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Featured researches published by Pelle Gustafson.


Acta Orthopaedica Scandinavica | 1994

Soft tissue sarcoma. Epidemiology and prognosis in 508 patients.

Pelle Gustafson

We have evaluated epidemiology, prognosis and the association between metastases and local recurrence in a series of adult patients with soft tissue sarcoma (STS) of the extremity and trunk wall. 508 patients were diagnosed in the Southern Swedish Health Care Region from 1964 through 1989. The series was population-based, i.e., all patients within a defined area were included, irrespective of where treated, thereby avoiding selection bias in referral and follow-up. Epidemiology. The annual incidence was 18 per million. The median age was 64 years. One third of the tumors were subcutaneous, and these were smaller than the deep-seated tumors. Malignant fibrous histiocytoma and grade IV were the commonest. Differences were noted in clinicopathologic features among histotypes. The 5-year metastasis-free survival rate (MFSR) was 0.6. The crude local recurrence rate was 0.3. The majority of metastases and local recurrences occurred within 3 years. The referral pattern to the tumor center has become more favorable over time; in the last 5 years half of the subcutaneous and four fifths of the deep-seated tumors were referred before surgery. Prognostic factors. Tumor size, tumor necrosis, and vascular invasion were strong and independent prognostic factors for metastasis in a histologically mixed series. In MFH, storiform and pleomorphic subtype, tumor necrosis and tumor size were associated with a poor prognosis. Tumor necrosis and vascular invasion independently worsened the prognosis in leiomyosarcoma. In liposarcoma, tumor necrosis and in synovial sarcoma, tumor size were the only important prognostic factors. Tumor size, tumor necrosis, and vascular invasion were used in a prognostic system which identified two thirds of all patients with a 5-year MFSR of 0.8 and one third of the patients with a 5-year MFSR of 0.3. Metastasis and local recurrence. The causal association proposed for local recurrence and metastasis should be interpreted with caution. We suggest that highly malignant tumors combine local and distant aggressiveness, and that local recurrence is a marker of risk, and not necessarily a cause of, metastasis. Conclusions. 1. Population-based series are preferable when studying epidemiology in soft tissue sarcoma. 2. We propose that tumor size, tumor necrosis, and vascular invasion are strong and reliable factors that can be used to improve prognostic accuracy. 3. There is a growing body of evidence against a causal relationship between local recurrence and metastasis.


Journal of Clinical Oncology | 2001

Clinicopathologic Re-Evaluation of 100 Malignant Fibrous Histiocytomas: Prognostic Relevance of Subclassification

Christopher D. M. Fletcher; Pelle Gustafson; Anders Rydholm; Helena Willén; Måns Åkerman

PURPOSE Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome. PATIENTS AND METHODS Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors. RESULTS In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors. CONCLUSION This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.


European Journal of Cancer | 2000

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

Clement Trovik; Henrik C. F. Bauer; Thor Alvegård; Harald Anderson; Carl Blomqvist; Ö. Berlin; Pelle Gustafson; Gunnar Sæter; A. Wallöe

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.


Acta Orthopaedica Scandinavica | 1994

Soft tissue sarcoma should be treated at a tumor center: A comparison of quality of surgery in 375 patients

Pelle Gustafson; Karsten E. Dreinhöfer; Anders Rydholm

We analyzed the quality of surgery in a population-based series of 375 patients with primary soft tissue sarcoma of the extremity (n 329) and trunk wall (n 46). The quality was measured as the total number of operations performed for the primary tumor--biopsy, excision, reexcision--and the local recurrence rate. A comparison was made between patients referred to our tumor center before surgery (n 195), after surgery (n 102), and not referred for the primary tumor (n 78). The total number of operations for the primary tumor in patients not referred was 1.4 times higher, and in patients referred after surgery 1.7 times higher than in patients referred before surgery. The local recurrence rate in patients not referred was 2.4 times higher, and in patients referred after surgery 1.3 times higher than in patients referred before surgery. Our findings show that patients with soft tissue sarcoma should be treated at a tumor center, and that they should be referred before surgery.


Journal of Clinical Oncology | 1991

Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma.

