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.

Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation

Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level Ⅱ), middle neck (levels Ⅲ and Va), and lower neck (levels Ⅳ and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6% , 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Generating femtosecond coherent X-ray pulses in a diffractionlimited storage ring with the echo-enabled harmonic generation scheme

To study ultrafast processes at the sub-picosecond level, novel methods based on coherent harmonic generation technologies have been proposed to generate ultrashort radiation pulses in existing ring-based light sources. Using the High Energy Photon Source as an example, we numerically test the feasibility of implementing one coherent harmonic generation technology, i.e.,the echo-enabled harmonic generation(EEHG) scheme, in a diffraction-limited storage ring(DLSR). Two different EEHG element layouts are considered, and the effect of the EEHG process on the electron beam quality is also analyzed. Studies suggest that soft X-ray pulses, with pulse lengths of a few femtoseconds and peak powers of up to1 MW, can be generated by using the EEHG scheme, while causing little perturbation to the regular operation of a DLSR.

新辅助化疗联合放疗与同期放化疗对上行型鼻咽癌疗效的比较:毒性和预后的回顾性分析

背景与目的在调强放射治疗(intensity?modulated radiotherapy, IMRT)的时代,新辅助化疗(neoadjuvant chemotherapy, NACT)在治疗上行型鼻咽癌(nasopharyngeal carcinoma, NPC)中的作用被低估了。本研究旨在比较NACT结合IMRT(NACT+RT)与同期放化疗(concurrent chemoradiotherapy,CCRT)对治疗上行型鼻咽癌的疗效。方法分析2009年12月至2011年7月期间用NACT+RT或CCRT治疗的214例上行型鼻咽癌患者的临床数据。在214例患者中,98例接受了NACT+RT治疗,116例接受了CCRT治疗。用Kaplan?Meier法分析存活率,并用log?rank检验比较存活曲线。结果两组患者在4年总生存率、局部区域无复发生存率、无远处转移生存率和无进展生存率均没有显著差异(均P> 0.05)。然而,CCRT组患者在放疗期间比NACT+RT组患者表现出更严重的急性不良反应,包括白细胞减少(30.2%vs. 15.3%, P=0.016)、中性粒细胞减少(25.9%vs.11.2%, P=0.011)和黏膜炎(57.8%vs.40.8%, P=0.028)。放疗结束后,CCRT组患者表现出较高比例的口腔干燥症(21.6%vs. 10.2%, P=0.041)和听力损失(17.2%vs. 6.1%,P=0.023)。结论 NACT+RT和CCRT两组的治疗结果相似。然而,CCRT组会导致更高比例的急性和迟发性毒性。因此,NACT+RT可能是治疗上行型鼻咽癌更好的方法。

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。

Determination of groundwater flow regimes based on the spatial non-local distribution of hydraulic gradient:Model and validation

The groundwater flow in natural aquifers can change from the Darcy flow to the non-Darcian flow due to a variety of causes,such as the increase of the Reynolds number in the highly permeable media or the decrease of the hydraulic gradient below a threshold in the low-permeability media,while the representative flow regime cannot be reliably determined using the traditional criteria.To address this challenge,this paper proposes a new term called the equivalent hydraulic gradient(EHG)by generalizing the differential form of the Darcy’s law using a spatial integral of the upstream hydraulic head.The nonlocal spatial variation of the hydraulic head difference between upstream and downstream zones is assumed to be the potential cause of the transition of the groundwater flow regimes.This assumption is analogous to the common assumption used for quantifying the anomalous pollutant transport in the geological media.Applications of this idea show that the EHG concept could distinguish three main flow regimes,namely the Super-Darcy flow,the Darcy flow,and the Sub-Darcy flow,although the Super-Darcy flow regime is rarely observed in the laboratory column flow experiments.Results of this study therefore shed lights on the interpretation of the fundamental dynamics of the groundwater moving in various heterogeneous aquifers,and may lead to the rebuilding of the hydrodynamics of the surface water,the groundwater,and the soil.

Comparative role of real-world study and traditional randomized controlled trials in head and neck cancer:a literature-based analysis

To the Editor:In the era of evidence-based medicine,the traditional randomized controlled trials(RCT)is on the top of the pyramid of evidence hierarchy.With well-controlled inclusion and exclusion criteria,randomization,and strict intervention protocol,traditional RCT construct the ideal medical circumstance,under which the causal relationship between the outcome and intervention can be better interpreted.However,it will also make the external validity and generalizability of traditional RCT limited.

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.