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Backgrounds Despite publication of international guidelines, there are notable controversial points of clinical target volume (CTV) delineation in nasopharyngeal carcinoma (NPC). Recently, scholars proposed a novel way of delineation of CTV in NPC—individualization of CTV delineation based on T classification and spread patterns, which yielded excellent long-term local control with limited late toxicities. The aim of this study was to clarify the anatomic patterns and pathways of local recurrence of NPC and provide a clinical reference for the delineation of CTV. Methods A total of 869 patients with non-metastatic NPC were treated with intensity-modulated radiation therapy (IMRT) at our institution between 2009 and 2010. Among the 57 cases of local/locoregional recurrence, 52 cases with traceable radiotherapy plans and magnetic resonance imaging at the time of the first diagnosis of recurrence were included. Anatomical structures and gross tumor volume of local recurrence were contoured. The incidence of relapse of each anatomic structure, route of local recurrence, and their correlation were analyzed. Results Locally advanced disease had a significantly increased risk of recurrence in the posterior nasal cavity and a trend towards higher risk of recurrence in the clivus, lateral pterygoid muscle, and hypoglossal canal. Based on the incidence of local recurrence, we constructed a high-risk map for the early and locally advanced stages. Local recurrences were classified into five routes, where anterior extension accounted for the majority (30.8%), and caudal tumor extension pathway had the lowest incidence (5.8%). There was a significant correlation between the local recurrences of neural foramina and neighboring anatomical structures along each pathway. All cases relapsed at unilateral cavernous sinus, most at the same side of primary tumor. Based on our findings, we proposed some suggestions on delineations of CTV, based on T classification and local extension pattern. Conclusions Local recurrence of NPC varied according to T classification, followed a stepwise pattern, spread via neural foramina, and recurred at ipsilateral cavernous sinus. This provides meaningful clinical evidence for delineation of CTV, especially individualized delineation.

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.

Nasopharyngeal carcinoma (NPC) arises from the epithelial cells located in the nasopharynx and has a distinct geographic distribution. Chronic Epstein-Barr virus (EBV) infection, as its most common causative agents, can be detected in 100% of NPC types. In-depth studies of the cellular and molecular events leading to immunosuppression in NPC have revealed new therapeutic targets and diverse combinations that promise to benefit patients with highly refractory, advanced and metastatic NPC. This paper reviews the mechanisms by which NPC cells to circumvent immune surveillance and approaches being attempted to restore immunity. We integrate existing insights into anti-NPC immunity and molecular signaling pathways as well as targeting therapies in anticipation of broader applicability and effectiveness in advanced metastatic NPC.

BackgroundSquamous cell cancers in the hypopharynx (HP) and cervical esophagus (CE) are different diseases with different staging systems and treatment approaches. Pharyngoesophageal junction (PEJ) tumor involves both the hypopharynx and the cervical esophagus simultaneously, but few reports focused on PEJ tumors. This study aimed to clarify clinical characteristics and the treatment approaches of PEJ tumors.Patients and MethodsA total of 222 patients with squamous cell carcinoma in the HP, PEJ, and CE were collected between January 2008 and June 2018 in Fudan University Shanghai Cancer Center. We compared different lymph node metastatic patterns of three diseases above and the survival of different tumor locations, different lymph node metastasis, and different radiotherapy approaches.ResultsFor HP, PEJ, and CE cancer, the upper and middle cervical lymph node metastatic rates were 85.7%, 47.1%, and 5.8%, respectively; the lower cervical lymph node metastatic rates were 36.7%, 42.9%, and 35.0%, respectively; and the mediastinal lymph node metastatic rates were 2.0%, 72.9%, and 80.6%, respectively. The 3-year overall survival rates were 69.5% in the HP group, 52.0% in the PEJ group, and 69.6% in the CE group (p = 0.024). No survival differences were found between the involved-field-irradiation and elective-node-irradiation subgroups among PEJ tumors (p = 0.717 for OS and p = 0.454 for PFS, respectively).ConclusionHP cancers had a high prevalence in all cervical lymph node metastases, while CE cancers had a lower prevalence in the cervical and mediastinal lymph node metastases. PEJ cancer had the combined metastatic patterns of both HP and CE cancers. Involved field irradiation was feasible in chemoradiotherapy for PEJ cancers.

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.

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.

ObjectiveTo analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).MethodsA total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).ResultsA total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cyclesConclusionPlatinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.

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

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.

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

// 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

// 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.

