An Interpretation of CSCO/ASCO International Guideline of Chemotherapy in Combination with Radiotherapy for Definitive-intent Treatment of Stage Ⅱ-Ⅳa Nasopharyngeal Carcinoma in 2021
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摘要:
Ⅱ~Ⅳa期鼻咽癌主要治疗方式是放疗联合化疗。调强放射治疗时代，化疗的介入时机与具体实施仍存争议。以往有关鼻咽癌的临床指南对于具体的放疗技术、剂量分割以及放疗与化疗联合应用的具体方案通常阐述的比较笼统，并可能缺乏具体的实践指导性，2021年CSCO和ASCO鼻咽癌联合国际指南细致阐明了有关Ⅱ~Ⅳa期鼻咽癌根治性放化疗的模式与具体实施建议，本文旨在对该指南的具体细节进行解读。
Abstract:Radiotherapy combined with chemotherapy is the main treatment for stage Ⅱ-Ⅳa nasopharyngeal carcinoma (NPC). In the era of intensity-modulated radiation therapy, the timing and implementation of chemotherapy are still controversial. In the past, the clinical guidelines for NPC generally described the specific radiotherapy technology, dose fractionation and the specific scheme of combined application of radiotherapy and chemotherapy, and may lack specific practical guidance. The joint international guidelines for NPC by CSCO and ASCO elaborates the mode and specific implementation recommendations of radical chemoradiotherapy for stage Ⅱ-Ⅳa NPC. This article aims to interpret the specific details of the guideline.
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0 引言
食管癌是因消化道肿瘤死亡的主要原因之一，食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）约占全球食管癌的90%[1]，因早期症状不明显，确诊时大部分患者已处于进展期，失去最佳根治手术时机，根治性同步放化疗（concurrent chemoradiotherapy, CCRT）是进展期ESCC的主要治疗方案[2]。临床实践中放化疗后的急性不良反应（acute adverse reactions, AAR）仍然困扰着医师和患者，且AAR随剂量的积累而增加，以中晚期患者为著[3]。铂类化疗通常会引起以血液学毒性和胃肠道毒性为主的不同类型急性不良反应，≥3级AAR可导致剂量减少、治疗延迟甚至终止放化疗，从而疗效不佳[4]。因此，个体化治疗方案有利于平衡疗效和AAR，使更多的患者获益。ESCC同步放化疗前CT检查既可评估肿瘤临床分期，亦可定量评估骨骼肌等身体成分变化[5]。有研究[2-6]表明骨骼肌量减少与多种癌症生存期缩短及治疗时AAR增加相关，去脂肪身体成分（主要为骨骼肌量）存在差异，放化疗后AAR亦不同，且大多数进展期ESCC患者因吞咽困难、疼痛、全身炎性反应和代谢率增加存在不同程度的骨骼肌量减少等，但进展期ESCC放化疗前肌肉减少症相关身体成分与同步放化疗AAR的关系仍存在争议。Dijksterhuis等[6]认为食管癌治疗前骨骼肌密度降低、肥胖型肌少症与3~4级剂量限制性毒性有关，而Ota等[7]发现治疗前骨骼肌减少症与化疗相关AAR无关；本研究目的是探讨进展期ESCC患者放化疗前骨骼肌减少症相关的身体成分变化与AAR、生存率的相关性。
1 资料与方法
1.1 病例选择及一般资料
回顾性收集徐州市肿瘤医院2018年8月—2022年7月期间符合标准的患者。纳入标准：（1）经病理确诊且临床TNM分期Ⅱ期以上（AJCC第8版[2]）、预行同步放化疗的进展期ESCC患者；（2）可检索到治疗前血清白蛋白及中性粒细胞与淋巴细胞比例，包括L3双侧横突层面的中上腹部CT、胸部CT；（3）美国东部肿瘤协作组评分标准≤2分且年龄 > 18岁，无主要器官功能障碍；排除肿瘤相关资料不全（如身高、体重、肿瘤治疗相关不良反应等）的患者。本研究通过徐州市肿瘤医院伦理委员会审批。
