title: Adaptive Neoadjuvant Chemotherapy Guided by (18)F-FDG PET in Resectable Non-Small Cell Lung Cancers: The NEOSCAN Trial.
abstract: BACKGROUND
  Although perioperative chemotherapy improves survival in patients with resectable lung cancers, systemic recurrence remains common. Neoadjuvant chemotherapy permits response assessment and an opportunity to switch treatment regimens. Response measured by fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) correlates with clinical outcomes better than computed tomography (CT) does. This trial assessed PET-measured response rate to alternative chemotherapy in patients with a suboptimal PET response after two cycles of neoadjuvant chemotherapy.
  
  
  METHODS
  This phase II study enrolled patients with resectable stage IB-IIIA lung cancers (primary tumor ≥ 2 cm and peak standard uptake value [SUVpeak] ≥ 4.5). Patients had a pretreatment (18)F-FDG PET/CT scan before two cycles of cisplatin (or carboplatin) plus gemcitabine (squamous cell carcinoma) or pemetrexed (adenocarcinoma) and then a repeat PET/CT scan. If SUVpeak in the primary tumor decreased by at least 35%, patients continued the initial chemotherapy. Individuals with less than a 35% PET response were switched to vinorelbine plus docetaxel. Postoperative radiotherapy was recommended to all patients with positive N2 nodes. A Simon's optimal two-stage design was used to evaluate the primary end point of a PET Response in Solid Tumors-defined response rate to vinorelbine plus docetaxel in previously nonresponding patients.
  
  
  RESULTS
  Forty patients were enrolled. Fifteen patients (38% [95% confidence interval: 38-53]) had less than a 35% decrease in SUVpeak, and 13 received vinorelbine plus docetaxel. The study met its primary end point with 10 of 15 PET metabolic responses to alternate therapy (67%). Chemotherapy toxicities never precluded surgical exploration.
  
  
  CONCLUSIONS
  Utilizing (18)F-FDG PET/CT to assess response and change preoperative chemotherapy in nonresponding patients can improve radiographic measures of response. This adaptive approach can also be used to test new drugs, attempting to optimize perioperative chemotherapy to achieve better long-term outcomes.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address: chaftj@mskcc.org.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Chaft
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mark
authors.initials: M
authors.lastname: Dunphy
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Jarushka
authors.initials: J
authors.lastname: Naidoo
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hellmann
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Woo
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Downey
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: (18)F-FDG PET; Adaptive clinical trial; Neoadjuvant therapy; Non–small cell lung cancer