Search

Background: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population., Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing., Findings: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group., Interpretation: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma., Funding: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/μL v 335 cells/μL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.

Background: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy., Materials and Methods: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation., Results: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities., Conclusion: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy., Methods and Materials: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test., Results: The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D 1cc , and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002)., Conclusions: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma., Design: Open-label, non-inferiority, multicentre, randomised, phase 3 trial., Setting: Three Chinese hospitals between 20 November 2017 and 3 December 2018., Participants: Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement., Interventions: Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy., Main Outcome Measures: Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than -8%., Results: 568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3% v 95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of -0.2% ((one sided 97.5% confidence interval -3.6 to ∞), P non-inferiority <0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5% v 35.1%, P=0.01) and late dysphagia (24.0% v 34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference -5.6 (95% confidence interval -9.1 to -2.0), P=0.002), role functioning (-5.5 (-7.4 to -3.6), P<0.001), social functioning (-6.2 (-8.9 to -3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference)., Conclusion: Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma., Trial Registration: ClinicalTrials.gov NCT03346109., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Sun Yat-Sen University Clinical Research 5010 Program (2017019), the National Natural Science Foundation of China (81930072, 82172870, 82272740), the Key-Area Research and Development Program of Guangdong Province (2019B020230002) and the Overseas Expertise Introduction Project for Discipline Innovation (111 Project, B14035) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS)., Methods: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression., Results: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005)., Conclusion: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We previously demonstrated that real-time monitoring of plasma Epstein-Barr virus DNA (EBV DNA) during chemoradiation therapy defined 4 distinct phenotypic clusters of nasopharyngeal carcinoma. In particular, the treatment-resistant group, defined as detectable EBV DNA at the end of radiation therapy, had the worst prognosis and is thought to have minimal residual disease., Methods and Materials: This is the first phase 2 trial to use a targeted agent, apatinib (an inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase), in the treatment-resistant group. Eligible patients had plasma EBV DNA > 0 copies/mL at the end of radiation therapy (±1 week). Patients received apatinib (500 mg, once daily) until disease progression, unacceptable toxicity, or for a maximum of 2 years. The primary endpoint was disease-free survival (DFS)., Results: Twenty-five patients were enrolled and 23 patients who received apatinib were included in the analyses. Three-year DFS was 47.8% and overall survival was 73.9%. Patients with plasma vascular endothelial growth factor-A ≤150 pg/mL at 28 days after the initiation of treatment had significantly better 3-year DFS (66.7% vs 14.3%; P = .041) and overall survival (88.9% vs 42.9%; P = .033). The most common adverse event of grade ≥3 was nasopharyngeal necrosis (26%), oral/pharyngeal pain (22%), and hand-foot syndrome (22%). Nineteen patients had serial EBV DNA data. Fourteen patients had plasma EBV DNA clearance (turn to 0), and 5 (36%) of these 14 patients had disease recurrence or death, whereas all 5 patients without EBV DNA clearance had disease recurrence or death (3-year DFS: 64.3% vs 0%; P = .001)., Conclusions: The use of antiangiogenic agents shortly after radiation therapy might increase the risk of necrosis. This approach needs to be avoided until translational and preclinical studies reveal the underlying mechanism of interaction between radiation therapy and antiangiogenic agents., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

Objectives: We aimed to develop and validate radiologic scores from [ 18 F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC)., Methods: A total of 542 T3N1M0 patients who underwent pretreatment [ 18 F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation., Results: The sensitivity of [ 18 F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p < 0.001) for diagnosing histologically proven metastatic cervical lymph nodes. Radiologic lymph node characteristics were independent risk factors for FFS (all p < 0.05). High-risk patients (n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort., Conclusions: T3N1M0 patients were accurately staged by both [ 18 F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC., Key Points: • [ 18 F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [ 18 F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy., (© 2022. The Author(s).)

Background: The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma., Methods: This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18-65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0-N1 disease (according to International Union Against Cancer-American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66-70 Gy (for the involved cervical lymph nodes), 60-62 Gy (for the high-risk target volume), and 54-56 Gy (for the low-risk target volume) were administered in 30-33 fractions, five fractions per week. Patients with stage II-IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed., Findings: Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46-59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7-99·7] in the UNI group vs 96·3% [93·8-98·8] in the WNI group; difference -1·4% [95% CI -4·6 to 1·8]; p non-inferiority <0·0001). Although acute radiation-related toxic effects were similar between the groups, the incidence of late toxicity was lower in the UNI group than in the WNI group, including any-grade hypothyroidism (66 [30%] of 222 patients vs 87 [39%] of 221), skin toxicity (32 [14%] vs 55 [25%]), dysphagia (38 [17%] vs 71 [32%]), and neck tissue damage (50 [23%] vs 88 [40%]). No patients died during treatment. After treatment, one patient in the WNI group died from a non-cancer-related cause (dermatomyositis)., Interpretation: Elective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0-N1 nasopharyngeal carcinoma., Funding: Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: We aimed to develop and prospectively validate a risk score model to guide individualized concurrent chemoradiotherapy (CCRT) for patients with stage II nasopharyngeal carcinoma (NPC) in intensity-modulated radiotherapy (IMRT) era., Materials and Methods: In total, 1220 patients who received CCRT or IMRT alone were enrolled in this study, including a training cohort (n = 719), a validation cohort (n = 307), and a prospective test cohort (n = 194). Patients were stratified into different risk groups by a risk score model based on independent prognostic factors, which were developed in the training cohort. Survival rates were compared by the log-rank test. The validation and prospective test cohorts were used for validation., Results: Total tumor volume, Epstein-Barr virus DNA, and lactate dehydrogenase were independent risk factors for failure-free survival (FFS, all p < 0.05). A risk score model based on these three risk factors was developed to classify patients into low-risk group (no risk factor, n = 337) and high-risk group (one or more factors, n = 382) in the training cohort. In the high-risk group, CCRT had better survival rates than IMRT alone (5-year FFS: 82.6% vs. 74.0%, p = 0.028). However, there was no survival difference between CCRT and IMRT alone either in the whole training cohort (p = 0.15) or in the low-risk group (p = 0.15). The results were verified in the validation and prospective test cohorts., Conclusion: A risk score model was developed and prospectively validated to precisely select high-risk stage II NPC patients who can benefit from CCRT, and thus guided individualized treatment in IMRT era., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions., Methods: The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients., Results: PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78)., Conclusion: PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment., (© 2021. The Author(s).)