1.2 CT检查及身体成分测量
同步放化疗前所有患者行胸部及上腹部能谱CT扫描（美国GE，Discovery CT-750HD），并将图像传输至工作站（ADW4.7，美国），根据文献描述方法[8]，采用半自动化手工测量，以腰3横突为标志，在连续两层轴位图像上测量骨骼肌[（包括腰肌、椎旁肌（竖脊肌、腰方肌）和腹壁肌（腹横肌、内外斜肌、腹直肌）]和脂肪组织的横截面积（人工勾画腹壁肌肉、皮下脂肪、内脏脂肪边界，骨骼肌以-29~190 HU、皮下脂肪及肌肉间脂肪以-190~-30 HU、内脏脂肪以-150~-50 HU为阈值，软件自动算出骨骼肌、皮下脂肪、内脏间脂肪体积，再除以5 mm层厚），取两次平均值为骨骼肌面积（total muscle area, TMA）、皮下脂肪面积、内脏间脂肪面积，同时测量腰大肌的CT值，再通过公式：骨骼肌指数（skeletal muscle index, SMI）=TMA（cm2）/身高2（m2）、无脂骨骼肌量（fat-free mass, FFM, kg）=6.06+0.3×TMA（m2）、无脂体指数（fat-free mass index, FFMI）（kg/m2）=总FFM/身高2（m2）、脂肪量（fat mass, FM）（kg）=11.2+0.042×L3（皮下脂肪+内脏间脂肪量）、脂肪指数（fat mass index, FMI）（kg/m2）=总FM/身高2（m2）[8]，计算出SMI、FFMI、FMI；体表面积（body surface area, BSA）（m2）={[高度（cm）×体重（kg）]/3 600}1/2。以SMI < 55 cm2/m2（男）、SMI < 39 cm2/m2（女）为标准诊断肌肉减少症[8]，本组病例分为肌少症组和非肌少症组。
1.3 治疗方案、急性不良反应评估
所有患者均接受三维适形调强放疗，参照食管造影、CT及胃镜显示食管癌病灶及阳性淋巴结情况勾画靶区，并适当修改邻近危险器官剂量，95%计划靶区处方剂量为56~64 Gy，1次/天，5次/周，1.8~2 Gy/次，28~32次完成，心脏、肺平均剂量分别≤30 Gy、15 Gy，脊髓最大剂量≤45 Gy。同步接受2周期FP方案化疗：5-Fu 450~500 mg/m2×5 d，顺铂25~30 mg/m2×（3~5）d；28 d为1周期；为消除混杂因素影响，对肌少症组和非肌少症组的1周期、2周期顺铂总剂量行统计学分析，结果显示肌少症组1周期、2周期顺铂总剂量分别为143.25（四分位数12.75）mg、142.50（四分位数14.75）mg和非肌少症组144.75（四分位数9.75）mg、143.00（四分位数10.13）mg，差异无统计学意义（Z=-1.140、-0.981, P=0.254、0.327）。
根据CTCAE5.0版评价血液系统AAR（0~4级）[9]，美国RTOG急性放射损伤分级标准评价急性放射性肺炎（0~4级）、急性放射性食管炎（0~4级）[10]。
1.4 随访
通过查询电子病历或电话回访患者（或家属）或定期门诊复查，随访至食管癌进展或患者死亡或截止日期，以月作为随访单位，记录患者发生急性不良反应情况及生存情况。
1.5 统计学方法
数据分析采用SPSS25.0及Graph Pad Prism8.0.1软件包。Fisher' s精确检验或χ2检验分析数据在肌少症组和非肌少症组间的差异。S-W检验对连续性数据行正态分布检验，再用独立样本t检验分析符合正态分布数据（x±s）及非参数检验分析不符合正态分布数据（中位数（四分位数））在两组间的差异。单因素分析筛选出与≥3级AAR有统计学意义的变量，Logistic回归模型进一步分析其影响因素。Kaplan-Meier法计算生存率及Log rank检验比较两组间生存率的差异。α=0.05（双尾）为检验水准。
2 结果
2.1 食管鳞状细胞癌患者临床基本情况及身体参数分布
132例进展期ESCC患者（Ⅲ期35例、ⅣA期59例、ⅣB期38例）纳入本研究中，男93例、女39例，中位年龄64（四分位数6）岁，同步放化疗前65.9%（87/132）患者存在肌少症，中位年龄64（四分位数8）岁，34.1%（45/132）患者无肌少症，中位年龄64（四分位数9）岁；颈段及胸上段34例、胸中段51例、胸下段22例、食管胃交界处癌25例。FFMI与BSA呈中度相关（r=0.593, P < 0.001），见图 1。与非肌少症组相比，肌少症组SMI、BMI、FMI、FFMI和骨骼肌密度较低（P < 0.001、0.036、 < 0.001、0.001、0.026）；但治疗前ECOG-PS、血清白蛋白、中性粒细胞淋巴细胞比值、肿瘤位置及临床分期在两组间比较差异均无统计学意义，见表 1。
