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PubMed1981

Comparative single-cell and flow DNA analysis of bone sarcoma.

Five chondrosarcomas and seven osteosarcomas were analyzed by single-cell DNA cytophotometry, in both imprint preparations and tissue sections, and by means of flow DNA cytophotometry. A comparative analysis of the DNA distribution curves of each tumor, as determined by these three methods, showed a good correlation with respect to the modal DNA values. In addition, there was a strong correlation between the proportion of tumor cells with an increased DNA value (hyperploid cells) in imprint preparations and in tissue sections of each tumor as determined by single-cell DNA cytophotometry. Flow cytophotometry appears to be the method of choice for the determination of the aneuploid modal DNA value of a tumor cell population, while single-cell cytophotometry of identified cells seems more appropriate for the determination of the proportion of hyperploid cells in a tumor cell population. In this respect, single-cell and flow DNA cytophotometry may be considered complementary. For the demonstration of the existence of aneuploidy in a tumor cell population, however, the three investigated methods seem to be equivalent. Previous studies using single-cell cytophotometry have shown that DNA determinations in chondrosarcoma as well as in other tumors provide significant prognostic information. For routine clinical work, however, as an adjunct to the conventional histopathologic malignancy grading, single-cell cytophotometry is a rather time consuming procedure, while flow cytophotometry offers a rapid and convenient means of determining the nuclear DNA content. The present study clearly showed that flow DNA cytophotometry may be applied to sarcoma of bone.

Bone Neoplasms↗
PubMed1995

Alpha radiation risk coefficients for liver cancer, bone sarcomas, and leukemia.

This study compares published risk coefficients with those determined from dose rates established by postmortem radiochemical analysis of tissues from two whole body donors to the U. S. Transuranium and Uranium Registries, both of whom had been injected with Thorotrast approximately four decades prior to death. The dose data from these cases were used in combination with published latent periods and epidemiologic study results to calculate the following risk coefficients: 0.020 liver cancers Gy-1, 0.002 bone sarcomas Gy-1, and 0.032 leukemias Gy-1. These compare with the ranges of 0.013 to 0.074 liver cancers Gy-1, 0.0016 to 0.0120 bone sarcomas Gy-1, and 0.005 to 0.060 leukemias Gy-1 reported in the literature. The results of this study are generally consistent with previously reported values with two exceptions: the values for bone sarcomas fall below the range given by BEIR IV and the values for leukemia are a factor of 6 greater than those reported by BEIR IV. This suggests that the BEIR IV risk coefficient for bone sarcomas may be too high, and that for leukemia may be too low.

Aged↗
PubMedDate not supplied

Pancreatic metastases in bone sarcomas: CT demonstration.

Two patients with bone sarcomas were found to have pancreatic masses on routine follow-up CT. Although pancreatic metastasis most often occurs in a setting of widely disseminated disease, it may occur as an isolated finding, most often asymptomatic. It may also be responsible for clinical pancreatitis. Both of these presentations have significant implications for further management.

Adult↗
PubMed1990

Results of multidisciplinary limb salvage in 240 consecutive bone sarcomas.

From 1979 to 1989, 240 bone sarcomas of limbs were treated by a multidisciplinary limb salvage protocol. The tumors included 112 osteosarcomas, 71 chondrosarcomas, 3 fibrosarcomas, 10 malignant histiocytofibromas, 40 Ewing's sarcomas and 4 other rarer sarcomas. Patients mean age was 28.6 yr (range 4-91 yr). The average tumor size was 13.5 cm (3-43 cm). There were 2 grade IA, 21 IB, 1 IIA, 188 IIB, and 28 III B according to Enneking's classification. Extratumoral en bloc resection was performed in all cases (large in 113, marginal in 121, intrafocal in 6) by the same surgeon. In poor responders to preoperative chemotherapy with Ewing's sarcomas or osteosarcomas, 35 Grays postoperative radiotherapy was administered. Ewing's sarcomas and osteosarcomas received short preoperative and long postoperative chemotherapy. At last follow-up (median 60 months, range 6-120 months), 150 patients were disease-free; 4 were under treatment and had visible disease; 86 had died. Actuarial disease-free survival rate for patients seen with localized previously untreated disease was 83% at 2 yr and 77% at 3 yr. Fifteen local recurrences were observed (6%). Statistical analysis confirmed the poor prognosis factors of visible metastasis, proximal location and large tumor size, and pointed out the major prognostic value of therapeutic factors: the effectiveness of chemotherapy in Ewing's sarcoma and osteosarcomas, and the adequacy of surgery in all cases. Limb salvage can be performed by a well experienced multidisciplinary team in 96% of limb sarcomas without major risk of local recurrence. However, amputation is safer if the surgeon lacks experience.

