title: Treatment of large osteosarcoma in children: new approach.
abstract: OBJECTIVE
  To improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule.
  
  
  METHODS
  A study group included 46 children aged from 7 to 18 years, mean age - 12 years. In 68% of the patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed. In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the same doses.
  
  
  RESULTS
  Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin + cisplatin: the depth of leucopenia was significantly higher (p < 0.05), the duration of agranulocytosis is similar after such therapies. In the study group, 69.6% patients have reached grade 3-4 pathomorphosis. Organ-conserving surgery was performed in 86.9% of the patients. Local tumor recurrence was registered in 15.2% patients of the study group. 5-year relapse-free survival was achieved in 62 ± 10% (p = 0.02), the overall 5-year survival - 76.5 ± 9% (p = 0.02).
  
  
  CONCLUSIONS
  Introduction of ifosfamide at a dose of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-operative chemotherapy, pre-operative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organ-conserving surgery significantly improves efficacy of the therapy in patients with large tumor volume.
authors.affiliation: Municipal Clinical Oncological Center, Kyiv, Ukraine. vadym_kobys@mail.ru
authors.forename: V L
authors.initials: VL
authors.lastname: Kobys
authors.forename: V F
authors.initials: VF
authors.lastname: Konovalenko
authors.forename: N V
authors.initials: NV
authors.lastname: Repinа
authors.forename: T S
authors.initials: TS
authors.lastname: Golovko
authors.forename: L O
authors.initials: LO
authors.lastname: Gulak
authors.forename: T O
authors.initials: TO
authors.lastname: Tarasova
authors.forename: E V
authors.initials: EV
authors.lastname: Zaharycheva
authors.forename: O F
authors.initials: OF
authors.lastname: Matyushok
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D057285:Precision Medicine; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate