A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115–20

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung

Cite this article: Bone Joint Res 2023;12(5):311–312.

Four cases of extra-osseous osteosarcoma were found among 242 cases recorded as osteosarcoma in the Swedish Cancer Registry during the years 1958 to 1968. The tumours occurred in middle-aged and elderly patients. Three of the tumours were situated in the proximal part of the thigh and one in the scapular region. Histopathologically, all tumours were subclassified as osteoblastic osteosarcomas. The patients were treated by primary local excision which in one case was followed by a radical en bloc excision of the entire tumour bed. All cases subjected to simple excision died of metastatic disease five to twenty-four months after diagnosis. The patient treated by en bloc excision is alive and apparently free from disease fourteen years after diagnosis

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value

Of tumours arising in otherwise normal bones, fibrosarcoma is about one-third as common as osteosarcoma and may have a very slightly better prognosis. A comparison of the aetiology and behaviour of forty-nine fibrosarcomata and 152 osteosarcomata indicates several similar features. Fibrosarcoma lacks the characteristic peak incidence in adolescence of osteosarcoma, but the age and sex distributions of both tumour types in patients of middle life--twenty-five to sixty-five years--are remarkably similar, even in their frequency. With fibrosarcoma, perhaps, lung metastases are fewer and appear later, thus contributing to the slightly better survival, but there is some increase in the proportion of extra-pulmonary secondaries. As with osteosarcoma, patients with fibrosarcoma show some increase in the length of post-metastatic survival when metastases are of later appearance. For the whole series the five-year crude survival rate was 21 per cent, better results being recorded for patients with histologically well differentiated tumours (30 per cent) and for long bone tumours when the patient was metastasis-free initially and the tumour was treated by prompt ablation (40 per cent). These are probably the best results one may expect for osseous fibrosarcoma without recourse to adjuvant antimetastatic therapy. Complete control of the primary tumour is likewise mandatory, and can be assured only by complete surgical removal when this is technically feasible

Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom postoperative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases

At re-examination of all osteosarcomata recorded in the Swedish Cancer Registry during the years 1958 to 1968, 11 cases of parosteal osteosarcoma were found. No case of so-called periosteal osteosarcoma was identified. The tumours constituted 1.6 per cent of all proved primary malignant bone tumours. The ages of the 11 patients (six women and five men) ranged from 17 to 62 years (average 33 years). The clinical and histopathological findings of this study and of those collected from a review of the literature suggest the occurrence of two different types of parosteal osteosarcoma: the predominant type is originally benign but has a definite malignant potential, causing metastases after long symptom-free intervals; the other type is highly malignant from the beginning. Primary amputation is recommended for the latter category of tumours, and compartmental, radical en bloc resection followed by regular review is recommended for the former

Two hundred and forty-eight high-grade central osteosarcomata were treated by amputation or disarticulation; in 5.2 per cent the tumour recurred at the amputation site. The following causes may be responsible for local recurrence: the level of the amputation is too close to the tumour; there is an unrecognised intramedullary extension of the tumour; during a previous block resection tumour cells may have been seeded in the soft tissues; the primary tumour was too extensive even for radical surgery; "skip" metastases may have been present; iatrogenic tumour implantation may have occurred while a biopsy was being performed during the course of an amputation. Treatment of the primary osteosarcoma should take all these possibilities into account. In our experience adjuvant chemotherapy has not significantly changed the frequency of local recurrences which should be treated by radical operation or, if this is not possible, by irradiation; chemotherapy may be used as an adjuvant. The prognosis of local recurrences is bad

The aim of this study was to assess a specific protocol for the treatment of patients with a parosteal osteosarcoma of the distal femur with limb salvage involving hemicortical resection and reconstruction using recycled pasteurised autograft and internal fixation. Between January 2000 and January 2010, 13 patients with a mean age of 26.5 years (17 to 39) underwent this procedure. All the tumours were staged according to Enneking’s criteria: there were eight stage IA tumours and five stage IB tumours. The mean follow-up was 101.6 months (58 to 142), and mean post-operative Musculoskeletal Tumour Society functional score was 88.6% (80% to 100%) at the final follow-up. All the patients had achieved bony union; the mean time to union was 11.2 months (6 to 18). Local recurrence occurred in one patient 27 months post-operatively. No patient had a pulmonary metastasis. A hemicortical procedure for the treatment of a parosteal osteosarcoma is safe and effective. Precise pre-operative planning using MRI is essential in order to define the margins of resection. Although it is a technically demanding procedure, gratifying results make it worthwhile for selected patients. Cite this article: Bone Joint J 2013;95-B:1275–9