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图 1 同步放化疗前进展期ESCC患者体表面积和无脂骨骼肌量的相关性Figure 1 Relationship between body surface area and fat free mass in advanced ESCC patients before concurrent chemoradiotherapy表 1 进展期食管鳞癌患者的基本情况Table 1 Demographics of patients with advanced ESCC
2.2 食管鳞状细胞癌同步放化疗期间急性不良反应发生、影响因素及治疗完成情况
132例进展期ESCC中，发生≥3级血液系统AAR为14例，≥3级放射性食管炎7例，≥3级放射性肺炎9例，4例同时发生≥3级血液系统AAR、放射性食管炎，2例同时发生≥3级血液系统AAR、放射性肺炎，1例同时发生≥3级放射性食管炎、放射性肺炎，最终23例发生≥3级总AAR，见表 2；与非肌少症组相比，肌少症组总AAR、血液系统AAR发生率高（P=0.045、0.034），见表 1。
表 2 进展期食管鳞状细胞癌同步放化疗急性不良反应情况Table 2 Acute adverse reactions in patients with advanced ESCC who received concurrent chemoradiotherapy
单因素、多因素分析显示SMI、肌肉减少症、脂肪指数、骨骼肌密度、骨骼肌总面积、无脂体指数、放疗剂量是发生≥3级AAR的影响因素，见表 3。32例患者化疗减量或暂停治疗，其中20例因AAR严重而致治疗依从性下降，8例因家庭经济原因而放弃继续治疗，4例未说明原因而放弃治疗；肌少症组的治疗依从性低于非肌少症组（P=0.035），见表 1。
表 3 进展期食管鳞癌同步放化疗≥3级急性不良反应影响单、多因素分析Table 3 Univariate and multivariate analyses of influencing factors of grade ≥3 AAR in patients with advanced ESCC who received concurrent chemoradiotherapy
2.3 食管鳞状细胞癌患者的生存结果
从2018年8月随访至患者死亡或至2022年7月，9例患者失访，失访率为6.82%，随访时间15.68（12.46）月。肌少症组生存率为22.98%（20/87）低于非肌少症组40.00%（18/45）（χ2=4.187, P=0.041）。肌少症组中位生存期[16.01（95%CI: 14.89~17.13）月]低于无肌少症组[19.27（95%CI: 14.45~24.09）月]（χ2=5.326, P=0.021），见图 2A。发生≥3级AAR的中位生存期[14.86（95%CI: 11.30~18.42）月]低于0~2级AAR[16.67（95%CI: 14.91~18.43）月]（χ2=5.470, P=0.019），见图 2B。在发生≥3级AAR患者中行分层分析发现，肌少症组中位生存期[12.13（95%CI: 10.15~14.11）月]低于无肌少症组[18.69（95%CI: 12.85~21.88）月]（χ2=4.466, P=0.035），见图 2C。
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图 2 132例进展期食管鳞状细胞癌的生存分析曲线Figure 2 Survival curves of 132 patients with advanced ESCCA: survival curves of patients with advanced ESCC with or without sarcopenia before concurrent chemoradiotherapy; B: survival curves of patients with advanced ESCC with grade≥3 or 1-2 AAR of concurrent chemoradiotherapy; C: survival curves of advanced ESCC patients with grade≥3 grade AAR and sarcopenia or non-sarcopenia.3 讨论
