title: How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors.
abstract: Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma.
  
  
  
  Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma.
  
  
  
  The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect.
  
  
  
  The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed.
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany. petra.temming@uk-essen.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Temming
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Arendt
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Viehmann
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia H D
authors.initials: CH
authors.lastname: Le Guin
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Schündeln
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Biewald
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mäusert
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Wieland
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bornfeld
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sauerwein
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Lohmann
authors.affiliation: Petra Temming, Marina Arendt, Anja Viehmann, Lewin Eisele, Claudia H.D. Le Guin, Michael M. Schündeln, Eva Biewald, Jennifer Mäusert, Regina Wieland, Norbert Bornfeld, Wolfgang Sauerwein, Dietmar R. Lohmann, and Karl-Heinz Jöckel, University Hospital Essen, Essen; Petra Temming, Dietmar R. Lohmann, and Karl-Heinz Jöckel, German Consortium for Translational Cancer Research, Heidelberg; and Angelika Eggert, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015353:Eye Enucleation / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005858:Germany; D040941:Heredity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D010641:Phenotype; D016016:Proportional Hazards Models; D019572:Retinal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D012175:Retinoblastoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D056286:Retinoblastoma Binding Proteins / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D014785:Vision, Ocular / Q000187:drug effects / Q000528:radiation effects
chemical_list: D014408:Biomarkers, Tumor; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D044767:Ubiquitin-Protein Ligases