Narayana A, Vaughan A T, Fisher S G, Reddy S P
Department of Radiation Oncology, Loyola University Medical Center and Hines V.A. Hospital, Maywood, IL 60153, USA.
Int J Radiat Oncol Biol Phys. 1998 Oct 1;42(3):557-62. doi: 10.1016/s0360-3016(98)00250-8.
The development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients, whose first tumor has been successfully treated. New methods of examining genetic changes have raised doubts about the validity of the widely held field cancerization hypothesis as the cause of SPTs, and an alternative hypothesis of monoclonal origin has been proposed. The objectives of this study were to look at the pattern of development of SPTs and the possible factors influencing the incidence of SPTs and the survival in early-stage laryngeal cancer with long-term follow-up.
One hundred forty-four consecutive patients of T1N0M0 squamous cell carcinoma of the true vocal cord treated with definitive radiotherapy between 1976 and 1992 were analyzed. The incidence, time to development, and survival of aerodigestive and other SPTs were noted. p53 overexpression indicating a mutated p53 gene was analyzed by immunohistochemistry.
With a median follow-up of 6 years (range 2-20 years), 42 patients developed a SPT, 24 in upper aerodigestive tract and lung and 18 at other sites. The actuarial incidence of developing a SPT at 5, 10, and 15 years was 23%, 44%, and 48.7% respectively. The median time interval for development of SPT in an upper aerodigestive tract was 21 months as opposed to 50 months for other sites (p = 0.02). The most common sites of SPTs included lung for upper aerodigestive tract; and prostate, followed by colon, for other sites. The actuarial risk of developing a nonaerodigestive SPT at 5 and 10 years was 35% and 55% respectively. p53 status affected neither the incidence of SPT nor the survival. SPTs were the leading cause of death in these early-stage laryngeal cancer patients.
The origin of SPTs seems to be multifactorial, involving both the field cancerization effect and an increased baseline genetic predisposition. Until more reliable genetic markers are developed, chemoprevention remains the best treatment option at preventing SPTs in these early-stage patients.
第二原发肿瘤（SPT）的发生是决定早期头颈癌患者生存的最重要因素，这些患者的首个肿瘤已得到成功治疗。检测基因变化的新方法对广泛认可的场癌化假说作为SPT病因的有效性提出了质疑，并且有人提出了单克隆起源的替代假说。本研究的目的是通过长期随访观察SPT的发生模式以及影响早期喉癌患者SPT发生率和生存的可能因素。
分析了1976年至1992年间连续接受根治性放疗的144例T1N0M0真性声带鳞状细胞癌患者。记录了气消化道及其他SPT的发生率、发生时间和生存情况。通过免疫组织化学分析p53过表达情况，其表明p53基因发生突变。
中位随访时间为6年（范围2至20年），42例患者发生了SPT，其中24例发生在上消化道和肺部，18例发生在其他部位。5年、10年和15年发生SPT的精算发生率分别为23%、44%和48.7%。上消化道发生SPT的中位时间间隔为21个月，而其他部位为50个月（p = 0.02）。SPT最常见的部位，上消化道为肺部；其他部位为前列腺，其次是结肠。5年和10年发生非气消化道SPT的精算风险分别为35%和55%。p53状态既不影响SPT的发生率，也不影响生存。SPT是这些早期喉癌患者的主要死亡原因。
SPT的起源似乎是多因素的，涉及场癌化效应和基线遗传易感性增加。在开发出更可靠的基因标志物之前，化学预防仍然是预防这些早期患者发生SPT的最佳治疗选择。
