SURVEILLANCE AND CHEMOPREVENTION FOR SECOND LUNG CANCERS

肺癌治疗的主要障碍之一是它的出现晚，治疗的选择主要是姑息性的。缺乏有效的治疗强调了重新评估当前管理策略的紧迫性。随着诊断技术的进步和对肿瘤生物学的了解，是时候重新审视早期肺癌检测的潜在影响，并探索新的治疗前沿，如化学预防。以前的研究表明，接受过根治性手术治疗的肺癌患者患第二原发癌(SPLC)的风险很高。然而，目前还没有关于监测或干预的具体指导方针。因此，这项试验性建议的目的是：1)评估联合痰分析(细胞学和免疫染色)、荧光(LIFE)支气管镜和螺旋CT作为监测SPLC和/或根治性手术治疗后复发的策略的可行性和可行性；2)评估环氧合酶-2(COX-2)抑制物在第二原发癌或复发肿瘤病变化学预防中的有效性和可行性；3)评估COX-2在该患者队列中的表达模式，以提供对COX-2抑制剂作用的生物学见解。为了实现这些目标，将招募120名有I期非小细胞肺癌(NSCLC)病史并接受根治性切除的患者。所有受试者都将按照预定的算法接受一系列检查，包括痰分析、纤维支气管镜检查和螺旋CT。受试者还将以双盲方式随机接受安慰剂或环氧合酶-2抑制剂-口服塞来昔布作为化学预防药物。由于肺癌特有的死亡率和存活率统计在拟议的五年计划中可能没有意义，因此将评估其他替代终点：SPLC的发展和/或癌症复发、TMN分期和可切除性，以及恶性前病变或早期病变的进展。此外，还将对系列组织和血清标本、呼吸和健康问卷进行存档，以供进一步分析。这一试点项目的发现将为后续肺癌检测的监测战略、呼吸道恶性前期或早期病变的管理以及未来化学预防试验的设计和进行提供重要的见解。

One of the major obstacles in treating lung cancer is its late presentation, when the options for treatment are primarily palliative. The lack of effective therapy underscores the urgency to reevaluate current management strategies. With recent advances in diagnostic technology and understanding of tumor biology, it is time to revisit the potential impact of early lung cancer detection and to explore new frontiers of treatment such as chemoprevention. Previous studies have shown that patients who have had curative surgical treatment for their lung cancer have a high risk of developing second primary lung cancer (SPLC). Yet, there are no specific guidelines for monitoring or intervention. Therefore, the objectives of this pilot proposal are to 1) evaluate the feasibility and impact of combined sputum analysis (cytology and immunostaining), fluorescence (LIFE) bronchoscopy and spiral CT as surveillance strategies for SPLC and/or recurrence after curative surgical treatment, 2) to evaluate the efficacy and feasibility of cyclooxygenase-2 (Cox-2) inhibition for chemoprevention of second primary tumors or recurrent neoplastic lesions, and 3) to evaluate the pattern of Cox-2 expression in this patient cohort to provide biologic insight into the role of cox-2 inhibitors. To achieve these objectives, 120 individuals with a history of stage I non-small cell lung cancer (NSCLC), who have had curative resection, will be recruited. All subjects will be followed with serial tests including sputum analysis, LIFE bronchoscopy and spiral CT according to a pre-determined algorithm. Subjects will also be randomized in a double blind fashion, to receive either placebo or a Cox-2 inhibitor-oral celecoxib as a chemopreventive agent. Because lung cancer-specific mortality and survival statistics may not be meaningful over the proposed five year project, additional surrogate end-points will be assessed: development of SPLC and/or cancer recurrence, TMN stage and resectability, and progression of pre- or early malignant lesions. Moreover, serial tissues and serum specimen, respiratory and health questionnaires will be archived for further analysis. The finding from this pilot project will provide important insight into surveillance strategies for detection of subsequent lung cancer, the management of pre- or early malignant lesions in the airway, and to the design and conduct of future chemopreventive trials.