Adolescent↗
PubMed1994

Magnetic resonance relaxation times of normal tissue in the course of chemotherapy: a study in patients with bone sarcoma.

To study the effect of chemotherapy on normal fat, skeletal muscle, and bone marrow, T1 and T2 relaxation times were measured in 15 patients with bone sarcoma before and after each cycle of preoperative chemotherapy. A section plane containing the tumor and if possible the nonaffected extremity was imaged with combined multiecho spin echo and inversion recovery pulse sequences. T1 and T2 relaxation times were calculated in the normal-appearing tissues. Although some variation was found in the values in the individual patient and between patients, no systematic changes of relaxation times of fat, muscle, or bone marrow occurred in the course of treatment. We conclude that the chemotherapy used in bone sarcoma has no effect on relaxation times of normal fat, muscle, and bone marrow, and that therefore these tissues may serve as a reference for the signal intensity of tumor.

Adipose Tissue↗
PubMed1999

Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy.

The aim of this study was to evaluate the value of three-phase dynamic bone scintigraphy (TPBS) in the assessment of the response of bone sarcomas to pre-operative chemotherapy and to correlate serial scintigraphic changes with histological findings. The study group comprised 27 patients (osteogenic sarcoma, n = 20; Ewing's sarcoma, n = 5; malignant fibrous histiocytoma, n = 2) with a mean age of 19.2 years. All patients received 99Tcm-methylene diphosphonate TPBS before and after pre-operative chemotherapy. Each phase of the imaging procedure was interpreted qualitatively and quantitatively. The percentage of tumour necrosis was analysed on resection materials following surgery. Histologically, 12 patients were non-responsive (tumour necrosis less than 90%) and 15 patients were responsive (tumour necrosis more than 90%). A decrease in the tumour blood flow ratio and extension were the most notable findings in the responders. The mean change in the tumour blood flow ratio following therapy was 58.7 +/- 8.3% and 19.9 +/- 26.6% (P < 0.005) in responders and non-responders respectively. The accuracy of three-phase imaging and static bone scintigraphy was 88% and 74% respectively. Since bone scintigraphy is a valuable technique owing to its ability to detect distant metastases in clinically early disease, TPBS should be helpful in monitoring therapy effects without any additional cost or radiation dose.

Adolescent↗
PubMed2003

Cytokine and cytokine receptor serum levels in adult bone sarcoma patients: correlations with local tumor extent and prognosis.

BACKGROUND AND OBJECTIVES: We analyzed the correlations between pretreatment serum levels of 11 cytokines and soluble cytokine receptors (interleukin 6 (IL-6); interleukin 8 (IL-8); interleukin 10 (IL-10); vascular endothelial growth factor (VEGF); basic fibroblast growth factor (bFGF); macrophage colony-stimulating factor (M-CSF); granulocyte colony-stimulating factor (G-CSF); interleukin 1 receptor antagonist (IL-1ra); sIL-2Ralpha; tumor necrosis factor receptor I (TNF RI), and TNF RII) with clinico-pathological features and survival of patients with bone sarcomas. METHODS: Altogether, 72 patients with bone sarcomas without distant metastases before treatment (26 osteosarcomas-36%, 23 chondrosarcomas-32%, 13 Ewing's sarcomas/PNET-18%, 10 giant-cell tumors-14%), 22 patients with benign non-inflammatory bone tumors and 50 age-matched healthy controls were included into this prospective study. RESULTS: Median serum levels of 9/11 cytokines, with the exception of sIL-2Ralpha and G-CSF, were significantly higher in sarcoma patients than in controls. Median serum levels of IL-6, IL-8, IL-1ra, TNF RI, and M-CSF were significantly higher in patients with bone sarcoma as compared to patients with benign bone tumors. In 45.9% of sarcoma patients, six or more cytokines and cytokine receptors, including those that are involved in bone destruction (e.g., IL-6 and IL-8) and bone formation (e.g., IL-1ra and TNFRI and TNFRII), were elevated in parallel. Serum levels of IL-6, IL-8, TNF RI, TNF RII, and VEGF correlated significantly with tumor size (<10 cm vs. >or=10 cm in diameter) and serum levels of IL-6, IL-8, TNF RI, and IL-1ra correlated significantly with local tumor extent (E2/4 vs. E5/6 according to the classification proposed by Spanier et al. 46). Moreover, serum levels of IL-1ra and IL-6 were significantly higher in patients with small tumors (<5 cm in diameter) infiltrating structures adjacent to the periosteum (E5/6) than in large tumors (>10 cm in diameter) but confined to the bone and periosteum (E < 4). The lowest median serum levels of 8/11 cytokines/cytokine receptors were found in patients with giant-cell tumors. In an univariate analysis, increased serum levels of IL-1ra, IL-6, IL-8, IL-10, sIL-2Ralpha, M-CSF, TNF RI, and TNF RII, the number of cytokines elevated, higher tumor grade, larger tumor size, greater local extent (E) and patients' age >35 years correlated with poor overall survival (OS) (P < 0.05). Similarly, high serum levels of IL-1ra, IL-6, TNF RI and TNF RII, tumor grade, tumor size, and tumor local extent (E) (P < 0.05) affected disease free survival (DFS) in univariate analysis. Multivariate analysis using Cox's proportional hazards model showed that high serum levels of IL-1ra (P = 0.039) and TNF RI (P = 0.048), the number of serum cytokines above normal cut-off values (0-1 vs. 2-5 vs. >or=6; P = 0.029), greater tumor local extent E (E2/4 vs. E5/6; P = 0.02) correlated significantly with shorter OS. Only E was found as an independent prognostic factor for DFS (P = 0.04). CONCLUSIONS: These findings indicate that cytokines and soluble cytokine receptors, both physiologically involved in bone destruction and bone formation, have an essential role in the progression of malignant bone tumors.

