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Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers. Funding Agencies|National Advisory Unit on sarcomas in Norway; Swedish Cancer Society

Importance Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain. Objective To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery. Design, Setting, and Participants In this open-label, randomized (1:1), multicenter phase 3 clinical trial conducted in Finland, Germany, Norway, and Sweden, 400 patients who had undergone macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were enrolled between February 2004 and September 2008. Data for this follow-up analysis were analyzed from September to November, 2019. Interventions Imatinib 400 mg/d administered orally for either 12 months or 36 months after surgery. Main Outcomes And Measures The primary end point was RFS; the secondary objectives included OS and treatment safety. Results The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198; 201 men and 196 women; median [IQR] age, 62 (51-69) years and 60 (51-67) years, during a median follow-up time of 119 months after the date of randomization, 194 RFS events and 96 OS events were recorded in the intention-to-treat population. Five-year and 10-year RFS was 71.4% and 52.5%, respectively, in the 36-month group and 53.0% and 41.8% in the 12-month group (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87;P = .003). In the 36-month group, 5-year OS and 10-year OS rates were 92.0% and 79.0%, respectively, and in the 12-month group 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83;P = .004). The results were similar in the efficacy population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded (36-month group, 10-year OS 81.6%; 12-month group, 66.8%; HR, 0.50; 95% CI, 0.32-0.80;P = .003). No new safety signals were detected. Conclusions and Relevance Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment. Trial Registration ClinicalTrials.gov Identifier:NCT00116935

11503 Background: Adjuvant imatinib improves recurrence-free survival (RFS) when administered after surgery to selected patients with operable gastrointestinal stromal tumor (GIST). It is uncertain whether overall survival (OS) improves, since imatinib improved OS in only one of the 3 large randomized trials conducted, and in this trial (the Scandinavian Sarcoma Group XVIII/German trial; SSGXVIII/AIO; NCT00116935) the statistical significance for OS remained borderline. The objective of the present analysis was to evaluate long-term OS of patients who participated in the SSGXVIII/AIO trial. Methods: SSGXVIII/AIO is an open-label, randomized (1:1), multicenter phase 3 trial. Four hundred patients who underwent macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were accrued between February 2004 and September 2008. Imatinib was scheduled to be administered 400 mg/day orally for either 12 months or 36 months after surgery. The patients were scheduled to be followed up for 10 years after study entry. Imaging of the abdomen was carried out periodically. The primary end point was RFS; the secondary objectives included OS and treatment safety. Results: The median follow-up time was 119 months. In the Intention-To-Treat Population 194 RFS events and 96 OS events were recorded. In the 36-month group, 5-year and 10-year RFS was 71.4% and 52.5%, and in the 12-month group, 53.0% and 41.8%, respectively (HR 0.66, 95% CI 0.49-0.87; P = .003). In the 36-month group, the 5-year and 10-year OS rates were 92.0% and 79.0%, and in the 12-month group, 85.5% and 65.3%, respectively (HR 0.55, 95% CI 0.37-0.83; P = .004). In the Efficacy Population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded, 10-year OS was 81.6% in the 36-month group and 66.8% in the 12-month group (HR, 0.50, 95% CI 0.32-0.80; P = .003). No new safety signals were detected. Conclusions: About 50% of deaths can be avoided during the first decade of follow-up after surgery with 3-year imatinib treatment as compared to 1-year treatment. Clinical trial information: NCT00116935 .

Background: High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival. Patients and methods: Patients aged

Purpose: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes. Methods: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS). Results: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour >= 10 cm in diameter. Conclusion: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy. (C) 2016 Elsevier Ltd. All rights reserved.

