title: Tumor volume as a potential imaging-based risk-stratification factor in trimodality therapy for locally advanced non-small cell lung cancer.
abstract: BACKGROUND
  The role of trimodality therapy for locally advanced non-small cell lung cancer (NSCLC) continues to be defined. We hypothesized that imaging parameters on pre- and postradiation positron emission tomography (PET)-computed tomography (CT) imaging are prognostic for outcome after preoperative chemoradiotherapy (CRT)/resection/consolidation chemotherapy and could help risk-stratify patients in clinical trials.
  
  
  METHODS
  We enrolled 13 patients on a prospective clinical trial of trimodality therapy for resectable locally advanced NSCLC. PET-CT was acquired for radiation planning and after 45 Gy. Gross tumor volume (GTV) and standardized uptake value were measured at pre- and post-CRT time points and correlated with nodal pathologic complete response, loco-regional and/or distant progression, and overall survival. In addition, we evaluated the performance of automatic deformable image registration (ADIR) software for volumetric response assessment.
  
  
  RESULTS
  All patients responded with average total GTV reductions after 45 Gy of 43% (range: 27-64%). Pre- and post-CRT GTVs were highly correlated (R² = 0.9), and their respective median values divided the patients into the same two groups. ADIR measurements agreed closely with manually segmented post-CRT GTVs. Patients with GTV ≥ median (137 ml pre-CRT and 67 ml post-CRT) had 3-year progression-free survival (PFS) of 14% versus 75% for GTV less than median, a significant difference (p = 0.049). Pre- and post-CRT PET-standardized uptake value did not correlate significantly with pathologic complete response, PFS, or overall survival.
  
  
  CONCLUSIONS
  Preoperative CRT with carboplatin/docetaxel/45 Gy resulted in excellent response rates. In this exploratory analysis, pre- and post-CRT GTV predicted PFS in trimodality therapy, consistent with our earlier studies in a broader cohort of NSCLC. ADIR seems robust enough for volumetric response assessment in clinical trials.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California 94305-5847, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kozak
authors.forename: James D
authors.initials: JD
authors.lastname: Murphy
authors.forename: Meike L
authors.initials: ML
authors.lastname: Schipper
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Donington
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhou
authors.forename: Richard I
authors.initials: RI
authors.lastname: Whyte
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
authors.forename: Chuong D
authors.initials: CD
authors.lastname: Hoang
authors.forename: Jose
authors.initials: J
authors.lastname: Bazan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Maxim
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.forename: Wendy Y
authors.initials: WY
authors.lastname: Hara
authors.forename: Andrew
authors.initials: A
authors.lastname: Quon
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.forename: Billy W
authors.initials: BW
authors.lastname: Loo
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000473:pathology* / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18