Adult↗
PubMed1990

Primary vascular bone sarcomas. A clinicopathological and immunohistochemical study of two cases.

Two cases of primary vascular bone sarcomas are reported. The first case presented a rather slow clinical course and a non-aggressive histological picture and was classified as hemangioendothelioma. The second was a frankly malignant tumor, already metastatic at the time of diagnosis, which was classified as angiosarcoma. Views concerning the nomenclature and the behavior of primary vascular bone sarcomas are also discussed.

Aged↗
PubMed1985

Surgical technique and results of limb sparing surgery for high grade bone sarcomas of the knee and shoulder.

Thirty-three patients with high grade bone sarcomas of the knee and shoulder treated by limb sparing surgery were evaluated. The histological diagnoses were osteosarcoma (25), chondrosarcoma (3), malignant fibro-histiocytoma (3), fibrosarcoma (1) and unclassified (1). The Surgical Stages were: Stage IIA (3), Stage IIB (28) and Stage III (3). The operative procedure consisted of three phases: tumor resection, skeletal reconstruction and soft tissue reconstruction. All resections obtained negative margins and were classified as, marginal excision (3), intracompartmental resections (28) and radical resections (2). Overall survival was 77%. Four of 33 patients (12.4%) required a secondary amputation. Local recurrence was 6% (2/33) with an average follow-up of 37.2 months. The most common complications were flap necrosis (33%) and transient nerve palsies (33%). There were 2 infections and one prosthetic dislocation. We believe that limb salvage surgery for high grade bone sarcomas need not be reserved for only those without extraosseous extension. Careful preoperative selection and attention to the three stages of a limb sparing procedure are important for a successful outcome. Presently, we consider the following as contraindications to resection: vascular involvement, pathologic fracture, inappropriate biopsy and infection.

Adolescent↗
PubMed1985

Phase II study of cisplatin in advanced osteogenic sarcoma. European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

The activity of cisplatin (CDDP) against advanced osteogenic sarcoma was evaluated in 37 of 50 patients registered by the members of the European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group between 1979 and 1982. All patients had measurable lung metastases. Thirty-one patients (84%) had received previous chemotherapy consisting mainly of high-dose methotrexate, doxorubicin, and vincristine. CDDP (100 mg/m2) was given as a 24-hour continuous infusion every 3 weeks for a minimum of two cycles, with appropriate fluids and diuretics. In the absence of impairment of the renal function and/or myelosuppression, the dose could be escalated by 20%. The overall response rate was 19% (seven responses among 37 patients), with one complete remission for 51 weeks and six partial remissions from 12 to 26 weeks. The median number of courses of CDDP administered was three, ranging from two to 11. Of 143 courses administered, only 18 (12%) had to be modified because of toxicity. In 16% of the patients some transient impairment of the renal function was observed. CDDP adds to the limited number of chemotherapeutic agents with useful properties in osteogenic sarcoma, and CDDP-containing combination chemotherapy regimens should be actively investigated.

Adolescent↗
PubMedDate not supplied

Induction chemotherapy for bone sarcoma in adults: correlation of results with erbB-4 expression.

