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PubMed2006

Surgical excision of bone sarcomas involving the sacroiliac joint.

Adequate (wide or marginal and uncontaminated) margins and reconstruction are difficult to achieve when performing an internal hemipelvectomy for bone sarcomas involving the sacroiliac joint. We evaluated whether adequate surgical margins could be achieved and if functional outcomes could be predicted based on the type of resection and reconstruction. Forty patients had resections of the sacroiliac joint. Vertical sacral osteotomies were through the sacral wing (n = 2), ipsilateral sacral foramina (n = 27), sacral midline (n = 9), or contralateral foramina (n = 2). Iliac resections were Type I, Type I-II with partial or total acetabular re-section, or Type I-II-III. Surgical margins were adequate in 28 of 38 patients (74%), two (7%) of whom experienced local recurrence, compared with seven of 10 (70%) patients with inadequate margins. Reconstruction consisted of restoring continuity between the spine and pelvis. Resection of the entire acetabulum and removal of the lumbosacral trunk were the two main determinants of function, as assessed using the Musculoskeletal Tumor Society score. There were no life-threatening or function-threatening complications. Internal hemipelvectomy with a limb salvage procedure can be achieved with adequate surgical margins in selected patients. Functional outcomes can be predicted based on the type of resection and reconstruction, which helps the surgeon plan the procedure and inform the patient.

Adolescent↗
PubMed1983

Radiation induced sarcomas of bone following therapeutic radiation.

Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed.

Bone Neoplasms↗
PubMed1993

Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group.

A practical grading system for soft tissue sarcomas was developed, based on 282 eligible patients entered in an EORTC adjuvant clinical trial. The primary tumours in this trial had to be adequately treated. Histopathological parameters, which appeared significant in two preceding studies, were tested. These parameters were differentiation of the tumour, presence and amount of necrosis, the presence and amount of myxoid areas and the number of mitoses. In addition, the size of the tumour was also analysed. The quantitative data (mitotic count and size of the tumour) were not a priori grouped, but were divided into categories based on the results of the statistical analysis. Based on a multivariate analysis only mitotic count, the presence or absence of necrosis and the size of the tumour were significantly correlated with the duration of survival or the time to distant metastases. Of these parameters, the mitotic count was the most important.

Adolescent↗
PubMed1994

Phase II study with docetaxel (Taxotere) in advanced soft tissue sarcomas of the adult. EORTC Soft Tissue and Bone Sarcoma Group.

BACKGROUND: Current regimens for treatment of distant metastases of soft tissues sarcomas result in response rates of about 25%. Therefore the search for active drugs remains a task for investigational groups. Taxoids offer a new class of cytostatic drugs. Docetaxel has been studied as a second line chemotherapy in advanced soft tissue sarcomas of the adult. PATIENTS AND METHODS: In a multi-center non-randomized phase II study docetaxel was administered at a dose of 100 mg/m2 in a 1-hour i.v. infusion q 3 weeks. RESULTS: Twenty-nine patients (pts), median age 52 yr, performance status WHO 0: 16 pts, WHO 1: 11 pts, WHO 2: 2 pts, were eligible. One patient had early death due to malignant disease, 1 patient died due to toxicity and progression, 1 pt refused after 1 course. Five partial responses (5/29 = 17%, C.I. 6%-36%) have been observed. Grade > or = 3 leucopenia occurred in 76% of patients and grade > or = 3 thrombopenia did not occur. Median nadir of neutrophils was 0.23 x 10(9)/l. Episodes of fever and documented infection have been observed in 10 and 5 pts respectively. Anaphylactoid type reactions occurred in 5 patients: ranging from flushing in 5 pts to cardiovascular symptoms in 1 pt. Sensory neurotoxicity was observed in 14 pts grade 1: 10 pts, grade 2: 3 pts, grade 3: 1 pt). Grade 1 motor neurotoxicity was experienced by 3 pts. Skin reactions (pruritus, erythema, urticaria, exfoliation grade 1: 11 pts, grade 2: 7 pts, grade 3: 1 pt, grade 4: 1 pt) in 20 pts, among them 9 patients with nail changes. Peripheral edema and fluid retention has been observed in 12 pts. CONCLUSION: Taxotere has activity in adult soft tissue sarcoma in second line, warranting studies on first line efficacy.

Adult↗
PubMed1991

Chondrosarcoma and other rare bone sarcomas.

The clinical staging of bone tumors, even rare ones, has been much improved with the availability of better imaging techniques. Once diagnosis of a rare bone tumor has been made, close consultation between clinician, radiologist, and pathologist is essential for optimal treatment. Recent advances in the staging procedures and better assessment of prognostic factors should allow for a more optimal individualized treatment plan.