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options., Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m 2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111., Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group., Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma., Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC., Methods: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided., Results: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed., Conclusions: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m 2 d1), cisplatin (60 mg/m 2 d1), and fluorouracil (600 mg/m 2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m 2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients., (© 2019 UICC.)

Background: Cisplatin-based concurrent chemoradiotherapy is currently considered to be the standard treatment regimen for patients with advanced nasopharyngeal carcinoma, but has well known side-effects such as gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin was developed to decrease the toxic effects induced by cisplatin, and in this trial we assessed whether a nedaplatin-based concurrent chemoradiotherapy regimen was non-inferior to a cisplatin-based regimen in patients with locoregional, stage II-IVB nasopharyngeal carcinoma., Methods: We did an open-label, non-inferiority, phase 3, randomised, controlled trial at two centres in China. Patients aged 18-65 years with non-keratinising stage II-IVB (T1-4N1-3 or T3-4N0) nasopharyngeal carcinoma, a Karnofsky score of at least 70, and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either nedaplatin 100 mg/m 2 or cisplatin 100 mg/m 2 on days 1, 22, and 43 for three cycles concurrently with intensity-modulated radiotherapy. Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre and clinical stage. Patients and clinicians were not masked to treatment allocation. The primary endpoint was progression-free survival at 2 years; non-inferiority was shown if the upper limit of the 95% CI for the difference in 2-year progression-free survival between the two groups did not exceed 10%. Analyses were by both intention to treat and per protocol, including all patients who received at least one complete cycle of chemotherapy. This trial is registered with ClinicalTrials.gov, number NCT01540136, and is currently in follow-up., Findings: Between Jan 16, 2012, and July 16, 2014, we randomly assigned 402 patients to nedaplatin-based (n=201) or cisplatin-based (n=201) concurrent chemoradiotherapy. In the intention-to-treat population, 2-year progression-free survival was 89·9% (95% CI 85·8-94·0) in the cisplatin group and 88·0% (83·5-94·5) in the nedaplatin group, with a difference of 1·9% (95% CI -4·2 to 8·0; p non-inferiority =0·0048). In the per-protocol analysis (cisplatin group, n=197; nedaplatin group, n=196), 2-year progression-free survival was 89·7% (95% CI 85·4-94·0) in the cisplatin group and 88·7% (84·2-94·5) in the nedaplatin group, with a difference of 1·0% (95% CI -5·2 to 7·0; p non-inferiority =0·0020). A significantly higher frequency of grade 3 or 4 vomiting (35 [18%] of 198 in the cisplatin group vs 12 [6%] of 200 in the nedaplatin group, p<0·0001), nausea (18 [9%] vs four [2%], p=0·0021), and anorexia (53 [27%] vs 26 [13%], p=0·00070) was observed in the cisplatin group compared with the nedaplatin group. 11 (6%) patients in the nedaplatin group had grade 3 or 4 thrombocytopenia compared with four (2%) in the cisplatin group (p=0·065). Patients in the cisplatin group had a higher frequency of any grade or grade 3 or 4 late auditory or hearing toxicities than did patients in the nedaplatin group (grade 3 or 4: three [2%] in the nedaplatin group vs 11 [6%] in the cisplatin group, p=0·030). No patients died from treatment-related causes., Interpretation: Our findings show that nedaplatin-based concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy for patients with locoregional, advanced nasopharyngeal carcinoma. Further investigations are needed to explore the potential use of this treatment as induction or adjuvant chemotherapy or in combination with other agents., Funding: National Key R&D Program of China, National Natural Science Foundation of China, Sun Yat-sen University Clinical Research 5010 Program, Sci-Tech Project Foundation of Guangzhou City, National Key Basic Research Program of China, Special Support Plan of Guangdong Province, Sci-Tech Project Foundation of Guangdong Province, Health & Medical Collaborative Innovation Project of Guangzhou City, National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, PhD Start-up Fund of Natural Science Foundation of Guangdong Province, Cultivation Foundation for the Junior Teachers in Sun Yat-sen University, and Fundamental Research Funds for the Central Universities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi., Materials and Methods: We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared., Results: Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential (P=0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable (P=0.322)., Conclusions: The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities., (Copyright © 2017. Published by Elsevier Ltd.)

