口咽癌明确治疗后的生存期主要取决于疾病的分期及承受标准治疗的能力。HPV-16阳性患者的生存期可能更好。[58]Nichols AC, Faquin WC, Westra WH, et al. HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009;140:228-234.http://www.ncbi.nlm.nih.gov/pubmed/19201294?tool=bestpractice.com[59]Lassen P, Eriksen JG, Hamilton-Dutoit S, et al. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27:1992-1998.http://www.ncbi.nlm.nih.gov/pubmed/19289615?tool=bestpractice.com[60]Fakhry C, Westra W, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261-269.http://jnci.oxfordjournals.org/cgi/content/full/100/4/261http://www.ncbi.nlm.nih.gov/pubmed/18270337?tool=bestpractice.com[100]Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28:4142-4148.http://www.ncbi.nlm.nih.gov/pubmed/20697079?tool=bestpractice.com[101]Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24-35.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943767/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/20530316?tool=bestpractice.com
对HPV-16诱发的口咽癌来说,由于观察到肿瘤蛋白E6在放疗中可以增加细胞凋亡的速度,这种蛋白的存在可能会提高生存期。[97]Pang E, Delic NC, Hong A, et al. Radiosensitization of oropharyngeal squamous cell carcinoma cells by human papillomavirus 16 oncoprotein E6∗I. Int J Radiat Oncol Biol Phys. 2011;79:860-865.http://www.ncbi.nlm.nih.gov/pubmed/21106305?tool=bestpractice.com肿瘤标本中表皮生长因子受体(EGFR)表达增加提示预后较差,在未来的前瞻性研究中应强调生物标志物的重要性。[98]Young R, Rischin D, Fisher R, et al. Relationship between epidermal growth factor receptor status, p16INK4A and outcome in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2011;20(6):1230-1237.http://www.ncbi.nlm.nih.gov/pubmed/21467228?tool=bestpractice.com将来,考虑到这些生物标志物的存在与否,传统的治疗方法可能会改变。
未来的前瞻性研究可能将HPV作为分组因素。相比高龄组(>50岁),低龄(<50岁)扁桃体癌有更好的肿瘤特异性生存率。目前还不清楚这种年龄相关获益与低龄患者HPV-16高感染率相关还是与其治疗耐受性好相关。[102]Nguyen NP, Ly BH, Betz M, et al. Importance of age as a prognostic factor fortonsillar carcinoma. Ann Surg Oncol. 2010;17:2570-2577.http://www.ncbi.nlm.nih.gov/pubmed/20559738?tool=bestpractice.comI期及II期口咽癌的生存率高,5年生存率约为80%到90%。[53]Cosmidis A, Rame JP, Dassonville O, et al. T1-T2 N0 oropharyngeal cancers treated with surgery alone: a GETTEC study. Eur Arch Otorhinolaryngol. 2004;261:276-281.http://www.ncbi.nlm.nih.gov/pubmed/14551793?tool=bestpractice.com[54]Parsons JT, Mendenhall WM, Stringer SP, et al. Squamous cell carcinoma of the oropharynx: surgery, radiotherapy, or both. Cancer. 2002;94:2967-2980.http://www3.interscience.wiley.com/cgi-bin/fulltext/93521249/HTMLSTARThttp://www.ncbi.nlm.nih.gov/pubmed/12115386?tool=bestpractice.com[66]Le Scodan R, Pommier P, Ardiet JM, et al. Exclusive brachytherapy for T1 and T2 squamous cell carcinomas of the velotonsillar area: results in 44 patients. Int J Radiat Oncol Biol Phys. 2005;63:441-448.http://www.ncbi.nlm.nih.gov/pubmed/16168837?tool=bestpractice.com[67]Levendag P, Nijdam W, Noever I, et al. Brachytherapy versus surgery in carcinoma of tonsillar fossa and/or soft palate: late adverse sequelae and performance status: can we be more selective and obtain better tissue sparing? Int J Radiat Oncol Biol Phys. 2004;59:713-724.http://www.ncbi.nlm.nih.gov/pubmed/15183475?tool=bestpractice.com治疗的发病率和死亡率是手术和放疗之间主要选择的因素。可切除的局部晚期疾病(Ⅲ,Ⅳ期),3年生存率为60%到70%。[74]Adelstein DJ, Saxton JP, Lavertu P, et al. A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck. 1997;19:567-575.http://www.ncbi.nlm.nih.gov/pubmed/9323144?tool=bestpractice.com[103]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.http://content.nejm.org/cgi/content/full/350/19/1945http://www.ncbi.nlm.nih.gov/pubmed/15128894?tool=bestpractice.com局部不可切除疾病(IVB期),三年生存率为40%-55%。[77]Bensadoun RJ, Benezery K, Dassonville O, et al. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: results at 2 years (FNCLCC-GORTEC). Int J Radiat Oncol Biol Phys. 2006;64:983-994.http://www.ncbi.nlm.nih.gov/pubmed/16376489?tool=bestpractice.com[76]Budach V, Stuschke M, Budach W, et al. Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the Radiotherapy Cooperative Clinical Trials Group of the German Cancer Society 95-06 Prospective Randomized Trial. J Clin Oncol. 2005;23:1125-1135.http://jco.ascopubs.org/cgi/content/full/23/6/1125http://www.ncbi.nlm.nih.gov/pubmed/15718308?tool=bestpractice.com[78]Staar S, Rudat V, Stuetzer H, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy: results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001;50:1161-1171 (erratum in: Int J Radiat Oncol Biol Phys 2001;51:569).http://www.ncbi.nlm.nih.gov/pubmed/11483325?tool=bestpractice.com[79]Semrau R, Mueller RP, Stuetzer H, et al. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006;64:1308-1316.http://www.ncbi.nlm.nih.gov/pubmed/16464538?tool=bestpractice.com[80]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 chemoradiotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004;22:69-76.http://jco.ascopubs.org/cgi/content/full/22/1/69http://www.ncbi.nlm.nih.gov/pubmed/14657228?tool=bestpractice.com[81]Calais G, Alfonsi M, Bardet E, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999;91:2081-2086.http://jnci.oxfordjournals.org/cgi/content/full/91/24/2081http://www.ncbi.nlm.nih.gov/pubmed/10601378?tool=bestpractice.com[82]Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Eng J Med. 1998;338:1798-1804.http://content.nejm.org/cgi/content/full/338/25/1798http://www.ncbi.nlm.nih.gov/pubmed/9632446?tool=bestpractice.com有转移的患者预后较差,中位生存期为7到10个月。[63]Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1126-1127.http://content.nejm.org/cgi/content/full/359/11/1116http://www.ncbi.nlm.nih.gov/pubmed/18784101?tool=bestpractice.com[89]Burtness B, Goldwasser MA, Flood W, et al. A phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23:8646-8654 (erratum in: J Clin Oncol. 2006;24:724).http://jco.ascopubs.org/cgi/content/full/23/34/8646http://www.ncbi.nlm.nih.gov/pubmed/16314626?tool=bestpractice.com
新的放射治疗技术,如调强放射治疗(IMRT),由于其对正常组织影响小,使患者的生活质量有潜在提高。头颈部癌症的患者行调强放疗后口干的报告率降低,且局部病灶控制或生存率无明显改变。由于其对咽部肌肉的影响减低,吞咽困难和误吸的发生率也会减少。[104]Guha S, Kelly CG, Guha R, et al. Intensity modulated radiation therapy (IMRT) in the treatment of squamous carcinoma of the oropharynx: an overview. J Cancer Sci Ther. 2012;4:077-083.目前标准的辐射剂量可能无法有效地控制预后不良的口咽癌,如表皮生长因子受体(EGFR)阳性肿瘤。未来,对这些患者,需要IMRT的剂量递增来达到更好的局部控制。[105]Gupta T, Jain S, Agarwal JF, et al. Prospective assessment of patterns of failure after high-precision definitive (chemo)radiation in head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2011;80:522-531.http://www.ncbi.nlm.nih.gov/pubmed/20646862?tool=bestpractice.comIMRT可以降低头颈部癌放化疗期间约3-4级的毒性,与传统放疗相比,可以提高放疗耐受性。[106]Al-Mamgani A, Van Rooij P, Tans L, et al. Toxicity and outcome of intensity-modulated radiotherapy versus 3-dimensional conformal radiotherapy for oropharyngeal cancer: a matched-pair analysis. Technol Cancer Res Treat. 2013;12:123-130.http://www.ncbi.nlm.nih.gov/pubmed/23098281?tool=bestpractice.com图像引导放射治疗(IGRT)是一种特殊类型的调强放射治疗(IMRT),是放射疗法中的很有前景的新技术,因为它降低了对正常组织的辐射剂量。[99]Nguyen NP, Ceizyk M, Vos P, et al. Feasibility of tomotherapy-based image-guided radiotherapy for locally advanced oropharyngeal cancer. PLoS One. 2013;8:e60268.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610680/http://www.ncbi.nlm.nih.gov/pubmed/23555938?tool=bestpractice.com