Volumetric measurements of target lesions: does it improve inter-reader variability for oncological response assessment according to RECIST 1.1 guidelines compared to standard unidimensional measurements?

PURPOSE: Target lesion selection is known to be a major factor for inter-reader discordance in RECIST 1.1. The purpose of this study was to assess whether volumetric measurements of target lesions result in different response categorization, as opposed to standard unidimensional measurements, and to evaluate the impact on inter-reader agreement for response categorization when different readers select different sets of target lesions. MATERIAL AND METHODS: Fifty patients with measurable disease from solid tumours, in which 3 readers had blindly and independently selected different sets of target lesions and subsequently reached clinically significant discordant response categorizations (progressive disease [PD] vs. non-progressive disease [non-PD]) based on RECIST 1.1 analyses were included in this study. Additional volumetric measurements of all target lesions were performed by the same readers in a second read. Intra-reader agreement between standard unidimensional measurements (uRECIST) and volumetric measurements (vRECIST) was assessed using Cohen's k statistics. Fleiss k statistics was used to analyse the inter-reader agreement for uRECIST and vRECIST results. RESULTS: The 3 readers assigned the same response classifications based on uRECIST and vRECIST in 33/50 (66%), 42/50 patients (84%), and 44/50 patients (88%), respectively. Inter-reader agreement improved from 0% when using uRECIST to 36% when using vRECIST. CONCLUSIONS: Volumetric measurement of target lesions may improve inter-reader variability for response assessment as opposed to standard unidimensional measurements. However, in about two-thirds of patients, readers disagreed regardless of the measurement method, indicating that a limited set of target lesions may not be sufficiently representative of the whole-body tumour burden.

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.

CT-based whole-body tumor volumetry versus RECIST 1.1: Feasibility and implications for inter-reader variability.

PURPOSE: To investigate whether volumetric measurements of the whole-body tumor volume (WBTV) are feasible and whether they improve inter-reader variability in patients in whom conventional RECIST 1.1 assessment yielded discordant results. METHODS: 50 patients (29 male, 21 female, mean age 60.9 ±â€¯12.3 years) with metastases of solid tumors in whom three readers had selected different sets of target lesions and subsequently reached different results for response assessment (progressive vs. non-progressive disease) when using RECIST 1.1 were included. In a second read, all readers performed volumetric measurements of the WBTV on neck/chest/abdomen/pelvis CTs and measured the time needed for these measurements. Cohen's kappa and Fleiss kappa statistics were used to compare the intra- and inter-reader agreement for response assessment. RESULTS: In 8/50 patients (16 %), the WBTV was too extensive for volumetric measurements and these patients were therefore excluded. In the remaining 42 patients, WBTV measurements required a mean time of 18 min and 9 s. Readers assigned the same response categorizations based on unidimensional RECIST measurements and WBTV measurements in 15/42 patients (33 %), 24/42 patients (57 %) and 30/42 patients (71 %) for reader 1,2 and 3 respectively. When performing response assessment based on WBTV measurements, the three readers agreed in 40/42 patients (95 %) regarding the distinction progressive vs. non-progressive disease, resulting in a near-perfect agreement on a patient-based level (Fleiss' κ = 0.921, 0.95-CI:0.746-1.095). CONCLUSIONS: WBTV measurements yielded an almost perfect inter-reader agreement in a cohort of patients, in which three readers reached discordant response assessment results when following conventional RECIST 1.1 guidelines. This supports the hypothesis, that a limited subset of metastases may not be sufficient to accurately assess response-to-treatment.