Purpose Three years of adjuvant imatinib therapy are recommended for patients with GI stromal tumor (GIST) with high-risk features, according to survival findings in the Scandinavian Sarcoma Group XVIII/AIO (Arbeitsgemeinschaft Internistische Onkologie) trial. To investigate whether the survival benefits have persisted, we performed the second planned analysis of the trial. Patients and Methods Eligible patients had macroscopically completely excised, KIT-positive GIST with a high risk of recurrence, as determined by using the modified National Institutes of Health criteria. After surgery, the patients were randomly assigned to receive imatinib for either 1 or 3 years. The primary objective was recurrence-free survival (RFS), and the secondary objectives included survival. Results A total of 400 patients were entered onto this open-label study between February 4, 2004, and September 29, 2008. During a median follow-up of 90 months, 171 recurrences and 69 deaths were detected. Patients assigned to the 3-year group had longer RFS than those assigned to the 1- year group; 5-year RFS was 71.1% versus 52.3%, respectively (hazard ratio [HR], 0.60; 95% CI 0.44 to 0.81; P < .001), and survival was 91.9% versus 85.3% (HR, 0.60; 95% CI, 0.37 to 0.97; P = .036). Patients in the 3-year group survived longer in the subset with centrally confirmed GIST and without macroscopic metastases at study entry (93.4% v 86.8%; HR, 0.53; 95% CI, 0.30 to 0.93; P = .024). Similar numbers of cardiac events and second cancers were recorded in the groups. Conclusion Three years of adjuvant imatinib therapy results in longer survival than 1 year of imatinib. High 5-year survival rates are achievable in patient populations with high-risk GIST.

BACKGROUND Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown. METHODS The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint. RESULTS On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years. CONCLUSIONS Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations. Cancer 2004. © 2004 American Cancer Society.

� � � � � � � � � � � � � � � � Musculoskeletal sarcomas call for multidisciplinary management by a “tumor team” of specialized orthopedic surgeons, radiologists, pathologists, tumor biologists (e.g. molecular and cytogenetics, DNA cytometry), cytologists, radiotherapists, and oncologists (Figure 1). Only a few such teams existed in Scandinavia during the 1970s. With the inception of the Scandinavian Sarcoma Group (SSG) in 1979, several new teams were started, each with regional responsibility for centralized treatment of sarcoma patients. Together, Denmark, Finland, Iceland, Norway and Sweden have a population of 25 million. These countries have similar social structures, with modern medical services covering all inhabitants and an effective registration of all cancer patients. The similarity of the

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 4.5 μM 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.

10505 Background: Three years of adjuvant IM is recommended after surgery for patients (pts) with high-risk GIST with an IM-sensitive mutation. This recommendation is based on the findings from the SSGXVIII/AIO trial that compared 1 year (Arm A) to 3 years (Arm B) duration of administration of adjuvant IM. After a median follow-up of 4.5 yrs, 3 yrs of IM resulted in superior recurrence-free survival (RFS) and overall survival (OS), but the OS benefit was based only on 37 events. Methods: Pts with high-risk GIST according to the modified NIH risk stratification who had GIST resected macroscopically completely were eligible. The pts were randomly assigned 1:1 to Arm A or B, and were scheduled to receive IM 400 mg/day either for 12 or 36 months after surgery. Tumor histology was reviewed centrally after randomization. The study protocol was amended in October 2006 to exclude pts who had completely resected metastatic disease from the study. We now present the second planned analysis of the trial based on a m...

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 198688 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.

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.

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.

(1999). 25th Meeting of the Scandinavian Sarcoma Group. Acta Orthopaedica Scandinavica: Vol. 70, No. sup289, pp. 22-38.

(1999). Chemotherapy in osteosarcoma. Acta Orthopaedica Scandinavica: Vol. 70, The Scandinavian Sarcoma Group: Twenty years' experience, pp. 74-82.

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...

(1998). Scandinavian Sarcoma Group. Acta Orthopaedica Scandinavica: Vol. 69, No. sup282, pp. 25-43.

According to figures from the National cancer registries in the Nordic countries the incidence of all soft tissue sarcomas is highest in Iceland, especially in the capital area of Reykjavik. The reasons for this is unknown but referral pattern, autopsy figures or geographic factors may he of importance. Possible explanations will he discussed. The incidence of bone sarcomas, on the other hand, is similar to that in the other countries. We evaluated incidence, diagnostic and treatment policy and prognostic factors for soft tissue and bone sarcomas in Iceland during a 40-year-period which is unique for a whole nation. Patients and methods: 17 I soft tissue sarcomas were reported to the cancer registry (excluding sarcomas in internal organs such as uterus and gastrointestinal tract, dermatotibrosis protuberans, Kaposi sarcoma and mesothelioma). The average age-standardized incidence was 1.8/100.000 for men and 1.6/100.000 for women. Malignant fibrous histiocytoma, liposarcoma and leiomyosarcoma comprised more than half of the tumors diagnosed. All tumors were examined by microscopic slides by two independent pathologists (BAA and KRB). All cases were graded using both a three (1-111) and four (I-IV) scale system. 107 bone sarcomas were reported to the cancer registry during the period with chondrosarcoma (38 cases) and osteosarcotna (2 1 cases) being commonest. The age-standardized incidence is 1.0/100.00 for women and 1.6/100.000 for men. Re.su1t.s; Prognostic factors for survival were assessed by Cox's multivariate analysis and included: age, sex, tumor localization, histopathological subtype, tumor size malignancy grade, year of diagnosir and DNA ploidy status. The strongest prognostic factors for wf t tissue sarcomas were malignancy grade, tumor size, and year of diagnosis. There has been a more than 50% reduction in mortality risk during the period. We did not find DNA ploidy status as a prognostic factors for the soft tissue sarcomas. Exact prognostic figures for the bone sarcomas are not available at this time. Conclusion: During the last two decades the prognostic procedures have changed dramatically with the advent of fine needle aspiration, CT scans and more recently the MRI technique. Concurrently the surgical treatment has changed to better margins, more limb sparing procedures and the treatment and follow up has been more centralized. A close collaboration with the SSG has enabled us to discuss all complicated newly diagnosed cases and several have been sent to Lund for treatment. This cooperation has had a very positive impact for both doctors and patients with more favourable survival experience and better quality of life of our patients.

