Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs.

Ewing sarcoma family tumors (EWS), which include classic Ewing's sarcoma in addition to primitive neuroectodermal tumor and Askin tumor, are the second most common variety of primary bone cancer to afflict adolescents and young adults. Multi-disciplinary care incorporating advances in diagnosis, surgery, chemotherapy, and radiation has substantially improved the survival rate of patients with localized Ewing sarcoma to nearly 70%. Unfortunately, those advances have not significantly changed the long-term outcome for those with metastatic or recurrent disease; 5-year survival remains less than 25%. This apparent therapeutic plateau exists despite extensive effort during the last four decades to optimize the efficacy of cytotoxic chemotherapy through combination of chemotherapies of mechanistically diverse action, dose-dense scheduling (provided as frequently as every 2 weeks), increased adjuvant treatment duration, and higher dosage per cycle (facilitated with parallel strides in supportive care incorporating growth factors). As has already occurred for malignancies such as breast or colon cancer, the "-omics-based" revolution has enhanced our understanding of the molecular changes responsible for Ewing's tumor formation and identified a number of potential targets (such as IGF-1R or mTOR) amenable to biological therapy. It has also created both a challenge and an opportunity to develop predictive biomarkers capable of selecting patients most likely to benefit from targeted therapy. In this review, we discuss current standard-of-care for patients with Ewing's sarcoma and highlight the most promising experimental therapies in early-phase clinical trials.

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

BACKGROUNDThe objective of the current study was to determine the incidence, clinical and pathologic characteristics, and outcome of patients with conventional osteosarcoma who developed metachronous tumors after treatment for the primary tumor and prevention of pulmonary metastases.METHODSThe medical records of 270 pediatric patients (younger than age 18 years) were reviewed. The prevention and absence of pulmonary metastases was confirmed by chest radiographs and computerized scans of the lungs. Radionuclide bone scans were used to confirm the absence of skeletal metastases.RESULTSEleven patients with metachronous tumors were identified. Index primary tumors involved the femur (n = 8), the tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n = 4). Two patients later developed second metachronous tumors. The interval between identification of the primary tumor to development of the single metachronous tumors varied from 11 months to 78 months and from 12 months to 42 months for synchronous multifocal tumors. Metachronous tumors were treated with single‐agent cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis. Pulmonary metastases were not detected in 10 of 11 patients at the time metachronous tumors were discovered. In the 11th patient, synchronous pulmonary metastasis with the metachronous tumor was noted. Three patients had a prior history of bilateral retinoblastoma. The Li–Fraumeni syndrome may have been present in another patient. Six patients died. Five patients have survived for 20+ to 50+ months after the appearance, treatment, and resection of metachronous tumors.CONCLUSIONSWith improvement in the cure rate, metachronous osteosarcoma should be recognized as an important sequela in long‐term survivors. The etiology of this disease is unknown. Speculation rests on a skeletal multicentric origin, which includes an inherited predisposition to develop osteosarcoma in retinoblastoma and in the Li–Fraumeni syndrome. Meticulous follow‐up is required to permit early detection and successful therapeutic intervention. Cancer 2003. © 2003 American Cancer Society.

Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.