Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials.
Du Cheng-Run,Ying Hong-Mei,Kong Fang-Fang,Zhai Rui-Ping,Hu Chao-Su
Radiation oncology (London, England)
BACKGROUND:To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. METHODS:Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). RESULTS:Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). CONCLUSION:With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity.
10.1186/s13014-015-0377-9
Nasopharyngeal carcinoma.
Chen Yu-Pei,Chan Anthony T C,Le Quynh-Thu,Blanchard Pierre,Sun Ying,Ma Jun
Lancet (London, England)
Nasopharyngeal carcinoma is characterised by distinct geographical distribution and is particularly prevalent in east and southeast Asia. Epidemiological trends in the past decade have shown that its incidence has declined gradually but progressively, and mortality has been reduced substantially. These findings probably reflect lifestyle and environmental changes, enhanced understanding of the pathogenesis and risk factors, population screening, advancements in imaging techniques, and individualised comprehensive chemoradiotherapy strategies. In particular, plasma Epstein-Barr virus (EBV) DNA has been used for population screening, prognostication, predicting treatment response for therapeutic adaptation, and disease surveillance. Moreover, the widespread application of intensity-modulated radiotherapy and optimisation of chemotherapy strategies (induction, concurrent, adjuvant) have contributed to improved survival with reduced toxicities. Among the existing developments in novel therapeutics, immune checkpoint therapies have achieved breakthroughs for treating recurrent or metastatic disease and represent a promising future direction in nasopharyngeal carcinoma.
10.1016/S0140-6736(19)30956-0
Establishment of prognostic factors in recurrent nasopharyngeal carcinoma patients who received salvage intensity-modulated radiotherapy: A meta-analysis.
Yue Qiuyuan,Zhang Mingwei,Chen Yunbin,Zheng Dechun,Chen Ying,Feng Meimei
Oral oncology
Local recurrence remains a major cause of therapeutic failure in patients with nasopharyngeal carcinoma (NPC) and the effective treatment of recurrent NPC (r-NPC) is still a challenge. Intensity-modulated radiotherapy (IMRT) is considered as a favorable technique in the management of r-NPC, especially for extensive lesions. However, local r-NPC is a highly heterogeneous disease and the survival outcome following salvage IMRT varies. Furthermore, due to varied samples and therapeutic protocols, no consensus has been reached in the establishment of prognostic values. Hence, we used Medline and Embase electronic databases to conducted a meta-analysis to generate the best estimation of the prognostic factors in local r-NPC following salvage IMRT. Finally, a total of 783 patients in seven studies were enrolled. Overall, the pooled HR for OS of recurrent T stage and recurrent tumor volume was 1.77 (95% CI = 1.15-2.39) and 2.12 (95% CI = 1.42-2.82), without any heterogeneity. In addition, despite a significant association was observed in the pooled HR of significant compliance for OS, however, significant heterogeneity was also observed (I = 76.6%, p = 0.039). Furthermore, no significant association was observed among the pooled HRs for OS in terms of age, gender, recurrent time interval, synchronous nodal recurrence, chemotherapy and total re-irradiation dose. Therefore, the present meta-analysis demonstrated that recurrent T stage and tumor volume may serve as the prognostic factors for OS in patients with r-NPC who received salvage IMRT. The other factors such as age, gender, and optimal re-irradiation dose warranted further investigation.
10.1016/j.oraloncology.2018.04.017
With or without reirradiation in advanced local recurrent nasopharyngeal carcinoma: a case-control study.
Liu Li-Ting,Chen Qiu-Yan,Tang Lin-Quan,Zhang Lu,Guo Shan-Shan,Guo Ling,Mo Hao-Yuan,Zhao Chong,Guo Xiang,Chen Ming-Yuan,Qian Chao-Nan,Zeng Mu-Sheng,Hong Ming-Huang,Shao Jian-Yong,Sun Ying,Ma Jun,Mai Hai-Qiang
BMC cancer
BACKGROUND:The study aimed to evaluate the long-term outcome in patients with advanced local recurrent nasopharyngeal carcinoma (NPC) treated with or without reirradiation. METHODS:A total of 44 patients treated without reirradiation (non-RT + chemotherapy) were matched with 44 patients treated with reirradiation (re-RT+/-chemtherapy) by age, sex, Karnosky performance score (KPS), rT stage, rN stage, and time interval between initial radiation and recurrence (TI). Overall survival (OS) rate and time to progression (TTP) rate were assessed using Kaplan-Meier method, log-rank test, and Cox regression analysis. RESULTS:From March 2008 to December 2013, a total of 88 well-balanced rT3-4 N0-1 NPC patients were retrospectively analyzed. After a median follow-up of 27 months (range: 6-85), the 5-year OS rate and TTP rate was 23.4 %, 39.0 % in the non-RT + chemotherapy group and 27.5 %, 49.8 % in the re-RT+/-chemtherapy group, respectively. Multivariate analysis showed that significant toxic effect was the only significant prognosticator correlated with OS (HR: 2.15, 95 % CI = 1.02-4.53, p = 0.044). No statistically significant survival differences were observed between the two treatment groups in either univariate or multivariate analyses. CONCLUSION:Compared with reiradiation, treating advanced local recurrent NPC with chemotherapy alone warrants further validation in the view of its similar survival and more acceptable toxicities.
10.1186/s12885-016-2803-2
Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: a 10-year experience.
Liu Juan,Yu Huapeng,Sun Xicai,Wang Dehui,Gu Yurong,Liu Quan,Wang Huan,Han Wade,Fry Allison
International journal of clinical oncology
BACKGROUND:Our aim was to review the outcomes of endoscopic nasopharyngectomy performed on a large series of patients with residual or recurrent nasopharyngeal carcinomas and to identify the prognostic factors. METHODS:Ninety-one patients with residual (10) and recurrent (81) nasopharyngeal carcinomas who underwent endoscopic nasopharyngectomy were enrolled in our study. Clinical information including gender, age, medical history, symptoms, radiographic findings, tumor stage, treatment, recurrence time, postoperative pathological examination, complications, and outcomes at last follow-up visit was collected. The survival curves and multivariate survival analysis were analyzed using the Kaplan-Meier and Cox proportional hazards model. RESULTS:Our study included 71 men and 20 women with a median age of 51 years. The lesions were staged as follows: rT1, 30; rT2, 13; rT3, 29; and rT4, 19. No serious operative or postoperative complication was observed. The median follow-up period was 23 months (range, 4-109 months). Tumor necrosis was identified in 40 of 91 patients. At the last follow-up, 42 patients were free of disease, 10 were alive with disease, and 39 had died. At 2- and 5-year follow-up, the overall survival rates were 64.8% and 38.3%, respectively; the disease-free survival rates were 57.5% and 30.2%, respectively, for the two periods. Multivariate analysis showed that T classification (P = 0.02) and tumor necrosis (P = 0.024) were independent risk factors. CONCLUSIONS:Endoscopic nasopharyngectomy is a feasible and effective surgical treatment for recurrent and residual nasopharyngeal carcinomas.
10.1007/s10147-017-1143-9
Endoscopic nasopharyngectomy in recurrent nasopharyngeal carcinoma: a case series, literature review, and pooled analysis.
