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PubMed2002

[The role of radiotherapy in the treatment of bone neoplasms].

Primary malignant bone neoplasms are relatively rare. The most common bone tumors are osteosarcoma,Ewing's sarcoma,chondrosarcoma, fibrosarcoma,malignant fibrous histiocytoma of bone, giant cell tumor, aneurysmal bone cyst and chordoma. These tumors are generally considered to be a radioresistant entities, but it has been suggested that radiotherapy may be effective in a palliative and in some curative situations, if a sufficient dose is given to an adequate volume. Only for the management of primary Ewing's sarcoma the radiation therapy is an essential part in the multimodal therapy concept. The most common bone neoplasms and the role of the radiotherapy are discussed in these chapter.

Adolescent↗

PubMed1984

[Malignant soft tissue tumors].

This article is a survey of actual aspects. With regard to frequency, the malignant fibrous histocytoma comes first, followed by lipo- and fibrosarcoma, synovial sarcoma, malignant schwannoma, malignant tumours proceeding from arteries and veins and the unstriated musculature. Staging and grading of these tumours are difficult. Until now their overall TNM-classification was not possible due to insufficient hard criteria.

Adult↗

PubMed1995

The antitumor effect of hyperthermia combined with fluorouracil and its analogues.

The effectiveness of 5-fluorouracil (5-FU), FT-207 and FT-207 + uracil in combination with two repetitions of 43 degrees C hyperthermia in the treatment of the Meth-A-Fibrosarcoma and Sarcoma-180 was examined in vivo in BALB/c mice. The antitumor effect was evaluated in terms of inhibition of tumor growth by measuring the tumor for 7 days. The 5-FU concentration in each tumor was also monitored. Hyperthermia combined with FT-207 or FT-207 + uracil showed a synergistic effect for the inhibition of growth of both tumors which was not observed with 5-FU. There were no significant differences in the intratumoral concentration of 5-FU in unheated or heated Sarcoma-180 for any drug treatment after the first hyperthermia treatment, except for significant decreases in the group given 5-FU with the first hyperthermia treatment. After the second hyperthermia treatment, significant decreases in the concentration of 5-FU and FT-207 + uracil were observed. In the Meth-A-Fibrosarcoma, the intratumoral concentration of 5-FU decreased significantly in the group given 5-FU and increased significantly in the group given FT-207 + uracil after the first hyperthermia treatment, while there were significant decreases in 5-FU, FT-207 and FT-207 + uracil administered with the second hyperthermia treatment. Hyperthermia combined with FT-207 or FT-207 + uracil is considered to be effective.

Animals↗

PubMed2000

Biomaterial-induced sarcoma: A novel model to study preneoplastic change.

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.

Animals↗

PubMed2001

Tumors in long-term rat studies associated with microchip animal identification devices.

Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis.

Animal Identification Systems↗

PubMed2004

[Pathology and histology of soft tissue sarcomas in the upper extremity: adults].

PURPOSE/BACKGROUND: Clinicopathologic characterization and demonstration of histologic findings in six common soft tissue sarcomas of the upper extremity in adult patients. RESULTS/CONCLUSION: Clinicopathologic findings and histologic features of the following malignant soft tissue tumours are compiled: epithelioid sarcoma, synovial sarcoma, clear cell sarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH). All these tumours show typical clinical presentations and characteristic histological findings.

Adolescent↗

PubMed2000

Sarcomas arising in dermatofibrosarcoma protuberans: a reappraisal of biologic behavior in eighteen cases treated by wide local excision with extended clinical follow up.

