title: Germ Cell Cancer and Multiple Relapses: Toxicity and Survival.
abstract: OBJECTIVE
  A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment for disseminated disease.
  
  
  METHODS
  From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse and death were identified and compared with the International Prognostic Factors Study Group (IPFSG) classification.
  
  
  RESULTS
  In total, 268 patients received more than one line of treatment for disseminated GCC. Approximately half of patients (n=136) died as a result of GCC. The 132 remaining patients, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal impairment (HR, 8.3; 95% CI, 3.0 to 23.2), neurologic disorders (HR, 6.3; 95% CI, 3.1 to 12.6), and death as a result of other causes (HR, 2.6; 95% CI, 1.6 to 4.2). In large part, the IPFSG classification was confirmed in our population; however, we could not confirm the primary site and the level of human chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15).
  
  
  CONCLUSIONS
  Patients with GCC who survive after more than one line of treatment for disseminated disease have a highly increased risk of late toxicity and death as a result of causes other than GCC. Therefore, they should be candidates for life-long follow-up. The IPFSG classification was confirmed in this unselected population.
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Lauritsen
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Maria G G
authors.initials: MG
authors.lastname: Kier
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mette S
authors.initials: MS
authors.lastname: Mortensen
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Bandak
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ramneek
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels V
authors.initials: NV
authors.lastname: Holm
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Agerbaek
authors.affiliation: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, and Gedske Daugaard, Copenhagen University Hospital, Copenhagen; Maria G.G. Kier, Danish Cancer Society Research Center, Strandboulevarden, Copenhagen; Ramneek Gupta, Technical University of Denmark, Kongens Lyngby; Niels V. Holm, Odense University Hospital, Odense; and Mads Agerbaek, Aarhus University Hospital, Aarhus, Denmark. kirsten.gedske.daugaard@regionh.dk.
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D002945:Cisplatin / Q000627:therapeutic use; D016208:Databases, Factual; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D018572:Disease-Free Survival; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D009919:Orchiectomy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D019233:Retreatment; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide