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G Saeter

Publications and source records attributed to G Saeter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chemotherapy in soft tissue sarcoma. The Scandinavian Sarcoma Group experience.

The first chemotherapy study of soft tissue sarcoma (STS) by the Scandinavian Sarcoma Group was started in 1981 (SSG I). It evaluated the single agent adjuvant doxorubicin in a randomized setting in patients with high-grade STS. No improvement was noted in the overall survival or disease-free survival rate. More intense chemotherapy was thereafter (1991-1994) evaluated in a phase 2 study, introducing ifosfamide and a continuous infusion of etoposide with growth factor (SSG X). The response rate of previously untreated patients was high (42%), but complete remissions were few. Analysis of patients undergoing surgery after preoperative chemotherapy suggested an increased survival. A recent meta-analysis of adjuvant chemotherapy for localized resectable STS in adults, including the SSG I trial, indicated a better disease-free survival and possibly improved overall survival (Thierny et al. 1997). At present, we are studying whether such a benefit can be shown in patients with high-risk prognostic criteria by giving adjuvant ifosfamide and doxorubicin treatment after primary surgery (SSG XIII). In the latter SSG study, started on July 1, 1998, the adjuvant therapy is evaluated in a phase 2 study in selected patients with high-grade STS and other unfavorable prognostic factors.

Adult↗
PubMed1999

Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients.

We analyzed treatment and outcome in 104 Scandinavian patients with synovial sarcoma in the extremities or trunk wall, diagnosed between 1986 and 1994. Only surgically treated patients without metastases at diagnosis were included. Median follow-up of survivors was 6 (3-11) years. 34 patients developed metastases. The overall 5- and 7-year survival rates were 0.76 (95% CI 0.66-0.83) and 0.69 (0.58-0.78), respectively. Large tumor size and amputation were significantly associated with impaired metastasis-free survival. Patients with local recurrence had a higher risk of metastases following the local event. Local excision with inadequate margin was associated with a higher risk of local recurrence.

Adolescent↗
PubMed1999

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

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.

Adolescent↗
PubMed1999

Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway.

Malignant peripheral nerve sheath tumors (MPNSTs) are frequently associated with the disease neurofibromatosis type 1. Only few recurrent cytogenetic changes have been reported, including rearrangements of the short arm of chromosome 9. By fluorescence in situ hybridization with a centromere 9 probe, and by allelic imbalance studies with seven 9p21-23 markers in nine familial and three sporadic MPNSTs, we found interstitial deletions that supported CDKN2A as a possible target gene. Nine MPNSTs showed aberrations of CDKN2A by Southern blot analyses, and in four of these, expression of CDKN2A could not be detected by Northern blot analysis. No mutations of CDKN2A were identified by sequencing of the coding region, and gene inactivation by promoter methylation was not found. In the 9p allelic imbalance studies, a novel allele was detected at one locus in one tumor. Analyses of additional markers (n = 8) excluded mismatch repair deficiency as an important mechanism in the genesis of these tumors. The tumors were analyzed further for alterations in other candidate cell cycle-associated genes. In total, 11/12 MPNSTs showed DNA changes in one or more of the genes CDKN2A, CDKN2B, RB1, CDK4, MDM2, and CCND2. The present study suggests that disruption of the pRB pathway is common in MPNST, and that dose reduction of CDKN2A is particularly frequent and contributes to MPNST development. Genes Chromosomes Cancer 26:151-160, 1999.

Adolescent↗
PubMed1998

Molecular characterization of a novel amplicon at 1q21-q22 frequently observed in human sarcomas.