本研究结果显示，肌少症患者身体成分变化（骨骼肌密度减低、骨骼肌总面积减少、脂肪量增多）与发生≥3级AAR的风险相关。进展期ESCC患者BMI均≥18.5 kg/m2，他们面临的风险与BMI < 18.5 kg/m2的患者不同，因为他们可能已经存在骨骼肌消耗，但是往往又被正常或较大的体质量和脂肪组织所掩盖。目前临床实际工作中根据患者体表面积确定化疗药物剂量，这部分患者被注射的化疗药物剂量相对增加，因为在相同身高和体质量的患者中，其体表面积相等，注射的化疗药物相等，但是5-Fu和铂类化疗药（包括顺铂、奥沙利铂和卡铂）都是亲水药物，分布到脂肪体组织（主要为骨骼肌组织）中并进行分解代谢[5]。肌少症患者的骨骼肌量减少，导致单位体积骨骼肌内的化疗药物剂量增高，发生≥3级AAR的风险（主要为血液系统不良反应）可能会增加，肥胖型肌少症患者发生风险可能会更高。因此定量评估身体组成成分（尤其去脂肪骨骼肌量）可作为指导进展期ESCC患者个性化化疗药物剂量的补充因素，尤其肥胖型肌少症患者。
进展期ESCC患者放化疗前常规采用胸腹部CT检查评估肿瘤临床分期，本研究采用CT图像额外定量评估身体成分的变化具有高度客观性和可重复性，而且不增加患者辐射剂量及经济负担。如在L3双侧横突层面CT图像上以-190 HU~-30 HU为阈值测量肌肉间脂肪是评估肌肉脂肪变性的一种无创测量方法，与肌肉活检获得的肌肉内脂质含量相关性较好[11]；肌肉CT值与肌肉密度具有良好相关性，肌肉密度越低反映肌肉内脂肪浸润越多[12]；肌肉密度减低与肿瘤预后不良和生存率减低有关[13]。本组结果显示骨骼肌量减少、骨骼肌密度减低、脂肪增多是发生≥3级AAR的危险因素，肌少症和AAR同时存在的患者有生存期缩短的风险，与Ganju等[14]研究头颈部癌合并肌少症的结果相仿，发现37%头颈部癌合并肌少症接受放化疗后发生 > 1种AAR，以急性血液系统不良反应为著，45%的肌少症患者有化疗延迟、剂量减少或治疗中断，进一步导致生存期缩短。CT定量评估患者身体成分（骨骼肌密度、骨骼肌总面积、脂肪量）可成为临床营养护理过程的一部分，有利于及时发现肌少症患者，采取早期营养和体育运动等个体化的干预方案，遵守改良的运动计划有助于减轻骨骼肌消耗，有助于降低发生≥3级AAR的风险[5]。
本研究存在一定的局限性：因本研究采用回顾性设计，缺乏营养支持、体育锻炼和患者生活质量的信息，可能影响肌少症与≥3级AAR的关系；因本研究中≥3级的血液系统不良反应、放射性肺炎、放射性食管炎的患者数量较少，对其危险因素未单独进行统计学分析。此外，由于各种原因导致的食欲下降可能与≥3级AAR相互作用，未来研究需把治疗期间的食物摄入量、身体活动考虑在内。
综上所述，CT可额外定量评估人体身体组成成分，发现肌少症相关的身体成分（骨骼肌量总面积的减少、骨骼肌密度减低、脂肪增多）与发生≥3级急性不良反应风险相关，把其考虑到化疗药物给药剂量中，可降低进展期ESCC患者同步放化疗的急性不良反应的发生率、改善其预后。
Competing interests: The authors declare that they have no competing interests.作者贡献周亚娟、牟艳花：指南的学习与解读、资料收集及论文撰写胡德胜：参与指南的学习与解读、文章修改与补充 -
[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
[2] Chen YP, Ismaila N, Chua MLK, et al. Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage Ⅱ-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline[J]. J Clin Oncol, 2021, 39(7): 840-859. doi: 10.1200/JCO.20.03237
[3] Peng G, Wang T, Yang KY, et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional twodimensional radiotherapy for the treatment of nasopharyngeal carcinoma[J]. Radiother Oncol, 2012, 104(3): 286-293. doi: 10.1016/j.radonc.2012.08.013
[4] Kam MK, Leung SF, Zee B, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients[J]. J Clin Oncol, 2007, 25(31): 4873-4879. doi: 10.1200/JCO.2007.11.5501
[5] Pow EH, Kwong DL, McMillan AS, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial[J]. Int J Radiat Oncol Biol Phys, 2006, 66(4): 981-991. doi: 10.1016/j.ijrobp.2006.06.013
