Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J.

BACKGROUND: Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out. METHODS: To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible. RESULTS: The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy. CONCLUSIONS: We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.

Hyperthermic isolated regional perfusion with CDDP for bone and soft-tissue sarcoma of the lower limb: pharmacokinetics, thermal dose, toxicity, and feasibility.

The objectives of this study were to investigate the pharmacokinetics of cisplatin (CDDP) and the thermal dose, toxicity, and feasibility of hyperthermic isolated regional perfusion (HIRP) with CDDP for bone and soft-tissue sarcomas of the lower limb. A total of 43 patients were treated with HIRP using CDDP. The dose of CDDP administered was 62.9+/-11.8 mg/limb (20 mg/m(2) +20 approximately 30 mg). The mean highest CDDP concentration was 56.9 microg/ml as total platinum (tPt) and 49.0 microg/ml as free platinum (fPt). The tPt concentration remained higher than 10 microg/ml. The highest temperature within tumor was 42.3+/-1.4 degrees C on average. The complications of HIRP were grade II toxicity in 30 patients, grade III in 9, and grade IV in 4. The mean necrotic ratio in the resected specimen was 84.5%, and the effect was grade IV (no viable tumor cells) in 13 patients, grade III(>90% necrosis) in 12, grade II (50 to <90%) in 9, and grade I (<50%) in 4. We obtained favorable levels of platinum concentration of the perfusate using a lower CDDP dosage compared with previous studies of HIRP. Considering our results of the pharmacokinetics of CDDP and clinical efficacy, we propose a lower dosage of CDDP for HIRP in the treatment of osteosarcoma. Multimodality treatment of HIRP with preoperative chemotherapy and surgery is a relatively safe and reliable therapeutic option for patients with limb sarcomas, and our method offers excellent local control.

Distraction osteogenesis for knee arthrodesis in infected tumor prostheses.

Three patients had distraction osteogenesis as a salvage method for infected endoprostheses. At the first operation, the infected prosthesis was removed and stabilization was achieved with an external fixator to preserve limb length. An additional external fixator was applied later for distraction osteogenesis after ensuring that there was no infection. Osteotomy was done at two sites on the femur, or tibia and femur, respectively, as a second operation. A third surgery was done at the docking site at the edge of the transported bone fragments. Curettage, refreshing, and soft tissue release were done to enhance bone union. The healing index was 18.3 days/cm in Patient 1, 17.7 days/cm in Patient 2, and 33.0 days/cm in Patient 3. All patients walk without a cane. It has been shown that patients can obtain a long-lasting and weight-bearable leg with our method, because their viable bone establishes biomechanical stability. Loss of knee function, a longer treatment period, and pin site treatment are the weaknesses of our method. Our method is indicated for patients in whom systemic disease can be controlled well and who have longer life expectancy.

Parachordoma with multiple metastases.

We present a very rare case of parachordoma with local aggressiveness and widespread metastases. A 68-year-old male presented with a mass in his left calf. The lesion was depicted as a poorly marginated mass with inhomogeneous signal intensity on magnetic resonance imaging. The tumor invaded surrounding muscles, neurovascular bundles, and bones. Widespread metastasis to lung, bone, and skin developed after amputation surgery. The histologic features of primary and metastatic lesions were the same and consistent with parachordoma.

Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas.

PURPOSE: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with unresectable bone and soft tissue sarcomas. PATIENTS AND METHODS: We conducted a phase I/II dose escalation study of carbon ion radiotherapy. Fifty-seven patients with 64 sites of bone and soft tissue sarcomas not suited for resection received carbon ion radiotherapy. Tumors involved the spine or paraspinous soft tissues in 19 patients, pelvis in 32 patients, and extremities in six patients. The total dose ranged from 52.8 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (3.3 to 4.6 GyE/fraction). The median tumor size was 559 cm(3) (range, 20 to 2,290 cm(3)). The minimum follow-up was 18 months. RESULTS: Seven of 17 patients treated with the highest total dose of 73.6 GyE experienced Radiation Therapy Oncology Group grade 3 acute skin reactions. Dose escalation was then halted at this level. No other severe acute reactions (grade > 3) were observed in this series. The overall local control rates were 88% and 73% at 1 year and 3 years of follow-up, respectively. The median survival time was 31 months (range, 2 to 60 months), and the 1- and 3-year overall survival rates were 82% and 46%, respectively. CONCLUSION: Carbon ion radiotherapy seems to be a safe and effective modality in the management of bone and soft tissue sarcomas not eligible for surgical resection, providing good local control and offering a survival advantage without unacceptable morbidity.