A Population Based Study of Ketorolac and Ovarian Cancer Survival

卵巢癌是美国最致命的妇科癌症，大多数患者仍然死于化疗耐药， 复发性疾病。我们建议，FDA批准的止痛剂也可能具有抗肿瘤特性， 如果在卵巢癌手术期间或紧随其后给予该药，可减少复发并提高存活率。 外消旋R，S-酮咯酸(Toradol®或仿制药)是一种强非类固醇抗炎药 (非甾体类抗炎药)与手术结合使用。我们自2008年以来一直在研究酮咯酸，并已 令人信服的初步证据支持酮洛酸有助于降低卵巢癌的假说 死亡率。我们的工作进一步得到了与手术相关的复发和死亡率降低的报道的支持 酮咯酸在乳腺癌和肺癌患者中的应用。总而言之，这些令人信服的证据表明 酮咯酸将带来抗肿瘤的好处；然而，通过手术降低卵巢癌死亡率- 相关的酮咯酸(vs.no)尚未得到证实。我们建议解决我们知识中的这一差距 对卵巢癌病例进行了一项基于人群的队列研究。 我们假设在卵巢癌期间给予酮咯酸作为止痛剂的卵巢癌病例 在考虑了这些因素后，手术的总体存活率将比没有接受酮咯酸的患者要好。 如合并症、疾病分期及接受治疗等。为了解决这一假设，我们将使用 来自加拿大艾伯塔省和不列颠哥伦比亚省的现有人口卵巢癌病例队列，世卫组织 从2002年到2012年被诊断出死亡率一直持续到2020年，提供了8到18年的 后续行动。我们将完成新的医疗记录审查，以确定并存疾病和所有止痛药 卵巢癌手术中使用的麻醉剂。已有的现有数据/资源包括： 接受癌症治疗的详细情况，标准化的病理回顾，按当代对肿瘤进行分类 标准和组织微阵列(TMA)(所有组织类型)。使用这些TMA，我们将使用免疫组织化学 标记的染色可以定义患者的亚群，以解决我们的机械假说。 如果在外科手术期间给予酮咯酸可以显著提高存活率，那么使用酮咯酸 将是一种在正常医疗实践中提高存活率的有效和广泛适用的方法。

Ovarian cancer is the most deadly gynecologic cancer in the U.S. and most patients still die of chemo-resistant, recurrent disease. We propose that a FDA-approved analgesic may also have anti-tumor properties that will reduce recurrent disease and improve survival if given during or closely following ovarian cancer surgery. Racemic R,S-ketorolac (Toradol® or a generic equivalent) is an strong non-steroidal anti-inflammatory drug (NSAID) used in conjunction with surgeries. We have been investigating ketorolac since 2008 and have compelling preliminary evidence to support the hypothesis that ketroloac can help reduce ovarian cancer mortality. Our work is supported further by reported recurrence and mortality reduction with surgery-associated ketorolac administration in breast and lung cancer patients. Combined, this compelling evidence suggests that ketorolac will confer an anti-tumor benefit; however, a reduction in ovarian cancer mortality with surgery- associated ketorolac (vs. none) has not been demonstrated. We propose to address this gap in our knowledge with a population-based cohort study of ovarian cancer cases. We hypothesize that ovarian cancer cases that are given ketorolac as an analgesic during ovarian cancer surgery will have better overall survival than those who do not receive ketorolac, after accounting for factors such as co-morbidities, stage of disease and received treatment. In addressing this hypothesis, we will use an existing cohort of population-based ovarian cancer cases from Alberta and British Columbia, Canada, who were diagnosed from 2002 to 2012 with mortality followed through 2020, providing between 8 and 18 years of follow-up. We will complete de novo medical record reviews to ascertain co-morbidities and all analgesics and anesthesia used during surgery for ovarian cancer. Existing data/resources that are already in hand includes: details of cancer treatments received, standardized pathology review to classify the tumors by contemporary criteria, and tissue micro-arrays (TMAs) (all histotypes). Using these TMAs, we will use immunohistochemical staining of markers that may define subsets of patients to address our mechanistic hypothesis. If ketorolac given in the surgical period makes a substantial improvement in survival, then the use of ketorolac would be an efficient and widely applicable method to improve survival within normal medical practice.