Clement Trovik

Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-treated patients from the Scandinavian Sarcoma Group Register.

The prognostic importance of surgical margins on local recurrence rates and metastasis-free survival (MFS) was studied in 559 patients with soft tissue sarcoma of the extremities and trunk wall. The patients were all surgically treated, but received no adjuvant treatment. The median follow-up for the survivors was 7.4 (range: 0.1 - 12.5) years. Independent prognostic factors for MFS were analysed by Cox models. The overall 5-year MFS was 0.72 (95% confidence intervals (CI) 0.68 - 0.76). High histopathological malignancy grade (relative risk (RR) 3.0; 95% CI 1.5 - 6.3) and an inadequate surgical margin (RR 2.9; 95% CI 1.8 - 4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumour size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (RR 4. 4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (RR 1.1; 95% CI 0.8-1.7). This study confirms that, as regards metastasis, tumour-related risk factors (malignancy grade and tumour size) are more important risk factors than treatment-related factors. Local recurrence was associated with an increased metastasis rate, whereas inadequate surgical margin was a risk factor for local recurrence but not for metastasis. Hence, the proposed causal association between local recurrence and metastasis is doubtful, and if it exists is a weak association.

Cement is recommended in intralesional surgery of giant cell tumors : A Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years

Background Giant cell tumors of bone rarely metasta-size but often recur locally after surgery. There is limited knowledge about the risk of recurrence related to different types of treatment. Patients and methods We analyzed factors affecting the local recurrence rate in 294 patients with giant cell tumors of the extremities using prospectively collected material from 13 centers. The median follow-up time was 5 (0.2–18) years. Results A local recurrence was diagnosed in 57 of 294 patients (19%). The overall 5-year local recurrence rate was 0.22. Univariate analysis identified young age and intralesional surgery to be associated with a higher risk of recurrence. Based on multivariate analysis, the relative risk was 2.4-fold for intralesional surgery compared to more extensive operative methods. There was no correlation between tumor size, tumor extension, sex of the patient, tumor location, or fracture at diagnosis and outcome. In the subgroup of 200 patients treated with intralesional surgery, the method of filling (cement or bone) was known for 194 patients and was statistically highly significant in favor of the use of cement. Interpretation Intralesional surgery should be the first choice in most giant cell tumors, even in the presence of a pathological fracture. After thorough evacuation, the cavity should be filled with cement.

Monitoring referral and treatment in soft tissue sarcoma: Study based on 1,851 patients from the Scandinavian Sarcoma Group Register

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. Followup 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 Scandinavian Sarcoma Group skeletal metastasis register: Survival after surgery for bone metastases in the pelvis and extremities

INTRODUCTION The assessment of the prognosis for the individual patient is important for the choice of surgical treatment of skeletal metastases. In 1999 the Scandinavian Sarcoma Group (SSG) initiated the Skeletal Metastasis Register as a multicentric, prospective study to provide a scientific basis for treatment recommendations. To improve prognostication we analyzed the survival of patients with skeletal metastases surgically treated at 9 SSG centres. PATIENTS AND METHODS 460 patients with an average age of 64 years underwent 501 operations for non-spinal skeletal metastases. 7% were operated for more than one metastasis. Carcinoma of the breast, prostate, kidney and lung were the dominating primary tumors. RESULTS The survival rate was 0.4 at 1 year, 0.3 at 2 years and 0.2 at 3 years. Univariate analysis showed that survival was related to bone localization, skeletal metastatic load, presence of visceral metastases, Karnofsky performance score, primary tumor type, presence of a complete pathological fracture and preoperative hemoglobin content. Multivariate regression analysis showed that pathological fracture, visceral metastases, haemoglobin content < 7 mmol/L and lung cancer were negative prognostic factors for survival. Myeloma was the sole positive prognostic factor for survival.

Radiotherapy to Improve Local Control Regardless of Surgical Margin and Malignancy Grade in Extremity and Trunk Wall Soft Tissue Sarcoma: A Scandinavian Sarcoma Group Study

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.

