Development of a Model to Estimate the Association between Delay in Cancer Treatment and Local Tumor Control and Risk of Metastases

Abstract

Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.