(1995). The Sarcoma Group: Stockholm, April 26–28,1995. Acta Orthopaedica Scandinavica: Vol. 66, No. sup265, pp. 89-100.

(1994). Scandinavian Sarcoma Group. Acta Orthopaedica Scandinavica: Vol. 65, No. sup256, pp. 55-72.

(1993). Scandinavian Sarcoma Group Bergen: Norway, May 6-8, 1992. Acta Orthopaedica Scandinavica: Vol. 64, No. sup253, pp. 15-27.

Purpose Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. Methods and Materials A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986–1991, 1992–1997, and 1998–2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. Results The use of RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. Conclusion The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.

The aim was to evaluate the clinical impact of P-glycoprotein in primary non-metastatic high-grade osteosarcoma patients, treated with neoadjuvant chemotherapy protocols. P-glycoprotein was assessed by immunohistochemistry on paraffin-embedded tissue samples collected at time of diagnosis from 94 osteosarcoma patients, treated with the Italian Sarcoma Group/Scandinavian Sarcoma Group 1 (ISG/SSG 1) protocol. P-glycoprotein-positivity at diagnosis was found in 53/94 ISG/SSG 1 cases (56%) and emerged as the single factor significantly associated with an unfavourable outcome from survival and multivariate analyses. A comparative analysis of the subgroup of 94 patients considered for P-glycoprotein evaluation and the whole series of ISG/SSG 1 patients showed that this marker retained its prognostic value also in the latter group. In osteosarcoma patients treated with doxorubicin-based chemotherapy protocols, P-glycoprotein overexpression at diagnosis is an important adverse prognostic factor for outcome. P-glycoprotein evaluation can therefore constitute the basis for stratifying, at diagnosis, osteosarcoma patients for whom alternative treatments may be considered.

The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future.A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN).Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure.Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.

In Sweden from 1980 to 1995 there was an overall decrease of 56% in mean length of stay (MLOS) for surgical curative breast cancer treatment. The objective of this study was to separate the possible impact of tumour size and lymph node dissemination and changes in surgical procedures. All women diagnosed (n=13 290) with breast cancer between 1982 and 1995 were selected from the Southern Swedish Tumour Register. Data on LOS, diagnoses, and surgical procedures were obtained from the Swedish Hospital Discharge Register. A multi-factorial model was fitted to the data. Discharges where patients were treated with breast conserving surgery had more than two days shorter MLOS (-2.49, 95% CI -1.66) compared with mastectomy. Although TNM data imply a shift from T2 to smaller T1 among operated women the effect on MLOS is negligible when controlled for age, type of operation etc. Changes in clinical practice such as changes in operation technique can explain approximately 13% of the total decrease in MLOS.

In 1986, the Scandinavian Sarcoma Group initiated a Register of sarcoma patients who had been referred to tumor centers in Finland, Norway and Sweden. The Southern Sweden Sarcoma Register served as a model for the SSG Register (Rydholm 1983). All sarcoma centers in Norway (Bergen, Oslo, and Trondheim) and Sweden (Gothenburg, Linkoping, Lund, Stockholm, Umea) have continuously reported patients to the SSG Register. In these countries patients with sarcoma of the trunk wall and extremities are not treated outside of these referral centers except by mistake. Comparisons with the respective National Cancer Reg

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.

