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- Jebsen, Nina L., et al.
(författare)
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Five-year Results From A Scandinavian Sarcoma Group Study (SSG XIII) Of Adjuvant Chemotherapy Combined With Accelerated Radiotherapy In High-Risk Soft Tissue Sarcoma Of Extremities And Trunk Wall
- 2011
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 81:5, s. 1359-1366
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall. Methods and Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size >= 8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients. RT to a total dose of 36 Gy (1.8 Gy twice daily) was inserted between two chemotherapy cycles after marginal margin resection regardless of tumor depth or after wide-margin resection for deep-seated tumors. RT was boosted to 45 Gy in a split-course design in the case of intralesional margin resection. Results: A total of 119 patients were eligible, with a median follow-up of 5 years. The 5-year estimate of the local recurrence, metastasis-free survival, and overall survival rate was 12%, 59%, and 68%, respectively. The group receiving RT to 36 Gy had a local recurrence rate of 10%. In contrast, the local recurrence rate was 29% in the group treated with RT to 45 Gy. The presence of vascular invasion and low chemotherapy dose intensity had a negative effect on metastasis-free and overall survival. Toxicity was moderate after both the chemotherapy and the RT. Conclusions: Accelerated RT interposed between chemotherapy cycles in a selected population of patients with high-risk soft tissue sarcoma resulted in good local and distant disease control, with acceptable treatment-related morbidity. The greater radiation dose administered after intralesional surgery was not sufficient to compensate for the poorer surgical margin. Vascular invasion was the most important prognostic factor for metastasis-free and overall survival. (C) 2011 Elsevier Inc.
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| 3. |
- Jebsen, Nina L., et al.
(författare)
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Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall
- 2013
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 86:5, s. 949-955
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose-response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma. (C) 2013 Elsevier Inc.
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- Hall, Kirsten Sundby, et al.
(författare)
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Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)
- 2018
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Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 99, s. 78-85
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy.Methods: High-risk STS was defined as high-grade morphology (according to the Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size >= 8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m(2)) and ifosfamide (6 g/m(2)) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4.Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death.Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.
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| 5. |
- Olstad, Ole K, et al.
(författare)
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Molecular heterogeneity in human osteosarcoma demonstrated by enriched mRNAs isolated by directional tag PCR subtraction cloning.
- 2003
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Ingår i: Anticancer research. - 0250-7005. ; 23:3B, s. 2201-16
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Tidskriftsartikel (refereegranskat)abstract
- Directional tag PCR subtractive hybridization was applied to construct a cDNA library generated from three different human osteosarcoma (OS) target cell lines (OHS, SaOS-2 and KPDXM) from which normal osteoblast (NO) sequences were subtracted. After two consecutive subtractive steps more than 98% of the common mRNAs species were depleted, leading to effective enrichment of the remaining target sequences. After differential screening of 960 clones, 81 candidates were further studied by Northern blot analysis and 73 represented separate mRNA species. Fifty-three of these showed enriched mRNA levels, of which 36 represented known and 17 not previously published cDNAs or EST sequences. The mRNAs showed a 1.4- to 504-fold enrichment compared to the mRNA levels in NO cells. The known mRNAs are: Ribosomal protein S11, KSP-37, Tethering factor SEC34, FXYD6, Alpha enolase, G-s-alpha, GPR85, DAF, RPL35A, GIF, TAPA-1, ANAPC11, DCI, hsp27, MRPS7 homolog, eIF p110 subunit, DPH2L, HMG-14, FB1 protein, chondroitin-6-sulphonase, calgizzarin, RNA polymerase II subunit, RPL13A, DHS, gp96, HHP2, acidic ribosomal phosphoprotein P2, ANT-2, ARF1, AFG3L2, SKD3, phosphoglucoisomerase, GST pi, CKI gamma 2, DNA polymerase delta small subunit and TRAP delta. Sections of human osteosarcoma biopsies and a xenograft were studied by in situ analysis. Seven cDNAs highly expressed in Northern blot analysis were tested. Their in situ expression differed between the xenograft and human sections as did that of collagen I. In the xenograft made from one of the target cell lines (OHS), a fair to strong representation of 3 cloned mRNAs was observed while collagen I mRNA was not detectable. We conclude that the molecular heterogeneity of these tumors is considerable. These results ought to have implications for future work to describe phenotypic subtypes with the aim of improving the diagnosis of human osteosarcomas.
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| 6. |
- Sartor, Oliver, et al.
(författare)
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Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases : results from a phase 3, double-blind, randomised trial
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:7, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- Background Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range a-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. Methods In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2: 1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15.6 months [95% CI 13.5-18.0] vs 9.8 months [7.3-23.7]; hazard ratio [HR] = 0.66, 95% CI 0.52-0.83; p = 0.00037). The risks of external beam radiation therapy for bone pain (HR 0.67, 95% CI 0.53-0.85) and spinal cord compression (HR = 0.52, 95% CI 0.29-0.93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0.62, 95% CI 0.35-1.09), or the need for tumour-related orthopaedic surgical intervention (HR 0.72, 95% CI 0.28-1.82). Interpretation Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.
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| 7. |
- Smeland, Sigbjørn, et al.
(författare)
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Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years.
- 2011
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 82:2, s. 211-6
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Tidskriftsartikel (refereegranskat)abstract
- The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m²), cisplatin (90 mg/m²), and doxorubicin (75 mg/m²). 3 cycles were administered postoperatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m²) as a salvage strategy.
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| 8. |
- Smeland, Sigbjorn, et al.
(författare)
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Scandinavian experience in classical osteosarcoma Results of the SSG XIV protocol
- 2009
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Ingår i: Acta Orthopaedica. - 1745-3682. ; 80, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol was based upon the organisations experience from 3 previous osteosarcoma trials and was considered best standard of care for patients with extremity localised, non-metastatic osteosarcoma. We report the outcome of this protocol. Patients and methods From March 2001 to April 2005, 63 patients recruited from 10 centres in Finland, Sweden and Norway were included in this analysis. Patients received pre-operative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m(2)), cisplatin (90 mg/m(2)) and doxorubicin (75 mg/m(2)). Good histological responders continued with 3 cycles postoperatively whilst poor responders were salvaged with the addition of 3 cycles of ifusfamide (10-12 g/m(2)). Outcome data was compared to previous SSG osteosarcoma trials. Results With a median follow-up of 64 months for survivors, the projected metastasis-free and sarcoma-related survivals at 5 years were 69% and 77%, respectively. 84% of the patients were treated with limb salvage surgery (49 patients) or rotationplasty (4 patients). 3 toxic deaths (5%) were recorded, all related to acute chemotherapy toxicity. The 5-year metastasis-free survival of patients receiving salvage therapy was 47% compared to 89% for good histological responders that only received the 3 drug combination postoperatively. Interpretation Outcome in the SSG XIV protocol compares favourably to previous SSG osteosarcoma trials and other published trials. The addition of ifosfamide to poor responders as an add on treatment did not improve outcome for poor responders to a similar level as for good responders. In a multi-institutional setting limb salvage surgery can safely be used in more than 80% of the patients.
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