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PubMed1987

[Role of adriamycin in the therapy of bone sarcomas].

The improvement of bone sarcomas prognosis during the last fifteen years (60% disease free survival at 4 years for osteogenic sarcoma, 50% for Ewing's sarcoma) is due in a large measure, to introduction of chemotherapy. ADR is a very effective agent in the treatment of those tumors but its use is limited by its cardiotoxicity. In the current chemotherapy protocols, the best results are obtained with the combination of intensive ADR-HDMTX, ADR-CDDP in osteogenic sarcoma, and ADR-ACD-CTX in Ewing's sarcoma. The ADR-Ifosfamide association seems also to be promising.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

[Imaging of bone sarcomas].

Radiological study of bone sarcomas has been improved for the last ten years. Standard X-ray analysis is now more precise. CT and MRI are presently playing an important role for pretreatment local evaluation, assessment of treatment effectiveness and detection of recurrences.

Bone Neoplasms↗

PubMed1990

The reverse protraction factor in the induction of bone sarcomas in radium-224 patients.

More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis. In an earlier analysis [H. Spiess and C. W. Mays, in Radiation Carcinogenesis. (C. L. Sanders et al., Eds.) pp. 437-450. USAEC Symposium Series 29, CONF-720505, 1973] it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas. The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients. In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods. A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test. In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose. A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment. The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months. This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma.

Adolescent↗

PubMed1999

Dynamic MR imaging (DEMRI) of microcirculation in bone sarcoma.

If chemotherapy is to be effective against bone sarcoma, the cytotoxic agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of these agents in blood or cerebrospinal fluid, there have been no accurate or widely applicable methods of determining whether chemotherapeutic agents reach all regions of a solid tumor. This review discusses the use of dynamic contrast-enhanced magnetic resonance imaging (DEMRI) to assess the microcirculation and interstitium of bone sarcoma. DEMRI studies provide a means of exploring leakage of contrast agent into tumor interstitium (extracellular extravascular spaces [EES]). In clinical observations of numerous series of patients with bone sarcoma, measures of contrast uptake (access) have convincingly demonstrated a relationship with measures and predictions of the tumor's response to preoperative chemotherapy. The results of these studies have indicated that greater access at the time of presentation, greater decrease in access during therapy, and low access at the completion of preoperative therapy correspond to better response and longer disease-free survival. Although questions remain about how these novel dynamic imaging methods can best be used to measure drug access noninvasively, we are optimistic that such measures can be developed to reflect the range of biological variation within and between naturally occurring solid tumors.

Antineoplastic Agents↗

PubMed2006

Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe.

We investigated the association between occupational factors and risk of bone sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case-control study was conducted in 7 European countries in 1995-97. Ninety-six cases aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides. Response proportions were 90% among cases and 66% among controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for selected categories of job titles and branches of industry and for use of pesticides. We found an increased OR for bone sarcoma among blacksmiths, toolmakers, machine-tool operators (OR = 2.14, 95% CI 1.08-4.26), woodworkers (OR = 2.68, 95% CI 1.36-5.29) and construction workers (OR = 1.62, 95% CI 0.92-2.87). Ever users of pesticide had an OR of 2.33 (95% CI 1.31-4.13), with similar risks for exposure to insecticides and exposure to herbicides. Neither duration of employment in any of the analyzed occupational categories nor duration of use of pesticides showed an increasing trend in the risk of bone sarcoma. ORs of bone sarcoma were 1.03 (95% CI 0.23-4.57), 3.13 (95% CI 1.26-7.76) and 1.44 (95% CI 0.43-4.85) for the first, second and third tertile of days of use of pesticides. Our study suggests that novel and previously reported (woodworking) occupational factors play a role in the aetiology of bone sarcomas.

Adult↗

PubMed1998

High complication rate of reconstruction using Ilizarov bone transport method in patients with bone sarcomas.