Aim of the Study: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC)., Methods: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m 2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m 2 and fluorouracil 800 mg/m 2 /d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival., Results: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14)., Conclusion: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities., Registration Number: NCT00677118., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: We have attempted to validate two published nomograms in nasopharyngeal carcinoma (NPC) and individualize induction chemotherapy (IC) accordingly., Materials and Methods: From 2007 to 2011, 920 patients were included in the study. The validity of the nomograms was assessed by Harrell's concordance index (C-index), areas under the curve (AUC), and calibration curves. Disease-free survival (DFS) and overall survival (OS) by IC were evaluated in and out of risk stratified patients with and without propensity score matching analysis., Results: Compared with the 7th edition of the Union for International Cancer Control (UICC) staging system, Tang's nomogram better discriminated DFS (C-index 0.629 versus 0.569, P=0.002; AUC 0.635 versus 0.576, P=0.018), whereas Yang's nomogram had no advantage in predicting OS (C-index 0.648 versus 0.606, P=0.184; AUC 0.643 versus 0.604, P=0.157). Calibration curves indicated good agreement between predicted and observed DFS or OS probability. Without risk stratification, patients achieved no benefit from IC in DFS (P⩾0.101) or OS (P⩾0.370). However, among 580 high-risk patients stratified by Tang's nomogram, IC improved five-year DFS from 68.8 to 74.8% (P=0.072), and OS from 82.6 to 87.9% (P=0.065), and the improvement of DFS and OS increased to 9.3% (P=0.019) and 7.3% (P=0.036), respectively, in 426 propensity-matched patients., Conclusions: Tang's nomogram helps to stratify stage III-IVa-b NPC, and IC is beneficial to high-risk patients in clinical practice., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial., Methods: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m 2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m 2 on day 1), intravenous cisplatin (60 mg/m 2 on day 1), and continuous intravenous fluorouracil (600 mg/m 2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959., Findings: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%])., Interpretation: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities., Funding: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC., Patients and Methods: A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis., Results: In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb., Conclusions: In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic trials.

This study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) for stage II nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT). A total of 249 patients were retrospectively reviewed. All patients were treated with IMRT. One hundred forty-three patients treated with CCRT and 106 patients treated with IMRT alone. With a median follow-up of 59.4 months, adding concurrent chemotherapy did not statistically significantly improve the 5-year overall survival (OS) (89.7 % vs 99.0 %, p = 0.278), locoregional relapse-free survival (LRFS) (94.8 % vs 89.3 %, p = 0.167), and distant metastases-free survival (DMFS) (93.4 % vs 97.5 %, p = 0.349). The patients with CCRT significantly experienced more acute toxic effects. The main grades 3-4 toxicity reactions were mucositis (26.6 % vs 15.1 %, p = 0.03) and leukopenia/neutropenia (9.1 % vs 0.9 %, p = 0.005). In subgroup analysis of patients with concurrent platinum single-agent chemotherapy the 5-year OS (98.4 % vs 81.9 %, p = 0.013) and DMFS (96.9 % vs 84.4 %, p = 0.043) of patients with platinum every 3 weeks (Q3W) were significantly higher than those with platinum weekly (QW) and no significant difference for LRFS (96.8 % vs 90.4 %, p = 0.150). CCRT did not improve the survival of patients with stage II NPC but increased the acute toxicity reactions. Patients with platinum Q3W improved the 5-year OS and DMFS, compared with those with platinum QW.

Due to the low incidence of pretreatment anemia in nasopharyngeal carcinoma (NPC), the true prognostic impact of pretreatment anemia may be underestimated before. We retrospectively analyzed the association of pretreatment anemia with disease-specific survival (DSS), distant-metastasis-free survival (DMFS), and locoregional-relapse-free survival (LRFS) by Cox regression in a cohort of 5830 patients, stratifying by midtreatment anemia, smoking, body mass index (BMI), etc. Pretreatment anemia was significantly associated with adverse DSS (hazard ratio (HR) = 2.15, 95 % confidence interval (CI) 1.62-2.85, P < 0.001) and DMFS (HR = 1.53, 95 % CI 1.08-2.17, P = 0.018), comparing to patients with normal hemoglobin, after adjusting for covariates. Moreover, the association with DSS remained unchanged regardless of smoking status and clinical stage, whereas it was limited in the subgroups of above 45 years, male sex, and BMI <25 kg/m(2). With restriction to midtreatment anemic patients, pretreatment anemia was still strongly correlated with inferior DSS and DMFS. This study, in the largest reported cohort, is the first to show the adverse prognostic impact of pretreatment anemia on DSS and DMFS in NPC.

