依据TNM分期制定治疗方案。 包括手术切除、放疗、化疗或综合治疗。 目标是在彻底切除病变的前提下尽量保留器官功能。 手术、放疗、放化疗或综合治疗后宜行言语康复治疗。[40]National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. June 2015 [internet publication].http://www.nice.org.uk/guidance/ng12/resources/suspected-cancer-recognition-and-referral-1837268071621[41]NCCN Clinical Practice Guidelines in Oncology. Head and neck cancers. Version 2.2016 [internet publication].https://www.nccn.org/professionals/physician_gls/f_guidelines.asp
声门型或声门上型喉癌:T1和T2期
T1或T2期:N0M0的治疗包括单独手术或放疗。 部分喉手术(即:内镜下激光切除、喉裂开术、声带切除术、喉垂直部分切除术)或放疗在肿瘤控制和生存率上疗效相当。
声门型喉癌,喉保留手术局部肿瘤控制率在86%-98%,5年生存率为92%-97%。[10]Agrawal N, Ha PK. Management of early-stage laryngeal cancer. Otolaryngol Clin North Am. 2008;41:757-769.http://www.ncbi.nlm.nih.gov/pubmed/18570957?tool=bestpractice.com[42]Thomas L, Drinnan M, Natesh B, et al. Open conservation partial laryngectomy for laryngeal cancer: a systematic review of English language literature. Cancer Treat Rev. 2012 May;38(3):203-11.http://www.ncbi.nlm.nih.gov/pubmed/21764220?tool=bestpractice.com 尽管数据有差异,但是总体上治疗 T1 期和 T2 期喉癌的喉保留手术和放射疗法存活率相当。[3]Adams GL, Maisel RH. Malignant tumors of the larynx and hypopharynx. In: Cummings otolaryngology: head and neck surgery. Cummings CW, Flint PW, Harker LA, et al, eds. 4th ed. Philadelphia, PA: Elsevier Mosby; 2005:2222-2283.[43]Feng YW. Comparison of preoperative radiation and surgery with surgery alone for laryngeal carcinoma. Cancer Treat Rev. 2010;17:1949-52.[44]Forastiere AA, Ismaila N, Lewin JS, et al. Use of larynx-preservation strategies in the treatment of laryngeal cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2018 Apr 10;36(11):1143-69.http://ascopubs.org/doi/full/10.1200/JCO.2017.75.7385?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&http://www.ncbi.nlm.nih.gov/pubmed/29172863?tool=bestpractice.com 由经验丰富的医生进行的 T1 期病变内镜切除术,疗效可能优于根治性放射疗法。[44]Forastiere AA, Ismaila N, Lewin JS, et al. Use of larynx-preservation strategies in the treatment of laryngeal cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2018 Apr 10;36(11):1143-69.http://ascopubs.org/doi/full/10.1200/JCO.2017.75.7385?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&http://www.ncbi.nlm.nih.gov/pubmed/29172863?tool=bestpractice.comT1 期喉癌单独放射疗法生存率与手术治疗相当。
对于声门上型喉癌,开放性或内镜下手术与单纯放射疗法效果相当,尽管有研究报告开放手术时,局部肿瘤控制率更高。 [44]Forastiere AA, Ismaila N, Lewin JS, et al. Use of larynx-preservation strategies in the treatment of laryngeal cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2018 Apr 10;36(11):1143-69.http://ascopubs.org/doi/full/10.1200/JCO.2017.75.7385?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&http://www.ncbi.nlm.nih.gov/pubmed/29172863?tool=bestpractice.com T1和T2期喉癌,在条件允许的情况下经口显微激光手术可作为开放性手术、其他喉功能保留手术及放疗以外备选治疗方案。[45]Bradley PJ, Mackenzie K, Wight R, et al. Consensus statement on management in the UK: transoral laser assisted microsurgical resection of early glottic cancer. Clin Otolaryngol. 