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P Gustafson

Publications and source records attributed to P Gustafson.

At least 55 records · Page 3Linked to original sources

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↗

Size and timing of local recurrence predicts metastasis in soft tissue sarcoma. Growth rate index retrospectively analyzed in 134 patients.

Our study combined size and timing of the first local recurrence to create a growth rate index (GRI-ratio of size (cm) to timing (mo)) which we analyzed for an association with metastasis. We analyzed 134 locally recurrent tumors from a series of 460 adult patients with soft tissue sarcoma of the extremities and trunk wall who were diagnosed and treated between 1964 and 1990, with a median follow-up of 10 (2-28) years for survivors. None of the patients had metastases at diagnosis. One half (74) of local recurrences were from inadequately treated primaries, one half (71) were associated with metastases, and two thirds (89) were seen in non-center-treated patients. There were equal numbers of patients with GRI < or = 0.4 (low) and > 0.4 (high). Patients with a low GRI had a better 2-year metastasis-free survival (80 percent) than those with a high GRI (30 percent). High GRIs were associated with large, high grade primary tumors and a short metastasis-free interval in comparison to low GRI tumors. Time to local recurrence strongly correlated with the time to metastasis (R2 0.85, p < 0.001). GRI was a good discriminator of metastasis in patients with tumors larger than 5 cm and of malignancy grade IV. Our study suggests that clinical characteristics (e.g., GRI) of local recurrence rather than presence, per se, are important in predicting tumor behavior.

Adolescent↗

Proliferating cell nuclear antigen (PCNA) in high-grade malignant fibrous histiocytoma: prognostic value in 48 patients.

Grading based on histopathologic features is used to predict survival in soft-tissue sarcoma. However, variations in clinical behavior between tumors of the same grade motivate a search for additional factors that correlate with prognosis. Proliferating cell nuclear antigen (PCNA) is expressed in proliferating cells during the G1, S and G2-phases. To evaluate a prognostic implication of PCNA, the tumors of 48 patients with malignant fibrous histiocytomas (13 grade III, 35 grade IV) with a minimum follow-up of 2 years were immunohistochemically studied. We used PC10, a monoclonal antibody (MAb) directed against PCNA, which allows cell proliferation in formalin-fixed, paraffin-embedded tumor tissue to be evaluated. We applied a semiquantitative PCNA grading scheme to all stained nuclei of an entire slide. The 3-year metastasis-free survival rate was 0.87 for patients in grade A (low PLNA rate), and 0.14 for patients in grade C (high PLNA). Our findings show that immunohistochemical evaluation of cell kinetics in soft-tissue sarcomas by PCNA might be a useful adjunct to conventional tumor grading.

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↗

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

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.

Adult↗

Soft tissue sarcoma. Epidemiology and prognosis in 508 patients.

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.

Adolescent↗

Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content.

Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.

Abdominal Muscles↗

Metastasis-free survival after local recurrence of soft-tissue sarcoma.

We analysed metastasis-free survival after local recurrence in a population-based series of 432 patients treated for soft-tissue sarcoma of the extremities or trunk wall. Local recurrence was found in 124 patients; of these, 73 had no detectable metastases when the last local recurrence was diagnosed. No patient received chemotherapy for local recurrence. The 73 patients had a 5-year metastasis-free survival rate of 0.73 after the last local recurrence, compared with 0.47 in all 124 patients with local recurrence. The 5-year metastasis-free survival rate was 0.76 in the 308 patients who had never developed local recurrence, and 0.68 in the whole series. The selection of patients with local recurrence but no concurrent metastasis creates a subset of the population with a good prognosis; this makes it difficult to evaluate the effect of treatment for local recurrence on survival rate. In studies of prognosis this group of patients should be analysed separately from patients with primary tumours.

Actuarial Analysis↗

Soft tissue leiomyosarcoma. A population-based epidemiologic and prognostic study of 48 patients, including cellular DNA content.

BACKGROUND: Leiomyosarcoma of soft tissue is a rare tumor. There are different opinions regarding epidemiology and prognosis. METHODS: Epidemiology and prognosis were analyzed in a consecutive, population-based series of 48 patients with subcutaneous and deep-seated leiomyosarcoma in the extremities and trunk wall with a complete follow-up of a minimum of 3 years. Cutaneous tumors were not included. RESULTS: The annual incidence was 0.13/10(5). The ratio of men to women was 1.2, and the median age was 65 years. The thigh was the most common location. Almost half of the tumors were subcutaneous. The median tumor size was 6 cm (range, 1-25 cm). All patients were treated with surgery, and in 19 cases it was combined with adjuvant radiation therapy or chemotherapy. The cumulative 5-year survival rate was 64%. Multivariate analysis indicated that age of 60 years or greater (relative risk [RR] = 8) and intratumoral vascular invasion (RR = 4) were independent risk factors for death resulting from tumor. DNA aneuploidy (RR = 4) and tumor necrosis (RR = 3) were associated with poor prognosis, but did not reach statistic significance. CONCLUSIONS: Advanced age, vascular invasion, and DNA aneuploidy could be used to identify prognostic subgroups.

Adult↗

Selection bias in treatment of soft-tissue sarcoma.

We analysed 256 patients with primary soft-tissue sarcoma of the extremities diagnosed between 1970 and 1990 to see if tumour-related and host-related prognostic factors influenced both the selection of operation and the margin of clearance obtained at surgery. Amputation was more often performed in young patients, in those with distal tumours, and in those with deep-seated tumours. Inadequate surgical margins (those with a high risk of local recurrence) were more common in patients with deep-seated and large tumours than in patients with superficial and small tumours. These features of the tumour and the host, which have been shown to be prognostic for survival, also influenced the choice and performance of surgical procedures.

Adult↗

Necrosis observed on CT enhancement is of prognostic value in soft tissue sarcoma.

Fifty-one patients with deep-seated soft tissue sarcoma of the extremities and trunk wall were examined with contrast-enhanced CT for presence of nonenhanced tumor areas (CT necrosis). After a median follow-up time of 3 years, 19 of the 41 patients with CT necrosis had developed metastases, compared to none of the 10 patients who had tumors without CT necrosis. Tumors with CT necrosis were larger than tumors without, but in tumors of similar size, absence of CT necrosis was a favorable prognostic sign.

Adult↗

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

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.

Adolescent↗

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

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 0.42/10(5). 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.

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↗

Subcutaneous sarcoma. A population-based study of 129 patients.

We reviewed 129 patients with subcutaneous sarcoma diagnosed from 1964 to the end of 1985 in a population-based series of sarcoma cases from southern Sweden. The annual incidence was 0.4 per 100,000, comprising 32% of all soft-tissue sarcomas of the extremities or the trunk wall. Compared to deep-seated sarcomas, subcutaneous tumours were half the size at diagnosis, more common in the lower leg and foot, more often malignant fibrous histiocytoma, and of a lower grade of malignancy. None of the low-grade and only 7% of the high-grade tumours recurred locally after wide local excision without radiotherapy. The cumulative five-year survival for all 129 patients was 80%. Multivariate analysis identified only high grade of malignancy and the size of the tumour (greater than 5 cm) as independent prognostic factors. We conclude that systemic or local adjuvant therapy is not generally indicated for subcutaneous sarcoma because of the good prognosis and low local recurrence rate after wide excision.

Adolescent↗