There is a prevailing view that sarcomas arising in dermatofibrosarcoma protuberans (DFSP) have a higher risk of metastasis than ordinary DFSP, but these data are based on cases with variable and often suboptimal treatment. There has not been a large study of sarcomas arising in DFSP in which all cases were treated by wide local excision, thereby arguably altering outcome. Clinicopathologic features of 18 cases of sarcomas arising in DFSP treated by wide local excision and having follow up of at least 5 years were analyzed. An estimate of the proportion of sarcoma and DFSP was made. The number of mitotic figures and degree of CD34 immunoreactivity were assessed in each case. The cohort included 13 females and 5 males (age, 23-87 yrs; median, 47 yrs). The tumors involved the trunk (7), scalp (4), extremities (4), and inguinal region (3), and ranged from 1.5 to 7 cm (median, 4 cm). Sarcoma occurred de novo in 15 cases and in a recurrence in three. Sarcomas resembled fibrosarcoma (17) or malignant fibrous histiocytoma (1) and occupied between 20% and 80% of the tumor (median, 60%). Mitotic activity ranged from 2 to 16 per 10 high-power field (HPF; median 7 per 10 HPF) in the sarcomatous component and 0 to 3 per 10 HPF (median, 1 per 10 HPF) in the DFSP component. All tumors expressed CD34 in the DFSP component but only nine (50%) in the sarcomatous component. All patients were treated by wide local excision with negative margins; three additionally received radiation. Four patients (22%) developed recurrences, but none developed metastasis during the follow-up period of 62 months to 17 years (median, 81.5 mos). In contrast to earlier studies, we demonstrate that patients with sarcomas arising in DFSP do not have an increased risk of distant metastasis within a 5-year follow-up period, provided they are treated by wide local excision with negative margins. This probably reflects the fact that wide local excision results in eradication of local tumor, thereby eliminating the source for subsequent dissemination. However, we cannot completely exclude the possibility that tumors in which clear margins are achieved represent a less aggressive subset, as has been suggested for high-grade extremity sarcomas. Previous studies showing increased metastasis for sarcomas arising in DFSP should be re-evaluated to determine if, with treatment stratification, metastatic rate varies.

Adult↗

PubMed1999

Primary pulmonary sarcoma: a clinicopathologic study of 26 cases.

The clinical and pathologic features of 26 primary pulmonary sarcomas were analyzed. Fourteen patients were male and 12 were female; ranging in age from 18 to 75 years (mean, 48 yr). The tumors measured from 0.9 cm in greatest diameter to filling the entire hemithorax. Thirteen tumors were in the left lung and nine in the right lung; one was bilateral, two were in the pulmonary artery, and the location of one tumor was not available. The histologic diagnoses were malignant fibrous histiocytoma (7), synovial sarcoma (6), malignant peripheral-nerve sheath tumor (3), leiomyosarcoma (3), angiosarcoma (2), intimal sarcoma (2), fibrosarcoma (2), and one case of epithelioid hemangioendothelioma. Immunohistochemical and ultrastructural examination supported these diagnoses. Morphologically, the differential diagnosis often included sarcomatoid carcinoma or desmoplastic malignant mesothelioma Patients were treated with surgery, chemotherapy, radiation therapy, or a combination of these. Follow-up was available for 22 patients and ranged from 2 to 183 months (mean, 45 mo). Fourteen patients are free of disease, four died of disease, three are alive with disease, and one died of surgical complications. A variety of sarcomas, especially malignant fibrous histiocytoma and synovial sarcoma, arise within the pulmonary parenchyma. These tumors have the potential to behave aggressively but can be cured by resection, with or without adjuvant therapy. Immunohistochemistry and electron microscopy can be helpful in distinguishing primary pulmonary sarcoma from other tumors in the differential diagnosis.

Adolescent↗

PubMed1983

Histological and biochemical characterization of murine sarcomas.

A mouse fibrosarcoma and rat osteosarcoma were examined histologically and biochemically with regard to collagen content. The fibrosarcoma was composed of undifferentiated mesenchymal cells without distinct fibroblastic characteristics. Collagen production and deposition were consistent with those observed in cultured fibroblasts. Type I and type III collagens were evident as determined by immunofluorescence staining and biochemical analysis. The osteosarcoma appeared similar to bone with regard to a high content of type I collagen, limited calcification and poor vascularization. While these sarcomas do not histologically resemble their non-transformed counterparts, analysis of their macromolecular composition confirmed the identity of their presumed cell of origin. Similar methodology could be readily applied for identification and classification of human malignant sarcomas.

Amino Acid Sequence↗

PubMed2005

Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine.

Matrix metalloproteinases (MMP) are ubiquitous enzymes involved in extracellular matrix remodeling, and as a consequence in a number of physiological and pathological states, including development, wound healing and cancer. A crucial feature of cancer progression and metastasis is the disruption of extracellular matrix, and spreading of proliferating cancer cells. Modulation of MMP is a main target of cancer research. Using the mouse fibrosarcoma cell line WEHI 164, producing high amounts of MMP-2, we investigated whether we could modulate its production. We report that MMP-2 is under the control of nitric oxide (NO)/nitric oxide synthase (NOS) system. In addition, we show that NOS activity is controlled by opioids in a non-opioid receptor-related manner. Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) M) attenuates MMP-2 activity. We conclude that, as morphine is able to decrease metalloproteinase activity via the NO/NOS system, it may have a place in the treatment of several sarcomas including fibrosarcoma.

Animals↗

PubMed1988

Soft tissue tumors of the foot and ankle.