The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (22.9-27.5 kg/m2), and obesity (≥27.5 kg/m2). Propensity score matching method was used to identify patients with balanced characteristics and treatment regimen. Disease-specific survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival were estimated by Kaplan-Meier method and Cox regression.Following propensity matching, 115 (underweight vs normal), 399 (overweight vs normal), and 93 (obese vs normal) pairs of patients were selected, respectively. In univariate analysis, underweight patients had inferior DSS/OS (P = 0.042) and DMFS (P = 0.025) while both overweight and obese patients showed similar survival across all the endpoints (P ≥ 0.098) to those with normal weight. In multivariate analysis, underweight remained predictive of poor DSS/OS (P = 0.044) and DMFS (P = 0.040), whereas overweight (P ≥ 0.124) or obesity (P ≥ 0.179) was not associated with any type of survival.Underweight increased the risk of death and distant metastasis, whereas overweight or obese did not affect the survival of nasopharyngeal carcinoma. This provides support for early nutritional intervention during the long waiting time before treatment.

Background: Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage., Methods: We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression., Results: Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage., Conclusions: In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.

Objectives: The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study., Materials and Methods: Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis., Results: After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis., Conclusions: In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to evaluate initial hyperleukocytosis and neutrophilia as prognostic indicators in patients with nasopharyngeal carcinoma., Methods: A retrospective analysis of 5,854 patients identified from a cohort of 6,035 patients diagnosed with nasopharyngeal carcinoma was performed with initial hyperleukocytosis and neutrophilia analyzed as prognostic factors. Multivariate Cox proportional hazards analyses were applied., Results: Hyperleukocytosis was observed in 508 patients (8.7%). Multivariate analysis showed that initial hyperleukocytosis was an independent predictor of death (HR 1.40, 95%CI 1.15-1.70, p = 0.001), progression (HR 1.25, 95%CI 1.06-1.47, p = 0.007) and, marginally, distant metastasis (HR 1.21, 95%CI 0.97-1.52, p = 0.088). Neutrophilia was also an independent predictor of death (HR 1.46, 95%CI 1.18-1.81, p = 0.001), progression (HR 1.31, 95%CI 1.10-1.56, p = 0.003), and distant metastasis (HR 1.29, 95%CI 1.02-1.65, p = 0.036), after adjusting for prognostic factors and excluding hyperleukocytosis., Conclusion: Initial hyperleukocytosis and neutrophilia were independent, poor prognostic factors and may be convenient and useful biological markers for survival of patients with nasopharyngeal carcinoma.

Background: Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in advanced nasopharyngeal carcinoma (ANPC)., Methods: We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common Toxicity Criteria version 4.0: no leucopenia (grade 0), mild leucopenia (grade 1-2), and severe leucopenia (grade 3-4). Associations between leucopenia and survival were estimated by Cox proportional hazards model., Results: Of the 3826 patients, 2511 (65.6 %) developed mild leucopenia (grade 1-2) and 807 (21.1 %) developed severe leucopenia (grade 3-4) during treatment; 508 (13.3 %) did not. A multivariate Cox model that included leucopenia determined that the hazard ratios (HR) of death for patients with mild and severe leucopenia were 0.69 [95 % confidence interval (95 %CI) 0.56-0.85, p < 0.001] and 0.75 (95 %CI 0.59-0.95, p = 0.019), respectively; the HR of distant metastasis for patients with mild and severe leucopenia were 0.77 (95 %CI 0.61-0.96, p = 0.023) and 0.99 (95 %CI 0.77-1.29, p = 0.995), respectively. Leucopenia had no effect on locoregional relapse., Conclusions: Our results indicate that mild leucopenia during chemoradiotherapy is associated with improved overall survival and distant metastasis-free survival in ANPC. Mild leucopenia may indicate appropriate dosage of chemotherapy. We can identify the patients who may benefit from chemotherapy if they experienced leucopenia during the treatment. Prospective trials are required to assess whether dosing adjustments based on leucopenia may improve chemotherapy efficacy.

Background: The incidence of diabetes is increasing. But the impact of diabetes and prediabetes on survival of patients with nasopharyngeal carcinoma (NPC) has received little evaluation., Methods: In a cohort of 5,860 patients, we compared the disease specific survival (DSS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) of patients with diabetes, prediabetes and normoglycemia defined by pretreatment fasting plasma glucose (FPG) using Kaplan-Meier method, log-rank test and Cox proportional hazards model., Results: Comparing to normoglycemic patients, the diabetic and the prediabetic were generally older, fatter, had hypertension, heart diseases and hyperlipaemia and usually received radiotherapy alone. But both the diabetic and the prediabetic had similar DSS, LRFS and DMFS to normoglycemic patients, even adjusting for such important factors as age, gender, smoking, drinking, hypertension, heart diseases, body mass index, hyperlipaemia, titer of VCA-IgA and EA-IgA, pathology, T-stage, N-stage, chemotherapy and radiotherapy (P>0.05 for all). Additionally, the findings remained unchanged in sensitivity analysis by excluding patients with known diabetes history and in subgroups of the various factors., Conclusions: The diabetic and prediabetic NPC patients had similar survival to normoglycemic NPC patients. These data, in the largest reported cohort, are the first to evaluate the association between diabetes, prediabetes and the survival in NPC. The findings are relevant to patient management and provided evidence of the effect on this disease exerted by comorbidities.