Vlantis Alexander C,Lee Dennis L Y,Wong Eddy W Y,Chow Samuel M W,Ng Siu K,Chan Jason Y K
International forum of allergy & rhinology
BACKGROUND:To critically evaluate the use of endoscopic nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma (NPC) through a case series, systematic literature review, and pooled analysis. METHODS:A case series of 18 patients combined with systematic literature review and pooled analysis of PubMed, Web of Science, and Scopus search, identifying 576 papers. After excluding 307 papers as search engine duplicates, only 16 of the remaining papers had adequate patient data to be included. RESULTS:Our case series of 18 patients had a 2-year disease-free survival (DFS) and overall survival (OS) of 90.0% and 100%, respectively. The pooled analysis of 300 patients that had an endoscopic resection of recurrent NPC showed recurrence-free survival and overall survival were 85.8% and 82.9%, respectively. Most, 56.1%, were recurrent T1 lesions. Resection margins were negative in 90.2% of patients. Local recurrence occurred in 20.1% of patients. Major complications occurred in 13.6% of patients. The mean hospital stay was 5.8 days, the mean operating time was 228.3 minutes, and the mean operative blood loss was 163 mL. CONCLUSION:Endoscopic resection of recurrent NPC occurs with low surgical morbidity. However, further long-term evaluation with longer follow-up data is needed to evaluate if the survival data is comparable or better than open approaches.
10.1002/alr.21881
A 4-year review of surgical and oncological outcomes of endoscopic endonasal transpterygoid nasopharyngectomy in salvaging locally recurrent nasopharyngeal carcinoma.
Tang Ing Ping,Ngui Ling Xiu,Ramachandran Komathi,Lim Li Yun,Voon Pei Jye,Yu Kong Leong,Narayanan Prepageran,Carrau Ricardo
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
PURPOSE:To study the surgical and oncological outcomes of endoscopic endonasal transpterygoid nasopharyngectomy (EETN) in salvaging locally recurrent nasopharyngeal carcinoma (NPC). METHOD:This was a retrospective clinical record review study carried out at a tertiary centre from June 2013 until May 2017. A total of 55 locally recurrent NPC patients (rT1-rT4) underwent EETN performed by single skull base surgeon with curative intention with postoperative adjuvant chemotherapy but without postoperative radiotherapy. RESULTS:There were 44 (80.0%) males and 11 (20.0%) females, with mean age of 52.5 years. The mean operating time was 180 min (range 150-280 min). 85% (47/55) of patients achieved en bloc tumour resection. 93% (51/55) of patients obtained negative microscopic margin based on postoperative histopathological evaluation. Intraoperatively, one (1.8%) patient had internal carotid artery injury which was successfully stented and had recovered fully without neurological deficit. There were no major postoperative complications reported. During a mean follow-up period of 18-month (range 12-48 months) postsurgery, five patients (9.1%) had residual or recurrence at the primary site. All five patients underwent re-surgery. One patient at rT3 passed away 6 months after re-surgery due to distant metastasis complicated with septicaemia. The 1-year local disease-free rate was 93% and the 1-year overall survival rate was 98%. CONCLUSIONS:EETN is emerging treatment options for locally recurrent NPC, with relatively low morbidity and encouraging short-term outcome. Long-term outcome is yet to be determined with longer follow-up and bigger cohort study. However, a successful surgical outcome required a very experienced team and highly specialised equipment.
10.1007/s00405-019-05522-5
Five-year Survival Data on the Role of Endoscopic Endonasal Nasopharyngectomy in Advanced Recurrent rT3 and rT4 Nasopharyngeal Carcinoma.
The Annals of otology, rhinology, and laryngology
AIM:Endoscopic endonasal nasopharyngectomy (EEN) for recurrent nasopharyngeal carcinoma (rNPC) is being increasingly used due to the added high magnification, reduced morbidities associated with open procedures and good survival outcomes. Most studies looked at usage of EEN in patients with lower recurrent staging (rT1 and rT2) although more and more surgeons are studying the outcome of EEN in advanced rNPC (rT3 and rT4). The aims of this study were to report the long-term 5-year survival outcome of EEN performed in patients with advanced rNPC, and to determine any prognostic factors for patients' survival. METHODS:All patients who underwent EEN for advanced rNPC between January 2003 and December 2015 inclusive were analyzed. All surgeries were performed in University Malaya Medical Centre in Kuala Lumpur and Queen Elizabeth Hospital in Sabah. We reported the 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) and any related complications and significant prognostic factors. RESULTS:Twelve patients with rNPC (2 rT3 and 10 rT4) were followed-up over a mean duration of 44.8 months (range, 40-440 weeks). The 5-year OS was 50.0% (mean 44.75 months), DFS was 25.0% (mean 35.25 months) and the DSS was 58.3% (mean 43.33 months). No severe operative complications were encountered and no independent prognostic factors for survival outcome were identified. CONCLUSION:This is the first report in English that exclusively described the long-term 5-year survival data in patients with both rT3 and rT4 recurrent NPC after EEN. The data suggest that EEN is a feasible treatment to improve survival with minimal morbidities in patients with rT3 and rT4 recurrent NPC. However, more studies with larger patient size is recommended.