Aim To investigate the management for the indeterminate pulmonary nodules newly detected during the follow-up for nasopharyngeal carcinoma (NPC) patients. Methods Indeterminate pulmonary lesions were identified by searching medical records of NPC patients, who were followed-up with thoracic CT between April 2008 and February 2014. Indeterminate pulmonary nodules were defined as opacities that may be solitary or multiple, which were

The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiation therapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 54 patients (stage IIB: 6, stage III: 24, stage IVA-B: 24) with locoregionally advanced NPC were treated with cisplatin 25 mg/m(2) intravenously on days 1-3, and gemcitabine 1,000 mg/m(2) of 30-min intravenous infusion on days 1 and 8, every 3 weeks for two cycles as neoadjuvant chemotherapy. Two cycles of the same regimen were administered as adjuvant chemotherapy 28 days after the end of radiotherapy. The prescription doses were 66-70.4 Gy to the gross tumor volume (GTV), 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume and 54 Gy to the low-risk clinical target volume. The overall response rate to neoadjuvant chemotherapy was 88.6%. Toxicity was mainly grade 1/2 myelosuppression. All patients completed IMRT. The median follow-up duration was 30 months (range, 12-60 months). The 3-year locoregional control, metastasis-free rate and overall survival were 94.9%, 86.2% and 87.7%, respectively. Severe late toxicities included grade 3 trismus in one patient, grade 3 hearing impairment in one patient and cranial nerve XII palsy in one patient. No grade 4 late toxicities were observed. A combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced NPC is well-tolerated, convenient, effective and warrants further studies.

Purpose To summarize our experience and treatment results in lymph node–negative nasopharyngeal carcinoma treated in a single institution. Methods and Materials From January 2000 to December 2003, 410 patients with lymph node–negative nasopharyngeal carcinoma were retrospectively analyzed. The T-stage distribution was 18.8% in T1, 54.6% in T2 (T2a, 41 patients; T2b, 183 patients), 13.2% in T3, and 13.4% in T4. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas, including levels II, III, and VA. The dose was 64–74 Gy, 1. 8–2.0 Gy per fraction over 6.5–7.5 weeks to the primary tumor with 60Co or 6-MV X-rays, and 50–56 Gy to levels II, III, and VA. Residual disease was boosted with either 192Ir afterloading brachytherapy or small external beam fields. Results The median follow-up time was 54 months (range, 3–90 months). Four patients developed neck recurrence, and only 1 patient (0.2%) experienced relapse outside the irradiation fields. The 5-year overall survival rate was 84.2%. The 5-year relapse-free survival rate, distant metastasis-free survival rate, and disease-free survival rate were 88.6%, 90.6% and 80.1%, respectively. Both univariate and multivariate analyses demonstrated that T classification was the only significant prognostic factor for predicting overall survival. The observed serious late toxicities were radiation-induced brain damage (7 cases), cranial nerve palsy (16 cases), and severe trismus (13 cases; the distance between the incisors was ≤1 cm). Conclusion Elective levels II, III, and VA irradiation is suitable for nasopharyngeal carcinoma without neck lymph node metastasis.

Aims Nasopharyngeal carcinoma (NPC) is rare in young patients. The aim of this study was to provide an analysis of 42 patients under 20 years of age with locoregional disease treated in a single institution. Materials and methods Forty-two NPC patients aged ≤20 years (median age 16 years) represented only 2.3% of all NPC cases treated in our department between 2000 and 2003. Of these patients, 14 were stage II, 21 stage III, and seven stage IV, as diagnosed according to the 1997 American Joint Committee on Cancer (AJCC) staging system. Seventeen patients received radiotherapy alone and 25 had cisplatin-based chemotherapy additionally. The radiation dose to the primary tumour and involved nodes was 64–74Gy. Results After a median follow-up of 60 months, the 5-year locoregional control, overall survival and disease-free survival rates were 87, 79 and 73%, respectively. More than 50% of the relapses (6/11) were distant metastases. Patients with N0-1 had a lower distant metastasis rate compared with patients with N2-3, and the TNM stage grouping was found to be a marginally important prognostic factor for disease-free survival. The addition of chemotherapy failed to be of therapeutic value. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Conclusions The outcome of the present series was excellent, and matched well with other publications. A high systemic failure remains a major obstacle to cure young NPC patients. More efforts should be made to improve both survival and quality of life.