2009 Aug;34(4):367-73.http://www.ncbi.nlm.nih.gov/pubmed/19673988?tool=bestpractice.com 现在并没有充足的证据表明内镜手术技术优于放疗。[46]Higgins KM, Shah MD, Ogaick MJ, et al. Treatment of early-stage glottic cancer: meta-analysis comparison of laser excision versus radiotherapy. J Otolaryngol Head Neck Surg. 2009 Dec;38(6):603-12.http://www.ncbi.nlm.nih.gov/pubmed/19958721?tool=bestpractice.com[47]Warner L, Chudasama J, Kelly CG, et al. Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev. 2014 Dec 12;(12):CD002027.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002027.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25503538?tool=bestpractice.com 但是声带功能和生活质量方面两者相当。[48]Spielmann PM, Majumdar S, Morton RP, et al. Quality of life and functional outcomes in the management of early glottic carcinoma: a systematic review of studies comparing radiotherapy and transoral laser microsurgery. Clin Otolaryngol. 2010 Oct;35(5):373-82.http://www.ncbi.nlm.nih.gov/pubmed/21108747?tool=bestpractice.com
接受喉部分切除患者,在辅助放疗或放化疗前,推荐行颈淋巴结清扫术。 在一个需治数(NNT)限定为5的系统综述中,为N0和N+的头颈部鳞状细胞癌患者提供了适当的淋巴结治疗的建议。[49]Tandon S, Munir N, Roland NJ, et al. A systematic review and number needed to treat analysis to guide the management of the neck in patients with squamous cell carcinoma of the head and neck. Auris Nasus Larynx. 2011 Dec;38(6):702-9.http://www.ncbi.nlm.nih.gov/pubmed/21315526?tool=bestpractice.com
声门型或声门上型喉癌:T3期
T3 期肿瘤治疗包括同步放化疗或手术治疗。部分喉切除术[42]Thomas L, Drinnan M, Natesh B, et al. Open conservation partial laryngectomy for laryngeal cancer: a systematic review of English language literature. Cancer Treat Rev. 2012 May;38(3):203-11.http://www.ncbi.nlm.nih.gov/pubmed/21764220?tool=bestpractice.com 部分喉切除术或喉全切除术;对于精心挑选的患者,部分喉切除术可以保留发声和吞咽功能。对于原发性 T3 期肿瘤患者,选择手术还是同步放化疗仍有争议。[50]Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg. 2007 Dec;133(12):1270-6.https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/484903http://www.ncbi.nlm.nih.gov/pubmed/18086971?tool=bestpractice.com[51]Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90.http://www.ncbi.nlm.nih.gov/pubmed/2034244?tool=bestpractice.com 若需行喉全切除术,那么放化疗能够更好地保留言语和吞咽功能。然而,一项针对 7,000 多名来自美国国家癌症数据库的患者进行的回顾性观察队列研究发现,在 T3 期喉癌患者中,接受放化疗的患者的死亡风险明显高于行喉全切除术治疗(风险比=1.18;P=0.03)。[50]Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg. 2007 Dec;133(12):1270-6.https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/484903http://www.ncbi.nlm.nih.gov/pubmed/18086971?tool=bestpractice.com T3和T4期肿瘤单独放疗效果要比上文提到的治疗方案的效果差。[50]Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg. 2007 Dec;133(12):1270-6.https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/484903http://www.ncbi.nlm.nih.gov/pubmed/18086971?tool=bestpractice.com[3]Adams GL, Maisel RH. Malignant tumors of the larynx and hypopharynx. In: Cummings otolaryngology: head and neck surgery. Cummings CW, Flint PW, Harker LA, et al, eds. 4th ed. Philadelphia, PA: Elsevier Mosby; 2005:2222-2283.