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Radiation-induced osteosarcoma in the rat as a model for osteosarcoma in man.

A technique is described for the local induction of osteosarcoma in the rat by implanting (32)P-impregnated polyvinyl chloride discs into the distal femoral metaphysis. The incidence of osteosarcomata after 18 months was 28%. A comparison is made of the pathology of the radiation-induced osteosarcoma in the rat and the "spontaneous" osteosarcoma in man. The possible value of the rat osteosarcoma model is discussed.

Animals↗

Enhanced osteosarcoma growth produced in rats by osteosarcoma allografts.

Transplanted syngeneic osteosarcomas (induced by 32P in DA rats) grew significantly larger in DA rats receiving a simultaneous transplant of allogeneic osteosarcoma than in rats receiving syngeneic tumour only (P less than 0-01). Two other malignant allogeneic tumours, and allogeneic spleen cells, did not alter the growth of the transplanted syngeneic osteosarcomas. When the allogeneic osteosarcoma was given 7 days before the syngeneic tumour, the reverse effect (retardation) occurred. When given 7 days after the syngeneic tumour cells, the effect on both syngeneic and allogeneic tumour growth was variable. Some possible reasons for these findings are discussed, and the argument is presented that immunological phenonema are involved in the reaction.

Animals↗

Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma. European Osteosarcoma Intergroup.

PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m(2) and cisplatin (CDDP) 100 mg/m(2) planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.

Adolescent↗

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.

Adolescent↗

Establishment of an osteoblastic osteosarcoma cell line and effects of cell culture conditions on secretion of matrix metalloproteinases from the cultured osteosarcoma cells.

Osteosarcoma cells are useful for investigating bone metabolism as malignant counterpart of osteoblasts. In hematogenous metastases of osteosarcoma cells, the cells need to adjust to various changes in pericellular environment. The changes in pericellular environment may change intracellular environment and consequently the secretion of matrix metalloproteinases (MMPs) which destroy extracellular matrices. In this report, a new cell line, KOS-1, derived from human osteoblastic osteosarcoma was established, and we assumed various culture conditions containing ingredients of the extracellular matrix to make a comparative study on MMPs detected from the culture supernatants. A wide spectrum of MMPs, including MMP-1 and -3 which were increased in the presence of interleukin 1 beta, was detected in this cell line. Production of MMP-1, the enzyme which decomposes types I, II, III and X collagen, by the cells, was increased in the presence of type I collagen. MMP-3 (stromelysin-1) which degrades types III and IV collagen, laminin, fibronectin, proteoglycan, etc. was produced more abundantly in the presence of type IV collagen. MMP-2 (72-kd type IV collagenase/gelatinase A) activity was found to be increased in the presence of gelatin and type IV collagen. The MMPs production in cultured osteosarcoma cells was changed depending on the culture conditions. This indicates that the same osteosarocma cells produce different amounts and kinds of enzymes involved in local infiltration and remote metastases and increase the production of the enzymes most required under a specific environment.

Adolescent↗

Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group.

BACKGROUND: Due to the low incidence rate, the optimal strategy for the treatment of patients with spinal osteosarcoma is unknown. METHODS: Twenty-two patients with osteosarcoma of the spine (15 with tumors of the sacrum and 7 with tumors at other sites) who received chemotherapy according to the Cooperative Osteosarcoma Study Group protocol were analyzed. Six patients presented with metastasis, and 16 patients had no evidence of metastasis at the time of entry into the protocol. Of 12 patients who underwent excision of their tumors, 2 patients underwent wide excision, 3 patients underwent marginal excision, and 7 patients underwent intralesional excision. Eight patients received irradiation: Six patients received conventional radiotherapy only, one patient received neutron beam therapy, and one patient received samarium-153-ethylene diamine tetramethylene phosphonate therapy. Follow-up ranged between 24 months and 105 months (median, 47 months). RESULTS: The median survival was 23 months, and three patients have survived without disease for > 6 years. Patients with primary metastases (P = 0.004), large tumors (P = 0.010), and sacral tumors (P = 0.048) had lower overall survival compared with patients who had no metastasis, small tumors, and nonsacral tumors, respectively. There was a significant difference in overall survival between 5 patients who underwent either wide or marginal surgery and 17 patients who underwent either intralesional surgery or no surgery (P = 0.033). Among 17 patients who underwent no surgery or intralesional surgery, overall survival tended to be better in 7 patients who received irradiation compared with the overall survival in 10 patients who did not receive irradiation (P = 0.059). CONCLUSIONS: Patients with metastases, a large tumors, and sacral tumors had a poor prognosis in the current study with small numbers of patients. Wide or marginal excision of the tumor improved survival. Patients with osteosarcoma of the spine should be treated with a combination of chemotherapy and at least marginal excision for those with surgically accessible tumors. Postoperative radiotherapy may be beneficial.

