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Purpose: To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT)., Methods: Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation., Results: There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis., Conclusion: Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy., Objective: To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC., Design, Setting, and Participants: This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021., Exposures: Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF)., Main Outcomes and Measures: The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics., Results: Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65)., Conclusions and Relevance: The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC.

Background: Radiation-induced choanal stenosis (RICS) severely decreases life quality of patients with nasopharyngeal carcinoma (NPC) and originates from nasal mucositis, which depends on radiation dose. This self-controlled study aimed to find the correlations between dosimetric parameters and RICS., Methods: Totally 49 NPC patients treated with intensity-modulated radiotherapy from May 2010 to Aug. 2013 and diagnosed with RICS during follow-up were enrolled into this study. Minimum point dose, maximum point dose, mean dose (Dmean), dose covering ≥33% volume (D33), dose covering ≥66% volume (D66), and volume receiving ≥60 Gy (V60) were compared between the nasal cavities with and without RICS, through paired t-test. The parameters with difference would enter receiver operating characteristic analysis to determine their cutoff values. Then predicting abilities of the cutoff values were tested by Chi-square test., Result: The nasal cavities with RICS appeared to have higher Dmean, D33, D66 and V60, compared with those without RICS (P values were 0.014, 0.003, 0.006 and 0.010). Dmean ≥54.22 Gy, D33 ≥ 61.96 Gy, D66 ≥ 46.50 Gy and V60 ≥ 48.13% were demonstrated to be related with a higher risk of RICS., Conclusion: Dmean, D33, D66 and V60 of nasal cavity might be used as predictors of RICS. Their values needed to be controlled whenever possible, for ameliorating life quality of NPC patients.

Rationale: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice., Patient Concerns: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma., Diagnosis: They were diagnosed as refractory nasopharyngeal carcinoma., Interventions: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients., Outcomes: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein-Barr virus (EBV) DNA load., Lessons: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.

Concurrent chemotherapy (CCT) is used in locally advanced nasopharyngeal carcinoma (NPC) for improved local control, which could also be achieved by intensity-modulated radiotherapy (IMRT). And for N2-3 NPC, distant metastasis is the more important cause of death. This study aims to evaluate the value of CCT in N2-3 NPC when neoadjuvant chemotherapy (NACT) of sufficient cycles is performed to eradicate distant metastasis. It enrolled 959 patients diagnosed with TxN2-3M0 NPC from July 2011 to December 2015 and treated with NACT of 3-4 cycles and IMRT. A propensity score matching (PSM) was made between patients treated with and without CCT (called the CCT and non-CCT groups, respectively), using a series of clinical characteristics (age, gender, T stage, N stage, NACT regimen, and EBV DNA) as covariates. After PSM, the two groups of patients were compared on survivals and acute toxicities. The results indicated that no difference was seen in the overall, disease-free, recurrence-free or metastasis-free survivals between the two groups. But compared with the CCT group, the non-CCT group had a lower patient proportion of myelosuppression, nausea/vomiting, oral mucositis, cervical dermatitis, xerostomia, and grade 3/4 myelosuppression and oral mucositis (all P values were <0.001). Hence, CCT appeared to bring more acute toxicities, instead of survival benefit, to N2-3 NPC patients treated with NACT of ≥3 cycles and IMRT. It should be used with cautions in these patients., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the lymphocyte-monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease-specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C-index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1-2 vs. T3-4), N stage (N0-1 vs. N2-3) and pretreatment GPS (0 vs. 1-2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008, <0.001, 0.004, 0.018, and 0.004, respectively). A nomogram was established by involving all the factors above. Its C-index for predicting the DSS of the validation set was 0.734 (standard error 0.056). Pretreatment GPS, NLR, and LMR were independent prognostic factors of NPC. The nomogram based on them could be used to predict the DSS of NPC patients., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: With the improved overall survival (OS) of nasopharyngeal carcinoma (NPC) patients, the importance of quality of life (QoL) is increasingly being recognized. For some radiosensitive NPC patients, whether low-dose radiotherapy can improve the QoL without affecting clinical efficacy is unknown. This study aimed to assess the survival rates and QoL of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative (HPD)., Methods: Forty-six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed. All patients were restaged according to the 7th edition of the American Joint Committee on Cancer staging system. The radiotherapy plan was designed on the basis of pretreatment computed tomography. The OS, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were estimated using the Kaplan-Meier method. QoL was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group., Results: The 5-year OS, LRFS, DMFS, and DFS rates were 74.3%, 72.6%, 82.1%, and 61.2%, respectively. The corresponding 10-year rates were 38.4%, 62.9%, 78.5%, and 49.8%, respectively, and the 20-year rates were 27.7%, 51.4%, 78.5%, and 40.7%, respectively. None of the patients developed severe radiation-related complications, such as radiation-induced temporal lobe necrosis, hearing loss, trismus, and dysphagia., Conclusion: Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD, and this sensitivity was characterized by long-term survival without significant late treatment morbidities.

