Covid-19-related cervical cancer treatment interruption and role of neoadjuvant chemotherapy

项目总结/摘要 本申请是为了回应特别利益通知（NOSI）而提交的，该通知被确定为不- CA-21-033 局部晚期宫颈癌是南部非洲癌症死亡的主要原因， 需要放化疗在包括博茨瓦纳在内的几乎所有南部非洲国家， 只能从一个单一的中心获得，这造成了巨大的脆弱性。与其他几个国家一样， 博茨瓦纳的放射治疗单位因与COVID-19相关的边境而经历了长时间的停工 妨碍日常维护和维修的限制。宫颈癌延迟治疗的临床影响 人们对化疗的认识不足，使用“拖延”化疗来减轻化疗延迟的不良影响， 稀疏研究。目标是为以下时期提供有弹性和准备就绪的缓解战略： 流行病，武装冲突，政治起义和环境危机，我们利用收集的前瞻性数据， Thabatse癌症队列（2010年至今，n=4950）估计治疗延迟的持续时间 与宫颈癌分期进展以及新辅助治疗是否可以保留选择相关 在卫生系统长期中断期间进行治疗。分析将利用 仪器变量方法和两个自然实验： 博茨瓦纳（当前的Covid-19大流行和之前的两个时期）以及博茨瓦纳临床医生决定 在缺乏放射治疗的情况下提供“临时”化疗。

Project Summary/Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT- CA-21-033. Curative therapy for locally advanced cervical cancer, the leading cause of cancer death in southern Africa, requires chemoradiation. In nearly all countries in southern Africa, including Botswana, radiotherapy is only available from a single center, creating substantial vulnerability. Similar to several other countries, the radiotherapy unit in Botswana experienced prolonged downtimes due to Covid-19-related border restrictions preventing routine service and repair. The clinical impact of delayed treatment of cervical cancer is poorly understood and the use of `temporizing' chemotherapy to mitigate adverse effects of delays is sparsely studied. With the goal of informing resilient and ready mitigation strategies for periods of epidemic, armed conflict, political uprising, and environmental crises we utilize prospective data collected in the Thabatse cancer cohort (2010 to present, n=4950) to estimate the duration of treatment delay associated with cervical cancer stage progression and whether neoadjuvant therapy may preserve the option for curative therapy during periods of prolonged health system disruption. Analyses will utilize the instrumental variable methods and two natural experiments: unexpected loss of radiation therapy in Botswana (current Covid-19 pandemic and two prior periods) and the decision by Botswana clinicians to provide `temporizing' chemotherapy during lack of access to radiation.