| 1. |
- Ferrari, S, et al.
(författare)
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Neoadjuvant chemotherapy with high-dose ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: A joint study by the Italian and Scandinavian Sarcoma Groups
- 2005
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 23:34, s. 8845-8852
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To explore the effect of high-dose ifosfamide in first-line treatment for patients <= 40 years of age with nonmetastatic osteosarcoma of the extremity. Patients and Methods From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m(2)), methotrexate (12 g/m(2)), cisplatin (120 mg/m(2)), and doxorubicin (75 mg/m(2)). Postoperatively, patients received two cycles of doxorubicin (go mg/m(2)), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m(2)). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination. Results No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI 57% to 71%) and overall survival was 77% (95% CI 67% to 81%), whereas seven patients (4%) experienced local recurrence. Conclusion The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.
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| 2. |
- Picci, P., et al.
(författare)
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Computed tomography of pulmonary metastases from osteosarcoma: The less poor technique. A study of 51 patients with histological correlation
- 2001
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Ingår i: Annals of Oncology. - 1569-8041. ; 12:11, s. 1601-1604
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose is to evaluate the accuracy of computed tomography (CT) in the pulmonary staging of osteosarcoma. Patients and methods: Fifty-one patients presenting with osteosarcoma and at initial CT considered metastatic to the chest had lung surgery. Two teams of two senior radiologists independently reviewed all CT examinations. Their results were compared to the histological studies. Results: One hundred nineteen CT's were reviewed. The 2 teams found 247 and 268 nodules on the initial, and 143 and 146 nodules on the preoperative CT. Histological studies confirmed metastatic nodules in 29 patients. Two hundred four nodules were excised and studied. One hundred nine were metastases. The 22 patients without metastases had 53 negative nodules removed. In the 29 patients with metastases, 151 nodules were removed, and 42 were non-metastatic. The positive predictive value was 53% with regard to 'nodules', and 57% with regard to 'patients'. Only 4 out of 13 patients with one nodule at surgery were metastatic, but all patients with more than 7 nodules were metastatic. The 46 cases with several available CT's, showed that no change in the number of nodules was more frequent in benign lesions. Other criteria revealed no significant difference. Conclusion: CT positive predictive value is limited, but as surgery is the only way to cure metastatic patients, CT will still be used as the reference technique until a more specific approach can be found.
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| 3. |
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| 4. |
- Smeland, S, et al.
(författare)
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Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders
- 2003
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Ingår i: European Journal of Cancer. - 1879-0852. ; 39:4, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 muM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome. (C) 2003 Elsevier Science Ltd. All rights reserved.
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| 5. |
- Bauer, Hjärtcentrum, et al.
(författare)
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Monitoring referral and treatment in soft tissue sarcoma : Study based on 1,851 patients from the Scandinavian Sarcoma Group Register
- 2001
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Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 72:2, s. 150-159
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Tidskriftsartikel (refereegranskat)abstract
- This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 1986-88 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.
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| 6. |
- Elomaa, I, et al.
(författare)
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Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience
- 1999
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Ingår i: Acta Orthopaedica Scandinavica. Supplementum. - 0300-8827. ; 70:285, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.
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| 7. |
- Elomaa, I, et al.
(författare)
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Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol
- 2000
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Ingår i: European Journal of Cancer. - 1879-0852. ; 36:7, s. 875-880
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Tidskriftsartikel (refereegranskat)abstract
- The first Scandinavian protocol for Ewing's sarcoma, SSG IV, resulted in a local control rate of 74% and 5-year metastasis-free survival (MFS) of 43%. The second protocol, SSG IX, was started in order to improve upon these results. It featured four chemotherapy cycles, each consisting of two courses of VAI (vincristine, doxorubicin, ifosfamide) alternating with one course of PAI (cisplatin, doxorubicin, ifosfamide) at 3-weekly intervals. Total treatment time was 35 weeks. Local therapy was given at week 9. Inoperable or non-radically operated patients received hyperfractionated accelerated radiotherapy 1.5 Gy twice daily between chemotherapy courses to a total dose of 42-60 Gy, depending on surgical radicality and tumour localisation. 88 patients were included (58 male, 30 female, mean age 20 years; range 5-65 years). The tumour (73 M0 and 15 M1) was located centrally in 31 patients (35%), in the extremities in 34 (39%) and other sites in 23 (26%) of cases. The median size of tumour was 10 cm (range 2-23), soft tissue was invaded in 87%. Surgery was the local therapy for 60 (68%) patients: amputation in 8 and local excision in 52. The surgical margins were wide in 35 patients, marginal in 14 and intralesional in 3. Radiotherapy was given to 17 non-radically operated patients postoperatively and to 28 patients with inoperable tumours primarily. Histological responses were evaluated in 52 patients. 9 local recurrences were observed (10%). Distant metastases developed in 24 M0 patients (33%). The estimated 5-year MFS was 58% and overall survival (OS) 70% for M0 and 27% and 28% for M1 patients, respectively. Survival was favourable in patients with non-metastatic extremity tumours (90%) and tumours operated with wide margins (90%). Patients with a total necrosis after chemotherapy had a better OS than those with a partial or poor response (P=0.003). The toxicity (World Health Organisation) was acceptable (gastrointestinal G1-2; haematological G3-4). The SSG IX protocol gave better local control and survival rates than the SSG IV. Whether this is due to a higher therapeutic efficacy of the present protocol cannot be ascertained in this comparison with a historical control.
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| 8. |
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| 9. |
- Saeter, G, et al.
(författare)
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Prognostic factors in bone sarcomas
- 1997
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Ingår i: Acta Orthopaedica Scandinavica. Supplementum. - 0300-8827. ; 68:273, s. 156-160
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Tidskriftsartikel (refereegranskat)abstract
- Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].
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