after radiation exposure in adulthood. Results: The postradiotherapy group had significantly higher rates of multifocality (41.0% vs 20.9%, Pa = 0.014; 41.0% vs 16.7%, Pb = 0.044) than control group I, II and gross extrathyroidal extensions (25.6% vs 5.5%, Pa = 0.000; 25.6% vs 8.3%, Pb = 0.082) than the control group I. The rates of cervical lymph node metastasis did not differ between these groups (48.7% vs 35.5%, Pa = 0.144; 48.7% vs 33.3%, Pb = 0.231). Logistic analysis showed gross extrathyroidal extension was associated with the interval time and the tumor size, and lymph node metastasis was associated with the tumor size. Conclusions: History of exposure to radiotherapy of thyroid area in adulthood might be associated with more advanced features for PTC. Therefore, such patients require more positive treatment and closer follow-up to reduce the disease relapse. Methods: Between 2008 and 2016, thirty-nine PTCs diagnosed after radiotherapy more than 3 years were defined into the postradiotherapy group; 110 lesions of PTCs found by examination during the period of radiotherapy were defined into the control group I and 24 PTCs diagnosed after radiotherapy which could not cover thyroid area were defined as the control group II. Clinical and morphological characteristics were compared between groups. Logistic analyses were used to evaluate the risk factors of gross extrathyroidal extension and lymph node metastasis. Disease-free survival (DFS) was calculated from the date of surgery to the event and was plotted using Kaplan-Meier method.

This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m(2) and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.

The aim of the study was to evaluate the survival and toxicity of 364 patients with nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Cisplatin-based chemotherapy was given to patients with local-regionally advanced disease. The median follow-up was 26 months (range 3-62 months). The 2-year local failure-free survival, regional failure-free survival (RFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 97.6, 96.8, 89.1 and 93.5 %, respectively. Overall disease failures (at any site) were found in 60 patients. Eighteen patients experienced locoregional failures: seven were local only, seven were regional only and four were both local and regional. Forty-two patients developed distant metastases. Of these, 30 patients had single organ metastasis and 12 had multiple organ metastases. The most common acute toxicities were dermatitis, mucositis and xerostomia. Grade 0-2 dermatitis, mucositis and xerostomia occurred in 337 patients (92.6 %), 204 patients (56.1 %) and 364 patients (100 %), respectively. Grade 3 dermatitis, mucositis and xerostomia were seen in 27 patients (7.4 %), 160 patients (44 %) and 0 patients. No Grade 4 acute toxicities were observed. N stage was an independent prognostic factor for RFFS, DMFS and OS. Our preliminary results showed that IMRT provides excellent local-regional control for NPC, with acceptable acute toxicities. Distant metastasis remains the most difficult treatment challenge. More effective systemic chemotherapy should be explored.

Summary Objective To determine whether concurrent chemoradiotherapy (CCRT) can improve survival rates compared to the neoadjuvant chemotherapy (NACT) regimen in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Materials and methods A total of 338 patients with biopsy-proven NPC were randomly assigned to receive NACT followed by radical radiotherapy (RT) then adjuvant chemotherapy (AC) or CCRT followed by AC. Results With a median follow-up of 60 months, the 5-year overall survival (OS) rate did not differ significantly between two groups (75.5% vs 79.4% in CCRT and NACT group respectively, P = 0.47, HR = 0.84, 95%CI 0.53–1.33). Metastasis-free survival (MFS) rate was significantly improved by the CCRT (79.0% vs 86.9%, P = 0.05, HR = 0.59, 95%CI 0.35–1.00). Subgroup analysis indicated that the benefit of CCRT was derived from N0/N1 tumors (78.0% vs 93.5%, P = 0.05, HR = 0.35, 95%CI 0.12–0.99). Higher rates of mucositis (52.4% vs. 35.9% P = 0.02) and vomiting (13.7% vs. 4.7% P = 0.00) were noted in the CCRT arm. Late toxicities were similar in two groups. Conclusions The updated results demonstrated no significant survival benefit of CCRT over NACT in patients with locoregionally advanced NPC. CCRT only showed significant MFS efficacy in T3-4N0-1 populations.