Adolescent↗

Thrombospondin binds to the surface of human osteosarcoma cells and mediates platelet-osteosarcoma cell interaction.

We have previously shown that thrombospondin (TSP) is synthesized and secreted by human MG-63 osteosarcoma cells. In this study, the secretion and cell surface expression of TSP by two different human osteosarcoma cell lines (MG-63 and TE-85) as well as the involvement of TSP in the platelet-aggregating activity of these tumor cells were studied. Using a sandwich enzyme-linked immunosorbent assay, MG-63 cells secreted 3-fold as much TSP as TE-85 cells at 48 h (0.17 +/- 0.01 (SD) versus 0.06 +/- 0.006 micrograms/10(6) cells, P = 0.007). Binding of exogenous 125I-TSP to MG-63 and TE-85 cells in monolayer indicated that binding was time and concentration dependent, saturable, and inhibited by excess cold TSP. However, despite a similar affinity, MG-63 cells had 10-fold more TSP-binding sites than TE-85 cells (402,394 +/- 130,346 versus 36,748 +/- 7,708 TSP-binding sites/cell; P = 0.002). Similar binding differences of 125I-TSP were observed with both osteosarcoma cell lines in suspension. A fluorescence-activated cell-sorting analysis was used in conjunction with an anti-TSP polyclonal antibody, and binding of endogenous TSP to MG-63 and TE-85 cells in suspension was investigated. Addition of an anti-TSP antibody to MG-63 and TE-85 cells in suspension increased the mean fluorescence intensity 50-fold when compared to an irrelevant antibody. Moreover, the fluorescence intensity of MG-63 cells with an anti-TSP polyclonal antibody was increased by 40% when compared to TE-85 cells. Since TSP was expressed on the surface of osteosarcoma cells, the involvement of this glycoprotein in the platelet-aggregating activity of MG-63 and TE-85 cells was therefore investigated using an anti-TSP polyclonal antibody and two monoclonal antibodies (P10 and MA-II), the epitopes of which lie within the Mr 140,000 non-heparin-binding fragment and the Mr 25,000 heparin-binding fragment of TSP, respectively. Preincubation of MG-63 cells (1 x 10(6) cells/ml) with either an anti-TSP polyclonal antibody (100 micrograms/ml) or monoclonal antibody P10 (15 micrograms/ml) inhibited by 80% other platelet-aggregating activity of these tumor cells, while anti-TSP monoclonal antibody MA-II (15 micrograms/ml) had no effect. In sharp contrast, the anti-TSP polyclonal antibody (100 micrograms/ml) only exhibited a slight inhibitory effect on platelet aggregation induced by TE-85 cells when using a low concentration of tumor cells (0.6 x 10(6) cells/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies↗

Survival and management considerations in postirradiation osteosarcoma and Paget's osteosarcoma.

Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five-year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations.

Bone Neoplasms↗

Well-differentiated extraskeletal osteosarcoma. A soft-tissue homologue of parosteal osteosarcoma.

We describe a unique case of a low-grade extraskeletal osteosarcoma revealing both histologic and radiologic features reminiscent of parosteal osteosarcoma. The tumor, which had been present for 10 years, occurred in the left axilla of a 74-year-old black woman. To date, all the published cases of extraskeletal osteosarcoma have been high-grade neoplasms; to our knowledge, this is the first reported case of a low-grade extraskeletal osteosarcoma.

Aged↗

[A histological study on osteosarcoma. Part II: The mode of local extension of osteosarcoma].

The survival rate of patient with osteosarcoma has been increasing, owing to the development of adjuvant chemotherapy. Recently, the limb saving procedure in osteosarcoma has been attempted in many countries. Although we need knowledge about the mode of local extension of osteosarcoma in the planning of this surgery, there are few reports concerning the matter. The purpose of this paper is to make clear, morphologically, how tumor tissue extends across the epiphyseal plate, periosteum and bone marrow. The materials were 26 amputated extremities of osteosarcoma which had not received any chemotherapy or radiotherapy. Paraffin embedded macrosections were prepared and stained with HE and Masson stain. When epiphyseal plate was open or closing, 13 out of 14 cases (93%) showed transphyseal extension of tumor. Tumor extension along the vessels at the center of the plate and the epiphyseal artery was most common. Transmedullary extension showed three different types, infiltrative type (18 cases), lobular type (5 cases), and "skip" type (one case). None had capsule or pseudocapsule surrounding the tumor. As to the relationship between periosteal reaction and tumor involvement of cortex or medulla, periosteal reaction was located more proximally than cortical or medullary involvement in some cases. In other cases, however, cortical or medullary involvement was located more proximally than periosteal reaction. The gaps between the tips of the periosteal reaction and cortical or medullary involvement ranged from 0.5 to 1.5 cm. In the transperiosteal extension, it was confirmed that tumor cells had invaded the periosteum along the vessels penetrating the periosteum.