[52]Bourhis JS, Martin LA, ly-Schveitzer NS, 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 Oncology. 2012 Feb;13(2):145-53.http://www.ncbi.nlm.nih.gov/pubmed/22261362?tool=bestpractice.com[53]Ghadjar PS, Zimmermann FB. Concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer: 10-year follow-up of a randomized phase III trial (SAKK 10/94). Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):524-31.http://www.ncbi.nlm.nih.gov/pubmed/21300466?tool=bestpractice.com
顺铂可单独或结合 5-氟尿嘧啶使用。毒性反应较重的患者可换用卡铂或西妥昔单抗治疗。但是,与仅放射 + 顺铂治疗相比,西妥昔单抗另加顺铂结合放射治疗未使结局改善。[54]Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014 Sep 20;32(27):2940-50.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162493/http://www.ncbi.nlm.nih.gov/pubmed/25154822?tool=bestpractice.com 同样,与标准顺铂放化疗相比,改变的分次放射治疗 + 顺铂无任何优势。[55]Nguyen-Tan PF, Zhang Q, Ang KK, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014 Dec 1;32(34):3858-66.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239304/http://www.ncbi.nlm.nih.gov/pubmed/25366680?tool=bestpractice.com
放化疗后颈部肿物长期存在或喉切除术伴有颈部阳性发现时需行颈淋巴清扫术。[49]Tandon S, Munir N, Roland NJ, et al. A systematic review and number needed to treat analysis to guide the management of the neck in patients with squamous cell carcinoma of the head and neck. Auris Nasus Larynx. 2011 Dec;38(6):702-9.http://www.ncbi.nlm.nih.gov/pubmed/21315526?tool=bestpractice.com然而,放化疗后是否行颈部淋巴结清扫术仍有争议。[56]Wee JT, Anderson BO, Corry J, et al. Management of the neck after chemoradiotherapy for head and neck cancers in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009 Nov;10(11):1086-92.http://www.ncbi.nlm.nih.gov/pubmed/19880062?tool=bestpractice.com
术后可利用辅助化疗管理某些不良的肿瘤特征(如切缘阳性、>4 个淋巴结、囊外扩散)。[57]Lefebvre JL, Ang KK; Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: key issues and recommendations: a consensus panel summary. Head Neck. 2009 Apr;31(4):429-41.http://www.ncbi.nlm.nih.gov/pubmed/19283793?tool=bestpractice.com参考当地专科医生治疗方案作为给药指导。
同步放化疗比序贯放化疗或单独放疗可更好地保留喉功能和局部区域肿瘤控制。[58]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 Mar 1;31(7):845-52.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/http://www.ncbi.nlm.nih.gov/pubmed/23182993?tool=bestpractice.com
声门型和声门上型喉癌:T4期
治疗包括同步放化疗或手术治疗。 可能需要颈淋巴结清扫或辅助(术后)放疗。 无有效治疗方案或有相关治疗禁忌者应姑息性治疗,包括化疗。
若未累及软骨,放化疗和手术治疗效果相当。 若累及软骨,则推荐行全喉切除。[3]Adams GL, Maisel RH. Malignant tumors of the larynx and hypopharynx. In: Cummings otolaryngology: head and neck surgery. Cummings CW, Flint PW, Harker LA, et al, eds. 4th ed. Philadelphia, PA: Elsevier Mosby; 2005:2222-2283.[59]Hristov B, Bajaj GK. Radiotherapeutic management of laryngeal carcinoma. Otolaryngol Clin North Am. 2008 Aug;41(4):715-40.http://www.ncbi.nlm.nih.gov/pubmed/18570955?tool=bestpractice.com 病变侵及软骨,阳性或邻近切缘,多发颈淋巴结肿大,或包膜外侵者,推荐行术后辅助放疗。 放化疗后颈部病变持续存在或术后颈部淋巴结转移阳性者则需行颈淋巴清扫术。