10.1177/0003489419887410
Management of locally recurrent nasopharyngeal carcinoma.
Lee Anne W M,Ng Wai Tong,Chan Jimmy Y W,Corry June,Mäkitie Antti,Mendenhall William M,Rinaldo Alessandra,Rodrigo Juan P,Saba Nabil F,Strojan Primož,Suárez Carlos,Vermorken Jan B,Yom Sue S,Ferlito Alfio
Cancer treatment reviews
As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.
10.1016/j.ctrv.2019.101890
Salvage treatment using carbon ion radiation in patients with locoregionally recurrent nasopharyngeal carcinoma: Initial results.
Hu Jiyi,Bao Cihang,Gao Jing,Guan Xiyin,Hu Weixu,Yang Jing,Hu Chaosu,Kong Lin,Lu Jiade J
Cancer
BACKGROUND:Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC) after a definitive dose of radiotherapy (RT) is challenging and usually associated with severe toxicities. Intensity-modulated carbon ion RT (IMCT) offers physical/biologic advantages over photon-based intensity-modulated RT. Herein, the authors report their initial experience of IMCT in previously irradiated patients with locoregionally recurrent NPC. METHODS:Patients with locoregionally recurrent, poorly differentiated or undifferentiated NPC who underwent salvage therapy with IMCT at the Shanghai Proton and Heavy Ion Center between May 2015 and August 2017 were included in the current study. The IMCT doses were 50 to 66 Gray equivalent (GyE) (2.0-3.0 GyE/daily fraction), delivered via raster scanning technology. The 1-year overall survival, disease-specific survival, progression-free survival (PFS), local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were calculated. Univariate and multivariate analyses of PFS were performed to identify possible predictive factors. RESULTS:Among the 75 patients included, 4 patients, 14 patients, 29 patients, and 28 patients, respectively, had recurrent American Joint Committee on Cancer stage I, stage II, stage III, and stage IVA/B disease. With a median follow-up of 15.4 months (range, 2.6-29.7 months), the 1-year overall survival, disease-specific survival, PFS, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival rates were 98.1%, 98.1%, 82.2%, 86.6%, 97.9%, and 96.2%, respectively. A higher fraction size of 3 GyE (vs <3 GyE) or a higher biological equivalent dose significantly improved the PFS rate on univariate analysis, but not on multivariate analysis. No patient developed acute toxicity of grade ≥2 during IMCT. Late treatment-induced severe (grade 3 or 4) toxicities were infrequent, but included mucosal necrosis (9.3%), xerostomia (1.3%), and temporal lobe necrosis (1.3%). CONCLUSIONS:This initial experience in the first 75 patients with locoregionally recurrent NPC was encouraging. Carbon ion RT could provide promising survival rates with infrequent severe toxicities for patients with locoregionally recurrent NPC. Cancer 2018;124:2427-37. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
10.1002/cncr.31318
[Observation on clinical efficacy and prognosis analysis of endoscopic surgery treatment for rT1-rT2 recurrent nasopharyngeal carcinoma].
