title: The predictive value of18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy.
abstract: BACKGROUND
  Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated.
  
  
  OBJECTIVE
  to evaluate whether the early metabolic response, assessed by18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT.
  
  
  METHODS
  Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery.18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis.
  
  
  RESULTS
  Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeakof primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively).
  
  
  CONCLUSIONS
  In LA-NSCLC patients,18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.
authors.affiliation: Institute of Nuclear Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Mattoli
authors.affiliation: Department of Radiation Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.affiliation: Department of Radiation Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy. alessandra.castelluccia@gmail.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Castelluccia
authors.affiliation: Institute of Nuclear Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Scolozzi
authors.affiliation: Department of Radiation Oncology, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantini
authors.affiliation: Institute of Nuclear Medicine, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Rome, Italy.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Calcagni
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D059248:Chemoradiotherapy / Q000401:mortality*; D019583:Dose Fractionation, Radiation; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET-CT; Chemo-radiotherapy; NSCLC; PERCIST; Tumour response