[49]Tandon S, Munir N, Roland NJ, et al. A systematic review and number needed to treat analysis to guide the management of the neck in patients with squamous cell carcinoma of the head and neck. Auris Nasus Larynx. 2011 Dec;38(6):702-9.http://www.ncbi.nlm.nih.gov/pubmed/21315526?tool=bestpractice.com 然而颈部 N0 患者放化疗后颈淋巴清扫术的作用仍存争议。[56]Wee JT, Anderson BO, Corry J, et al. Management of the neck after chemoradiotherapy for head and neck cancers in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009 Nov;10(11):1086-92.http://www.ncbi.nlm.nih.gov/pubmed/19880062?tool=bestpractice.com 已有证据显示放疗后复发的患者行开放喉部分切除术局部肿瘤控制效果良好,尽管在目前这一技术尚未广泛使用。[60]Paleri V, Thomas L, Basavaiah N, et al. Oncologic outcomes of open conservation laryngectomy for radiorecurrent laryngeal carcinoma: a systematic review and meta-analysis of English-language literature. Cancer. 2011 Jun 15;117(12):2668-76.http://www.ncbi.nlm.nih.gov/pubmed/21287526?tool=bestpractice.com
化疗药物的选择同T3期肿瘤患者。 肿瘤生物学行为不良者术后需行辅助放疗(如:血管淋巴或周围神经侵犯,包膜外侵犯)。[57]Lefebvre JL, Ang KK; Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: key issues and recommendations: a consensus panel summary. Head Neck. 2009 Apr;31(4):429-41.http://www.ncbi.nlm.nih.gov/pubmed/19283793?tool=bestpractice.com
向治疗无效或因全身情况等无法接受治疗的患者提供支持治疗(如疼痛控制、心理咨询)。 尽管喉癌治疗中单独化疗不起作用,但其可作为一种姑息治疗辅助手段。[61]Ferlito A, Haigentz M Jr, Bradley PJ, et al. Causes of death of patients with laryngeal cancer. Eur Arch Otorhinolaryngol. 2014 Mar;271(3):425-34.http://www.ncbi.nlm.nih.gov/pubmed/23591796?tool=bestpractice.com 西妥昔单抗是单克隆抗体,特异性结合在上皮组织中表达的表皮生长因子受体 (EGFR),抑制表达 EGFR 的肿瘤细胞生长。尽管有研究表明放疗结合西妥昔单抗优于单独放疗,尚无随机对照试验比较西妥昔单抗与顺铂的优劣。[62]Caudell JJ, Sawrie SM, Spencer SA, et al. Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment. Int J Radiat Oncol Biol Phys. 2008 Jul 1;71(3):676-81.http://www.ncbi.nlm.nih.gov/pubmed/18355979?tool=bestpractice.com[63]Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78.http://www.nejm.org/doi/full/10.1056/NEJMoa053422#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/16467544?tool=bestpractice.com
同步放化疗比序贯放化疗或单独放疗可更好地保留喉功能和局部区域肿瘤控制。[58]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 Mar 1;31(7):845-52.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/http://www.ncbi.nlm.nih.gov/pubmed/23182993?tool=bestpractice.com
声门下型喉癌
声门下型喉癌,全喉切除加颈淋巴结清扫(包括切除甲状腺),术后放疗。
复发
体格检查包括喉镜是最重要的发现复发的检查方法。
在怀疑复发或肿瘤持续存在的情况下影像学检查和体格检查至关重要。 各种影像学检查均需活检确诊。[64]Brouwer J, Hooft L, Hoekstra OS, et al. Systematic review: accuracy of imaging tests in the diagnosis of recurrent laryngeal carcinoma after radiotherapy. Head Neck. 2008 Jul;30(7):889-97.http://www.ncbi.nlm.nih.gov/pubmed/18213716?tool=bestpractice.com 挽救性手术是可以且适合手术的复发性喉癌的标准治疗方案。 可考虑行术后再次放疗。 有治愈目标的再次放疗患者,应常规加做化疗。[65]American College of Radiology. ACR Appropriateness Criteria: retreatment of recurrent head and neck cancer after prior definitive radiation. 2014 [internet publication].https://acsearch.acr.org/docs/69506/Narrative/