Factors That Drive Heterogeneity of Response-to-Treatment of Different Metastatic Deposits Within the Same Patients as Measured by RECIST 1.1 Analyses.

RATIONALE AND OBJECTIVE This study uses the rate of between-reader variability under Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 as a metric to estimate the prevalence of biologic heterogeneity of individual metastases, and to determine whether this prevalence is modulated by the type of primary tumor, or type of treatment administered. MATERIALS AND METHODS Three radiologists independently used dedicated oncologic response-assessment software (MintLesion) to prospectively determine RECIST1.1 treatment response in contrast-enhanced computed tomography studies of 355 patients with metastatic disease of different primaries between 07/2015 and 12/2017. In 200 patients, readers had chosen different sets of target lesions; these cases were used for further analysis. Clinically significant heterogeneity of response was considered to be present when RECIST1.1 results differed regarding the distinction of progressive versus non-progressive disease. Rates of response heterogeneity were compared for different types of primary cancers, and different types of systemic treatment. RESULTS Heterogeneous treatment response was observed in 67 of 200 (34%) patients. Breast cancer was the only primary tumor associated with statistically significantly increased odds for heterogeneity of treatment response (Odds Ratio: 3.972, 0.95 Confidence Interval: 1.275-12.376, p = 0.017). No association was found between type of systemic treatment and rate of biologic heterogeneity. CONCLUSION Clinically significant heterogeneity of response-to-treatment is a frequent phenomenon, observed in about one-third of patients undergoing contemporary systemic therapies. Patients with breast cancer are more likely to exhibit such heterogeneity. Type of systemic treatment did not modulate the likelihood of exhibiting metastases with diverging treatment response.