Seven patients with malignant soft tissue tumors of the foot and ankle were retrospectively reviewed. Emphasis was placed on the value of various diagnostic modalities used preoperatively for staging and the adequacy of treatment rendered using current tumor surgery principles. The malignant tumors included synovial cell sarcoma (four), clear cell sarcoma (one), fibrosarcoma (one), and melanoma (one). Surgical management of the malignant lesions included intracapsular excision, marginal excision, wide excision, and radical amputation. Preoperative diagnostic and staging studies that were found to be helpful include ultrasonography, xeroradiography, triple-phase bone scan, and CT and magnetic resonance imaging (MRI) scans. Surgical guidelines include the use of longitudinal skin incisions to obtain excisional biopsies of smaller lesions, keeping the tourniquet inflated until either a benign diagnosis is made or until the definitive procedure is performed. Wide excision or partial foot versus radical amputation may be required depending on the size, location, and extent of malignant soft tissue sarcomas.

Adolescent↗

PubMed1979

Bioassay of azobenzene for possible carcinogenicity.

A bioassay of azobenzene for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered azobenzene at one of two doses, either 200 or 400 ppm, for 105 or 106 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered azobenzene at one of two doses, either 200 or 400 ppm, for 105 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially 400 or 800 ppm, for 38 weeks. Because of excessively lowered body weights in the dosed groups of the females, doses for the females were then reduced to 100 and 400 ppm, respectively, and administration at the lowered doses was continued for 67 or 68 weeks. The time-weighted average doses for the female mice were either 208 or 545 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls, and were generally dose related throughout the bioassay. Mortality was dose related in the male rats and the female mice, but was not significantly affected in either the female rats or the male mice. Survival was 70% or greater at week 90 on study in all dosed and control groups of each species and sex; thus, sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. In rats, a large number of sarcomas, including fibrosarcomas, hemangiosarcomas, and osteosarcomas in both males and females and malignant hemangiopericytomas in females, occurred in the spleen and other abdominal organs at incidences that were dose related in each sex (P<0.001) and that in direct comparisons were significantly higher (P<0.001) in the high-dose groups of each sex than in the corresponding control groups (males: controls, 0/20, low-dose 6/49, high-dose 31/49; females: controls 0/20, low-dose 5/50, high-dose 21/50). In mice, no tumors occurred in either males or females at incidences that were significantly higher in the dosed groups than in the corresponding control groups. It is concluded that under the conditions of this bioassay, azobenzene was carcinogenic (sarcomagenic) for F344 rats, inducing various types of sarcomas in the spleen and other abdominal organs of both males and females. The test chemical was not carcinogenic for B6C3F1 mice of either sex.

Journal Article↗

PubMed1986

Soft tissue sarcomas of the distal extremities.

Multimodality therapy and limb salvage procedures constitute a significant advance in the treatment of soft tissue sarcoma of the extremity. The applicability of these procedures to soft tissue sarcoma of the distal extremities was evaluated in a retrospective study of 159 such cases treated during a 10-year period. Thirty-seven patients were treated by operation alone, 57 had operation and adjuvant chemotherapy, and 65 had multimodal therapy. The distal extremities are unusual sites for soft tissue sarcomas and accounted for only 20% of our patients with sarcoma. The majority of patients were younger than 50 years and the sex distribution was approximately equal. The major histologic types were synovial cell sarcoma (18.2%), fibrosarcoma (15%), liposarcoma (13.8%), and rhabdomyosarcoma (13.8%). The 5-year survival rate was 72% with multimodality therapy, 72% for operation and chemotherapy, and 51% for operation alone. The local recurrence rate was 13% with operation alone, 9% with operation and adjuvant chemotherapy, and 12% with multimodality therapy. Based on our review, wide local excision and adjuvant chemotherapy proved to be as effective as multimodal therapy.

Adult↗

PubMed2002

Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases.

