title: A prognostic model including pre- and postsurgical variables to enhance risk stratification of primary mediastinal nonseminomatous germ cell tumors: the 27-year experience of a referral center.
abstract: BACKGROUND
  Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis.
  
  
  METHODS
  Between the years 1985 and 2012, 86 patients with PMGCT were treated at our center. Cox proportional hazards regression analysis was conducted in the population of nonseminomas to examine the prognostic effect of candidate factors on progression-free and OS. OS curves were compared using the Kaplan-Meier method and the log-rank test.
  
  
  RESULTS
  Mean age was 29.8 years (range, 15-63 years). Twenty-five patients (29.1%) had lung and 8 (9.3%) liver, bone, or brain metastases. Twelve patients (13.9%) received upfront high-dose chemotherapy and 45 patients (52.3%) underwent surgery after chemotherapy. Cox analyses included 61 evaluable primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs). The final model of factors indicating a poor prognosis included the combination of surgery and histological response (overall P = .011) and lung metastases (hazard ratio, 3.03; 95% confidence interval, 1.12-8.15; P = .028). The model showed a bootstrap-corrected Harrel c-statistic for OS of 0.66. A risk stratification model based on the combination of these factors and accounting for a 50% 5-year survival cutoff identified 2 groups (poor prognosis, n = 33 vs. good prognosis, n = 28) with distinct OS curves (P < .001). Preoperative serum tumor marker level was not associated with the final histology (P = .853, χ(2) test). Results were limited by small numbers.
  
  
  CONCLUSIONS
  Patients with PMNSGCT included 2 subpopulations with distinct prognosis, and therapeutic improvements are needed for patients with poor-risk features.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannatempo
authors.affiliation: Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lo Vullo
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Farè
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Raggi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Marongiu
authors.affiliation: Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scanagatta
authors.affiliation: Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Duranti
authors.affiliation: Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giovannetti
authors.affiliation: Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Girelli
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Nicolai
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Piva
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Biasoni
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Torelli
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Catanzaro
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stagni
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffezzini
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.affiliation: Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.affiliation: Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
mesh_terms: D000293:Adolescent; D000328:Adult; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D057285:Precision Medicine; D011379:Prognosis; D012044:Regression Analysis; D012306:Risk; D016019:Survival Analysis; D062606:Tertiary Care Centers; D013736:Testicular Neoplasms; D055815:Young Adult
keywords: Lung metastases; Mediastinal germ cell tumors; Pathological response; Prognostic factors; Surgery