title: Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib.
abstract: A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with repeated relapse after treatment with cytotoxic chemotherapy (carboplatin, gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab, sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA-, HER2- and DDR2-aberrations) were performed and failed initially to detect any driver mutation. While the patient suffered from rapid deterioration of her general condition, in particular from progressive dyspnea due to lung metastases, we implemented screening for RET- and ROS1 translocations into our molecular diagnostic program based on recent reports of these new molecular subgroups in lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor a ROS1-translocation. The patient was subsequently treated with crizotinib and experienced a pronounced clinical improvement corresponding to a complete metabolic response in (18)F-FDG-PET and a good and confirmed partial response in CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly discovered rare genetic lung cancer subtypes in routine molecular diagnostics.
authors.affiliation: Department I of Internal Medicine, Center for Integrated Oncology Köln-Bonn, University Hospital Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bos
authors.forename: M
authors.initials: M
authors.lastname: Gardizi
authors.forename: H U
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: L C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: T
authors.initials: T
authors.lastname: Geist
authors.forename: B
authors.initials: B
authors.lastname: Kaminsky
authors.forename: T
authors.initials: T
authors.lastname: Zander
authors.forename: L
authors.initials: L
authors.lastname: Nogova
authors.forename: M
authors.initials: M
authors.lastname: Scheffler
authors.forename: M
authors.initials: M
authors.lastname: Dietlein
authors.forename: C
authors.initials: C
authors.lastname: Kobe
authors.forename: A
authors.initials: A
authors.lastname: Holstein
authors.forename: D
authors.initials: D
authors.lastname: Maintz
authors.forename: R
authors.initials: R
authors.lastname: Büttner
authors.forename: J
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077547:Crizotinib; D005260:Female; D015321:Gene Rearrangement; D016161:Genes, Retinoblastoma; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human