Risk factors for avascular osteonecrosis in children with malignant tumors after thermochemotherapy

Full text: In children with locally advanced malignant tumors or recurrences after first-line treatment, loco-regional deep hyperthermia (RHT) at temperatures between 42-44 oC and platinum-based chemotherapy ± radiotherapy were administered in order to facilitate complete surgical resection. Growing understanding and clinical experience with RHT techniques disclosed an increasing number of children achieving a long-term remission. Therefore, we have also to focus on risk factors for late sequelae. Based on the current data available, in our patient population the most important and severe complication after RHT is avascular osteonecrosis of the femoral head. Although this complication can also be found after chemo- and/or radiotherapy alone, RHT may also be a risk factor for this complication. Aseptic ON in children and adolescents in caused by an interruption of the capital femoris epiphysis blood supply. Most children present with mild or intermittent pain in the anterior thight and a limb. The pertinent early physical findings include antalgic gait; muscle spasm with mild restriction of motion, especially abduction and internal rotation. In order to determine whether RHT contributes to development of ON in our patient population, we compared different treatment parameters in children and adults. In this analysis 72 patients aged between 1 - 72 years (median 16,1 years) with pelvic malignancies were included. Twenty-four patients were male and 48 female. RHT was performed with 3 annular phased array applicators constructed in the same way (Sigma-30, -40 and -60, BSD 2000, Medical Corporation, Salt Lake City, Utah, USA). The number of heat sessions per patient was 2-30. Frequencies ranged between 87-140 MHz. Maximum power supply ranged between 130-1300 Watts (W). Five different age groups were assigned: 1-5 years (22 pts), 6-10 years (6 pts), 11-15 years (7 pts), 16-20 years (9 pts), > 20 years (27 pts). The number of heat sessions was subdivided in the following groups: 1-8 sessions (32 pts), 9-16 sessions (34 pts), > 16 sessions (3 pts). Power supply per body weight was classified into four distinct groups: 1-10 W/kg (6 pts), 10 to <20 W/kg (44 pts), 20 to <30 W/kg (16 pts), ≥30 W/kg (4 pts). CEM43T90 categories: >100 min (3 pts), 50-100 min (2 pts), 20-50 min (6 pts), 10-20 min (18 pts), ≤10 min (41 pts). Severity of ON was defined: slight, moderate and severe. Seven out of 72 patients treated with RHT and chemotherapy ± radiotherapy developed ON, 1/7 double-sided. Appearance of aseptic ON is related to young age (5/7 pts < 5 years, 1/7 pts 5-10 years, 1/7 pts 11-15 years, no patient > 15 years), high power supply per body weight (2/7 pts 10-20 W/kg, 5/7 pts 20-30 W/kg) and high number of heat sessions (6/7 pts 9-16 sessions, 1/7 pts > 16 sessions). The present analysis showed that aseptic On can be a complication of RHT treatment in children and adolescents, which is not observed in adults. Pain or other skeletal symptoms after power supply of >20 W/kg body weight disclose a risk of osteochondrosis in young patients. We speculate that heat-induced reduction of blood perfusion and chondral injuries of the hip may be relevant for this specific complication in the pediatric age group. In the future 3D temperature measurement by MRI may be helpful to avoid dangerous temperatures in normal tissues. (author)