[6] Luo MS, Huang GJ, Liu HB. Oncologic outcomes of IMRT versus CRT for nasopharyngeal carcinoma: Ameta-analysis[J]. Medicine (Baltimore), 2019, 98(24): e15951. doi: 10.1097/MD.0000000000015951
[7] Du T, Xiao J, Qiu Z, et al. The effectiveness of intensity-modulated radiation therapy versus 2D-RT for the treatment of nasopharyngeal carcinoma: A systematic review and meta-analysis[J]. PLoS One, 2019, 14(7): e0219611. doi: 10.1371/journal.pone.0219611
[8] Co J, Mejia MB, Dizon JM. Evidence on effectiveness of intensity-modulated radiotherapy versus 2-dimensional radiotherapy in the treatment of nasopharyngeal carcinoma: Meta-analysis and a systematic review of the literature[J]. Head Neck, 2016, 38 suppl 1: E2130-E2142. http://europepmc.org/abstract/med/25546181
[9] Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase Ⅲ randomized Intergroup study 0099[J]. J Clin Oncol, 1998, 16(4): 1310-1317. doi: 10.1200/JCO.1998.16.4.1310
[10] Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: Radiation Therapy Oncology Group Phase Ⅱ trial 0225[J]. J Clin Oncol, 2009, 27(22): 3684-3690. doi: 10.1200/JCO.2008.19.9109
[11] Lee AW, Ngan RK, Tung SY, et al. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to inductionconcurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma[J]. Cancer, 2015, 121(8): 1328-1338. doi: 10.1002/cncr.29208
[12] Yang H, Chen X, Lin S, et al. Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial[J]. Radiother Oncol, 2018, 126(1): 37-42. doi: 10.1016/j.radonc.2017.07.020
[13] Ou X, Miao Y, Wang X, et al. The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels[J]. Radiat Oncol, 2017, 12(1): 137. doi: 10.1186/s13014-017-0869-x
[14] Zhang F, Cheng YK, Li WF, et al. Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: A retrospective analysis[J]. BMC Cancer, 2015, 15: 709. doi: 10.1186/s12885-015-1669-z
[15] Co JL, Mejia MBA, Dizon JMR. Evidence on effectiveness of upper neck irradiation versus whole neck irradiation as elective neck irradiation in node-negative nasopharyngeal cancer: A meta-analysis[J]. J Glob Oncol, 2018, 4: 1-11.
