Volumetric tumor growth in advanced non‐small cell lung cancer patients with EGFR mutations during EGFR‐tyrosine kinase inhibitor therapy

Abstract

Purpose Define volumetric tumor growth rate in advanced NSCLC patients with sensitizing EGFR mutations initially treated with EGFR-TKI therapy beyond progression. Methods The study included 58 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line gefitinib or erlotinib, who had baseline CT showing measurable lung lesion and at least two follow-up CTs while on TKI and experienced volumetric tumor growth. Tumor volume (mm3) of the dominant lung lesion was measured on baseline and follow-up CT scans during therapy. A total of 405 volume measurements were analyzed in a linear mixed effects model, fitting time as a random effect, to define the growth rate of the logarithm of tumor volume (logeV). Results A linear mixed effects model was fitted to predict growth of logeV, adjusting for time in months from baseline. LogeV was estimated as a function of time in months, in patients whose tumors have started growing after nadir: logeV=0.12*time+7.68 In this formula, the regression coefficient for time, 0.12/month, represents the growth rate of logeV (SE: 0.015; p<0.001). When adjusted for baseline volume, logeV0, the growth rate was also 0.12/month (SE: 0.015; p<0.001; logeV =0.12*months+0.72 logeV0+0.61). Conclusion Tumor volume models defined volumetric tumor growth after the nadir in EGFR-mutant advanced NSCLC patients receiving TKI, providing a reference value for the tumor growth rate in patients progressing after the nadir on TKI. The results can be further studied in additional cohorts to develop practical criteria which help to identify patients who are slowly progressing and can safely remain on EGFR-TKIs.

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

“…As tumor volume has also been shown to be a reproducible marker to characterize tumor response and progression and predict survival for advanced NSCLC treated with molecular targeted therapy including EGFR inhibitors(33,35,36), the utility of tumor volume in the setting of immune-related response evaluations can be tested in future studies. The response assessment of irRECIST is based on the sum of the target lesion measurements in each patient, and does not reflect different behaviors of individual lesions in one patient.…”

Dynamic monitoring of EGFR mutations in circulating cell-free DNA for EGFR-mutant metastatic patients with lung cancer: Early detection of drug resistance and prognostic significance

“…In addition to disease monitoring, parameters derived from cfDNA-based mutation quantification may also have prognostic significance. It has been well recognized that tumor burden expressed as the number of metastatic sites, uptake of 18 F-fluorodeoxyglucose measured by positron emission tomography, or tumor volume analyzed using special software associated well with patient survival (32)(33)(34)(35). However, the prognostic significance of genetic mutation concentrations in cfDNA is largely unknown (21,34).…”

Molecularly Targeted Therapies in Non–Small-Cell Lung Cancer Annual Update 2014

“…Prospective randomized studies are in process which will provide further guidance but retrospective studies suggest that response rates may be higher if the EGFR TKI is continued while chemotherapy is added. 64 …”