We performed five reconstructions by bone transport in patients with bone sarcoma: three osteosarcomas, one Ewing's sarcoma and one chondrosarcoma. Four sarcomas were in the distal femur and one in the shaft of the tibia. Four patients received multidrug chemotherapy. The average length of the skeletal defect after tumour resection was 17 (range 10-25) cm. All patients underwent double elongation from both proximal and distal sites of the bone defect. The average follow-up period was 48 (range 40-66) months, and the average duration of external fixation was 32 months (range 579-1340 days). In one case, bone formation was satisfactory, but in the other cases, it was poor and slow. The average treatment index was 95 (range 53-191) days per 1 cm of elongation. In one case, the bone fragment disappeared during the bone transport. In one case, the end of the bone protruded from the skin, and osteomyelitis set in. This patient underwent above-knee amputation due to failure of infection control. Three patients suffered talipes equinus. One patient died of pulmonary metastasis. Two patients had fair and three had poor function. This method is not recommended for patients with bone sarcoma who may have a poor prognosis, as it has an unacceptably high complication rate.

Adolescent↗

PubMed1982

Invasion of joints by primary bone sarcomas in adults.

In a retrospective macroscopic and microscopic study of celloidin-embedded macrosections from 45 adults with primary metaphyseal intraosseous sarcomas, we ascertained the incidence, extend, and mode of tumor extension into, across, or around articular cartilage into a joint. Invasion of articular cartilage by tumor occurred in more than one-third of the macrosections examined. In more than one-half of the cases, the sarcoma extended under the capsule insertion to involve the margin of the articular cartilage, thus leaving only a pseudocapsule between tumor and joint. Tumors frequently extended across or around the osseous-tendinous junction of the cruciate ligaments into the knee joint. Our findings have important implications for the surgical management of appendicular metaphyseal intraosseous sarcomas. For primary bone sarcomas, extraarticular resections should be considered seriously when limb salvage is contemplated, especially in the knee region.

Adolescent↗

PubMed1994

[Treatment of primary bone sarcoma of the jaws].

Head and neck bone sarcomas are very uncommon tumors. Therefore, treatment modalities are not clearly established. The medical record of 12 patients with bone sarcoma of the jaw were reviewed. Six patients with osteosarcoma underwent primary chemotherapy followed by wide surgical resection, radiation therapy or combined radiosurgical treatment. The 2 and 5 years survivals were 66% and 40% respectively. Five patients with chondrosarcoma were treated by wide surgical resection alone or combined with postoperative radiotherapy and possibly chemotherapy. All patients were alive; the mean follow-up was 9 years. One patient had Ewing's tumor. Osteosarcoma and chondrosarcoma in head and neck patients have a high rate of local recurrences. Surgery is the mainstay of treatment. Patients with voluminous tumors and high-grade lesions should receive postoperative radiotherapy. The role of chemotherapy has not been defined.

Adolescent↗

PubMed2005

Use of a vascularized fibula bone flap and intercalary allograft for diaphyseal reconstruction after resection of primary extremity bone sarcomas.

BACKGROUND: The standard treatment for primary bone sarcomas of the extremities has become chemotherapy and limb salvage surgery. However, the difficulties in achieving reliable long-term healing with allograft reconstruction have led us to use vascularized fibula transfer to enhance healing. METHODS: From 1992 to 2003, 14 vascularized fibula transfers were performed at our institution for bone reconstruction in 12 patients with bone sarcoma. Free vascularized fibula transfers were performed in 13 cases, and a pedicled vascularized fibula transfer in one case. The mean age was 25 years (range, 6 to 71 years). Locations included the femur (n = 10), humerus (n = 1), and tibia (n = 3). The mean length of the vascularized fibula transfer was 17.4 cm (range, 10 to 24 cm). Indications for use of a vascularized fibula transfer included allograft nonunion (n = 8), and primary diaphyseal bone defect reconstruction combined with an intercalary allograft (n = 6). For all allograft nonunions, a vascularized fibula transfer was used with an onlay technique. For segmental bone defects, an intramedullary technique was used in three cases and an onlay technique in two cases. RESULTS: The overall mean time for bone union after a vascularized fibula transfer was 8.6 months (range, 3 to 24 months): 10 months (range, 5 to 24 months) for patients with allograft nonunions, and 6 months (range, 3 to 8 months) for patients who underwent immediate segmental bone reconstruction. All but one patient had successful bone union. One patient with persistent nonunion required a second vascularized fibula transfer. The mean time from initial limb salvage surgery to full use of the reconstructed limb without restrictions was 28 months (range, 13 to 45 months) for patients treated with a delayed vascularized fibula transfer for an allograft nonunion and 6 months (range, 3 to 8 months) for patients who underwent immediate reconstruction with a vascularized fibula transfer combined with an allograft. CONCLUSIONS: The use of a vascularized fibula transfer combined with an intercalary allograft to reconstruct bone defects after tumor resection can prevent allograft nonunion and result in decreased time to bone healing, leading to earlier patient recovery and return of function.