[16] Li JG, Yuan X, Zhang LL, et al. A randomized clinical trial comparing prophylactic upper versus whole-neck irradiation in the treatment of patients with nodenegative nasopharyngeal carcinoma[J]. Cancer, 2013, 119(17): 3170-3176. doi: 10.1002/cncr.28201
[17] Gao Y, Zhu G, Lu J, et al. Is elective irradiation to the lower neck necessary for N0 nasopharyngeal carcinoma[J]. Int J Radiat Oncol Biol Phys, 2010, 77(5): 1397-1402. doi: 10.1016/j.ijrobp.2009.06.062
[18] Tang LL, Tang XR, Li WF, et al. The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement[J]. Oral Oncol, 2017, 69: 68-73. doi: 10.1016/j.oraloncology.2017.03.010
[19] Xiao F, Dou S, Li Y, et al. Omitting the lower neck and sparing the glottic larynx in node-negative nasopharyngeal carcinoma was safe and feasible, and improved patient-reported voice outcomes[J]. Clin Transl Oncol, 2019, 21(6): 781-789. doi: 10.1007/s12094-018-1988-z
[20] Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage Ⅱ nasopharyngeal carcinoma: Phase Ⅲ randomized trial[J]. J Natl Cancer Inst, 2011, 103(23): 1761-1770. doi: 10.1093/jnci/djr432
[21] Wang S, Li S, Shen L. Combined chemoradiation vs radiation therapy alone in stage-Ⅱ nasopharyngeal carcinoma: A meta-analysis of the published literature[J]. Curr Probl Cancer, 2018, 42(3): 302-318. doi: 10.1016/j.currproblcancer.2018.03.004
[22] Liu F, Jin T, Liu L, et al. The role of concurrent chemotherapy for stageⅡ nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A systematic review and meta-analysis[J]. PLoS One, 2018, 13(3): e0194733. doi: 10.1371/journal.pone.0194733
[23] Xu C, Zhang LH, Chen YP, et al. Chemoradiotherapy versus radiotherapy alone in stageⅡ nasopharyngeal carcinoma: A systemic review and meta-analysis of 2138 patients[J]. J Cancer, 2017, 8(2): 287-297. doi: 10.7150/jca.17317
[24] Huang X, Chen X, Zhao C, et al. Adding concurrent chemotherapy to intensity-modulated radiotherapy does not improve treatment outcomes for stageⅡ nasopharyngeal carcinoma: A phase 2 multicenter clinical trial[J]. Front Oncol, 2020, 10: 1314. doi: 10.3389/fonc.2020.01314
[25] Tang C, Wu F, Wang R, et al. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicenter randomized phaseⅡ clinical trial[J]. Am J Cancer Res, 2016, 6(9): 2064-2075. http://europepmc.org/articles/PMC5043115/?report=classic
[26] Wu X, Huang PY, Peng PJ, et al. Long-term follow-up of a phase Ⅲ study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma[J]. Ann Oncol, 2013, 24(8): 2131-2136. doi: 10.1093/annonc/mdt163
[27] Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: An update of the MAC-NPC meta-analysis[J]. Lancet Oncol, 2015, 16(6): 645-655. doi: 10.1016/S1470-2045(15)70126-9
[28] Chen L, Hu CS, Chen XZ, et al. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial[J]. Eur J Cancer, 2017, 75: 150-158. doi: 10.1016/j.ejca.2017.01.002
[29] Chan ATC, Hui EP, Ngan RKC, et al. Analysis of plasma Epstein-Barr virus DNA in nasopharyngeal cancer after chemoradiation to identify high-risk patients for adjuvant chemotherapy: A randomized controlled trial[J]. J Clin Oncol, 2018, 31: 3091-3100. http://d.wanfangdata.com.cn/periodical/ChlQZXJpb2RpY2FsRW5nTmV3UzIwMjEwMzAyEiAzYzUzYjY2NzQ5MDFmNzk5MDIwOTQ1NjA4OGM1NTliYxoIcDFhang0OGo%3D
[30] Tan T, Lim WT, Fong KW, et al. Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: A randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma[J]. Int J Radiat Oncol Biol Phys, 2015, 91(5): 952-960. doi: 10.1016/j.ijrobp.2015.01.002
