Search PubMed⌕ Search

Biomedical subjects

T Alvegård

Publications and source records attributed to T Alvegård.

14 recordsLinked to original sources

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↗

Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas.

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.

Adult↗

19p+ marker chromosome correlates with relapse in malignant fibrous histiocytoma.

In this study, we examined the relationship of 19p13 aberrations, usually leading to addition of unknown material (19p+), and ring chromosomes to clinical outcome in patients with malignant fibrous histiocytoma (MFH). Analysis of 69 MFHs revealed 19 tumors with 19p+ and 24 tumors with ring chromosomes. After a median follow-up period of 36 months, 24 patients developed metastases, and 27 patients developed local recurrences. Ten patients had both local recurrences and metastases. Local recurrence was more common in association with 19p+ than without. Metastasis was more common with 19p+ tumors in high-risk patients (tumor size > 5 cm and grade III-IV; n = 48) than those without 19p+. There was a trend suggesting fewer relapses after tumors with ring chromosomes. 19p+ may be an independent marker of unfavorable outcome in MFH.

Adult↗

Soft tissue sarcomas.

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.

Combined Modality Therapy↗

Bone sarcomas.

The literature on radiotherapy for sarcomas originating in bone is limited, and the disease is uncommon. Consequently, this review is based on only 28 scientific articles, including 6 randomized studies, I prospective study, and II retrospective studies. These studies involve 1,394 patients. Radiotherapy is of limited value for treating the primary tumors of osteosarcoma. The effects of prophylactic lung irradiation for treating osteosarcoma are unconfirmed. Radiotherapy represents an integrated component of primary treatment for Ewing's sarcoma, but different fractionation schedules should be assessed. Radiotherapy is of limited value in the treatment of chondrosarcoma.

Bone Neoplasms↗

Transplantation of bone marrow and peripheral stem cells.

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.

Bone Marrow Transplantation↗

Prognosis following locally recurrent soft-tissue sarcoma. A staging system based on primary and recurrent tumour characteristics.

We have shown that the clinical growth rate of local recurrence from soft-tissue sarcoma could be expressed as a growth-rate index (GRI) which was predictive for metastasis, and which was able to identify 2 equal populations of good (80% 2-year MFS) and poor survivors (33%). We now report the associations between characteristics of the primary and GRI, and combine primary and locally recurrent tumour characteristics in a staging system. We studied 460 adult patients with soft-tissue sarcomas of the extremities and trunk wall who were diagnosed and treated between 1964 and 1990, of whom 134 developed local recurrences and 151 metastases. The association of primary tumour size, histologic malignancy grade, depth, spontaneous necrosis, intratumoral vascular invasion and S-phase fraction with local recurrence, GRI and metastasis were examined. High GRI was associated with primary tumours that were larger, deeper, more malignant, underwent spontaneous tumour necrosis, demonstrated intravascular invasion and had a higher S-phase fraction. The same factors were also strongly associated with the incidence of metastasis. A multivariate analysis found GRI and primary tumour necrosis to be the strongest and most significant prognostic factors. GRI and tumour necrosis were combined in a staging system that identified groups with good survival (79 to 94% 2-year MFS), intermediate survival (61% 2-year MFS) and exceptionally poor survival (6% 2-year MFS). These findings validate our earlier assertion that high GRI reflects highly malignant tumours. A staging system composed of primary tumour necrosis and GRI can identify patients who may be suitable candidates for trials of adjuvant chemotherapy.

Adolescent↗

Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue sarcoma. Is prognostic significance histotype-specific?

Abnormal patterns of proliferation characterize the behavior of many tumors. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two cell cycle antigens which are expressed in proliferative states. Our study examines the prognostic value of these cell-cycle antigens in soft tissue sarcoma (STS). Paraffin-embedded primary tumor tissues from 185 patients (1980-92) were stained with the anti-PCNA antibody PC-10; 182 of these were stained with the antibody MIB-1 for Ki-67. Using PCNA (< or = 50; > 50%) and Ki-67 (< or = 10; > 10%) indices, we examined and compared metastasis-free survival (MFS) in a mixed-histotype group, as well as after subdivision into MFH and non-MFH groups. Fifty-seven patients developed metastases. The median follow-up for survivors was 6 (2-13) years. In the mixed series, the 2-year MFS for a PCNA index < or = 50 was 76%, and for an index > 50 56%. Survival predicted by Ki-67 index was comparable. PCNA index (but not Ki-67) strongly correlated with the incidence of metastasis in MFH tumors and predicted 2-year MFS of 81 vs 48%. In contrast, Ki-67 index (but not PCNA) strongly correlated with metastasis in non-MFH tumors and predicted 2-year MFS survival of 90 vs 45%. No correlation existed between PCNA and Ki-67 indices in the mixed histotype, MFH or non-MFH groups. In combination, a high PCNA and Ki-67 index correlated with poor survival, a high PCNA and lower Ki-67 index (or vice versa) with an intermediate survival, and low PCNA and Ki-67 indices with the best survival. The pattern of PCNA and Ki-67 expression raises the possibility of histotype specificity.

Adult↗

Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation--a marker of metastasis?

Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25-50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis-free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.

Adult↗

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

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.

Adult↗

Preoperative diagnosis of soft tissue tumours.

Over a period of 3 years in Southern Sweden 35 patients were seen with deep-seated limb sarcomas without metastases, 30 of whom were referred before any operation had been carried out. Thirty seven patients with deep-seated benign lesions were referred during the same period because of suspected malignancy. A preoperative diagnosis considered sufficient for a definitive operation was made from the clinical findings, aspiration cytology and radiographic examination, but without open biopsy, in 59 of these 67 cases. The differentiation between a benign and a malignant tumour was correct in all but one. The extent of excision necessary to achieve adequate margins for a soft-tissue sarcoma can often be reduced if open biopsy is avoided, with preservation of function. We conclude that treatment without open biopsy is possible in the great majority of patients with soft-tissue sarcoma.

Adult↗

Growth rate of pulmonary metastases from soft tissue sarcoma.

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.

Adult↗

Centralization of soft tissue sarcoma. Status in Sweden in 1982.

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.

Adolescent↗