Adolescent↗

An in vivo/in vitro experimental model system for the study of human osteosarcoma: canine osteosarcoma cells (COS31) which retain osteoblastic and metastatic properties in nude mice.

BACKGROUND: In this report we describe the establishment, characterization, and research utility of a cell line derived from a dog having a spontaneously occurring osteosarcoma. MATERIALS AND METHODS: Tumor samples were collected from a dog with a naturally occurring osteosarcoma and processed for light microscopy, electron microscopy, immunocytochemistry, immunohistochemistry, karyology, and cell culture. Established cells from passage 31 (COS31; canine Qsteosarcoma cells from passage 31) were inoculated subcutaneously between the scapula and in the right abdominal side of athymic nude mice and evaluated similarly. RESULTS: COS31 cells derived in cell culture and in nude mice had morphological and biochemical properties comparable in all respects to the original canine tumor specimen. CONCLUSIONS: The ability of COS31 cells to produce tumors in nude mice (i.e. a small animal model) typical of canine osteosarcoma (i.e. a large animal model) with a similar pathological and biological behavior (e.g. alkaline phosphatase and osteocalcin positive immunostaining, osteoid production, rapid growth, and wide spread metastases) demonstrates the potential utility of COS31 cells as a in vitro and in vivo model system in the development of new strategies in the treatment of human osteosarcoma.

Alkaline Phosphatase↗

Dedifferentiated high-grade osteosarcoma originating from low-grade central osteosarcoma of the fibula.

Low grade central osteosarcoma is a distinct, rare low grade malignant neoplasm characterized histologically by a spindle cell proliferation associated with trabecular bone formation. This tumor usually carries a good prognosis. However, it has the potential to recur, dedifferentiate, and metastasize subsequent to surgical treatment. In extremely rare occasions, LGCOS presents with areas of dedifferentiation upon initial patient evaluation. In this report we describe one such case affecting the fibula of a 39-year-old female, presenting with pain. Initial biopsy demonstrated a high-grade osteosarcoma. No areas of LGCOS were seen histologically. Following biopsy the patient received 3 months of chemotherapy at a different institution. However, the patient continued to exhibit symptoms. X-rays indicated a very aggressive tumor in the diaphysis of the proximal fibula, MRI revealed soft tissue involvement. The tumor and surrounding soft-tissues were excised en bloc at our institution. Microscopically, the lesion consisted of high-grade osteosarcoma as well as an underlying LGCOS that involved the cortex and medullary cavity of the fibula. The two histological components of the tumor were sharply delineated from one another. No chemotherapy effect was appreciated histologically or clinically. Eight months following the surgery, the patient died from lung metastases. This is the third documented case of dedifferentiated LGCOS at initial presentation. This case reveals that the low-grade component was also evident on preoperative radiographs.

Adult↗

Doxorubicin and cisplatin chemotherapy in high-grade spindle cell sarcomas of the bone, other than osteosarcoma or malignant fibrous histiocytoma: a European Osteosarcoma Intergroup Study.

There are limited data that define the role of chemotherapy in the treatment of high-grade spindle cell sarcomas of bone, other than osteosarcoma or malignant fibrous histiocytoma (MFH-B). This prospective study evaluates the effect of doxorubicin and cisplatin on these tumours. Thirty-seven patients, age 65 years, with spindle cell sarcoma of bone, except osteosarcoma or MFH-B, were included. Chemotherapy consisted of doxorubicin and cisplatin every 3 weeks for six cycles. Resection was performed after three cycles. In 15 patients with metastases, response assessment showed three complete responses (CR), four stable disease (SD), five progression; three were not evaluable. Median time to progression was 30 months (95% Confidence Interval (CI), 8-51 months) for the operable non-metastatic patients; median survival 41 months (95% CI, 16-82 months). Median time to progression in the metastatic group was 10 months (95% CI, 0-18 months) and median survival was 14 months (95% CI, 4-45 months). This study suggests a limited role for doxorubicin and cisplatin in metastatic high-grade spindle cell sarcoma of bone, other than osteosarcoma or MFH-B cases.

Adolescent↗

Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs.

BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.

Adolescent↗

[Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients].