[31] Fountzilas G, Ciuleanu E, Bobos M, et al. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: A randomized phaseⅡ study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation[J]. Ann Oncol, 2012, 23(2): 427-435. doi: 10.1093/annonc/mdr116
[32] Hui EP, Ma BB, Leung SF, et al. Randomized phaseⅡ trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma[J]. J Clin Oncol, 2009, 27(2): 242-249. doi: 10.1200/JCO.2008.18.1545
[33] Li WF, Chen NY, Zhang N, et al. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial[J]. Int J Cancer, 2019, 145(1): 295-305. doi: 10.1002/ijc.32099
[34] Sun Y, Li WF, Chen NY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase 3, multicentre, randomised controlled trial[J]. Lancet Oncol, 2016, 17(11): 1509-1520. doi: 10.1016/S1470-2045(16)30410-7
[35] Yang Q, Cao SM, Guo L, et al. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase Ⅲ multicentre randomised controlled trial[J]. Eur J Cancer, 2019, 119: 87-96. doi: 10.1016/j.ejca.2019.07.007
[36] Cao SM, Yang Q, Guo L, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase Ⅲ multicentre randomised controlled trial[J]. Eur J Cancer, 2017, 75: 14-23. doi: 10.1016/j.ejca.2016.12.039
[37] Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma[J]. N Engl J Med, 2019, 381(12): 1124-1135. doi: 10.1056/NEJMoa1905287
[38] Tan TH, Soon YY, Cheo T, et al. Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A systematic review and meta-analysis[J]. Radiother Oncol, 2018, 129(1): 10-17. doi: 10.1016/j.radonc.2018.02.027
[39] Frikha M, Auperin A, Tao Y, et al. A randomized trial of induction docetaxel-cisplatin-5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02)[J]. Ann Oncol, 2018, 29(3): 731-736. doi: 10.1093/annonc/mdx770
[40] Lee JY, Sun JM, Oh DR, et al. Comparison of weekly versus triweekly cisplatin delivered concurrently with radiation therapy in patients with locally advanced nasopharyngeal cancer: A multicenter randomized phaseⅡ trial (KCSG-HN10-02)[J]. Radiother Oncol, 2016, 118(2): 244-250. doi: 10.1016/j.radonc.2015.11.030
[41] Liang H, Li WX, Lv X, et al. Concurrent chemoradiotherapy with 3-weekly versus weekly cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: A phase 3 multicentre randomised controlled trial (ChiCTR-TRC-12001979)[J]. J Clin Oncol, 2017, 35: 6006. doi: 10.1200/JCO.2017.35.15_suppl.6006
[42] Ng WT, Tung SY, Lee V, et al. Concurrent-adjuvant chemoradiation therapy for stage Ⅲ-ⅣB nasopharyngeal carcinoma-exploration for achieving optimal 10-year therapeutic ratio[J]. Int J Radiat Oncol Biol Phys, 2018, 101(5): 1078-1086. doi: 10.1016/j.ijrobp.2018.04.069
[43] Lee AW, Tung SY, Ngan RK, et al. Factors contributing to the efficacy of concurrent-adjuvant chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Combined analyses of NPC-9901 and NPC-9902 trials[J]. Eur J Cancer, 2011, 47(5): 656-666. doi: 10.1016/j.ejca.2010.10.026
[44] Peng H, Chen L, Zhang Y, et al. Prognostic value of the cumulative cisplatin dose during concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A secondary analysis of a prospective phase Ⅲ clinical trial[J]. Oncologist, 2016, 21(11): 1369-1376. doi: 10.1634/theoncologist.2016-0105
[45] Chen YP, Tang LL, Yang Q, et al. Induction chemotherapy plus concurrent chemoradiotherapy in endemic nasopharyngeal carcinoma: Individual patient data pooled analysis of four randomized trials[J]. Clin Cancer Res, 2018, 24(8): 1824-1833. doi: 10.1158/1078-0432.CCR-17-2656
