Novel Functional Anatomic and Biomarker Indices of Radiation-Induced Female Sexual Toxicities in a Multi-Center Cohort

项目摘要摘要 到2020年，美国将有大约100万女性患者患有盆腔癌，其中大约一半人会 在治疗过程中接受了辐射。优化癌症导向和治疗方案的重要性 减少辐射不良反应和提高生活质量的支持性疗法越来越多。 被认可了。在癌症治疗对生活质量的许多方面产生不利影响的许多方面中，有能力 继续从事令人愉快的性行为，这是人类一生中的一项基本功能，以及 女性癌症幸存者长期被忽视的临床问题。目前毒性和正常组织的分类 在放射肿瘤学中，对女性勃起组织的解剖和关键功能(觉醒)的解释很差 和性高潮)与这些患者进行愉快的性行为的能力有关。此外，它还 是否观察到放射治疗后阴道和粪便微生物生态的变化还有待检验 增加对辐射引起的阴道毒性和性功能障碍的易感性，正如已经发生的那样 最近在辐射引起的胃肠道毒性的背景下进行了探索。因为大约70%的女性 由于盆腔恶性肿瘤现在至少存活5年，因此确定预测因素和发病机制是当务之急。 长期女性性功能障碍对改善性生活质量具有重要的总体作用 幸福。加快减轻或预防盆腔放射治疗相关女性性行为的进展 功能障碍，我提议的研究旨在1)建立一个功能解剖领域(皮肤科，阴道， 勃起)在多中心纵向队列中对长期放射性相关的性功能障碍进行分类 接受盆腔放射治疗的女性患者；2)定义和/或验证新的剂量学预测性行为 每个解剖领域的功能障碍；以及，3)确定定量成像和微生物组生物标志物指标 对特定性器官的辐射损伤。我提议的研究将是第一个分析 放射治疗对女性勃起解剖器官的影响，从而阐明女性勃起的解剖基础 不良的性功能结果，特别是那些与性唤醒和性高潮有关的结果，并在总体上促进 了解辐射对所有女性性解剖领域的影响。这些进步将使重新设计成为可能。 放射治疗方案以改善这种结果，并确定成像生物标记物以评估剂量- 数量反应和这类干预措施的有效性。此外，我们将率先测试 一种假说：观察到的阴道和粪便微生物生态的变化有助于增加 对辐射引起的阴道毒性和性功能障碍的易感性。我的目标是在以下领域开创关键发现 这些代表不足的科学领域提供了一种创新的、量身定制的预防、缓解、 以及治疗与放射治疗相关的女性性毒性。

Project Summary Abstract In 2020, about 1 million female patients in the US will be living with pelvic cancers, and roughly half of them will have received radiation during their course of treatment. The importance of optimizing cancer-directed and supportive therapies to minimize the adverse effects of radiation and improve quality of life is increasingly recognized. Among the many aspects of quality of life adversely impacted by cancer treatment is the ability to continue engaging in pleasurable sexual behaviors, an essential human function throughout the lifespan, and a clinical problem long overlooked in female cancer survivors. Current classifications of toxicity and normal tissues in radiation oncology account only poorly for the anatomy and critical function of female erectile tissues (arousal and orgasm) with respect to such patients' capacities to engage in pleasurable sexual behaviors. In addition, it has yet to be tested whether observed alterations of vaginal and stool microbiome ecology after radiotherapy contribute to increased susceptibility to radiation-induced vaginal toxicity and sexual dysfunction, as has been explored recently in the context of radiation-induced gastrointestinal toxicity. Because roughly 70% of women with pelvic malignancies now survive at least 5 years, it is imperative to identify predictors and mechanisms of long-term female sexual dysfunction to improve quality of life given the significant role of sexual activity in overall well-being. To accelerate advances in mitigating or preventing pelvic radiotherapy-associated female sexual dysfunction, my proposed research aims to 1) establish a functional anatomic-domain (dermatologic, vaginal, erectile) classification of long-term radiation-related sexual dysfunction in a multi-center, longitudinal cohort of female patients undergoing pelvic radiotherapy; 2) define and/or validate novel dosimetric predictors of sexual dysfunction in each anatomic domain; and, 3) identify quantitative imaging and microbiome biomarker indices of radiation damage to specific sexual organs. My proposed study will be the first to analyze the effects of radiotherapy on the erectile anatomic organs in females, and will thereby both elucidate the anatomic bases of adverse sexual function outcomes, especially those related to arousal and orgasm, and advance overall understanding of radiation effects for all female sexual anatomic domains. These advances will enable redesign of radiotherapy protocols to improve such outcomes and identification of imaging biomarkers to assess dose- volume response and the effectiveness of such interventions. In addition, we will be the first to test the hypothesis that observed alterations of vaginal and stool microbiome ecology contribute to increased susceptibility to radiation-induced vaginal toxicity and sexual dysfunction. I aim to pioneer key discoveries in these underrepresented scientific areas to provide an innovative, tailored approaches to prevention, mitigation, and treatment of radiotherapy-associated female sexual toxicities.