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Background: Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy., Objective: To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment., Materials and Methods: This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points., Results: Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups., Conclusion: DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy.

Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty-eight patients were treated in our institution. Survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome., (© 2010 Blackwell Publishing Ltd.)

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French regional cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objective: To update the SOR recommendations for the use of radiation therapy in the management of patients with osteosarcoma. This work was performed in collaboration with the French society against cancers in children and adolescent (SFCE)., Methods: Data have been identified by literature search using Medline (from January 1992 to October 2003). In addition several Internet sites were searched in October 2003., Results: The 3 mains standards are: 1) local and exclusive curative irradiation is not indicated as primary treatment for osteosarcoma or for local and operable recurrence, except for lesion in inaccessible sites or if the patient refuses surgery; 2) local and prophylactic adjuvant irradiation is not indicated for the treatment of osteosarcoma after chemotherapy (neoadjuvant and/or adjuvant) and complete macro or microscopic surgery, except for non-operable R1 or R2 surgical resection; 3) whole-lung prophylactic irradiation is not indicated in non-metastatic osteosarcoma. Systemic metabolic radiotherapy for pain treatment, using samarium-153 ethylenediaminetetramethylene phosphonic acid (Sm-153-EDTMP) can be offered to patients with painful metastatic osteosarcoma or in case of recurrent bone sites inaccessible to local therapies (surgery, external irradiation).

Background: The goal of this study was to assess the role of thoracoscopy (TS) and thoracotomy (TT) in the management of lung nodules in children with osteosarcoma., Methods: Charts of 16 osteosarcoma patients undergoing surgery for lung nodules were retrospectively analyzed for a correlation between nodule localization at CT scan, findings at surgery, and pathology., Results: Fourteen TSs were performed in 10 children, eight of which were converted: two for technical problems, and six for inconsistency between CT scan and intraoperative findings. In three converted cases, TT allowed detection of more nodules than CT scan and/or TS. Eight TTs were performed as primary intention in seven children, in one as secondary surgery after a previous TS. In three cases, TT detected more nodules than CT scan. Overall, TT detected more nodules than CT scan in seven of 16 cases (sensitivity, 56.2%), six of whom had a predicted bilateral involvement. Neoplastic tissue was present in lung samples of all but three patients (86.4%)., Conclusions: Lung nodules in osteosarcoma patients are usually metastases. CT scan is unreliable in detecting all the nodules, especially in the case of predicted bilateral involvement. If excision of all metastases is considered the goal of surgery, a TT approach should be chosen in patients with more than one thoracic nodule.

Unlabelled: This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery., Patients and Methods: Sixty-two patients (39 males, 23 females: median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)-doxorubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP-doxorubicin., Results: Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery; histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30-80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome., Conclusions: This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of osteosarcoma in children and adult., Methods: Data have been identified by literature search using Medline (1985-december 1998) and the expert groups personal reference lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of treatment. Once the guidelines were defined, the document was submitted for review to 27 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular, the 4 which have particular expertise in pediatric cancer management., Results: The main recommendations for osteosarcoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and the biopsy should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical biopsy must be of adequate size and performed by an experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres. Inclusion of high dose methotrexate is recommended for children, and the dose of methotrexate must be adapted for adults. Inclusion of children in SFOP protocols and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases which may be curative. Amputation is rarely appropriate. Inclusion of children in SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Twenty-two patients with metaphyseal primary malignant bone tumors (17 osteosarcomas, 5 Ewing's tumors) occurring before closure of the growth plate were examined with plain radiographs and MRI in order to determine the physeal or epiphyseal extent of the tumor. Results were correlated with the pathologic examination. Transphyseal spread was pathologically proven in 13 cases (59%): 12 cases of osteosarcoma and 1 case of Ewing's tumor (70% and 20%, respectively). There was no significant relation between epiphyseal invasion, age of patient, length of tumor or, in the cases of osteosarcoma, response to chemotherapy. Plain radiographs showed epiphyseal involvement in 4 cases and there were 10 false negatives. MRI revealed epiphyseal involvement in all cases; there were no false positives or false negatives. T1-weighted images in coronal or sagittal planes appeared to be sufficient. These findings are very useful in planning surgical limb salvage procedures and stress the ineffectiveness of the "barrier effect" of the growth plate against tumor spread.

The authors treated 188 patients with osteosarcoma by chemotherapy followed by surgery and additional chemotherapy (Rosen's T regimen). In 14% of cases, infectious, neurologic or cardiac complications were observed, which resulted in death in 2% of the patients. Forty-six per cent responded well to the primary chemotherapy, 76% of which are alive and disease-free, as opposed to merely 42% of the bad responders.

Phase II studies using ifosfamide both alone and combined with vindesine and cisplatin have shown the effectiveness of this drug in patients with Ewing's sarcoma (ES) who had relapsed during VAC (vincristine, actinomycin, cyclosphosphamide)/VAd (vincristine, Adriamycin) therapy. In November 1984, these results led the SFOP to adopt a protocol consisting of (1) initial chemotherapy with three cycles of IVA (ifosfamide, 3 g/m2 on days 1 and 2; actinomycin D, 750 mg/m2 on days 1-3; vincristine, 1.5 mg/m2 on day 1) alternating every 3 weeks with IVAd (vincristine on day 22; ifosfamide on days 21-23; Adriamycin, 60 mg/m2 on day 22); (2) radical surgery if possible; (3) local radiotherapy (RT); and (4) maintenance chemotherapy with alternating IVA and VAd (vincristine, Adriamycin) for up to 9 months. In May 1987, 87 patients with previously untreated ES entered the study; 61 had localized ES. To date, 54 patients with localized disease and 22 with metastatic disease have finished initial chemotherapy; 40 patients with localized disease have been evaluated. In all, 28 patients (70%) were in complete remission (17 patients) or had a tumor regression of greater than 50% 11 patients) and were considered to be good responders; 12 patients were considered to be poor responders. After local radiotherapy in all but 7 patients and surgical resection in 29, 52 of 54 were considered to be in clinical remission. A total of 13 patients with metastatic disease were good responders at the completion of the initial chemotherapy. These results confirm the efficacy of primary chemotherapy using ifosfamide for the treatment of ES. [ABSTRACT FROM AUTHOR]