Volumetric tumor growth in advanced non-small cell lung cancer patients with EGFR mutations during EGFR-tyrosine kinase inhibitor therapy: developing criteria to continue therapy beyond RECIST progression.
BACKGROUND
The objective of this study was to define the volumetric tumor growth rate in patients who had advanced nonsmall cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations and had initially received treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy beyond progression.


METHODS
The study included 58 patients with advanced NSCLC who had sensitizing EGFR mutations treated with first-line gefitinib or erlotinib, had baseline computed tomography (CT) scans available that revealed a measurable lung lesion, had at least 2 follow-up CT scans during TKI therapy, and had experienced volumetric tumor growth. The tumor volume (in mm3) of the dominant lung lesion was measured on baseline and follow-up CT scans during therapy. In total, 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 (log(e)V).


RESULTS
A linear mixed-effects model was fitted to predict the growth of log(e)V, adjusting for time in months from baseline. Log(e)V was estimated as a function of time in months among patients whose tumors started growing after the nadir: log(e)V = 0.12*time  + 7.68. In this formula, the regression coefficient for time, 0.12/month, represents the growth rate of log(e)V (standard error, 0.015/month; P < .001). When adjusted for baseline volume, log(e)V0, the growth rate was also 0.12/month (standard error, 0.015/month; P < .001; log(e)V = 0.12*months + 0.72 log(e)V0 + 0.61).


CONCLUSIONS
Tumor volume models defined volumetric tumor growth after the nadir in patients with EGFR-mutant, advanced NSCLC who were receiving TKI, providing a reference value for the tumor growth rate in patients who progress after the nadir on TKI therapy. The results can be studied further in additional cohorts to develop practical criteria to help identify patients who are slowly progressing and can safely remain on EGFR-TKIs.
Department of Radiology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
Mizuki
M
Nishino
Suzanne E
SE
Dahlberg
Stephanie
S
Cardarella
David M
DM
Jackman
Michael S
MS
Rabin
Nikhil H
NH
Ramaiya
Hiroto
H
Hatabu
Pasi A
PA
Jänne
Bruce E
BE
Johnson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D003266:Continuity of Patient Care; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects* / Q000235:genetics; D028761:Withholding Treatment
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
computed tomography; epidermal growth factor receptor tyrosine kinase inhibitors; lung cancer; tumor growth rate; tumor volume