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Neoadjuvant chemotherapy demonstrates favorable outcomes in pediatric germ cell tumors
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Children with newly diagnosed nongerminomatous germ cell tumors who received neoadjuvant chemotherapy with or without second-look surgery achieved high response rates and favorable survival outcomes, according to the results of a phase 2 study.
Primary germ cell tumors account for less than 4% of brain tumors of children in Western countries, according to study background. These tumors primarily affect children aged 10 to 12 years, with 90% of tumors diagnosed prior to age 20 years.
Stewart Goldman, MD, professor of pediatrics at Northwestern University Feinberg School of Medicine and division head of hematology, oncology and stem cell transplant in the department of neuro-oncology at Ann and Robert H. Lurie Children’s Hospital of Chicago, and colleagues sought to observe whether neoadjuvant therapy with or without second-look surgery would eliminate measurable disease in children with newly diagnosed nongerminomatous germ cell tumors (NGGCT) prior to radiotherapy.
The analysis included 102 patients (median age, 12 years; 76% boys) treated between January 2004 and July 2008. Over half of patients (53.9%) had pineal region masses. All children underwent six alternating chemotherapy cycles with carboplatin/etoposide and ifosfamide/etoposide.
Researchers recommended second-look surgery to patients who demonstrated less than complete response after induction chemotherapy. Prior to cranial irradiation, patients who did not achieve complete or partial response after chemotherapy with or without second-look surgery went on to receive high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem cell rescue.
Response to induction chemotherapy served as the primary endpoint.
The median follow-up was 5.1 years.
Sixty-nine percent of patients achieved a complete or partial response with neoadjuvant chemotherapy. Overall, 84% ± 4% of patients achieved 5-year EFS and 93% ± 3% achieved 5-year OS.
Fifteen patients underwent second-look surgery after induction chemotherapy. Two patients had residual NGGCTs, nine had teratomas and four had fibrosis/no evidence of tumor.
Sixteen patients recurred or progressed during follow-up, leading to seven deaths related to relapse. Ten patients experienced relapse at the site of primary disease, three patients relapsed at distant sites and one patient relapsed at primary and distant sites.
Increased alpha-fetoprotein levels served as a negative prognostic variable that neared statistical significance (EFS, 78%; OS, 91%); however, histologic subtype and increased beta-human chorionic gonadotropin levels did not significantly correlate with worsened outcomes.
Therapy-related toxicity did not account for any deaths. The most common grade 3 or grade 4 adverse events included transient and expected anemia (range of incidence during cycles of chemotherapy administered during induction, 17.6% to 30.3%), neutropenia (29.4% to 31.5%) and thrombocytopenia (11.8% to 31.5%).
However, less than 5% of patients developed transient febrile neutropenia during therapy.
“A future publication will present our findings regarding tumor location correlated with the extent of resection and morbidity and whether more aggressive surgical procedures might be considered in these patients,” Goldman and colleagues concluded. “In conclusion, we showed that the neoadjuvant chemotherapy regimen, with or without second-look surgery, used in this study is not only feasible and well tolerated but also produces high response rates and OS rates for children and adolescents with NGGCTs." – by Cameron Kelsall
Disclosure: Goldman reports no relevant financial disclosures. One researcher reports stock ownership in Johnson & Johnson and an associate editorship role with The Journal of Pediatrics.
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