Purpose To explore patterns of node distribution in nasopharyngeal carcinoma (NPC) based on the 2013 updated guidelines for neck node levels. Methods and materials We retrospectively reviewed the imaging documents of 3100 cases of newly diagnosed NPC between January 2010 and January 2013. All patients received an MRI scan. The scan range extended from 2cm above the anterior clinoid process to the inferior margin of the sternal end of the clavicle. All MR images were evaluated by the multi-disciplinary treatment group of NPC. Results A total of 2679 (86.4%) cases had involved lymph nodes. The detailed distribution was: level Ia 0, level Ib 115 (4.3%), level IIa 1798 (67.1%), level IIb 2341 (87.4%), level III 1184 (44.2%), level IVa 350 (13.1%), level IVb 28 (1.0%), level Va,b 995 (37.1%), level Vc 49 (1.8%), level VI 0, level VIIa 2012 (75.1%), level VIIb 178 (6.6%), level VIII 53 (2.0%), level IX 2, level Xa 2, level Xb 3. Among patients with level VII involvement, only 6 (0.3%) were located at the medial group. Of the patients with level II disease, the upper borders of metastatic nodes in 25.9% cases were beyond the caudal edge of C1. Patients with level VIII, or IX, or X node metastasis were always with extensive ipsilateral lymphadenopathy, and the total number of involved nodes was ⩾6. There were 35 cases of lymphadenopathy beyond the range of the updated guidelines, located inside the trapezius muscles, but posterior to level V. Conclusions This is the first description of nodal spread patterns based on the updated consensus guidelines. Involvement of the retropharyngeal nodes was mainly located at the lateral group, the medial group was rarely seen. The suggested upper border of level II cannot fully cover all the involved level II nodes. The posterior level V border is not enough to cover all level V lymphadenopathies for NPC.

Objective To evaluate the effectiveness and toxicities in T4 nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT) combined with chemotherapy. Methods This is a retrospective analysis of 81 patients treated with intensity-modulated radiotherapy (IMRT). All the primary tumors were attributed to T4 stage according to the AJCC2010 staging system. And the distribution of disease by N stage was N0 in 13.6%, N1 in 30.9%, N2 in 37%, and N3 in 18.5%. Cisplatin-based chemotherapy was offered to all patients. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) scoring criteria. Chemotherapy-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Prognostic factors were assessed by univariate analysis. Results With a median follow-up of 37 months, 12 patients experienced local regional failure and total distant metastasis occurred in 18 patients, representing the major mode of failure. Ten patients died. Among them, 70% died of distant metastasis. The 3-year actuarial rates of local failure–free survival (LFFS), regional failure–free survival (RFFS), distant failure–free survival (DFFS), overall survival (OS), and progression–free survival (PFS) were 83.8%, 97.4%, 81.3%, 90%, and 69.7%, respectively. Acute and late toxicities were mild or moderate. Conclusions IMRT provides excellent local-regional control for T4 NPC. Distant metastasis remains the major cause of treatment failure. Further explorations of the sequence and regimen of systemic therapy are needed in the future.

To evaluate the role of double-phase (99m)Technetium labeled sestamibi ((99m)Tc-MIBI) single-photon emission computed tomography/compute tomography (SPECT/CT) in predicting the response to neoadjuvant chemotherapy with docetaxel-based regimen in patients with nasopharyngeal carcinoma. Thirty-nine pathologically proven nasopharyngeal carcinoma patients participated in this prospective study. Before treatment, early and delayed SPECT/CT images were obtained 5 min and 2 h after an intravenous injection of 25-30 mCi (99m)Tc-MIBI. All patients received neoadjuvant chemotherapy consisting of docetaxel, cisplatin plus 5-fluorouracil for two cycles. The relationships between the efficacy of neoadjuvant chemotherapy and early uptake ratio (EUR), delayed uptake ratio (DUR) and washout rate (WR) of (99m)Tc-MIBI were evaluated. The EUR of (99m)Tc-MIBI (2.8 ± 0.97) in the lesions which were sensitive to chemotherapy was significantly higher (p 0.001) compared with that (1.69 ± 0.46) in the insensitive lesions. The difference of the DUR between the sensitive (1.65 ± 0.58) and the insensitive (1.06 ± 0.62) was also statistically significant (p = 0.011). However, the WR of (99m)Tc-MIBI was not significantly different between the two groups. When a EUR of 1.97 and a DUR of 1.06 were used as the cutoff value, the sensitivity, specificity, positive and negative predictive values were 76.1, 87.5, 97.2 and 38.8 % for EUR, 91.3, 67.5, 90 and 66.6 % for DUR, respectively. These results suggest that the early and delayed uptake ratios of (99m)Tc-MIBI calculated with SPECT/CT may have predictive value for identifying the response to neoadjuvant chemotherapy with docetaxel-based regimen in NPC patients.

The aim of this study is to investigate the status and dose-volume relationship of hypothalamic-pituitary-thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma (NPC). The hormone levels of 98 patients treated with IMRT were retrospectively reviewed. Hormone values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone, adrenocorticotropic hormone, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were tested. The pituitary and thyroid glands were re-contoured to obtain dose-volume histograms. The relationship between the dose distributions and hormone values was analyzed, as well as combined chemotherapy, age, gender, stages and interval time. The median follow-up period was 17 months. Median values of mean radiation dose to the pituitary and thyroid were 51.2 and 49.72 Gy. Evidences of hormone disorder were found in 54.1% patients. About 33.7% patients experienced dysfunction of TSH, 20.4% of sexual axis and 11.2% of PRL. Twenty-nine patients presented central hypothyroidism, while 4 patients developed primary hypothyroidism. Dosimetric analysis showed that thyroid axis was significantly associated with Vt30-50 and Dmean of thyroid, V40 (p = 0.000) was the most significant parameters. In addition, TSH and FT4 were correlated with volume of pituitary receiving above 55 Gy (Vp55; p = 0.014, 0.035). Vp55 was most significantly influencing factor of PRL axis (p = 0.044) and gonad axis (p = 0.047). TSH dysfunction was more common with interval time longer than 10 months and age older than 45 years in both univariate and multivariate analysis. FSH and PRL were affected by both gender (p = 0.009, 0.001) and age (p = 0.004, 0.012). Hormone changes were not affected by either clinical stages or combined chemotherapy. At the era of IMRT, a high rate of endocrine deficiency was still seen. Hypothalamic-pituitary-thyroid dysfunction is more common in NPC patients. Regular monitoring is needed.

Background To analyze patterns of local-regional failure after primary intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods A total of 370 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a simultaneous integrated boost (SIB) technique at the total prescribed dose of 66-70.4Gy (2.0-2.2Gy per fraction). The location and extent of local-regional failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. The dose of radiation received by Vrecur (volume of recurrence) was calculated and analyzed with dose-volume histogram (DVH). Failures were classified as: "in field" if 95% of Vrecur was within the 95% isodose, "marginal" if 20% to 95% of Vrecur was within the 95% isodose, or "outside" if less than 20% of Vrecur was inside the 95% isodose. Results With a median follow up of 26 months, 25 local-regional failures were found in 18 patients. The 1- and 2-year actuarial local-regional control rates for all patients were 99.7% and 95.5% respectively. Among the 22 local–regional failures with available diagnostic images, 16 (64%) occurred within the 95% isodose lines and were considered in-field failures; 3 (12%) were marginal and 3 (12%) were outside-field failures. Conclusions Intensity-modulated radiotherapy provides excellent local-regional control for NPC. In-field failures are the main patterns for local-regional recurrence. Reducing the coverage of critical adjacent tissues in CTV purposefully for potential subclinical diseases was worth of study. Great attention in all IMRT steps is necessary to reduce potential causes of marginal failures. More studies about radioresistance are needed to reduce in-field failures.

We investigated the value of magnetic resonance sialography for evaluating xerostomia induced by intensity-modulated radiotherapy for nasopharyngeal carcinoma.Fourteen patients with nasopharyngeal carcinoma were treated with intensity-modulated radiotherapy. Salivary function was assessed by magnetic resonance sialography and subjective evaluation criteria pre-treatment, 1 week and 1 year post-radiotherapy. A magnetic resonance sialography categorical scoring system was used to compare the visibility of salivary ducts.The average mean dose was 38.93 Gy to the parotid glands and 59.34 Gy to the submandibular glands. Before radiotherapy, the visibility scores of both the parotid and submandibular ducts increased after secretion stimulation. The scores decreased and the response to stimulation was attenuated 1 week post-radiotherapy. For most of the parotid ducts, the visibility score improved at 1 year post-radiotherapy both at rest and under stimulation, but not for the submandibular ducts. With a median follow-up of 12.3 months, 8/12 patients had grade 1 xerostomia and 4/12 had grade 2 xerostomia.Magnetic resonance sialography allows non-invasive evaluation of radiation-induced ductal changes in the major salivary glands and enables reliable prediction of radiation-induced xerostomia.

Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m(2)/day on day 1), cisplatin (25 mg/m(2)/day on days 1-3), and 5-fluorouracil (500 mg/m(2)/day on days 1-3).The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6-43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment.Neoadjuvant-adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.

Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.