NCCN头颈部肿瘤临床实践指南2017.2版（16）
目录
放疗技术1-8
RAD-A，1/5：
●靶区勾画和最佳剂量分布需要有头颈部影像学的经验以及对肿瘤转移方式的透彻理解。靶区的划定、剂量的确立、分割（联合或不联合同步化疗）和正常组织剂量限制的标准仍在探索中。依据肿瘤的分期、肿瘤的部位、物理师的培训/经验以及现有的设备，可适当地采用IMRT或其他适形技术（三维适形、螺旋断层放疗、 容积旋转调强放疗[VMAT]和质子束治疗[PBT]）。* 照射工艺、技术、分割和化疗选择之间存在着密切的相互作用，从而出现了大量的联合方案，这些可能影响毒性或肿瘤控制。多学科密切合作和管理对制订治疗计划和设置放射靶区至关重要，特别是当放疗用于术后或诱导化疗后。9在制订诊疗计划时可使用FDG-PET/CT或增强MRI的融合技术。
●先进的放疗技术，比如IMRT、IGRT（影像引导下的放射治疗）和PBT，在一些特定情况下，可能提供临床相关的优势，避开重要危及器官（OARs），如脑、脑干、耳蜗、半规管、视交叉和神经、其他颅神经、视网膜、泪腺、角膜、脊髓、臂丛、黏膜、唾液腺、骨（颅底和下颌骨）、咽缩肌、喉和食管；在仍能实现局部肿瘤控制的同时降低迟发的、正常组织损害风险。这些危及器官显著避开剂量的表现，反应了最佳的临床实践。
●由于这些技术的优势包括紧密的适形剂量和周围正常组织陡峭的剂量坡度，靶区的确定和勾画以及治疗执行的确认需要密切的监测以避开肿瘤区域缺失的风险及随后局部肿瘤控制的下降。初始的诊断性影像检查（增强CT、MRI、PET和其他影像学）有助于靶区的确定。需要影像学引导以提供每日精确治疗的保证。
●由于上述特定的临床情况相对少，因此不太可能通过随机研究去验证这些观点。有鉴于此，应考虑采用最有效减少危及器官剂量（有临床意义的）而又不影响靶区覆盖的方式和技术。
注解：
*：有关放疗技术的更多资源，请参阅美国放射学会指南：
http://www.acr.org/Quality-Safety/Standards-Guidelines/Practice-Guidelines-by-Modality/Radiation-Oncology.
RAD-A，2/5：
调强放疗（IMRT）
IMRT已被证明在口咽、鼻旁窦和鼻咽癌患者可通过减少唾液腺、颞叶、听力结构（包括耳蜗）和视觉组织的照射剂量来有效减少长期毒性。IMRT用于其他部位的肿瘤（比如口腔、喉部、下咽、唾液腺）正在探索中，可能根据治疗医师酌情采用。螺旋断层放疗和容积弧形调强放射治疗（VMAT）是IMRT的先进模式。
调强放疗（IMRT）、 质子束放疗（PBT）和剂量分割10-12
IMRT或PBT的靶区剂量和分割有多种方式。在整个放疗过程的每次分割治疗中，同步推量照射（SIB）技术使用不同的“剂量绘制”（肉眼可见肿瘤 66-74Gy；亚临床病灶 50-60Gy)。4SIB通常用于常规分割（5 f/周）和“6 f/周加速分割”。5序贯（SEQ）技术通常在起始期（第1-5周）采用低剂量，序贯推量期（第6-7周）采用高剂量（使用2-3个分开的剂量计划），通常用于标准分割和超分割。同步推量加速计划可能使用“调整的序贯（Modified SEQ）”剂量计划，6周内亚临床靶区每日给予1次剂量，在治疗的最后12天每天追加一个推量。6
质子束放疗
对于那些原发灶在眼周围和/或侵犯眼眶、颅底、和/或海绵窦，延伸至颅内或存在广泛的神经旁侵犯，以及那些以根治为目标和/或那些治疗后预期能获得长时间生存的患者，得到高度适形的剂量分布尤其重要。非随机的单中心临床报告和系统对比，显示出在上述所提及的特定临床情况下质子治疗的安全性和有效性。29-49
RAD-A，3/5：