Tumor response to preoperative chemotherapy is an important prognostic factor for localized, operable extremity osteosarcoma. Other clinical variables include tumor size and location, age and sex, and serum enzymes. Advances in molecular oncology yielded a second group of factors such as multidrug resistance status, loss of heterozygosity of RB gene, and HER2/erbB-2 expression. The aim of this study was to investigate the expression and the prognostic value of the newly described erbB-4 receptor in specimens from adults with bone sarcomas treated by pre- and postoperative chemotherapy. Thirty-three patients with non-metastatic bone sarcoma have been treated by two doxorubicin-based induction chemotherapy regimen, followed by limb sparing surgery and tailored adjuvant chemotherapy. Pre-chemotherapy tissue specimens were investigated for the expression of erbB-4 receptor and post-induction specimens were assessed for pathological response. The clinical response rates were 32-36%. The degree of induced necrosis was correlated with the disease-free survival (DFS). Patients achieving >/=90% necrosis had an improved DFS over patients with poor histological response. ErbB-4 expression was significantly associated with poor histologic response and shorter DFS. ErbB-4 expression may be used for prognostication of adults with bone sarcomas.

Adult↗
PubMed1988

Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.

Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.

Adult↗
PubMedDate not supplied

Phase II study of recombinant alfa-2a interferon in patients with advanced bone sarcomas.

Twenty previously treated patients with advanced bone sarcomas received thrice weekly im 50 X 10(6) IU/m2 doses of human alfa-interferon (interferon alfa-2a, recombinant; Roche). Seventeen patients had metastatic osteosarcomas and one each had fibrosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma. Two patients with osteosarcoma and the one with malignant fibrous histiocytoma experienced objective partial tumor regression for 1, 3, and 2 months, respectively. Fever, anorexia, myalgia, fatigue, lethargy, and moderate myelosuppression were observed commonly, and some patients developed mild nausea, vomiting, and diarrhea. No patient withdrew because of toxicity and no dose reductions were necessary except adjustments for changes in body surface area secondary to weight loss.

Bone Neoplasms↗
PubMed1991

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents.

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.

Adolescent↗
PubMedDate not supplied

Limb salvage surgery for primary bone sarcoma of the lower extremities: long-term consequences of endoprosthetic reconstructions.

BACKGROUND: Adjuvant chemotherapy and endoprosthetic replacement for bone sarcomas of the lower extremity is well established. The specific long-term consequences of these endoprosthetic reconstructions for the patient's affected limb are unknown. METHOD: The oncologic results and the survival of the endoprostheses were reviewed in 32 patients with primary bone sarcoma of the femur or proximal tibia. There were 26 high-grade sarcomas, and 6 low-grade sarcomas. A proximal femoral endoprosthesis was used for reconstruction in 4 patients, a total or push-through femoral endoprosthesis in 11 patients, a distal femoral endoprosthesis in 15 patients, and a proximal tibial endoprosthesis in two patients. RESULTS: Median survival was 10 years (range, 1.1 to 18.9 years) for patients with high-grade sarcoma, and 8.1 years (range, 7.1 to 10 years) for patients with low-grade sarcomas. Distant metastases developed in seven patients (22%), all with stage IIB sarcoma, with concomitant local recurrence in 3 patients (9%). Five-year overall and disease-free survival rates for high-grade sarcomas were 81% and 73%, respectively. The overall endoprosthetic survival rate was 87% at 5 years, 80% at 10 years, and 56% at 15 years. Median follow-up of the original endoprostheses was 8.3 years (range, 0.6 to 18.7 years). Endoprosthesis-related complications occurred in 13 patients (41%); most complications were mechanical failures. The highest complication rate was found in distal femoral replacements (60%); amputation was necessary in both patients treated with a proximal tibial endoprosthesis. Five endoprostheses (16%) were revised. An amputation of the involved limb was performed in four patients (13%): in two patients because of local recurrence and in the other two patients because of infection. For patients alive at follow-up, the median functional Enneking evaluation score was 22 points (range, 12 to 28 points), with the highest functional scores in patients with a distal femoral endoprosthesis, and the lowest functional scores in patients with total or push-through femoral replacements. CONCLUSION: Endoprosthetic reconstructions gave satisfying functional results in most patients after long-term survival. However, the proximal tibial and distal femoral endoprosthesis are particularly at risk for long-term endoprosthetic complications requiring additional surgical procedures.

Adolescent↗
PubMed1982

The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study.

The volume doubling time of primary bone sarcomas and lung metastases was determined by measurements made on serial radiographs. For the primary tumors, the volume doubling times were log-normally distributed and varied in the range of 20--200 days with a mean around 50 days. The volume doubling times of the metastases also showed a log-normal distribution in the range of 10--100 days, but with a mean twice as short as that of the primates. Radiation therapy was given with three--four doses of 20--25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by the application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistence of any viable, neoplastic cells. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The several late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors.

Adolescent↗