Adolescent↗

PubMed1993

Phase II study of miltefosine (hexadecylphosphocholine) in advanced soft tissue sarcomas of the adult--an EORTC Soft Tissue and Bone Sarcoma Group Study.

The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with oral miltefosine at a dose of 50 mg thrice daily in patients with metastatic soft tissue sarcomas. No responses were seen in 18 evaluable patients. Toxicity consisted mainly of nausea/vomiting. It is concluded that oral miltefosine has no activity in soft tissue sarcoma.

Administration, Oral↗

PubMed1994

Phase II study of liposomal muramyl tripeptide phosphatidylethanolamine (MTP/PE) in advanced soft tissue sarcomas of the adult. An EORTC Soft Tissue and Bone Sarcoma Group study.

The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with intravenous muramyl tripeptide phosphatidylethanolamine (MTP/PE) at a dose of 4 mg once weekly in 20 patients with metastatic soft tissue sarcomas. Responses were not seen in 19 evaluable patients. Toxicity consisted mainly of a mild flu-like syndrome after 62% of drug administrations. It is concluded that MTP/PE at this dose and schedule has no activity in metastatic soft tissue sarcoma.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Bone sarcomas as second malignant neoplasms following childhood cancer.

This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood. Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States. The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import. The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed. The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma). Anthracyclines significantly shortened the interval by about 3 years. The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest. The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions. However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed.

Age Factors↗

PubMed2004

Outcome of flat bone sarcomas (other than Ewing's) in children and adolescents: a study of 25 cases.

We analysed the clinical features and outcome of young patients with non-Ewing's flat bone sarcoma treated during the era of contemporary chemotherapy. The characteristics and outcome of 25 patients (15 males and 10 females) with primary or radiation-related flat bone sarcoma treated in the Pediatrics Department at the Institut Gustave Roussy from 1981 to 1999 were reviewed. In all, 20 patients had osteosarcoma, four chondrosarcoma and one malignant fibrous histiocytoma. The age at diagnosis ranged from 2 to 23 years (median, 15 years). Nine tumours were located in the craniofacial bones, 11 in the pelvis and five in flat bones at other sites. Four patients had metastatic disease at diagnosis. Radiation-associated flat bone osteosarcoma was diagnosed in 10 out of 25 cases. The projected overall survival and event-free survival (EFS) rates at 5 years were 45.1 and 34.3% for all the 25 patients. The EFS rate of patients with second bone sarcoma was similar to that of patients with de novo flat bone sarcoma (P=0.1). The aim of treatment was curative for 24 patients, 23 of whom were treated with intensive chemotherapy regimens and 19 with surgery. Significant adverse prognostic factors on survival included incomplete surgical resection (P=0.001) and use of regimens without pre- and postoperative chemotherapy (P=0.007). Nine of the 25 patients were treated with pre- and postoperative chemotherapy and complete surgical resection. Among them, eight are alive with no disease. Radical surgical resection is the overriding prognostic factor for flat bone sarcomas in young patients. Nevertheless, our results suggest a more favourable outcome since the advent of intensive chemotherapy.

Adolescent↗

PubMed2000

Internal hemipelvectomy for bone sarcomas in children and young adults: surgical considerations.