Local recurrence of soft tissue sarcoma A Scandinavian Sarcoma Group Project

The aim of this project was to investigate the diagnosis, treatment and consequences of local recurrence of soft tissue sarcoma (STS). It is based on patients reported to the Karolinska Hospital Sarcoma Register and the Scandinavian Sarcoma Group Register. Demographic and treatment data, based on 1613 adult patients reported to the Scandinavian Sarcoma Group Register by sarcoma centers in Norway, Sweden and Finland are presented. They all had STS of the extremities or trunk wall, and were diagnosed between 1986 and 1995. One third of the tumors were subcutaneous and two thirds deep-seated. The median size was 7 (1-35) cm and 75% were high grade. Metastases at presentation were diagnosed in 8% of the patients. Two thirds of the patients were referred to a sarcoma center before surgery. The preoperative morphologic diagnosis was made by fine-needle aspiration cytology in 72%. Among patients with final treatment for primary tumor at a sarcoma center (n = 1331), the surgical margins were wide or better in 76% of subcutaneous lesions, and in 58% of deep-seated lesions. Adjuvant radiotherapy has not generally been considered indicated after wide or compartmental excisions in Scandinavia. Overall, 23% of patients managed by surgery had adjuvant radiotherapy. Among patients with an intralesional or marginal excision, 44% had postoperative radiotherapy. Patients treated outside of sarcoma centers were seldom referred for radiotherapy. The crude local recurrence rate was 225/1331 (17%) among the patients with final treatment for primary tumor at a sarcoma center. The local recurrence rate after local surgery for high-malignant deep-seated STS was 103/391 (26%). The rate was 25/64 (39%) after an intralesional/marginal margin without postoperative radiotherapy versus 28/119 (24%) when radiotherapy was given. Fine-needle aspiration cytology (FNAC) was used to diagnose suspected local recurrences. 95 FNAC were performed in 86 patients from Karolinska Hospital. There were 47 local recurrences, of which 44 were diagnosed correctly by FNAC; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. 39 patients proved to have benign lesions in the scar examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in 4 cases FNAC was inconclusive. The inconclusive or false cytological diagnoses had no serious clinical consequences. Among 205 patients with local recurrence identified in the SSG Register 1987-1995, 169 patients were surgically treated. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence was treated using surgery with a marginal margin alone, compared to 0.28 if treated using either surgery with a marginal margin and radiotherapy, or a wide margin (p = 0.0008). In extremity STS, the amputation rate for local recurrences was 0.22, compared to 0.09 for primary tumors. The overall 5-year MFS was 0.72 (95% CI 0.68-0.76). High histopathological malignancy grade (Relative Risk 3.0; 95% CI 1.5-6.3) and an inadequate surgical margin (2.9; 95% CI 1.8-4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumor size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (4.4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (1.1; 95% CI 0.8-1.7). In conclusion, it is unlikely that local recurrence of STS is a major source of metastases. It nevertheless represents a costly, complicated and emotionally difficult problem. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved for center-operated patients without increasing the amputation rate. Instead, local control will improve by giving radiotherapy to all patients after marginal surgery, and to selected patients with wide margins. Radiotherapy is indicated especially after a previous open biopsy or when a local recurrence might lead to an amputation. Furthermore, radiotherapy seems indicated after local recurrence, regardless of margin or grade. The most effective way of reducing costs and detriment associated with local recurrence is to increase referral to sarcoma centers before biopsy or surgery as primary surgical margins would then improve.

Treatment of local recurrences of giant cell tumour in long bones after curettage and cementing: A SCANDINAVIAN SARCOMA GROUP STUDY.

We retrospectively studied local recurrence of giant cell tumour in long bones following treatment with curettage and cementing in 137 patients. The median follow-up time was 60 months (3 to 166). A total of 19 patients (14%) had at least one local recurrence, the first was diagnosed at a median of 17 months (3 to 29) after treatment of the primary tumour. There were 13 patients with a total of 15 local recurrences who were successfully treated by further curettage and cementing. Two patients with a second local recurrence were consequently treated twice. At the last follow-up, at a median of 53 months (3 to 128) after the most recent operation, all patients were free from disease and had good function. We concluded that local recurrence of giant cell tumour after curettage and cementing in long bones can generally be successfully treated with further curettage and cementing, with only a minor risk of increased morbidity. This suggests that more extensive surgery for the primary tumour in an attempt to obtain wide margins is not the method of choice, since it leaves the patient with higher morbidity with no significant gain with respect to cure of the disease.