姑息性放疗
●对于晚期肿瘤，当不适合接受以根治为目标的治疗时，应考虑姑息性放疗。
●目前对头颈部肿瘤适宜的姑息性放疗方案尚没有达成普遍共识。对于那些全身状况不适合行标准放疗或那些广泛转移的患者，如果放疗毒性是可接受的，姑息性放疗可考虑用于缓解和预防局部症状。放疗方案应个体化制定；当治疗目的为姑息性时，应避免严重的放疗毒性。推荐的放疗方案包括：
►50 Gy/20 f；13
►37.5 Gy/15 f (若耐受性好，考虑追加5次至总剂量50 Gy)；
►30 Gy/10 f；
►30 Gy/5 f：** 每周2次，每2次治疗之间间隔≥3 天，和14
►44.4 Gy/12 f，分3周期（每个周期，连续2天，间隔6小时给予2次分割剂量，而且第二周期后治疗必须除外脊髓)。15,16 间隔1-3周应进行重新评估。
●当鼓励应用更短的治疗周期时，必须根据分割剂量的大小仔细评估脊髓和神经组织的剂量耐受。
●仔细评估患者的临床表现、治疗耐受性、肿瘤反应、和/或全身进展。其他姑息/支持治疗在有指征情况下，包括止痛、营养支持、靶向治疗或化疗（见支持治疗NCCN指南）。
三维适形放疗、SBRT、 PBT或 IMRT17-28
●强烈建议患者在再程放疗前，由大规模头颈部肿瘤中心的多学科团队评估。
●出现新发病灶的时间距离先前的放疗应该超过6个月。
●再程放疗前，患者的ECOG功能状态评分应在0-1分。
●治疗小组必须能够制定一个再程放疗计划，根据靶区体积和先前的放射治疗与预期的再放疗之间的时间间隔来限制CNS组织的放射累积剂量。
●放疗靶区应仅包括已知的病变，没必要对其他区域进行预防性放疗。
●SBRT技术建议选择用于那些无颈动脉周围侵犯的患者。
●目前所应用或研究的SBRT计划，范围为30-44 Gy/5 f。
●对于那些无法切除的头颈部肿瘤患者，应强烈推荐参与再程放疗的临床研究机会。
注解：
**：对于终末期肿瘤患者，由于预后非常有限，患者可以接受更多的高分割计划。
RAD-A，4/5：
参考文献：
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RAD-A，5/5：
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33.Russo AL, Adams JA, Weyman EA, et al. Long-term outcomes after proton beam therapy for sinonasal squamous cell carcinoma. Int J Radiation Oncol Biol Phys 95(1):368-376.
34.Dagan R, Bryant C, Li Z, et al. Outcomes of sinonasal cancer treated with proton therapy. Int J Radiat Oncol Biol Phys 2016;95(1):377-385.
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36.Holliday EB, Bhattasali O, Kies MS, et al. Effective use of intensity-modulated proton therapy for robust delivery of post-operative radiation for head and neck adenoid cystic carcinoma. Int J Part Ther 2016;533-543.