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. (Less)

(1997). Chemotherapy for osteosarcoma and Ewing's sarcoma. Acta Orthopaedica Scandinavica: Vol. 68, The Scandinavian—Australian Symposium on the Management of Bone and Soft Tissue Sarcomas, pp. 120-125.

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].

The local and systemic invasiveness of soft-tissue sarcomas may depend upon an interaction between the primary tumour and the extracellular matrix in which the proteolytic enzyme, urokinase plasminogen activator (uPA), may have an important role. We analyzed the expression of uPA in soft-tissue sarcoma using a luminescent immunoassay technique, and examined the relationships between different uPA levels and tumour characteristics and behaviour. We evaluated 69 adult patients with surgically treated soft-tissue sarcomas (MFH 43, leiomyosarcoma 8, liposarcoma 5, synovial sarcoma 4, others 9) of the extremities and trunk wall. Sixteen developed local recurrences, 26 developed metastases, and 5 had both. The median follow-up for survivors was 55 (30-80) months. The median uPA level was 1.4 (0.04-10.6) ng/mg protein. Increasing uPA levels correlated with increasing grade, malignant fibrous histiocytomas, leiomyosarcomas, DNA non-diploidy, tumour necrosis, local recurrence, and metastasis. Storiform-pleomorphic MFH had higher uPA levels than the myxoid variant. A cut-off value of 0.25 ng/mg protein was identified, above which local recurrence and metastasis occurred more frequently. High uPA levels appear to reflect the malignant phenotype in soft-tissue sarcoma, thus supporting the role of uPA as a prognostic indicator.

This synthesis of the literature on radiotherapy related to bone marrow transplantation is based on 59 scientific articles, including 5 randomized studies and 20 retrospective studies. These studies involve 2563 patients. Bone marrow transplantation is a rapidly expanding treatment method where whole-body irradiation can play an important role. The literature review reveals that treatment methods for whole-body irradiation are highly heterogeneous. Standardization would be desirable. Fractionated and single-dose, whole-body irradiation are probably of equal value when the dose and technique are optimal. Cataracts seem to be more common following a single dose. Fractionated treatment is more resource intensive, but less burdensome for patients. For advanced-stage leukemia and some other diseases, eg, myeloma, international experience has shown that a combined treatment strategy (high-dose cyclophosphamide and whole-body irradiation) is probably superior to chemotherapy (cyclophosphamide and busulfan) alone. For many other hematological malignancies at less advanced stages, conditioning methods are probably of equal value.

This synthesis of the literature on radiotherapy for sarcomas originating in the body's soft, supportive tissues, ie, muscle, connective tissue, and fatty tissue is based on 71 scientific articles, including 4 randomized studies, 5 prospective studies, and 26 retrospective studies. These studies involve 3,444 patients. Over 90% of patients with soft tissue sarcomas in the arms and legs can be treated in a way that preserves the extremities. Subcutaneous and intramuscular sarcomas can be treated surgically with little functional loss or risk for local recurrence without adjuvant radiotherapy. To avoid amputation, surgery is often combined with radiotherapy for treatment of local relapse. Adequate surgical margins are usually difficult to achieve for head/neck tumors and retroperitoneal tumors, and therefore surgery is often combined with radiotherapy to reduce the risk for local relapse. Pre- and postoperative radiotherapy are similar. A disadvantage of preoperative radiotherapy is that it reduces the opportunity for exact diagnosis and determining morphobiologic sarcoma parameters. To further improve treatment results for advanced sarcomas, it is necessary to introduce other fractionation schedules, mainly hyperfractionation. This places greater demands on radiotherapy, mainly for staff resources. Combining radiotherapy and local intraarterial chemotherapy involves greater risks for complications and has not shown better treatment results than pre- or postoperative radiotherapy alone, and it is not recommended as standard treatment for soft tissue sarcomas. Intraoperative treatment methods should be targeted for further study and development.