A retrospective analysis was performed of eight patients with an open triradiate cartilage, who underwent resection for osteosarcoma and reconstruction of the proximal femur with a hemiarthroplasty, in order to identify changes of acetabular development. An analysis of the centre-edge angle, teardrop-to-medial prosthesis distance, superior joint space, teardrop-to-superior prosthesis distance, degree of lateral translation, and arthritic changes, was performed on serial radiographs. The median age at the time of the initial surgery was 11 years (5 to 14). All patients developed progressive superior and lateral migration of the prosthetic femoral head. Following hemiarthroplasty in the immature acetabulum, the normal deepening and enlargement of the acetabulum is arrested. The degree of superior and lateral migration of the prosthetic head depends on the age at diagnosis and the length of follow-up

Immunoscintigraphy using radioisotope-labelled monoclonal antibody prepared against osteosarcoma 791T cells was used to detect a primary osteosarcoma. The eight-centimetre tumour was detected using rectilinear scintigraphy of 131I-labelled antibodies. Image enhancement was achieved by subtraction of blood-pool radioactivity labelled with technetium-99m. The ratio of tumour to non-tumour uptake of radioactivity (5:1) suggested that antibody targeting of therapeutic agents is feasible

The foregoing suggestions may be summarised in the following recommendations for the treatment of osteogenic sarcoma. 1. Deep x-ray therapy in high dosage, followed by local resection, should be given serious trial especially: 1) in the upper limb; 2) in the group with atypical clinical or radiographic signs, or histology resembling that of inflammatory lesions; 3) with Grade I histology; and 4) in the young. 2. Deep x-ray therapy followed at once by amputation should be used for osteogenic sarcoma if : 1) local resection would leave a lower limb more unstable than an artificial leg ; or 2) if response to x-rays is poor. 3. Deep x-ray therapy alone should be used: 1) if the patient is unsuitable for, or refuses, any operation ; and 2) palliatively, if metastases are present or the tumour is too advanced, or the patient is not fit for radical treatment. 4. Amputation alone should be used palliatively, for pain or fungation, when x-ray therapy has failed to relieve, or is not readily obtainable. 5. Biopsy and histological grading must be performed in every case. A histological diagnosis is most important. Coley (1949) and MacDonald and Budd (1943) support this view. 6. The records of every possible case should be sent to and discussed by a group with special experience of these tumours

We report the results of limb salvage for non-metastatic osteosarcoma of the distal tibia using resection arthrodesis, autogenous fibular graft and fixation by an Ilizarov external fixator. In six patients with primary osteosarcoma of the distal tibia who refused amputation, treatment with wide en bloc resection and tibiotalar arthrodesis was undertaken. The defect was reconstructed using non-vascularised free autogenous fibular strut graft in three patients and a vascularised pedicular fibular graft in three, all supplemented with iliac cancellous graft at the graft-host junction. An Ilizarov external fixator was used for stabilisation of the reconstruction. In five patients sound fusion occurred at a mean of 13.2 months (8 to 20) with no evidence of local recurrence or deep infection at final follow-up. The mean post-operative functional score was 70% (63% to 73%) according to the Musculoskeletal Tumour Society scoring system. All five patients showed graft hypertrophy. Union of the graft was faster in cases reconstructed by vascularised fibular grafts. One patient who had a poor response to pre-operative chemotherapy developed local tumour recurrence at one year post-operatively and required subsequent amputation

We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first-degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy

We reviewed the surgical treatment and oncological results of 40 patients with pathological fractures from localised osteosarcoma of the long bones to determine the outcome of limb salvage in their management. All had had adjuvant chemotherapy. There were 26 males and 14 females with a median age at diagnosis of 18 years (2 to 46) and a median follow-up of 55 months (8 to 175). We performed limb salvage in 27 patients and amputation in 13. The margins of resection were radical in five patients, wide in 26, marginal in six, wide but contaminated in two and intralesional in one. Local recurrence developed in 19% of those treated by limb salvage and in none of those who had an amputation. The cumulative five-year survival of all the patients was 57% and in those treated by limb salvage or amputation it was 64% and 47%, respectively (p > 0.05). Limb-sparing surgery with adequate margins of excision can be achieved in many patients with pathological fractures from primary osteosarcoma without compromising survival, but the risk of local recurrence is significant

Of 41 consecutive patients with newly diagnosed osteogenic sarcoma admitted to the Children's Orthopedic Hospital and Medical Center in Seattle, Washington, between 1952 and 1977, 19 treated before 1973 did not receive adjunctive chemotherapy (histological group) whereas after 1972 22 have been so treated (chemotherapy group). Chemotherapy consisted primarily of high doses of methotrexate and adriamycin for 16 months after surgical treatment. Patients in the historical group have been observed for a minimum of nine years (six patients) or until death (13 patients). The 13 surviving patients in the chemotherapy group have been followed for a minimum of three years (median five years) and all 12 disease-free patients have been off therapy for between one and a half and five and a half years (median three years). Overall, the chemotherapy group has had a significant increase in both survival (p = 0.03) and disease-free survival (P = 0.02) compared to the historical group. In 35 patients with localised disease at diagnosis, the three-year disease-free survival and the three-year survival rates were 18 per cent and 41 per cent respectively in the historical group, and 67 per cent and 78 per cent (life table estimates) respectively in the chemotherapy group. With adjunctive chemotherapy only one of the seven patients developing pulmonary metastases did so later than nine months after diagnosis. The superior results in the chemotherapy group could not be accounted for by differences in age, sex, presence of metastases at diagnosis, histopathology, location of primary tumour, type of initial or subsequent surgical treatment, or the use of standard or computerised lung tomography. Although the use of historical controls in this study does not exclude other changes as contributing to the observed improvement in outcome, our data support the contention that adjunctive chemotherapy improves both the disease-free survival and the overall survival of patients with osteosarcoma and rarely delays the onset of recurrent or metastatic disease

The existence of pulmonary metastases in patients presenting with osteosarcoma is known to indicate a poor prognosis. Lung resection of solitary lesions is now a standard treatment approach, but with limited successful long-term results. We report the progress of a 16-year-old girl with osteosarcoma of the proximal tibia who underwent 11 lung resections for pulmonary metastases over a two-year period, and who has since then been free of disease for seven years

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 by combined surgery and chemotherapy (vincristine, adriamycin and methotrexate in medium doses) for 18 months. The follow-up ranges from 30 to 80 months (mean = 48 months). Twenty-six patients remained free from any evidence of disease, two had local recurrences but no metastases and 27 had metastases (four of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in patients who had segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with an "historical" group (94 osteosarcoma patients treated by operation alone in our Institute between 1960 and 1971) showed that the percentage of patients free from evidence of disease was higher in the group who receiving chemotherapy. In addition, the appearance of metastases in this group was delayed (mean = 16 months) as compared with the historical controls (mean = 8 months). On the other hand, after the same kind of operative treatment, the rate of local recurrences and the time of their appearance was almost identical in both groups

The level of bone resection for osteosarcoma depends on the pre-operative evaluation of the extent of intramedullary tumour. We compared the accuracy of magnetic resonance imaging (MRI), computerised tomography (CT), and isotope bone scanning with the actual extent of the tumour in the resected specimens from 34 patients with primary osteosarcoma of a long bone. The extent of medullary tumour was defined accurately in 23 of 24 MRI scans (96%) and 24 of 32 CT scans (75%). A flexion contracture of a joint close to the tumour was an important cause for inaccurate measurements from both MRI and CT scans. Isotope bone scanning was inaccurate: its role is now confined to detecting skeletal metastases and skip lesions