Background: Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC., Methodology/principal Findings: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups., Conclusions/significance: IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.

Background: Cigarette smoking is associated with the etiology of nasopharyngeal carcinoma; however, the influence of smoking on survival in patients with established nasopharyngeal carcinoma remains unknown., Methods: We retrospectively analyzed 1,849 patients with nasopharyngeal carcinoma who were categorized as never, former, and current smokers. Cumulative effect of smoking was defined in terms of pack-years. Associations between cigarette exposure and survival were estimated by Cox proportional hazards model., Results: The risks of death, progression, locoregional relapse, and distant metastasis were significantly higher for former and current smokers (all P ≤ 0.002) than never smokers. Heavy smokers with high pack-years had HRs for death of 3.31 [95% confidence interval (CI), 2.58-4.26; P < 0.001], for progression of 2.53 (95% CI, 2.03-3.16; P < 0.001), and for distant metastasis of 2.65 (95% CI, 1.89-3.70; P < 0.001). Specifically, in the cohort of 495 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, we obtained similarly significant results. All of the survival outcomes remained significant in multivariate analyses., Conclusions: Pretreatment cigarette smoking is an independent, poor prognostic factor for patients with nasopharyngeal carcinoma, which is associated with increased risk of death, progression, locoregional relapse, and distant metastasis, with the risk increasing with pack-years., Impact: It is clear that cigarette smoking not only promotes carcinogenesis in the normal nasopharyngeal epithelium, but also affects the survival of patients with nasopharyngeal carcinoma., (©2013 AACR.)

Purpose: To evaluate the 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC) in patients treated with intensity-modulated radiotherapy., Methods and Materials: We performed a retrospective data review from 512 patients with biopsy-proven, nonmetastatic NPC in our cancer center (South China) between January 2003 and December 2006., Results: The local relapse-free survival rates (LRFS) and disease failure-free survival rates (DFS) in the 6th edition system T1 and T2a stages were not significantly different (P=0.629 and P=0.820), while the LRFS and DFS of T1 and T2 using the 7th edition system were significantly different (P=0.019 and P=0.009). The LRFS and DFS between T2 and T3 in the 7th edition systems were lack of significance (P=0.874 and P=0.589). The total difference in distant metastasis-free survival rate and DFS between N0 and N3 was slightly larger using the 7th edition system than the 6th edition. The nodal dimension of a cervical lymph node was not a significant prognostic factor., Conclusions: We observed a better segregation of survival curves by using the 7th edition system. It seems reasonable to downstage T3 as T2 and reject nodal greatest dimension from the N-staging system in the future revised edition., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone., Methods: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118., Findings: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy)., Interpretation: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials., Funding: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) with lung metastasis alone has been reported as a relatively favorable prognostic group, and combined modality treatment might be indicated for selected cases. However, the prognostic factors determining survival of this group and the indication of combined therapy have not been thoroughly studied., Methods: We retrospectively reviewed 246 patients of NPC with lung metastasis(es) alone presented at diagnosis or as the first failure after primary treatment from 1993 to 2008 in an academic tertiary hospital. Univariate and multivariate survival analyses of post-metastasis survival (PMS) and overall survival (OS) were carried out to determine the prognostic factors., Results: The 3-year, 5-year, and 10-year of PMS and OS for the whole cohort were 34.3%, 17.0%, 8.6% and 67.8%, 45.4%, 18.5%, respectively. The median PMS (45.6 months vs. 23.7 months) and OS (73.7 months vs. 46.2 months) of patients treated with combined therapy was significantly longer than that of those treated with chemotherapy alone (P < 0.001). Age, disease-free interval (DFI) and treatment modality were evaluated as independent prognostic factors of OS, while only age and treatment modality retain their independent significance in PMS analysis. In stratified survival analysis, compared to chemotherapy alone, combined therapy could benefit the patients with DFI > 1 year, but not those with DFI ≤ 1 year., Conclusions: Age ≤ 45 years, DFI > 1 year, and the combined therapy were good prognostic factors for NPC patients with lung metastasis(es) alone. The combination of local therapy and the basic chemotherapy should be considered for these patients with DFI > 1 year.

S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell-like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.

Background and Objective: Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases. Lung metastasis is one of the most important causes of death for patients with NPC. Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival. This study was to find a more effective treatment modality and prognostic factors for the group., Methods: Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed. Survival rate was calculated by the Kaplan-Meier method. The difference of survival between the patients treated by different modalities was evaluated by the log-rank test. The Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were conducted., Results: The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy ± chemotherapy group, and 96.4% in operation ± chemotherapy group (P < 0.01). The most promising progression-free survival (PFS) and overall survival (OS) were obtained with operation ± chemotherapy and followed by radiotherapy ± chemotherapy. Both of them showed much better efficacy than chemotherapy (P < 0.001). The Cox multivariate analysis showed that recurrent distant metastases and/or relapse of NPC affected the survival (OR = 2.087, 95% CI = 1.277-3.410, P = 0.003). The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic factors., Conclusions: Operation ± chemotherapy and radiotherapy ± chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and OS. Chemotherapy is recommended for patients with higher T stage of NPC, size of metastatic tumor ≥ 3 cm, pulmonary hilar and/or mediastinal lymph node metastasis.

