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

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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.