Anders Rydholm; Pelle Gustafson; B Rööser; Helena Willén; Måns Åkerman; K Herrlin; Thor Alvegård

From 1980 through 1986, 119 patients with soft tissue sarcomas of the extremities were referred to our tumor center either before surgery (n = 78) or immediately after incisional biopsy or marginal excision (n = 41). The tumors were classified according to anatomic location at admittance as subcutaneous (n = 40), intramuscular (n = 30), and extramuscular tumors (n = 49). Open biopsy was omitted in 75 of the 78 patients referred before surgery; the preoperative diagnosis was based on physical and radiographic findings and fine-needle aspiration cytology. The surgical intention for subcutaneous tumor was to obtain a wide margin, which required a cuff of fat tissue around the tumor and inclusion of the deep fascia beneath the tumor. A wide margin for an intramuscular tumor implied no open biopsy and an unbroken muscle fascia or thick muscle cuff around the tumor (primary myectomy). The 70 patients with subcutaneous and intramuscular tumors were all treated by local surgery. A wide margin was obtained in 56 patients who were not given radiotherapy. During a median follow-up of 5 years (range, 3.5 to 10 years), four of these 56 patients--47 of whom had high-grade malignant tumors--had a local recurrence. We conclude that routine combination of limb-sparing surgery with adjuvant radiotherapy is not necessary in patients with soft tissue sarcoma. Two thirds of soft tissue sarcomas of the extremities are primarily subcutaneous or intramuscular tumors, the majority of which can be treated by local surgery without local adjuvant therapy with a local recurrence rate of less than 10%, irrespective of malignancy grade.


Cancer | 1991

Is local recurrence of minor importance for metastases in soft tissue sarcoma

Pelle Gustafson; Bo Rööser; Anders Rydholm

The authors analyzed the relationship between treatment, local recurrence, and metastases in a population‐based series of 375 patients with soft tissue sarcoma of the extremities and the trunk wall. Treatment was inadequate (marginal excision alone) in 107 patients, local recurrence occurred in 112, and 128 patients developed metastases. Local recurrence was 3.5 times more common after inadequate treatment than after adequate and 2.5 times more common in patients with metastases than in those without. However, metastases were only 1.2 times more common after inadequate treatment than after adequate. Of the 128 patients who developed metastases, 63 had local recurrence and 65 had not. In these two subgroups the timing of metastases and the distribution of clinicopathologic factors—age, sex, tumor size, localization, depth, histotype, and malignancy grade—were similar. These findings indicate that local recurrence is of minor importance for development of metastases in soft tissue sarcoma. The increased local recurrence rate in metastatic tumors may be an expression of the aggressiveness of the primary tumor; highly malignant tumors combine a potential both for local and distant spread.


Acta Orthopaedica Scandinavica | 2001

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

Henrik C. F. Bauer; Clement Trovik; Thor Alvegård; Örjan Berlin; Martin Erlanson; Pelle Gustafson; Ragnhild Klepp; Torgil R Möller; Anders Rydholm; Gunnar Sæter; Ola Wahlström; Tom Wiklund

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.


Genes, Chromosomes and Cancer | 2001

Clinical impact of molecular and cytogenetic findings in synovial sarcoma

Ioannis Panagopoulos; Fredrik Mertens; Margareth Isaksson; Janusz Limon; Pelle Gustafson; Björn Skytting; Måns Åkerman; Raphael Sciot; P Dal Cin; I Samson; Mariola Iliszko; J Ryoe; Maria Debiec-Rychter; A Szadowska; Otte Brosjö; Olle Larsson; Anders Rydholm; Nils Mandahl

Synovial sarcoma is an aggressive soft‐tissue tumor that accounts for up to 10% of soft‐tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis‐free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT‐PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT‐SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5‐year metastasis‐free survival rates of 0.58 and 0.0, respectively (P = 0.02).


Cancer | 1991

Malignant fibrous histiocytoma of soft tissue. A population-based epidemiologic and prognostic study of 137 patients.

Bo Rööser; Helena Willén; Pelle Gustafson; Thor Alvegård; Anders Rydholm

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.


Cancer | 2005

Core-needle biopsy performed by the cytopathologist : A technique to complement fine-needle aspiration of soft tissue and bone lesions

Henryk A. Domanski; Måns Åkerman; Birgitta Carlén; Jacob Engellau; Pelle Gustafson; Kjell Jonsson; Fredrik Mertens; Anders Rydholm

Fine‐needle aspiration cytology (FNAC) is gaining increased popularity in the diagnosis of musculoskeletal lesions; and, in many patients, a definitive diagnosis can be rendered from aspiration smears alone. The main limitation of FNAC of soft tissue and bone neoplasms is in the evaluation of tissue architecture. In addition cytologic specimens are not always adequate for ancillary studies.

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Henrik C. F. Bauer

Karolinska University Hospital

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Clement Trovik

Haukeland University Hospital

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