Background and Objective: It is controversial for the irradiation level and dose of the regional prevention for naspharyngeal cancer (NPC) with one or both cervical lymph node-negative neck. The study was to analyze the proophylactic irradiation of cervical lymph nodes for Stage -N0 NPC patients., Methods: From January 2002 and December 2004, 205 NPC patients with negative lymphadenopathy diagnosed by imaging, were retrospectively analyzed. Before treatment, each patient underwent CT or MRI. Facial-cervical portals and 6-8 MV photons were used in radiotherapy. Doses applied were 60-80 Gy to the nasopharynx and 46-64 Gy to the neck without lymphadenopathy. Consecutive radiotherapy was performed employing conventional fractionation of 2 Gy/fraction, once a day, for a total of five fractions per week. Chemotherapy was administered to 60 patients. Median follow-up was 44 months. The survival function was calculated according to the Kaplan-Meier method. A log-rank test was used to compare the differences in survival. The Cox proportional hazards model was used for multivariate analysis. A total of 205 patients with stage-N0 NPC were divided into an upper-neck irradiation group and an entire-neck group., Results: The 3-year overall survival rate (OS) was 92.9% and the 3-year disease-free survival rate (DFS) was 91.9%. A total of 88 patients received irradiation to the upper neck and 117 to the entire neck. The rate of regional failure for the upper-neck group and the entire-neck group were 2.27% and 0%, respectively (P>0.05). The rates of regional failure in patients with T1-, T2-, T3- and T4-stage disease were 0, 3.08%, 0, and 0, respectively (P>0.05). The rates of regional failure in the patients both without and with local failure were 1.03% and 0, respectively (P>0.05). The 1-and 3-year OS for the upper-neck group were 97.7% and 94.2%, and the 1- and 3-year OS for the entire-neck group were 97.4% and 91.9% (P=0.950). The 1- and 3-year DFS for the upper-neck group were 96.6% and 92.9%, and the 1- and 3-year DFS for the entire-neck group were 95.6% and 90.9% (P= 0.730). In multivariate analysis, sex (P=0.039) and T stage (P=0.004) were independent prognosis factors for patients with stage-N0 NPC., Conclusions: Prophylactic irradiation to the upper neck does not influence regional failure or long-term survival in the patients with stage-N0 NPC. Radiotherapy to the upper neck (levels II, III, VA) is recommended for the patients with stage-N0 NPC. Involvement of the parapharyngeal space, T stage, and the rates of local failure do not influence regional failure in these patients. Sex and T stage were independent prognosis factors of stage-N0 NPC patients.

Purpose: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma., Methods and Materials: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment., Results: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages., Conclusion: Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.

Background & Objective: Docetaxel and cisplatin (DDP) are effective drugs for head and neck tumors. Stage II-III clinical trial of TP regimen (docetaxel combined DDP) for head and neck tumors has completed. This study was to compare the efficacy and toxicity of TP regimen and PF regimen [DDP combined 5-fluorouracil (5-FU)] in treating nasopharyngeal carcinoma (NPC), to provide a new chemotherapeutic regimen for NPC., Methods: Twenty NPC patients treated in Cancer Center of Sun Yat-sen University between Oct. 1, 2005 and Mar. 1, 2006 were subjected to study group (TP group). Twenty patients were chosen randomly from the 45 NPC patients treated with PF regimen between May 1, 2004 and Sep. 30, 2005 as control group (PF group). Both groups received concurrent radiotherapy. The efficacy and adverse events of the 2 groups were compared., Results: The mean number of chemotherapy cycles was significantly higher in TP group than in PF group (3.85 cycles vs. 2.75 cycles, P<0.001). After induction chemotherapy, in TP group, 18 achieved partial remission (PR) and 2 had stable disease (SD) for nasopharyngeal lesions, 7 achieved complete remission (CR), 11 achieved PR and 2 had SD for regional lymph nodes; in PF group, 17 achieved PR and 3 had SD for nasopharyngeal lesions, 2 achieved CR, 15 achieved PR and 1 had SD for regional lymph nodes. After concurrent chemoradiotherapy, all in TP group and 18 in PF group achieved CR for nasopharyngeal lesions, and 19 in TP group and 15 in PF group achieved CR for regional lymph nodes. There was no significant difference in efficacy between the 2 groups (P>0.05). The occurrence rates of grade 3-4 neutropenia were significantly higher in TP group than in PF group (40.5% vs. 0% after induction chemotherapy, 40.5% vs. 10.2% after concurrent radiochemotherapy, P<0.05). The occurrence rates of anemia and thrombocytopenia were significantly lower in TP group than in PF group (P<0.05). The uses of antibiotics and parenteral nutritional support in the 2 groups were similar., Conclusion: The efficacy of TP regimen on NPC is similar to that of PF regimen, and the adverse events are tolerable, but the long-term outcomes and toxicities need to be further investigated.

