title: Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts gefitinib response in association with epidermal growth factor receptor mutations.
abstract: Female, non-smoker, Asian ethnicity and adenocarcinoma histology are the major clinical predictors of gefitinib response in non-small cell lung cancer, as shown in previous studies. Recently, response to gefitinib has been associated with epidermal growth factor receptor (EGFR) mutations. Higher rates of mutation were seen in females, patients with adenocarcinomas, the Asian population and never-smokers, which may explain the clinical response predictors. The presence of diffuse micronodular pulmonary metastasis on chest imaging as a novel clinical predictor of its response is proposed here. Two cases of lung adenocarcinomas in men presenting with diffuse micronodular pulmonary metastasis were encountered. Both patients showed a major response to gefitinib. The dramatic reduction of micronodular pulmonary nodules throughout both lungs on computed tomography scans was achieved after treatment for a couple of months with 250 mg of oral gefitinib. In the molecular analysis, one patient had a heterozygous delL746-A750 mutation and the other had a heterozygous L858R EGFR mutation. In conclusion, patients with lung adenocarcinoma, even men, who presented with bilateral diffuse micronodular metastatic spread to the lungs tended to have an activated EGFR mutation. Therefore, they are most likely to receive benefits from molecular target drugs such as gefitinib and possibly erlotinib.
authors.affiliation: Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan. kmakoto@med.kochi-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Bandobashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uemura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ohtsuki
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D000077156:Gefitinib; D017353:Gene Deletion; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D011799:Quinazolines; D000077156:Gefitinib