Lan G P,Weng J J,Si Y F,Deng Z X,Huang B,Zhang B J,Qin Y
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery
To investigate the feasibility of endoscopic surgery for treatment of rT1-rT2 recurrent nasopharyngeal carcinoma. The clinical data and of 57 patients who had recurrence of the primary lesion after treatment of nasopharyngeal carcinoma from February 2011 to December 2015 were retrospectively analyzed. The patients were re-staged according to Union for International Cancer Control(UICC, 2010) staging system for nasopharyngeal carcinoma before surgery. Patients suitable for surgery underwent endoscopic surgery to remove nasopharyngeal lesions; those combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time; patients with positive surgical margins of pharyngeal lesions and cervical lymph node extramembranous filtration were treated with radiotherapy combined with chemotherapy; patients unsuitable for surgery were treated with radiotherapy combined with chemotherapy directly. All patients were followed up regularly to observe clinical efficacy and survival. Fifty-seven patients were re-staged according to UICC(2010) staging system for nasopharyngeal carcinoma: 19 cases in stage Ⅰ,30 cases in stage Ⅱ, 6 cases in stage Ⅲ and 2 cases in stage Ⅳ,including 27 cases in stage rT1, 30 cases in stage rT2, and 43 cases in stage rN0,6 cases in stage rN1,6 cases in stage rN2,2 cases in stage rN3. Forty-four cases of primary lesions were sected for endoscopic surgery. Patients combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time, with 6 cases of positive surgical margins of pharyngeal lesions and 4 cases of cervical lymph node extramembranous infiltration, who were treated with radiotherapy combined with chemotherapy after surgery. Thirteen patients received radiotherapy combined with chemotherapy directly. At a median follow-up of 36 months, the 3-year overall survival rate of 57 patients was 61.4%. The 3-year overall survival rates of patients in stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 73.7%, 63.3%, 33.3%, 0.0% respectively. Kaplan-Meier survival curve analysis showed a significant difference in the overall survival rate of patients in different stages(=0.002). The 3-year overall survival rates of rT1 and rT2 patients were 63.0%, 60.0% respectively, and KaplanMeier survival curve analysis showed no significant difference in the overall survival rate between rT1 and rT2 patients(=0.707). The 3-year overall survival rates of patients in stages rN0, rN1, rN2, rN3 were 69.8%, 50.0%, 33.3%, 0.0% respectively, and Kaplan-Meier Survival curve analysis showed a significant difference in overall survival between patients in different rN stages(=0.002). The 3-year overall survival rate was 68.2% in 44 surgical patients, and 38.5% in 13 non-surgical patients. Kaplan-Meier survival curve analysis showed significant difference in overall survival rate between surgical and non-surgical patients(=0.014). Endoscopic surgery for recurrent nasopharyngeal carcinoma is a safe and effective treatment to improve survival.
10.13201/j.issn.1001-1781.2019.04.012
Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: A meta-analysis.
Leong Yiat Horng,Soon Yu Yang,Lee Khai Mun,Wong Lea Choung,Tham Ivan Weng Keong,Ho Francis Cho Hao
Head & neck
BACKGROUND:The purpose of this clinical review was to summate the published data for the long-term outcomes of reirradiation with intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). METHODS:We searched biomedical literature databases for eligible studies published from January 2005 to September 2016. Outcomes of interests were 5-year local failure-free survival, distant failure-free survival, overall survival (OS), and toxicities. Meta-analysis was performed using a random effects model. RESULTS:We found 4 comparative and 8 noncomparative studies (n = 1768). Reirradiation was associated with pooled event rates of 72% (95% confidence interval [CI] 66%-78%; I = 84%), 85% (95% CI 82%-88%; I = 69%), and 41% (95% CI 36%-47%; I = 80%) for 5-year local failure-free survival, distant failure-free survival, and OS, respectively, with significant heterogeneity among the study results. The pooled event rate for grade 5 toxicities was 33% (95% CI 30%-35%; I = 0%) with minimal heterogeneity. CONCLUSION:Reirradiation with IMRT for locally recurrent NPC could confer long-term disease control and survival but is associated with significant mortality.
10.1002/hed.24993