Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Introduction:It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy(IMRT).Minimizing planning target volume(PTV) margins with more precise target localization techniques can achieve this goal.This study aimed to quantify the extent to which organs at risk(OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma(NPC).Methods:Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins,which were reduced or unchanged following cone beam computed tomography online correction.The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage.Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing.Results:Improvements in target coverage occurred with margin reduction,and significant improvements in dosimetric parameters were observed for all OARs(P<0.05) except for the right optic nerve,chiasm,and lens.Doses to OARs decreased at a rate of 1.5%to 7.7%.Sparing of the left parotid and right parotid,where the mean dose(D_(mean)) decreased at a rate of 7.1%and 7.7%,respectively,was greater than the sparing of other OARs.Conclusions:Significant improvements in OAR sparing were observed with margin reduction,in addition to improvement in target coverage.The parotids benefited most from the online imaging-guided approach.

包含转移区域颈部淋巴结区和治疗前血清Epstein-Barr病毒DNA拷贝数的综合模型对预测N1期鼻咽癌远处转移的预后价值

背景与目的根据美国癌症联合委员会(American Joint Committee on Cancer,AJCC)分期系统第7版,50%以上的鼻咽癌(nasopharyngealcarcinoma,NPC)患者在初诊时为N1期。然而,对N1期NPC患者的研究相对较少,其转移风险也不乐观。本研究旨在评估转移区域淋巴结大体肿瘤区(gross tumor volume of metastatic regional lymph node,GTVnd)和治疗前血清EB病毒(Epstein-Barr virus,EBV)DNA拷贝数对N1期NPC患者远处转移的预测价值,并为该类型患者建立包含GTVnd和EBVDNA拷贝数的综合预后模型。方法本研究对2009年11月至2012年2月期间,在中山大学肿瘤防治中心接受治疗的787例新诊断的非转移性、经组织学证实的N1 NPC患者病历进行了分析。使用面积求和方法测量计算机断层扫描获取的GTVnd。治疗前采集血样,定量检测血浆EBV的DNA拷贝数。使用受试者工作特性(receiver operating characteristic,ROC)曲线分析来评价GTVnd的临界点,并且使用ROC曲线下面积来评估GTVnd的预测有效性。通过Kaplan-Meier分析评估生存率,使用log–rank检验比较生存曲线。采用Cox比例风险回归模型进行多变量分析。结果 GTVnd>18.9mLvs.≤18.9mL患者的5年无远处转移生存率(distantmetastasis-freesurvival,DMFS)分别为82.2%和93.2%(P <0.001),EBV DNA拷贝数> 4000拷贝/mL vs.≤4000拷贝/mL患者的5年DMFS为83.5%vs. 93.9%(P <0.001)。在Cox回归模型中对GTVnd、EBV DNA拷贝数和T分期进行校正后,GTVnd> 18.9 mL和EBV DNA拷贝数> 4000拷贝/mL与预后不良显著相关(均P <0.05)。根据GTVnd和EBV DNA拷贝数的组合,将所有患者分为低风险、中风险和高风险组,5年DMFS分别为96.1%、87.4%和73.8%(P <0.001)。多变量分析证实了该模型对远处转移风险分层的预后价值[风险比(hazard ratio,HR)=4.17;95%置信区间(confidence interval,CI):2.34–7.59;P <0.001)]。结论 GTVnd和血清EBV DNA拷贝数是预测N1期NPC患者远处转移的独立预后因素。包含GTVnd和EBV DNA拷贝数的预后模型可以改进此类患者的转移风险分层。

Individualized elective irradiation of the clinically node-negative neck in definitive radiotherapy for head and neck squamous cell carcinoma

Background:Oral cavity(OC),oropharyngeal(OP),hypopharyngeal(HP),and laryngeal(LA)squamous cell carcinoma(SCC)have a high incidence of regional lymph node metastasis(LNM).Elective irradiation for clinically node-negative neck is routinely administered to treat lymph nodes harboring occult metastasis.However,the optimal elective irradiation schemes are still inconclusive.In this study,we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node-negative neck of these four types of cancer.Methods:From July 2005 to December 2018,793 patients with OC-SCC,464 with OP-SCC,413 with HP-SCC,and 645 with LA-SCC were recruited retrospectively.Based on the actual incidence of LNM and the tumor characteristics,risk factors for contralateral LNM,as well as node level coverage schemes for elective irradiation,were determined using logistic regression analysis.Additionally,we developed a publicly available online tool to facilitate the widespread clinical use of these schemes.Results:For the ipsilateral node-negative neck,elective irradiation at levels Ⅰ-Ⅲ for OC-SCC and levels Ⅱ-Ⅳa for OP-,HP-and LA-SCC are generally recommended.In addition,level Ⅶa should be included in patients with OPSCC.Multivariate analyses revealed that posterior hypopharyngeal wall and post-cricoid region involvement were independently associated with level Ⅶa metastasis in HP-SCC(all P<0.05).For the contralateral node-negative neck,multivariate analyses revealed that ipsilateral N2b2-N3,tumors with body midline involvement,and degree of tumor invasion were the independent factors for contralateral LNM(all P<0.05).In patients who require contralateral neck irradiation,levels Ⅰ-Ⅱ are recommended for OC-SCC,and additional level Ⅲ is recommended for patients with ipsilateral N3 disease.Levels Ⅱ-Ⅲ are recommended for OP-,HP-,and LA-SCC,and additional level Ⅳa is recommended for patients with advanced T or ipsilateralNclassifications.Furthermore,additional level Ⅶa is recommended only for OP-SCC with T4 and ipsilateral N3 disease.Conclusion:Based on our findings,we suggest that individualized and computer-aided elective irradiation schemes could reduce irradiation volumes in OC-,OP-and HP-SCC patients,as compared to current guidelines,and could thus positively impact the patients’quality of life after radiotherapy.