BACKGROUND: Owing to twenty years of multicentric interdisciplinary cooperation, the COSS group has been able to collect data on a large group of osteosarcoma patients treated by neoadjuvant therapy. This paper reviews results achieved in patients with localized extremity tumors. PATIENTS AND METHODS INCLUSION CRITERIA: Registration into a completed neoadjuvant COSS-Study. Histologically confirmed, primary, localized, high-grade, central osteosarcoma of an extremity; age < 40 years; no pretreatment; interval diagnosis to chemotherapy < or = 3 weeks; no severe comorbidity. Chemotherapy: HD-methotrexate +/- doxorubicin +/- cisplatin +/- ifosfamide +/- BCD. Scheduled local therapy: Surgery. RESULTS: 925 evaluable patients from 101 institutions. Median age 15 years, m:f 1.4:1. Primary site: femur 510, tibia 251, humerus 100, fibula 51, other 13. Tumor-size < 1/3 of the involved bone 616, > or = 1/3 304. Definitive surgery in 903/925 cases, 443 limb salvage procedures. Good response (> 90% necrosis) in 469/806 (58.2%) evaluated tumors. Median follow-up for surviving patients: 5.42 years. Actuarial survival after 5 and 10 years: 72.5% (95%-CI 69.3-75.7) and 66.3% (62.5-70.0), relapse-free 62.1% (58.7-65.4) and 59.4% (55.8-63.0). 683/925 alive (601 first remission), 242 deceased (212 tumor progression, 30 other causes). 66.2% (97.3%) of all relapses within 2 (5) years. Prognosis correlates with tumor-size (< vs. > or = 1/3: 69.9% vs. 58.3% at 10 years) and -site (tibia: 74.2%, humerus: 54.5%) and -response (good vs. poor: 78.2% vs. 52.5%) (all p < 0.01). Actuarial 10-year survival by response grading I-VI according to Salzer-Kuntschik 80.9%, 82.8%, 71.1%, 60.7%, 47.7%, 27.3%. COSS-studies with preoperative 4-drug therapy more efficacious than less aggressive protocols. No impact of doxorubicin scheduling (sequential: rapid vs. 48 h-continuous infusion) or cisplatin scheduling (randomized: 5 h vs. 72 h-infusion) on prognosis detected. CONCLUSIONS: Intensive multiagent chemotherapy and delayed surgery for localized extremity osteosarcoma led to excellent oncologic results in the COSS-studies. Tumor-size, -site, and -response as well as the intensity of upfront chemotherapy correlated with outcome. Giving doxorubicin and cisplatin by continuous infusions did not result in discernible prognostic disadvantages.

Adolescent↗

A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup.

PURPOSE: A randomized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens, and to evaluate the feasibility of conservative surgery in this setting. Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy. With extension of the study, eventual accrual was sufficient to compare disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between July 1983 and December 1986, the European Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high-grade extremity osteosarcoma onto a randomized trial that compared doxorubicin (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100 mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour infusion, every 4.5 weeks times four. In the majority of patients (179), chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9 weeks in both groups. RESULTS: Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after conservative surgery were acceptable. With a median follow-up of 53 months, DFS at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64% versus 50%, is not different significantly (P = .10). In a subset of 66 patients for whom pathologic data on the resected specimen were available, DFS (P = .003) and OS (P = .008) were better for those who demonstrated > or = 90% necrosis. CONCLUSION: A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results, which are similar to those that have been achieved in cooperative group studies of longer, more complex multiagent chemotherapy, and provide the basis for a direct comparison in the next EOI study.

Adolescent↗

Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.

Adolescent↗

The age of osteosarcoma patients is increasing. An epidemiological study of osteosarcoma in Sweden 1971 to 1984.

We conducted an epidemiological study of osteosarcoma in Sweden from 1971 to 1984 to investigate whether the typical features of the disease had changed. Of 294 osteosarcoma patients reviewed, 249 had primary skeletal tumours, and for these the mean annual incidence was 2.1 per million, without any clear trend over time. The mean male/female ratio for the period was 1.6 again with no consistent pattern over time; nor was there any significant change in the distribution of tumours according to location. The only feature which showed a significant change over the 14-year period was the mean age of the patients, being at its lowest (19 years) in 1972 and at its highest (40 years) in 1981. Excluding the 22 patients with craniofacial tumours, the remaining 227 also showed a significant increase in mean age. Analysis of the annual age distribution disclosed an increasing fraction of patients older than those in the classical age peak between 10 and 29 years. A large number of trials have shown improved survival in osteosarcoma over the last 15 years, which has been attributed mainly to adjuvant chemotherapy. The change we have observed in age distribution should also be taken into account in the evaluation of the results of treatment; it may be that older patients have a better prognosis.

Adolescent↗