Liposarcoma : Outcome Based on the Scandinavian Sarcoma Group Register

The aim was to study the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population‐based patient sample, and to establish whether treatment was according to the Scandinavian Sarcoma Group (SSG) treatment guidelines.BACKGROUND The aim was to study the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population-based patient sample, and to establish whether treatment was according to the Scandinavian Sarcoma Group (SSG) treatment guidelines. METHODS The SSG Pathology Board reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review, 237 patients without metastasis were analyzed for local recurrence rate in relation to surgical margins, radiotherapy, occurrence of metastasis, and survival. RESULTS Seventy-eight percent of the patients were primarily operated on at a sarcoma center, 45% with wide margins. All patients operated on outside the center had nonwide margins. Low-grade lesions constituted 67% of cases. Despite nonwide surgery, only 58% of high-grade lesions were treated with postoperative radiotherapy. The risk of local recurrence after nonwide surgery, without irradiation, was 47% for high-grade lesions. The estimated 10-year, local recurrence-free and metastasis-free survival in the low-grade group was 87% and 95%, respectively. In the high-grade group, it was 75% and 61%, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma center and histological type dedifferentiated liposarcoma. For metastases, they were old age, large tumor size, high grade, and histological type myxoid liposarcoma with a round cell component. Radiotherapy showed significant effect on local recurrence rate for the same grade and margin. CONCLUSIONS Patients with liposarcoma should be treated at specialized centers. Postoperative radiotherapy decreases the local recurrence rate. To maintain quality and provide support for further trials, reporting to quality registers is crucial.

Consequences of local recurrence of soft tissue sarcoma : 205 patients from the Scandinavian Sarcoma Group Register

From the Scandinavian Sarcoma Group Register, information on 1,224 surgically-treated patients with soft tissue sarcoma (STS) of the extremity or trunk wall, diagnosed between 1987 and 1995, was collected. 205 patients, one third of whom were referred to a center with a local recurrence, had a total of 284 local recurrences. This analysis describes the treatment for these local recurrences, complications and risk of further recurrences. 169 patients were surgically treated for their first local recurrence. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence had been treated with only surgery with a marginal margin, compared to 0.28 if treated with surgery with a marginal margin and radiotherapy or with a wide margin (p = 0.0008). In extremity STS, the crude amputation rate for local recurrences was 0.22 (31 of 142)--i.e., higher than for primary tumors 0.09 (96 of 1065) (p < 0.0001). A high local recurrence rate after treatment outside of sarcoma centers has earlier been shown. We conclude that the consequences of local recurrence in terms of morbidity and costs justifies referral of STS patients for multidisciplinary evaluation and multimodality treatment.

Local recurrence of deep-seated, high-grade, soft tissue sarcoma 459 patients from the Scandinavian Sarcoma Group Register

This study was based on 459 adult patients with deep, high-grade, soft tissue sarcoma of extremities or trunk wall reported to the Scandinavian Sarcoma Group Register (1986-1993). All patients had their definitive surgery for primary tumor at a sarcoma center. The median follow-up was 7.5 (3-12) years. 204 patients are still alive. 68 patients had amputations and 391 underwent limb-sparing surgery. Among 183 patients with intralesional or marginal margins after limb-sparing surgery, 65% had postoperative radiotherapy and 9% of the 198 patients with wide margins. The local recurrence rate after limb-sparing surgery was 26%. The rate with an intralesional or marginal margin was 39% without postoperative radiotherapy versus 24% when radiotherapy was given. It was 25% after a wide margin, and no recurrences were noted among the 10 patients with a compartmental surgical margin. Among patients with a wide margin, a subset fulfilling criteria for a myectomy was defined. The local recurrence rate was 26% among these 62 and there was no advantage of myectomy over other wide margins. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved in center-operated patients without increasing the amputation rate. Instead, increased use of radiotherapy in all patients with inadequate margins, and to a larger extent in those with wide margins will improve local control.