title: Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.
abstract: OBJECTIVE
  This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors.
  
  
  METHODS
  Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation.
  
  
  RESULTS
  The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA. sgoldman@luriechildrens.org.
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Fisher
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Allen
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Robertson
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Chuba
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Bernadine
authors.initials: B
authors.lastname: Donahue
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Kretschmar
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Tianni
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Allen B
authors.initials: AB
authors.lastname: Buxton
authors.affiliation: Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D024162:Second-Look Surgery; D013852:Thiotepa / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin; D007069:Ifosfamide