AIMS: Pelvic bone sarcomas in children and young adults are rare, and associated with a poor prognosis and a high rate of local recurrence. Primary goals of treatment include prevention of local recurrence and distant metastases. A secondary goal is maintenance of quality of life by avoiding major amputative surgery. This is why internal hemipelvectomy (a limb-sparing surgery) is advocated whenever possible. The focus of our presentation is surgical issues in the context of resection and reconstruction of the pelvis in the first two decades of life. MATERIALS AND METHODS: Between January 1988 and June 1998, 27 patients were treated and operated on (follow-up time 1.5-12 years). There were 17 males and 10 females. Their age ranged between 2 and 22 years. There were 24 patients with Ewing's sarcoma (ES) and three with other bone sarcomas. In 19 patients the tumour involved the entire or part of the iliac bone (in some cases with extension to the sacrum). In five patients the tumour involved the pubis and/or ischium. In three patients the tumour involved the sacrum with some extension to the posterior iliac bone. All patients received neoadjuvant and adjuvant chemotherapy and radiotherapy with different protocols (related to the origin of referral). RESULTS: Twenty-seven patients underwent internal hemipelvectomy. According to Enneking's classification there were: type I-10; type II-one; type III-six; type IV-five (including one localized sacrectomy); type I+IV-five patients. In 15 patients some kind of reconstruction was needed and in 12 no reconstruction was done. Four wound infections occurred that were managed successfully by surgical debridement, antibiotics and local wound care. In one case removal of the 'implant' was needed. No primary or secondary amputations were performed in the series. The rate of local recurrence was 22%. Functional status at the last follow-up visit or before death, according to the AMSTS functional rating system: excellent-six; good-17; fair-three and poor-one. All patients except the one poor result maintained their walking ability during the follow-up time. CONCLUSIONS: Internal hemipelvectomy is achievable in most cases and justified for better quality of life in children, adolescents and young adults with sarcomas. Further efforts are needed to improve the reconstructive options in the pelvis.

Adolescent↗

PubMed1978

Radiation-induced soft-tissue and bone sarcoma.

From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed.

Adolescent↗

PubMed2001

Surgery for primary bone sarcomas of the pelvis.

Primary bone sarcomas of the pelvis represent the most challenging problem in limb-saving surgery. Chondrosarcoma is the most common type, followed by osteosarcoma and Ewing's sarcoma. The symptoms are often vague, so that the diagnosis is made late, when the tumor has already reached a large size. Nowadays hindquarter amputation is reserved for complex tumors involving the sacrum, the sciatic nerve, the iliac vessels or the bladder. Internal hemipelvectomy should be undertaken whenever possible; the reconstructive techniques are based on the three anatomic regions concerned: ilium, periacetabular area, and pubis. Complications occur in more than 50% of the patients. The 5-year survival rate is about 55%. Special scores, such as the MSTS/ISOLS and the TESS score, should be used to make the various studies comparable.

Bone Neoplasms↗

PubMed1993

An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas.

PURPOSE AND METHODS: Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin. RESULTS: Between 1987 and 1989, 340 eligible patients were randomized. Significantly more myelosuppression, a higher response rate (17% v 32%; P < .002) and longer time to progression (4 v 6 months; P < .02) were observed for patients who received ifosfamide. An overall survival advantage for the two-drug regimen (12 v 13 months; P = .04) was not significant by multivariate analysis. CONCLUSION: In all three randomized trials of doxorubicin with and without ifosfamide (Eastern Cooperative Oncology Group [ECOG], European Organization for Research and Treatment of Cancer [EORTC], and this study), the response rate was higher for the ifosfamide-containing arm, significantly so in this and the ECOG studies. An improved response rate may be particularly important for the preoperative management of high-grade, borderline resectable lesions or pulmonary metastases, particularly in younger patients. In older patients, or for low-to intermediate-grade lesions, doxorubicin and DTIC followed by ifosfamide on progression is preferred.

Adolescent↗

PubMed1992

Preliminary results in heavy charged particle irradiation of bone sarcoma.

Between 1979 and 1989, 17 patients with unfavorable bone sarcoma were treated wholly or in part with heavy charged particle irradiation (helium and/or neon ions) at the University of California Lawrence Berkeley Laboratory. The majority of tumors were located near critical structures such as the spinal cord or brain. Gross tumor was present in all but two patients at the time of irradiation. Six patients were treated for recurrent disease. Histologies included osteosarcoma, Ewing's sarcoma, and recurrent osteoblastoma. Four of the osteosarcomata were believed to have been induced by previous therapeutic irradiation for various tumors. Follow-up time since initiation of radiation ranged from 7 to 118 months (median 40 months). The 5-year Kaplan-Maier local control rate was 48%; the corresponding survival rate was 41%. Over half the patients succumbed to distant metastases despite the majority of patients receiving chemotherapy. In this preliminary study, we have shown that heavy charged particle irradiation can be effectively used for control of bone sarcoma. A Phase II trial is warranted to determine optimal treatment for unresectable or gross residual disease.

Antineoplastic Combined Chemotherapy Protocols↗