In a recent comparative genomic hybridization (CGH) study of a panel of sarcomas, we detected recurrent amplification of 1q21-q22 in soft tissue and bone tumours. Amplification of this region had not previously been associated with sarcoma development, but occasional amplification of CACY/S100A6 and MUC1 in 1q21 had been reported for melanoma and breast carcinoma respectively. Initial screening by Southern blot analysis showed amplification of S100A6, FLG and SPRR3 in several sarcomas and, in a first attempt to characterize the 1q21-q22 amplicon in more detail, we have now investigated the amplification status of these and 11 other markers in the region in 35 sarcoma samples. FLG was the most frequently amplified gene, and the markers located in the same 4.5-Mb region as FLG showed a higher incidence of amplification than the more distal ones. However, for most of the 14 markers, amplification levels were low, and only APOA2 and the anonymous marker D1S3620 showed high-level amplifications (> tenfold increases) in one sample each. We used fluorescence in situ hybridization (FISH) to determine the amplification patterns of two overlapping yeast artificial chromosomes (YACs) covering the region between D1S3620 and FLG (789f2 and 764a1), as well as two more distally located YACs in nine selected samples. Six samples had amplification of the YAC containing D1S3620 and, in three, 764a1 was also included. Five of these tumours showed normal copies of the more distal YACs; thus, it seems likely that an important gene may be located within 789f2, or very close. Two samples had high copy numbers of the most distal YACs. Taken together, FISH and molecular analyses indicate complex amplification patterns in 1q21-q22 with at least two amplicons: one located near D1S3620/789f2 and one more distal.

Biomarkers↗
PubMed1998

Ewing's sarcoma treatment in Scandinavia 1984-1990--ten-year results of the Scandinavian Sarcoma Group Protocol SSGIV.

A report on the long-term follow up of the first cooperative Scandinavian Sarcoma Group study in Ewing's sarcoma of bone is presented. Fifty-two previously untreated patients entered the study between 1984 and 1990. Half of the tumors were located in the extremities and one quarter in the pelvis. The combined modality treatment consisted of 5 cycles of chemotherapy--including vincristine, methotrexate, doxorubicin, cyclophosphamide, bleomycin and dactinomycin. The first two cycles were followed by local resection or amputation in 35 patients and by radiotherapy alone in 17 patients. When surgery was not performed, was incomplete or yielded poor margins radiotherapy was given at a dose of 40-60 Gy. Local tumor relapses developed in 10 patients and in all but one patient were accompanied by metastatic disease. Five patients had metastasis at diagnosis and distant metastases developed after primary treatment in 27 patients after a median of 14 months. The median follow-up time for the 20 surviving patients is 10 years. At 5 years the tumor-related survival was 46% and the metastasis-free survival 43%. Late tumor relapses occurred in 4 patients, which reduced the 10-year tumor related survival to 41% and the metastasis-free survival to 38%. Histopathological tumour response correlated with survival with 5-year metastasis-free survival rates of 73% for the good responders and 35% for the poor responders.

Adolescent↗
PubMed1997

Continuous intratumoral microdialysis during high-dose methotrexate therapy in a patient with malignant fibrous histiocytoma of the femur: a case report.

We used a microdialysis technique to assay intratumoral methotrexate (MTX) levels during high-dose (12 g/m2 given as a 4-h infusion) therapy in a 43-year-old man with a malignant fibrous histiocytoma in the medial femoral condyle. Additional microdialysis probes were implanted in muscle tissue contralateral to the tumor and in an antecubital vein. Microdialysis was attempted during the initial two high-dose courses, but the two latter probes were removed at the start of the second treatment cycle due to leakage. No attempt to correct for microdialysis recovery was made. The intratumorally localized probe gave reproducible data on tumor MTX exposure of 9.3-14% of unbound systemic MTX. There was a close correlation between tumor and systemic levels for both MTX and its major extracellular metabolite 7-hydroxymethotrexate. Although limited to the study of MTX pharmacokinetics in a single subject, the experiment demonstrates that intratumoral microdialysis may provide data on tumor drug exposure, although of an indirect nature and dependent on the probe characteristics, the flow rate, and, possibly, the time after probe implantation. We propose that the application of microdialysis may prove useful for elucidation of the relationship between local drug exposure and the therapeutic response in normally inaccessible compartments during cancer pharmacotherapy.

Adult↗
PubMed1997

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Adolescent↗
PubMed1997

The outcome of advanced soft tissue sarcoma patients with complete tumour regression after either chemotherapy alone or chemotherapy plus surgery. The Scandinavian Sarcoma Group experience.

The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone (n = 14) or CT followed by surgery (n = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) (P = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS P value 0.004, DSS P value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS P value 0.02, DSS P value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

Adolescent↗
PubMed1997

Prognostic factors in bone sarcomas.

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].

Adolescent↗