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全身治疗原则
全身治疗的选择应该根据患者的特点（PS,治疗目标）而个体化
CHEM-A，1/5：
●针对全身状态良好的局部晚期患者首选的放化疗路径仍为同步顺铂+放疗。
●可应用以顺铂为基础的诱导化疗，序贯基于放疗的局部治疗（如，序贯性放化疗）。然而，联合诱导化疗对比开始直接接受最新水平的同步放化疗（首选顺铂，1类证据）在总生存上尚未有证据提示有改善。对比诱导化疗后序贯放化疗以及单独同步放化疗的随机III期临床研究仍在进行中，联合诱导化疗尚没有令人信服的生存获益。
●因担心毒性，不推荐顺铂为基础的诱导化疗后序贯高剂量、每3周一次的顺铂同步放化疗。1,2
●诱导化疗后，可选择多种方式用于放疗为基础的治疗。单纯放疗对比放疗+每周卡铂或西妥昔单抗治疗，均在这些选择中。
鳞状细胞癌
唇、口腔、口咽、下咽、声门型喉癌、声门上喉癌、筛窦癌、上颌窦癌、原发灶不明：
●初始全身治疗+同步放疗
►高剂量顺铂3,4（首选）（1类推荐）
►西妥昔单抗5（对于口咽癌、下咽癌和喉癌，为1类推荐；对于唇癌、口腔癌、筛窦癌、上颌窦癌、原发灶不明肿瘤为2B类推荐）
►卡铂/静脉滴注5-FU（1类推荐）6,7
►5-FU/羟基脲8
►顺铂/紫杉醇8
►顺铂/静脉滴注5-FU9
►卡铂/紫杉醇10（2B类推荐）
►每周顺铂40mg/m2 (2B类推荐)11,12
●术后放化疗
►顺铂13-17（对于高危**非口咽癌为1类推荐）
鼻咽：
●放化疗后序贯辅助化疗
►顺铂+放疗，序贯顺铂/5-FU18-19
或卡铂/5-FU20（卡铂/5-FU为2B类推荐）
●顺铂+放疗后无辅助化疗21（2B类推荐）
唇、口腔、口咽、下咽、声门型喉癌、声门上喉癌、筛窦癌、上颌窦癌、原发灶不明：
●诱导*/序贯化疗
►多西紫杉醇/顺铂/5-FU22-24（若选择诱导化疗，为1类推荐）
►紫杉醇/顺铂/静脉滴注5-FU25
►诱导化疗后，用于同步放化疗的药物通常包括每周卡铂或西妥昔单抗1,26,27
鼻咽：
●诱导（3类推荐）/序贯放化疗
►多西紫杉醇/顺铂/5-FU28
►多西紫杉醇/顺铂（2B类推荐）29
►顺铂/5-FU23
►顺铂/表阿霉素/紫杉醇
►诱导化疗后，用于同步放化疗的药物通常包括每周顺铂19或卡铂26
注解：
*诱导治疗的证据和共识类别因部位而异。（见头颈部目录里中特定部位的肿瘤）
**不良特征：淋巴结包膜外扩散和/或阳性切缘。
CHEM-A，2/5：
●全身治疗的选择应该根据患者的特点（PS，治疗目标）而个体化。
●除非另有规定，下方的方案对于鼻咽癌或非鼻咽癌均可用。
复发，无法切除或转移癌
（不适于手术或放疗）
●联合治疗
►顺铂或卡铂/5-FU/西妥昔单抗30（非鼻咽癌）（1类推荐）
►顺铂或卡铂/多西紫杉醇31或紫杉醇32
►顺铂/西妥昔单抗33（非鼻咽癌）
►顺铂/5-FU32,34
► 顺铂或卡铂/多西紫杉醇/西妥昔单抗35（非鼻咽癌）
►顺铂或卡铂/紫杉醇/西妥昔单抗36,37（非鼻咽癌）
►卡铂/西妥昔单抗38（鼻咽癌）
►顺铂/吉西他滨39（鼻咽癌）
►吉西他滨/长春瑞滨40（鼻咽癌）
●单药治疗
►顺铂33,41
►卡铂42
►紫杉醇43
►多西紫杉醇44,45
►5-FU41
► 甲氨蝶呤46,47
►西妥昔单抗48（非鼻咽癌）
►吉西他滨49（鼻咽癌）
►卡培他滨50
►阿法替尼51(非鼻咽癌,当在含顺铂的化疗中或化疗后疾病进展时）（2B类推荐）
► Pembrolizumab52,53(非鼻咽癌,当在含顺铂化疗中或化疗后疾病进展时）
►Nivolumab54(非鼻咽癌,当在含顺铂化疗中或化疗后疾病进展时）（1类推荐 ）
CHEM-A，3/5：
1.Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 2013;31:853-859.
