Automated image analysis tool for tumor volume growth rate to guide precision cancer therapy: EGFR-mutant non-small-cell lung cancer as a paradigm

Abstract

Purpose: To develop an automated analytic module for calculation of tumor growth rate from serial CT scans and to apply the module and evaluate reproducibility in a pilot cohort of advanced NSCLC patients with EGFR mutations treated with EGFR tyrosine kinase inhibitors. Materials and Methods: The module utilized a commercially available image-processing workstation equipped with a validated tumor volume measurement tool. An automated analytic software module was programmed with the capability to record and display serial tumor volume changes and to calculate tumor volume growth rate over time and added to the workstation. The module was applied to evaluate the tumor growth rate in a pilot cohort of 24 EGFR-mutant patients treated with EGFR inhibitors, and reproducibility was tested by two independent thoracic radiologists. Results: The module analyzed chest CT scans from 24 patients (5 males, 19 females; median age: 61) with a median of 8 scans per patient, totaling 227 scans and provided a graphical display with an automated and instant calculation of tumor growth rate after the nadir volume for each patient. High inter and intraobserver agreements were noted for tumor growth rates, with concordance correlation coefficients of 0.9323 and 0.9668, respectively. Interpretation of slow versus fast tumor growth using previously identified threshold of ≤0.15/month had a perfect interobserver agreement (κ=1.00), and an excellent intraobserver agreement (κ=0.895). Conclusions: The present study describes the development of an image analytic module for assessing tumor growth rate and the data demonstrates the functionality and reproducibility of the module in a pilot cohort of EGFR-mutant NSCLC patients treated with EGFR-TKI. The image analytic module is an initial step for clinical translation of the tumor growth rate approach to guide cancer treatment in precision oncology.

Tumor volume dynamics and tumor growth rate in ALK-rearranged advanced non-small-cell lung cancer treated with crizotinib

“…Effective precision therapy for patients with lung cancer harboring targetable oncogenic drivers has been shown to demonstrate a characteristic pattern of tumor burden dynamics during treatment period, noted as an initial marked decrease of tumor burden during the first 2–6 months followed by a period of gradual tumor regrowth after nadir due to acquired resistance [ [25] , [26] , [27] , [28] , 34 ]. Given this characteristic pattern noted in different cohorts of oncogenic driver mutations treated with effective targeting agents, objective assessment of tumor growth rate from serial CT scans during therapy will help to guide therapeutic decisions beyond RECIST progression in these patients.…”

“…As described previously, a linear mixed effects model, fitting time as a random effect [ 37 ], was fitted to the repeated measures of volume data to estimate the effect of time and other prognostic factors on tumor growth [ 26 , 28 ]. The tumor volume, originally obtained in mm 3 , was transformed to the natural logarithm scale (log e V) [ 26 , 28 , 34 ]. The first model was built adjusting only for time in months from baseline.…”

“…Tumor volume can capture three-dimensional tumor burden from CT data, has been shown to be more reproducible than RECIST-based size measurements, and thus can accurately characterize smaller tumor burden changes than RECIST [ [30] , [31] , [32] , [33] ]. Based on these advantages, volumetric tumor growth rate after nadir has been characterized in EGFR -mutant advanced NSCLC patients treated with EGFR inhibitors and provided a reference value of 0.12/month for the logarithm of the volume (log e V) as an overall tumor growth rate in these patients [ 26 , 28 , 34 ]. This approach, established in EGFR -mutant patients, can be applied to other cohorts of patients treated with effective targeted therapy to evaluate their specific quantitative characteristics of tumor growth.…”

Imaging of Precision Therapy for Lung Cancer: Current State of the Art

“…In patients with EGFR-mutant advanced NSCLC treated with erlotinib or gefitinib, the tumor growth rate after initial response was 0.12 per month for the logarithm of the volume (originally measured in cubic millimeters), proposing a reference value to define slow progression in this subpopulation with NSCLC (85,89). Further efforts are ongoing to translate these investigational approaches into the clinical setting (90).…”

Tumor Growth Rate After Nadir Is Associated With Survival in Patients With EGFR-Mutant Non–Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

“…15,16 The pattern of initial response, nadir, and subsequent regrowth is reproducibly observed in patients with EGFR mutations and in patients with anaplastic lymphoma kinase (ALK) rearrangements treated with effective targeted therapy. [5][6][7][8][16][17][18][19] As an example, our previous report has characterized the volumetric tumor growth rate after nadir in patients with EGFR-mutant advanced NSCLC treated with erlotinib or gefitinib and provided a reference value of 0.12/mo for the logarithm of the volume (log e V) as an overall tumor growth rate in these patients using a linear mixed-effects model. The overall growth rate after nadir of 0.12/mo was reproduced in the external validation cohort, demonstrating the consistency of the tumor growth rate after nadir among EGFR-mutant patients treated with EGFR-TKIs.…”