Adolescent↗
PubMed1993

Amplification of c-myc oncogene and absence of c-Ha-ras point mutation in human bone sarcoma.

The genomic organization of four oncogenes, c-myc, c-myb, c-Ha-ras, and v-fms, was analyzed in 21 patients with malignant bone tumors. Amplification of the c-myc proto-oncogene without rearrangement was the sole abnormality detected in four tumors: two chondrosarcomas, one osteosarcoma, and one lymphoma of bone. DNA hybridizations with c-myb, c-Ha-ras, and v-fms probes disclosed no structural gene abnormalities. Point mutations at the 12th codon of the c-Ha-ras gene were investigated with the polymerase chain reaction technique; no alterations were detected. The observed amplification of the c-myc there was not related to histologic type, grade, surgical stage, or ploidy level of the tumors. The results indicated that c-myc amplification, presumed to be involved in the development of malignancy in a variety of solid tumors, is encountered sporadically in malignant bone tumors; however, this occurs without relation to common histopathologic features. The clinical significance of oncogene amplification in bone sarcoma remains to be established.

Adolescent↗
PubMed1986

Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience.

Histopathologic peer review of specimens from 216 consecutive patients with soft-tissue or bone sarcomas on Southeastern Cancer Study Group protocols was performed by a panel of three pathologists. Subtype of sarcoma, degree of confidence in diagnosis, and grade were compared with agreement or disagreement in pathologic opinion from the primary member institution v the pathology review panel. The most common soft-tissue sarcoma was leiomyosarcoma, followed by malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, malignant schwannoma, and rhabdomyosarcoma. There was total agreement between the primary pathologist and reviewer in 66% of cases. However, 12 cases (6%) were considered on review to not be sarcomas. In 27% of cases the subtype of sarcoma was felt to be incorrect by reviewers. Discordant diagnoses were more common when the confidence of the pathologist was less and when the tumor was of higher grade. There was no improvement in frequency of agreement in the second half of the study, despite educational workshops. We conclude that histologic peer review is important in sarcoma studies and is essential in many patients with presumed sarcomas.

Bone Neoplasms↗
PubMed2001

Functional evaluation in distal femoral endoprosthetic replacement for bone sarcoma.

A multicenter study of successfully treated patients (mean age, 36.7 years) with a minimum 1-year followup (average, 35.4 months) after distal femoral endoprosthetic replacement for bone sarcoma was done using the 1987 and 1993 versions of the Musculoskeletal Tumor Society, the Short Form-36, and the Toronto Extremity Salvage Score functional evaluation criteria. Fifty-six patients (28 women and 28 men) fulfilled the criteria. Thirty-one Kotz prostheses (fixed hinge, uncemented) and 25 Modular Replacement System Prostheses (rotating hinge, cemented) were used. Thirty-five patients walked without aids, 19 used a cane, and two used crutches or a walker. The Musculoskeletal Tumor Society 1987 mean score was 28.1. The Musculoskeletal Tumor Society 1993 mean score was 80.4. The Toronto Extremity Salvage Score mean was 81.6. The Short Form-36 Physical Component Score had a mean of 43.2 and Mental Component Score mean of 54.2. The two groups of implants were comparable, except for the length of bone resection. Multivariate regression analysis revealed that patient age, existence of a pathologic fracture, and type of prosthesis all significantly accounted for differences in functional outcome as measured by the Musculoskeletal Tumor Society 1993, the Toronto Extremity Salvage Score, and the Short Form-36 Physical Component Score scales. Although both implants provided satisfactory function, the Musculoskeletal Tumor Society 1993 and the Toronto Extremity Salvage Score results were significantly better with the Modular Replacement System prosthesis. The effect of possible differences among surgeons or institutions was not addressed.

Adult↗
PubMed1996

Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients.

