Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer
Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer
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DOI：
10.1200/jco.2011.38.4099
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发表时间：
2012-06-10
影响因子：
45.3
通讯作者：
Ang, K. Kian
中科院分区：
文献类型：
--
作者：
Gillison, Maura L.;Zhang, Qiang;Ang, K. Kian
目的：吸烟与口咽癌存活相关，但癌症进展或死亡随着吸烟增加而增加到何种程度尚不清楚。患者和方法入选1991 - 1997年放疗（放射治疗肿瘤组[RTOG] 9003）或2002 - 2005年放化疗（RTOG 0129） III期临床试验的口咽癌患者通过替代物、p16免疫组化和标准化问卷评估肿瘤人乳头瘤病毒状态和烟草暴露。通过Cox比例风险模型估计烟草暴露与总生存期（OS）和无进展生存期（PFS）之间的关系。结果RTOG 9003和RTOG 0129中p16阳性肿瘤的患病率分别为39.5%和68.0%。两项试验中p16阳性患者吸烟的中位包年均低于p16阴性患者（RTOG 9003: 29 v 45.9包年，P = 0.02； RTOG 0129: 10 v 40包年，P < 0.001）。在校正p16和其他因素后，两项试验的进展（PFS）或死亡（OS）风险每包年增加1%（两项试验的风险比[HR]为1.01；95% CI为1.00至1.01;P = 0.002）或吸烟每年增加2%（两项试验的风险比[HR]为1.02；95% CI为1.01至1.03;P < 0.001）。在RTOG 9003中，考虑到包年和其他因素后，放疗期间吸烟的患者死亡风险增加了一倍（HR, 2.19; 95% CI, 1.46 ~ 3.28），第二原发肿瘤的风险每包年增加1.5% （HR, 1.015; 95% CI, 1.005 ~ 1.026）。结论口咽癌的进展和死亡风险与烟草暴露在诊断和治疗期间直接相关，与肿瘤p16状态和治疗无关。
PurposeTobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown.Patients and MethodsPatients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models.ResultsPrevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026).ConclusionRisk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.