Abnormalities of chromosome 2p23 with expression of ALK1 and p80 occur in both inflammatory myofibroblastic tumor (IMT) and anaplastic large cell lymphoma. This immunohistochemical study investigates whether the ALK family of neoplasms includes fibroblastic-myofibroblastic, myogenic, and spindle cell tumors. Formalin-fixed paraffin-embedded archival tissues from 10 IMTs and 125 other soft tissue tumors were stained for ALK1 and p80 with standard immunohistochemistry. ALK1 and/or p80 reactivity was observed in a cytoplasmic pattern in IMT (4/10; 40%), malignant peripheral nerve sheath tumor (4/10; 40%), rhabdomyosarcoma (6/31; 19%), leiomyosarcoma (1/10; 10%), and malignant fibrous histiocytoma (1/11; 9%). No staining was observed in nodular fasciitis, desmoid, infantile myofibromatosis, infantile fibrosarcoma, synovial sarcoma, leiomyoma, or myofibrosarcoma. Alveolar rhabdomyosarcomas (4/16; 25%) displayed a distinctive dot-like cytoplasmic positivity. No cases displayed nuclear reactivity. Fluorescent in situ hybridization on 12 of the positive cases revealed a combination of abnormalities including ALK break-apart signals, nucleophosmin (NPM)/ALK fusions, or extra copies of 2p23. This study demonstrates that in addition to IMT, abnormalities of ALK1 and p80 expression with a variety of structural chromosomal changes are found in several sarcomas, especially rhabdomyosarcoma and malignant peripheral nerve sheath tumor. Although immunoreactivity in non-IMTs cannot distinguish between structural abnormalities involving 2p23 or additional copies of 2p23, it supports the concept of ALK involvement in a larger group of neoplasms, some of which have other documented clonal abnormalities. In IMT, immunohistochemistry for ALK1 and p80 is useful as an indicator of a 2p23 abnormality, but it must be interpreted in the context of histologic and other clinicopathologic data if used as an adjunct to differential diagnosis.

Activin Receptors, Type I↗

PubMed1999

Expression of P53, MDM2 and Ki-67 antigens in soft tissue sarcomas.

The expression of P53 and MDM2 proteins was examined by immunohistochemistry in 115 soft-tissue sarcomas (STSs), including 32 malignant peripheral nerve sheath tumours, 27 liposarcomas, 18 leiomyosarcomas, 16 synovial sarcomas, 14 fibrosarcomas and 8 dermatofibrosarcomas, to investigate their possible association with clinicopathologic features and proliferative rate. Positivity for P53 and MDM2 was found in 9.7% and 28.1% tumours, respectively. The fraction of P53 and MDM2 positive tumours was the highest in leiomyosarcomas (16.7% and 17.2%, respectively) and the lowest in dermatofibrosarcomas (0% and 4.3%, respectively). Overall, P53(-)/MDM2(+) phenotype predominated (20.2%), while 7.9% of tumours were both P53 and MDM2 positive, and 1.8% of tumours were only P53 positive. P53 accumulation was associated with a high histological malignancy grade and a higher proliferative rate. MDM2 immunoreactivity was revealed in tumours of all malignancy grades and there was no association between MDM2 positivity and tumours proliferative activity. These results suggest that P53 overexpression underlays rather late events in the oncogenesis of STSs, which might be a determinant of their proliferative rate. In contrast, MDM2 deregulation seems to be an early rather than a late event in STSs, which may occur without involving stabilization and inactivation of P53 gene.

Adult↗

PubMed1992

The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues.

The effects of glutamine-enriched total parenteral nutrition (TPN+GLN) were studied in tumor-bearing rats because glutamine can benefit host tissues but also may stimulate tumor growth. Rats were implanted with the methylcholanthrene-induced fibrosarcoma (MCA sarcoma) and were studied when the tumor constituted less than 5% of carcass weight (small tumor) and when the tumor constituted 10% of carcass weight (large tumor). Provision of 20% of TPN protein as glutamine produced a significant increase in the arterial glutamine level and maintained the skeletal muscle intracellular glutamine concentration (2.02 +/- 0.1 versus 1.39 +/- 0.07 mumol/g, p less than 0.01). Concurrently, hindquarter GLN fractional release increased nearly threefold (p less than 0.05) in the TPN+GLN group. Glutamine-enriched total parenteral nutrition did not affect carcass weight, tumor weight, tumor DNA content, or tumor glutaminase activity. Furthermore, DNA flow cytometric analysis did not demonstrate any difference in percentage of aneuploid tumor cells within the G1, S, or G2M cell cycles. However, the ratio of aneuploid to diploid cells within the tumor mass increased by 20% in animals receiving glutamine. Glutamine-enriched total parenteral nutrition had no effect on tumor glutathione (GSH) levels. No increase in hepatic GSH levels was observed, but gut mucosal GSH levels were 20% greater in the TPN+GLN group (p less than 0.05). The provision of glutamine-enriched TPN may be beneficial to the host by maintaining skeletal muscle glutamine stores and by supporting gut GSH biosynthesis. In this tumor model, TPN+GLN does not appear to increase tumor size, tumor DNA content, or tumor glutamine metabolism, but the ratio of tumor cells to host infiltrating cells within the tumor mass appears to be increased.

Animals↗

PubMed1983

The feline oncornavirus-associated cell membrane antigen (FOCMA) is related to, but distinguishable from, FeLV-C gp70.