Background & Objective: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are easily to produce human anti-murine antibody response at present clinical use. This may influence therapeutic effect. This study was to evaluate the short-term and long-term efficacy and toxicity of the humanized anti-EGFR monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC)., Methods: Patients with newly diagnosed stage III-IVb (UICC 1997) NPC, who had moderate or strong EGFR expression, were randomized into radiotherapy alone group or radiotherapy combined h-R3 group. Similar dosage and technique of radiotherapy was administered in both groups. The combination group received weekly intravenous infusion of 100 mg h-R3 during radiotherapy. The short-term efficacy was evaluated according to WHO criteria. The survival was analyzed by Kaplan-Meier method., Results: A total of 35 patients were enrolled, 17 in radiotherapy alone group and 18 in combination group. During treatment, only 1 patient withdrew from the combination group. The overall complete remission (CR) rates at the end of treatment, 5 and 17 weeks after treatment were significantly higher in combination group than in radiotherapy alone group (72.2% vs. 35.3%, 83.3% vs. 41.2%, and 83.3% vs. 47.1%, P<0.05). Median follow-up time was 31.9 months (range, 4.2-40.7 months). No significant differences in 3-year locoregional control, distant metastasis-free survival and overall survival rates between the 2 groups were found. Except for 1 patient suffered from grade 2 vomiting, no patient developed other adverse events in combination group. No significant differences in radiotherapy-related adverse events between the 2 groups were observed., Conclusions: h-R3 is a safe drug which may enhance the response of advanced NPC patients to radiotherapy. However, h-R3 seems not to significantly affect the long-term outcomes.

Background & Objective: Induction chemotherapy plus concurrent radiochemotherapy may prolong disease-free and overall survival of advanced nasopharyngeal carcinoma (NPC) patients. This study was to compare the long-term efficacy of induction chemotherapy plus concurrent radiochemotherapy and radiotherapy alone on advanced NPC., Methods: Clinical data of 535 advanced NPC patients, treated in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998, were analyzed. Of the 535 patients, 75 were treated with 3-5 cycles of induction and concomitant chemotherapy of PF regimen (cisplatin combined 5-fluorouracil) plus radiotherapy, 460 were treated with radiotherapy alone. The survival statuses of the 2 groups were compared. Prognostic factors were analyzed by Cox regression analysis. Cumulative survival rate was analyzed by Kaplan-Meier method., Results: The 5-year overall and disease-free survival rates were significantly higher in radiochemotherapy group than in radiotherapy group (78.15% vs. 55.27%, 71.55% vs. 48.99%, P<0.05). For the patients with stage III tumors, the median overall and disease-free survival term were significantly longer in radiochemotherapy group than in radiotherapy group (94.5 months vs. 85.1 months, 89.5 months vs. 82.9 months, P<0.05). For the patients with stage IVa tumors, the same results were obtained (82.4 months vs. 44.4 months, 69.6 months vs. 40.3 months, P<0.05). Cox regression analysis showed that clinical stage and chemotherapy were dependent prognostic factors of advanced NPC., Conclusion: Induction chemotherapy plus concurrent radiochemotherapy could prolong the survival of patients with advanced NPC.

Background & Objective: Nasopharynx is a commonly involved site of non-Hodgkin's lymphoma (NHL), but the differences of clinical characteristics, prognosis, and treatment strategy between B-cell and NK/T-cell nasopharyngeal NHL have seldom been reported. This study was to investigate the clinical manifestations and treatment outcomes of primary B-cell and NK/T-cell nasopharyngeal NHL at early stage, and evaluate the prognostic differences, so as to provide evidences for treatment optimization., Methods: Clinical data of 80 patients with previously untreated nasopharyngeal NHL at early stage, admitted from May 1987 to Nov. 2003, were reviewed. Of the 80 cases, 48 were B-cell original (B group), 32 were NK/T-cell original (T group). Of the 80 patients, 42 received chemoradiotherapy, 31 received chemotherapy alone, and 7 received radiotherapy alone. Most chemotherapy-treated patients received CHOP regimen (cyclophosphamide, vincristine, adriamycin, and prednisone) for 1-10 cycles (median 5 cycles). Radiotherapy was given with high energy photon beams combined with high energy electron beams in conventional fractionation, with the total dose of 30-70 Gy (median 52 Gy). Treatment patterns of the 2 groups were similar, but B group received more chemotherapy cycles than T group did., Results: The 5-year overall survival rate and 5-year progression-free survival rate were significantly higher in B group than in T group (69.5% vs. 35.5%, P=0.003; 53.3% vs. 28.9%, P=0.032). Cox multivariate regression analysis suggested that B-cell phenotype, no B symptoms, and local control were independent favorable predictors of overall survival, while B-cell phenotype and good treatment response were independent favorable predictors of progression-free survival. Univariate stratified analysis with Kaplan-Meier method showed that, for B group, the cumulative 5-year overall survival rate was 68.1% in the 19 patients received chemotherapy alone, 61.7% in the 25 patients received chemoradiotherapy, and 100% in the 4 patients received radiotherapy alone (P=0.311); for T group, the cumulative 5-year overall survival rate was 0% in the 12 patients received chemotherapy alone, 44.1% in the 17 patients received chemoradiotherapy, and 33.3% in the 3 patients received radiotherapy alone (only 1 patient survived for 60 months)(P=0.020)., Conclusions: Among the patients with primary nasopharyngeal NHL at early stage, those with B-cell phenotype may have better prognosis as compared with those with NK/T-cell phenotype. The patients with NK/T-cell phenotype often suffered from B symptoms, with poor response to chemotherapy. Radiotherapy or chemoradiotherapy should be more emphasized in this group of patients.