2.Adelstein DJ, Moon J, Hanna E, et al. Docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin in patients with advanced squamous cell head and neck cancer: A Southwest Oncology Group phase II trial (S0216). Head Neck. 2010;32:221-228.
3.Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31:845-852.
4.Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21(1):92-98.
5.Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21-28.
6.Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004;22:69-76.
7.Bourhis J, Sire C, Graff P, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol 2012;13:145-153.
8.Garden AS, Harris J, Vokes EE, et al. Preliminary results of Radiation Therapy Oncology Group 97-03: A randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol 2004;22:2856-2864.
9.Taylor S, Murthy A, Vannetzel J, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 1994;12:385-395.
10.Suntharalingam M, Haas ML, Conley BA, et al. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys 2000;47:49-56.
11.Beckmann GK, Hoppe F, Pfreundner L, et al. Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer. Head Neck 2005;27:36-43.
12.Medina JA, Rueda A, de Pasos AS, et al. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol 2006;79:34-38.
13.Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-1944.
14.Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-1952.
15.Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843-850.
16.Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys 1996 Dec 1;36:999-1004.
17.Cooper JS, Zhang Q, Pajak TF, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012;84:1198-1205.
CHEM-A，4/5：
18.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 Clin Oncol 1998;16:1310-1317.
19.Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2005;97:536-539.
20.Dechaphunkul T, Pruegsanusak K, Sangthawan D, et al. Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5- fluorouracil in locally advanced nasopharyngeal carcinoma. Head Neck Oncol 2011;3:30.
21.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. Lancet Oncol 2012;13:163-171.
22.Vermorken JB, Remenar E, van Herpen C, et al; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357(17):1695-1704.
23.Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357(17):1705-1715.
24.Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation.
J Natl Cancer Inst 2009;101:498-506.
25.Hitt R, López-Pousa A, Martínez-Trufero J, et al. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol 2005;23:8636-8645.
26.Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial. Eur J Cancer 2007;43:1399-1406.
27.Haddad R, O'Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 2013;14:257-264.
28.Bae WK, Hwang JE, Shim HJ, et al. Phase II study of docetaxel, cisplatin and 5FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced npc. Cancer Chem other Pharmacol 2010; 65:589-595.
29.Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol 2009;27:242-249.
30.Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-1127.
31.Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest 2007;25:182-188.
32.Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23:3562-3567.
33.Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo versus cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An Eastern Cooperative Oncology Group Study. J Clin Oncol 2005;23:8646-8654.
34.Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus flurouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous cell carcinoma of the head and neck: A Southwest Oncology Group Study. J Clin Oncol 1992;10:1245-1251.
35.Guigay J, Fayette J, Dillies A-F, et al. Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial GORTEC 2008-03 [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract 5505.
36.Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012;13:35-46.
37.Herbst RS, Arquette M, Shin DM, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005;23:5578-5587.
CHEM-A，5/5：
38.Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005;23:3568-3576.
39.Jin Y, Cai XY, Shi YX, et al. Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2012 Oct;138(10):1717-25.
40.Chen C, Wang FH, Wang ZQ, et al. Salvage gemcitabine-vinorelbine chemotherapy in patients with metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol 2012;48:1146-1151.
41.Jacobs C, Lyman G, Velez-García E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck J Clin Oncol 1992;10:257-263.
42.Al-Sarraf M, Metch B, Kish J, et al. Platinum analogs in recurrent and advanced head and neck cancer: a Southwest Oncology Group and Wayne State University Study.Cancer Treat Rep 1987;71:732-736.
43.Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol 2009;129:1294-1299.
44.Catimel G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol 1994;5:533-537.
45.Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer 2004;40:2071-2076.
46.Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol 2009;27:1864-1871.
47.Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol 1992;10:1245-1251.
48.Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 2007;25:2171-2177.
49.Zhang L, Zhang Y, Huang PY, et al. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol 2008;61:33-38. Epub 2007 Mar 20.
50.Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer 2010;102:1687-1691.
51.Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol 2015;16:583-594.
52.Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956-965.
53.Chow LQ, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol 2016.
54.Ferris R, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856-1867.
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