The feline oncornavirus-associated cell membrane antigen (FOCMA) on the surface of feline lymphosarcoma (LSA) cells is defined as the target(s) recognized in immunofluorescence (IFA) tests by antibody in sera of cats relatively resistant to development of FeLV (feline leukemia virus) LSA and FeSV (feline sarcoma virus) fibrosarcoma. The specificities of antibodies in cat FOCMA-typing sera and the nature of the LSA antigens recognized were investigated in the present study. FOCMA sera obtained from viremic cats were separable into at least two classes : those which contained antibodies against the envelope glycoprotein (gp70) of subgroup C FeLV and those which did not contain antibodies against any subgroup of FeLV. The first class of sera could be further subdivided into three groups: those whose FOCMA reactivity could be completely absorbed, partially absorbed, or not absorbed by FeLV-C antigens. The second class of sera could be further subdivided into two groups: those whose FOCMA reactivity could be partially absorbed and those whose activity could not be absorbed by FeLV-C. The results indicate that the FOCMA reactivity exhibited by some viremic cat sera can be partially, if not entirely, attributed to antibodies not crossreactive with FeLV virion antigens. A consistent property of all FOCMA sera in this study is the ability to bind to 70-kDa proteins on the surface of LSA cells. Staphylococcus aureus V8 protease partial digest maps of 70-kDa proteins purified from 12 primary feline LSAs (five FeLV positive and seven FeLV negative) all showed 18-, 14-, and 10-kDa fragments. V8 maps of FeLV-C gp70 showed similarly sized fragments while the maps of the RD114, FeLV-A, and FeLV-B gp70s were distinct. However, in a subgroup-specific radioimmunoassay for FeLV-C gp70-related antigens, the LSA 70-kDa proteins were found to be serologically related to, but distinct from, FeLV-C gp70. The results on the antigenic variations among LSA 70-kDa proteins and the antibodies which bind them are entirely consistent with previous studies indicating heterogeneity among FOCMA determinants.

Animals↗

PubMed2002

Second malignant neoplasms in long-term survivors of osteosarcoma: Memorial Sloan-Kettering Cancer Center Experience.

BACKGROUND: The authors investigated the incidence and relative risk of secondary malignant neoplasms in long-term survivors of osteosarcoma. METHODS: A comprehensive list of 509 patients with primary osteosarcoma treated at our institution between February 1973 and March 2000 was identified. All study patients received chemotherapy and/or surgery on one of six different protocols (T4, 5, 7, 10, 12, and CCG-7921/POG-9351). Chemotherapy was scheduled for up to 40 weeks with some variations in the actual treatment period and consisted of various combinations of the following agents: high-dose methotrexate, doxorubicin, bleomycin, cyclophosphamide, dactinomycin, vincristine, cisplatin, and ifosfamide. RESULTS: Secondary malignant neoplasms (SMN) occurred in 14 of 509 patients. Only one had pulmonary metastasis at diagnosis and subsequent multiple recurrences that required thoracotomies and further modification of the chemotherapy regimen. The median age at diagnosis for osteosarcoma was 16.6 years (range, 3.1-74.4 years). The median follow-up was 5.2 years (range, 0.1-25.0 years). The time interval from diagnosis of the primary osteosarcoma to the development of SMN was 1.3-13.1 years (median, 5.5; 95% confidence interval [CI], 3.6-9.6). The most common SMN occurred in the central nervous system (n = 4): anaplastic glioma, meningioma, high-grade glioma, and maxillary astrocytoma. There were two cases of acute myeloid leukemia and one case each of myelodysplastic syndrome, non-Hodgkin lymphoma, high-grade pleomorphic sarcoma, leiomyosarcoma, fibrosarcoma, breast carcinoma, and mucoepidermoid carcinoma. The overall 5 and 10-year cumulative incidences of SMNs were 1.4% +/- 1.1% and 3.1% +/- 1.8%. The standardized incidence ratio was 4.6 (95% CI, 2.53-7.78, P = 0.00001) for the cohort and 3.64 (95% CI, 1.82-6.52, P = 0.0007) when patients with a history of retinoblastoma or Rothmund-Thomson syndrome were excluded. CONCLUSIONS: The overall incidence of secondary malignancies in long-term survivors of osteosarcoma was significantly higher than the expected incidence of cancer in the general population. However, the standardized incidence ratios were much lower than those reported for Hodgkin disease and retinoblastoma. Although additional follow-up is warranted, the successes of current treatment regimens consisting of intensive, high-dose chemotherapy in combination with topoisomerase II inhibitors outweigh the risks.

Adolescent↗