Background & Objective: The influence of age on treatment outcome and survival of nasopharyngeal carcinoma (NPC) patients has seldom been reported. This study was to explore the clinical characters of aged NPC patients., Methods: A total of 754 patients with histopathologically proven NPC from Jan. 1, 2000 to May 1, 2002 were divided to adult group (<60 years old, 647 patients) and aged group (> or =60 years old, 107 patients). The difference of disease characters, treatment patterns, and other complications between these two groups were analyzed. The influence of age on survival was analyzed with COX regression model., Results: There was no difference between the two groups in disease characters, radiation dose, and interval time. However, the proportion of the patients received chemotherapy was significantly larger in adult group than in aged group (254/647 vs. 29/107, P=0.016), while the occurrence of complications was more frequent in aged group than in adult group (40/107 vs. 19/647, P<0.001). The 3-year tumor-specific survival rate was significantly lower in aged group than in adult group (72.90% vs. 82.95%, P=0.010). COX multivariable analysis showed that age and '92 Fuzhou N stage were independent prognostic factors, and the odds ratio (OR) of age was 1.604 (95% CI: 0.929-2.768) (P=0.026)., Conclusions: Aged NPC patients have worse 3-year survival than adult patients, which may be related to the high risk of chemotherapy and less possibility to tolerate enough doses and cycles. But age itself is still a poor prognostic factor when excluding the influence of chemotherapy.

Background & Objective: On the basis of our previous research, this study was to validate the rationality of AJCC/UICC staging system (1997) of nasopharyngeal carcinoma (NPC), and to provide some suggestions., Methods: Survival data of 915 NPC patients, received radical radiotherapy alone in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998, were analyzed with Life table, Cox regression, Kaplan-Meier, and log-rank methods., Results: Cox regression analysis showed that the 5-year survival rate of the 915 patients was significantly correlated to their age and tumor stage classified according to AJCC/UICC (1997) staging system; while that of the 803 patients no more than 60 years old was only significantly correlated to tumor stage. Life table analysis validated that the tumor stage classified according to AJCC/UICC staging system can roughly predict the prognosis, but the differences between stage I and IIa, or IVa and IVb were not significant. Kaplan-Meier analysis showed no significant differences of survival rate between stage T1 and T2a, or T3 and T4 when adjusted by N classification, and between stage N2 and N3a, or N3a and N3b when adjusted by T classification. Therefore, we adjusted stage T2a to T1, stage N1 with inferior cervical nodes metastasis to N2, combined stage N3a and N3b to N3, adjusted stage IIa to I, stage IIb to II, and stage IVb to IVa. After the modifications, the differences among stages I-IVa, T1-T4 (adjusted by N classification) and N0-N3 (adjusted by T classification) were significant., Conclusion: Taking the impact of age on the prognosis and the interaction between T stage and N stage into consideration, the above modifications should be included when renewing the AJCC/UICC staging system (1997).

Objective: To analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone., Methods: 34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node., Results: The 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months., Conclusion: It may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.

Background & Objective: Along with the development of treatments, different tumor staging systems are coexisted and have been modified. This study was to validate the rationality of the Fuzhou staging system (1992) of nasopharyngeal carcinoma (NPC), and to provide some suggestions., Methods: A total of 915 NPC patients received radical radiotherapy alone in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998. The 1-, 3-, and 5-year follow-up rates were 98.7%, 95.2%, and 91.7%, respectively. The survival data were analyzed with Life table, Cox regression, Kaplan-Meier, and log-rank methods., Results: The 1-, 3-, and 5-year overall survival rates of the 915 patients were 87.69%, 72.73%, and 64.44%; the 1-, 3-, and 5-year disease-freely survival rates were 86.87%, 69.72%, and 58.33%, respectively. Cox regression analysis showed that the 5-year survival statuses of the 915 patients were significantly correlated with their age and the tumor stage classified by the Fuzhou staging system (1992); the 5-year survival statuses of the 803 patients no more than 60 years old were only significantly correlated with tumor stage, and had no correlation with their age. Life table analysis validated that the tumor stage classified by Fuzhou staging system (1992) can roughly predict the prognosis, but the difference between the 5-year survival rates of stage I and II patients was not significant. Kaplan-Meier analysis showed no significant difference between survival statuses of stage T1 and T2 patients when adjusted by N classification. Therefore, we adjusted stage T2 without parapharyngeal space invasion to stage T1, stage T3 with carotid vagina invasion to stage T2, stage T4 with paranasal sinus involvement to stage T3, stage T3 with cranial nerve injury to stage T4, and stage N1 with bilateral lymph nodes involvement to stage N2. After the modifications, the differences among stage I to IVa, stage T1 to T4 (adjusted by N stage), or stage N0 to N3 (adjusted by T stage) were significant., Conclusion: Taking the impact of age on the prognosis and the interaction between T stage and N stage into consideration, the above modifications of should be included when renewing the Fuzhou staging system (1992).