Treatment of large osteosarcoma in children: new approach

Aim - 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. 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. 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-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-oper- osteosarcoma along with individualization of pre-oper along with individualization of pre-operative chemotherapy, pre-oper ative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organconserving surgery significantly improves efficacy of the therapy in patients with large tumor volume. Key Words: osteosarcoma, children, pseudocapsule tumors, tumor volume, chemotherapy

Assessment of the dalargin effect on the level of vitamin D and melatonin in blood serum in patients with malignant bone tumors and polymorbidity

Background. Involved in many cascades of biological regulatory reactions, calcium, vitamin D and melatonin create a single metabolic pattern, maintaining the dynamic balance of bone tissue homeostasis. Nevertheless, these regulatory molecules, as structural and functional elements of bone tissue, play a crucial role in various cellular processes associated with oncogenesis and tumor progression. Synthetic peptide dalargin has wound healing, reparative, anti-inflammatory, antioxidant, immunomodulatory, anticarcinogenic, antitumor, and antimetastatic effects. The purpose of the study was to investigate the synthetic neuropeptide dalargin influence on the dynamics of vitamin D and melatonin blood serum le­vels as part of the treatment algorithm of patients with bone malignant tumors of the lower extremities and pelvis with polymorbidity and endoprosthetics. Materials and methods. The study inclu­ded a control (first) group and a main (second) group of clinical observation of patients with malignant bone lesions. The serum melatonin content was measured by enzyme immunoassay using reagent kits (No. RE54021) from IBL-Hamburg GmbH (Germany). Serum levels of 25-hydroxycalciferol (25(OH)D) were determined by the immunochemiluminescent method on an ARCHITECT 25-OH Vitamin D Controls automatic analyzer. Results. In patients who received dalargin, more pronounced positive dynamics were established in the normalization of 25(ОН)D and melatonin levels, and there was no exacerbation of concomitant diseases. In contrast to the data of patients who did not receive dalargin, in the group where it was used, there were no relapses or metastases of the tumor du­ring 14 months. A comparison of the 25(ОН)D and melatonin le­vels in patients 6–7 months and 12–14 months after treatment shows a tendency to recovery of indicators only in patients who were additionally treated with dalargin (p < 0.01). Conclusions. The study showed the possibility of using the neuropeptide dalargin to increase the effectiveness of the treatment of patients with primary malignant tumors with the burden of polymorbidity by influencing the levels of vitamin D and melatonin in the blood serum