Background: The purpose of this study was to investigate the relationship between pretreatment nutritional status and prognosis of nasopharyngeal carcinoma (NPC)., Methods: Pretreatment nutritional status was evaluated by ideal body weight percentile (IBW%) and serum albumin for 512 patients with NPC who underwent radical radiotherapy. Kaplan-Meier methods, log-rank test, and a Cox model were applied for survival analysis., Results: Before radiotherapy, IBW% <90% was related to poorer overall survival (OS) and distant metastasis-free survival (DMFS; p = .031 and p = .012, respectively); albumin ≤43.0 g/L was related to poorer OS and DMFS (p < .001 and p = .042, respectively); both IBW% and albumin were independent prognostic factors for OS; those patients with IBW% <90% and albumin ≤43.0 g/L simultaneously had the worst OS and DMFS., Conclusion: Decrease of pretreatment IBW% and albumin was related to poorer survival of NPC., (Copyright © 2013 Wiley Periodicals, Inc.)

Aims: To improve prediction efficiency by incorporating complete blood count (CBC) into the TNM system on 5 year disease-specific survival (DSS) for patients with nasopharyngeal carcinoma (NPC)., Materials and Methods: The CBC of 3237 patients undergoing radiotherapy was retrospectively evaluated. In total, 2820 patients treated with non-intensity-modulated radiotherapy (IMRT) were randomly divided into development (1895 patients) and validation cohorts (925 patients). The association of potential risk factors with 5 year DSS was tested by Cox proportional hazards analysis and a prognostic index was created by assigning weighted scores proportional to a regression coefficient to each factor. Each cohort was divided into low, intermediate and high prognostic index. The prognostic index was validated in the validation cohort and compared with the TNM system on prediction of 5 year DSS. Validation was repeated in another independent group of 417 patients treated with IMRT., Results: Eight independent prognostic factors were identified: gender, age, T or N stages, anaemia or thrombocytosis during radiotherapy, continuous reduction in haemoglobin, high neutrophil-lymphocyte ratio before radiotherapy. Each was assigned a number of points. The area under curve (AUC) of the prognostic index was larger than that of Union Internationale Contre le Cancer/American Joint Cancer Committee TNM system 2009 (0.697 versus 0.619, P < 0.001)., Conclusion: A CBC-based prognostic index was developed and had a higher prediction efficiency on 5 year DSS in NPC than the TNM system alone., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC., (Copyright © 2012 Wiley Periodicals, Inc.)

Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors. However, prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC). To clarify whether the level of serum enzymes is linked to the prognosis of NPC, we reviewed the pretreatment data of lactate dehydrogenase(LDH), alkaline phosphatase (ALP), and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center. Patients were grouped according to the upper limit of normal values of LDH, ALP, and GGT. The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes, and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes. Finally, a Cox proportional hazards model was used to identify the independent prognostic factors. We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival (P = 0.009 and 0.035, respectively), and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival (P = 0.037 and 0.039, respectively). In multivariate analysis, increased LDH level was identified as an independent prognostic factor for overall survival. Therefore, we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.

Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma., Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease (▵Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specific survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS)., Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with ▵Hb of >11.5 g/L than in those with ▵Hb of ≤11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS., Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine the specific serum peptide profile by comparing the serum differences between nasopharyngeal carcinoma patients (NPC) and normal control subjects, and to provide a diagnostic model of nasopharyngeal carcinoma., Methods: Pre-treatment serum samples of NPC and normal control subjects were collected and assayed by MALDI-TOF MS analysis. The peptides were extracted with magnetic beads coated with WCX. Mass spectrographic data were analyzed with ClinProt(TM) software. The specific serum peptide model of NPC was established by using genetic algorithms. The sensitivity and specificity of model were tested by blind testing., Results: The serum peptidome patterns of nasopharyngeal carcinoma was obtained. Differential expression of 99 peptide peaks was deteced, and the 808.99 Da, 834.61 Da, 3954.82 Da, 8141.88 Da peptide peaks showing statistically significant differences between the two groups, were used to establish the diagnostic model for nasopharyngeal cancer. The recognition rate and predictive power of the model were 90.0% and 84.3%, respectively. The sensitivity and specificity of the model were 80.0% and 64.0% determined by blind testing, respectively., Conclusions: Significant differences of serum peptide peaks are detected between NPC and normal control groups. The established specific serum peptide model may have certain application in the diagnosis of nasopharyngeal carcinoma, and provides the basis for discovering specific tumor markers of nasopharyngeal carcinoma.

Background and Objective: Anemia can not only reduce the quality of life of patients with cancer, but also affect their survival. This study was to investigate the prognostic value of hemoglobin (Hb) level in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy., Methods: Clinical data of 520 NPC patients received definitive radiotherapy between 2000 and 2002 at Sun Yat sen University Cancer Center were analyzed. Patients were stratified into normal Hb level and anemia groups according to their Hb levels before, during, and after radiation. Anemia was defined according to World Health Organization criteria as Hb level < 130 g/L in men and < 120 g/L in women. Hb continuous decrease group and non decrease group were defined according to Hb changes in the patients during radiotherapy. Loco regional recurrence free survival (LRFS) and overall survival (OS) rates were estimated using the Kaplan Meier method. Multivariate analysis was performed using the Cox model to analyze the prognostic factors., Results: Before radiation, the 5 year LRFS rates were 60.9% in anemia group and 63.9% in normal Hb level group (P = 0.337); the 5 year OS rates were 65.2% and 71.0%, respectively (P = 0.299). During radiation, the 5 year LRFS rates were 56.7% in anemia group and 67.9% in normal Hb level group (P = 0.013); the 5 year OS rates were 61.0% and 75.9%, respectively (P = 0.001). After radiation, the 5 year LRFS rates were 59.6% in anemia group and 64.9% in normal Hb level group (P = 0.169); the 5 year OS rates were 65.0% and 71.9%, respectively (P = 0.090). The 5 year LRFS and OS rates were significantly lower in Hb continuous decrease group than in Hb non decrease group (59.1% vs. 69.3%, P = 0.032; 66.2% vs. 76.4%, P=0.011). Multivariate analysis showed that the continuous decrease of Hb was an independent prognostic factor for OS., Conclusion: The change in Hb level during radiotherapy is an important prognostic factor affecting the OS of NPC patients.

Background and Objective: Given the limited information regarding the impact of BMI on treatment outcomes for nasopharyngeal carcinoma, we sought to examine the relationship between body mass index (BMI) and cancer control after radiotherapy., Methods: We compared clinic outcome information across BMI groups from 1,489 patients treated with radiotherapy between 1990 and 2003. Multivariate analysis was used to determine if BMI significantly predicted adverse recurrence., Results: In comparison with normal group, there were statistical difference in age, T staging, N staging, and clinical staging (P<0.0001). In survival analysis, in comparison with under-weight group, we could found the hazard ratio was less than one, in the risk of death, cancer recurrence and local recurrence. Meanwhile, the hazard ratio gradually declined when the body weight increased. In univariate survival analysis, under-weight patient had a significant decrease in overall survival,(P<0.0001). When Cox regression model was applied to multivariate analysis, we could found age, T staging, N staging, and BMI grades could be a significant independent prognosis factors(P<0.05)., Conclusion: Under-weight patients had a significant decrease in overall survival rate, distant metastasis failure-free survival, and local relapse-free survival. Pretherapy BMI grades could be a significant independent prognosis factors.