Epidemiology and prognosis were analyzed in a consecutive, population‐based series of 137 patients with malignant fibrous histiocytoma of soft tissue in the extremities and trunk wall, with a complete follow‐up of minimum 3 years. All but one patient were treated by surgery in 28 cases combined with adjuvant radiotherapy or chemotherapy. The annual incidence was 0.42/105. The ratio men to women was 1.1. The median age was 64 years (range, 22 to 87 years). The thigh was the most common location. The median size was 6 cm. Superficial tumors constituted 43% and were smaller than deep‐seated tumors. Eighty‐three tumors were storiform‐pleomorphic, 53 were myxoid, and one was of inflammatory type. The myxoid tumors were smaller and more often superficial. The cumulative 5‐year survival rate for all patients was 0.7, but differed markedly between the histologic types; it was 1.0 in patients with myxoid tumors and 0.5 in patients with storiform‐pleomorphic tumors. In the 77 patients with storiform‐pleomorphic tumors without metastases at presentation, only tumor size larger than 10 cm and tumor necrosis independently impaired survival. The 23 patients who had none of these risk factors had a 5‐year survival rate of 0.8. (Less)

Two-hundred and forty adult patients with a high-grade soft tissue sarcoma were treated surgically in 18 hospitals participating in the Scandinavian Sarcoma Group Protocol I. The patients were randomized to either postoperative doxorubicin or control; patients whose surgical margin was judged marginal also received radiotherapy. The outcome after different surgical margins was analyzed in 185 tumors of Grades III or IV in the extremities. The total cumulative local tumor control was 91 percent (168 of 185) after a median of 47 months. The cumulative local control rates in the surgical groups were: compartmental or wide amputation--37/37 (100 percent), compartmental local excision--23/24 (96 percent), wide local excision--77/84 (92 percent), marginal excision and radiotherapy--19/21 (90 percent), and marginal excision alone (reevaluated margin)--12/19 (63 percent, significantly lower than others). The risk of local recurrence was 13 times higher after marginal than after compartmental surgery (P = 0.02) and 3 times higher if the tumor was larger than 10 cm (P = 0.05). The treatment with doxorubicin did not influence the risk of local recurrence. The survival rates did not differ significantly in the groups.

The growth rate of pulmonary metastases was analyzed in eleven patients with soft tissue sarcoma. In cases where more than two examinations were available the growth rate seemed to be exponential. In all but one case microscopic pulmonary spread was calculated to be present when the primary tumor was diagnosed. Tumor doubling time varied between 8 and 198 days in different patients. The variation in growth rate between various nodules in the same patient was much less pronounced but nevertheless considerable, which might, at least partly, be explained by tumor cell polyclonality. Computed tomography of the chest may detect pulmonary metastases earlier than conventional radiography and is therefore recommended in the preoperative work-up in soft tissue sarcoma.

From 1981 to 1986, 240 patients with primary, malignancy grade III or IV soft-tissue sarcoma were entered into a randomized adjuvant chemotherapy multicenter trial, conducted by the Scandinavian Sarcoma Group. After a median follow-up time of 46 (2-97) months, a multivariate analysis of risk factors for metastases was performed in 138 radically operated on patients with tumors of the extremities. Adjuvant single-agent doxorubicin did not improve the metastasis-free survival. Histologic malignancy grade IV, tumor size greater than 10 cm, vascular invasion by tumor, and male sex were identified as risk factors. Patients with no or one risk factor had a 5-year metastasis-free survival of 0.7, with two risk factors 0.5, and with three or four risk factors 0.2. The combination of different risk factors provides a prognostic model for soft tissue sarcomas, which could be a basis for therapeutic trials.

We analyzed the management of all the patients with soft tissue sarcoma located in the trunk and extremities in Sweden in 1982. The total fraction of patients referred to musculoskeletal tumor centers for definitive treatment was 0.6. In more than four fifths of the patients operated on at the centers, surgery was performed with a wide or radical margin compared with one fifth of the patients treated at other hospitals. In our center specifically, 10 patients with soft tissue lesions that turned out to be benign were referred per every unoperated on sarcoma patient. The treatment of soft tissue sarcomas outside tumor centers is less than optimal, and centralization is associated with substantially increased referral of patients with benign tumors to catch the majority of soft tissue sarcomas in the virgin state. Information to peripheral hospitals about indications for referral of patients with soft tissue lesions has been effective in our region.

A Ewing's sarcoma of the thigh in a 9-year-old boy was diagnosed by light microscopy, electron microscopy, and chromosomal analysis performed on fine needle aspirates.

Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo.To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery.Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria.Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery.The primary end point was RFS; the secondary end points included overall survival and treatment safety.Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P.001; 5-year RFS, 65.6% vs 47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P = .02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated, but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups, respectively, discontinued imatinib for a reason other than GIST recurrence.Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence.clinicaltrials.gov Identifier: NCT00116935.