[46] Petit C, Lee AWM, Carmel A, et al. Network-meta-analysis of chemotherapy in nasopharyngeal carcinoma (MAC-NPC): An update on 8, 221 patients[J]. J Clin Oncol, 2020, 38: 6523. doi: 10.1200/JCO.2020.38.15_suppl.6523
[47] Lee AWM, Ngan RKC, Ng WT, et al. NPC-0501 trial on the value of changing chemoradiotherapy sequence, replacing 5-fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma[J]. Cancer, 2020, 126(16): 3674-3688. doi: 10.1002/cncr.32972
[48] Lee AWM, Tung SY, Ng WT, et al. A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity[J]. Cancer, 2017, 123(21): 4147-4157. doi: 10.1002/cncr.30850
[49] Chen Y, Sun Y, Liang SB, et al. Progress report of a randomized trial comparing long-term survival and late toxicity of concurrent chemoradiotherapy with adjuvant chemotherapy versus radiotherapy alone in patients with stage Ⅲ to IVB nasopharyngeal carcinoma from endemic regions of China[J]. Cancer, 2013, 119(12): 2230-2238. doi: 10.1002/cncr.28049
[50] Lee AW, Tung SY, Chan AT, et al. A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma[J]. Radiother Oncol, 2011, 98(1): 15-22. doi: 10.1016/j.radonc.2010.09.023
[51] Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80. doi: 10.1016/S0140-6736(19)30956-0
[52] Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: A phase 3 multicentre randomised controlled trial[J]. Lancet Oncol, 2012, 13(2): 163-171. doi: 10.1016/S1470-2045(11)70320-5
[53] Wee J, Tan EH, Tai BC, et al. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage Ⅲ and Ⅳ nasopharyngeal cancer of the endemic variety[J]. J Clin Oncol, 2005, 23(27): 6730-6738. doi: 10.1200/JCO.2005.16.790
[54] Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial[J]. Eur J Cancer, 2007, 43(9): 1399-1406. doi: 10.1016/j.ejca.2007.03.022
[55] Chitapanarux I, Kittichest R, Tungkasamit T, et al. Two-year outcome of concurrent chemoradiation with carboplatin with or without adjuvant carboplatin/ fluorouracil in nasopharyngeal cancer: A multicenter randomized trial[J]. Curr Probl Cancer, 2021, 45(1): 100620. doi: 10.1016/j.currproblcancer.2020.100620
[56] Twu CW, Wang WY, Chen CC, et al. Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid[J]. Int J Radiat Oncol Biol Phys, 2014, 89(1): 21-29. doi: 10.1016/j.ijrobp.2014.01.052
[57] Liu YC, Wang WY, Twu CW, et al. Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients[J]. Oral Oncol, 2017, 64: 15-21. doi: 10.1016/j.oraloncology.2016.11.008
[58] Chen JH, Huang WY, Ho CL, et al. Evaluation of oral tegafur-uracil as metronomic therapy following concurrent chemoradiotherapy in patients with non-distant metastatic TNM stage Ⅳ nasopharyngeal carcinoma[J]. Head Neck, 2019, 41(11): 3775-3782. doi: 10.1002/hed.25904
[59] Wang WY, Lin TY, Twu CW, et al. Long-term clinical outcome in nasopharyngeal carcinoma patients with post-radiation persistently detectable plasma EBV DNA[J]. Oncotarget, 2016, 7(27): 42608-42616. http://europepmc.org/articles/PMC5173160/
[60] Wu Y, Wei XY, Yuan ZL, et al. Phase Ⅱ study of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma[J]. Chin J Cancer Res, 2020, 32(5): 665-672.
[61] Lee AW, Ng WT, Pan JJ, et al. International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma[J]. Radiother Oncol, 2018, 126(1): 25-36. doi: 10.1016/j.radonc.2017.10.032
[62] 中国临床肿瘤学会《CSCO鼻咽癌诊疗指南》[M]. 北京: 人民卫生出版社, 2020: 20-34. Chinese society of Clinical Oncology《CSCO guidelines for diagnosis and treatment of nasopharyngeal carcinoma》[M]. Beijing: People's Medical Publishing House, 2020: 20-34.
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