BACKGROUND: Several reports have shown a prolonged survival after surgical treatment of pulmonary metastases from soft tissue sarcomas. However, it is still unclear which prognostic factors predict a favorable outcome. Series are not comparable and the data are conflicting. Therefore, a multi-institutional study was undertaken to analyze prognostic factors in selecting patients for resection of pulmonary metastases from soft tissue sarcomas. METHODS: This report is a retrospective study of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group. Two hundred fifty-five patients underwent complete resection of lung metastases from soft tissue sarcomas. Cases with chondrosarcoma and small round cell sarcomas like Ewing sarcoma were excluded. RESULTS: The 3 year and 5 year overall postmetastasectomy survival rates were 54% and 38%, respectively. The disease free postmetastasectomy survival rates were 42% and 35%, respectively. Analysis of prognostic factors for a more favorable outcome revealed disease free intervals of 2.5 years or more, following a resection with microscopically free margins, age less than 40 years, and Grade I and II tumors. These prognostic factors have an independent influence on overall survival, using a multivariate Cox regression model. CONCLUSIONS: Surgical excision of lung metastases from soft tissue sarcomas is well accepted and should be considered as a first line of treatment if preoperative evaluation indicates that complete clearance of the metastases is possible. Further investigation is needed before chemotherapy can be recommended as additional therapy.

Adolescent↗
PubMed1998

High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.

The activity and toxicity of single-agent standard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin. A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received (A) doxorubicin 75 mg m(-2) on day 1 (112 patients), (B) epirubicin 150 mg m(-2) on day 1 (111 patients) or (C) epirubicin 50 mg m(-2) day(-1) on days 1, 2 and 3 (111 patients); all given as bolus injection at 3-week intervals. A median of four treatment cycles was given. Median age was 52 years (19-70 years) and performance score 1 (0-2). Of 314 evaluable patients, 45 (14%) had an objective tumour response (eight complete response, 35 partial response). There were no differences among the three groups. Median time to progression for groups A, B and C was 16, 14 and 12 weeks, and median survival 45, 47 and 45 weeks respectively. Neither progression-free (P = 0.93) nor overall survival (P = 0.89) differed among the three groups. After the first cycle of therapy, two patients died of infection and one owing to cardiovascular disease, all on epirubicin. Both dose schedules of epirubicin were more myelotoxic than doxorubicin. Cardiotoxicity (> or = grade 3) occurred in 1%, 0% and 2% respectively. Regardless of the schedule, high-dose epirubicin is not a preferred alternative to standard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas.

Adult↗
PubMed2001

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.

Adult↗
PubMed1997

Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients.

Recent data suggest that deletion of p16INK4 and mutation of TP53 are among the most common genetic events in the development of human cancer, since the codified proteins act as brakes of the abnormal cell cycle. As the molecular events leading to the development of pediatric bone sarcomas remain unclear, we analyzed 75 osteosarcoma and Ewing sarcoma samples from 43 pediatric patients to search for alterations at the TP53 or p16INK4 tumor suppressor genes. By means of PCR-DGGE (polymerase chain reaction and denaturing gradient gel electrophoresis) we detected TP53 point mutations in 18.6% of the tumor samples, but no constitutional mutations. In the analysis of p16INK4, 7% of the samples harbored deletions of the gene but no point mutations were detected by SSCP (single strand conformation polymorphism) analysis, just the polymorphism Ala-->Thr at codon 148. These data support the hypothesis that TP53 alterations may play a role in the development of pediatric bone tumors and that the primary mechanism of inactivation of p16INK4 seems to be homozygous deletion rather than point mutation.

Bone Neoplasms↗
PubMed1986

DNA microspectrophotometry of bone sarcomas in tissue sections as compared to imprint and flow DNA analysis.

The aim of the present study was to establish an upper limit of diploidy for microspectrophotometric (MSP) DNA measurements in sections of mesenchymal tissue analyzing DNA data of a large number of normal cell populations. The reliability of this upper limit of diploidy for discriminating between diploid and hyperploid bone sarcomas was tested by analyzing the same tumors by MSP in imprint preparations and flow cytometry (FCM). The median DNA value of control cells in tissue sections was given arbitrary value of DNA index (DI) 1.0, denoting the diploid DNA content. The proportion of cells with DNA values exceeding DI 1.25 (greater than DI 1.25) was determined for each normal cell population. The maximum percentage of cells with DNA values exceeding DI 1.25, encountered by analysis of 91 normal cell populations in tissue sections, was 31%. This percentage was set as an upper limit of diploidy. Hence, tumors with a higher percentage of cells greater than DI 1.25 were classified as hyperploid. When we applied this criterion, 31 of 36 sarcomas analyzed by MSP in tissue sections were hyperploid, which was in complete agreement with FCM and MSP in imprints of the same tumors. Apart from discriminating between diploid and hyperploid tumors, an attempt was made to determine peak DNA values of sarcomas analyzed in tissue sections. Peak DNA values, as defined by a minimum of 30% of the cells within a class width of DI 0.25, could be determined for 23 of 36 tumors. These peak DNA values correlated well with corresponding peaks obtained by FCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms↗