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Biomedical subjects

P Gustafson

Publications and source records attributed to P Gustafson.

At least 19 recordsLinked to original sources
PubMed2000

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.

Adolescent↗
PubMed1999

[Surgery provides symptomatic relief in skeletal metastases].

The skeleton is the third most common site of metastasis, after the lungs and the liver. Although metastasis to bone is associated with considerable morbidity, it is seldom the direct cause of death. Orthopaedic treatment of imminent or existing pathological fractures has been associated with a dismal outcome until recently, when the treatment principles of trauma surgery and arthroplasty began to be applied in cases of skeletal metastasis. The article consists in a report of 141 patients with symptoms of skeletal metastasis to the pelvis or extremities, where the indication for surgery was pathological fracture in 85 per cent of cases, the femur being the commonest site, followed by the humerus. A third of the patients had breast cancer. Median survival was six months in the series as a whole. At follow-up after one week, four months, and one year, outcome was rated as good or very good by 98, 99 and 100 per cent of the patients, respectively.

Aged↗
PubMed1999

Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts.

Aneurysmal bone cyst (ABC) is a benign bone lesion for which no previous cytogenetic data exist. We describe the finding of clonal chromosome aberrations in three tumors; two had a t(16;17)(q22;p13) as the sole anomaly, and the third had a del(16)(q22) as the only change. These findings show that somatic mutations contribute to the development of ABC and furthermore indicate that bands 16q22 and 17p13 may harbor genes of importance in this process.

Adolescent↗
PubMed1999

Prognostic implications of various models for calculation of S-phase fraction in 259 patients with soft tissue sarcoma.

The S-phase fraction (SPF) in flow cytometric DNA histograms in soft tissue sarcoma (STS) can be calculated in various ways. The traditional planimetric method of Baisch has been shown to be prognostic, but is hampered by a failure rate of around 40%. We therefore tested other models to see if this rate could be decreased with retained prognostic value. In 259 STS of the locomotor system the SPF was calculated according to Baisch and with commercial parametric MultiCycle software using different corrections for background. Using the Baisch model, 159 histograms could be evaluated for SPF. The 5-year metastasis-free survival rate (MFSR) was 0.94 for the low-risk group (defined with SPF), and 0.53 for the high-risk group. In the low-risk group, four of the seven patients who developed metastasis did so after 5 years Using the MultiCycle software, SPF could be calculated in 253 tumours. Depending on type of background correction used, the 5-year MFSR varied between 0.67 and 0.82 for the low-risk group, and between 0.47 and 0.53 for the high-risk group. The late metastasis pattern in the low-risk group was never seen using the MultiCycle software. We conclude that in paraffin archival material, calculation of SPF according to Baisch is preferable in clinical use due to better separation between low-risk and high-risk groups, and also the possibility to identify patients who metastasize late.

Adolescent↗
PubMed1999

Soft tissue sarcoma of the upper extremity: descriptive data and outcome in a population-based series of 108 adult patients.

We report a population-based, 29-year review of 108 adult patients with soft tissue sarcoma of the upper extremity who had a minimum follow-up period of 3 years. Fifty tumors were localized in the upper arm, 8 in the elbow, 40 in the forearm, and 10 in the hand. Thirty-four tumors were subcutaneous and 74 were deep-seated. The median tumor size was 6 cm. Malignant fibrous histiocytoma was the most common histotype (n = 43), and grade IV (on a 4-grade scale) was the most common malignancy grade (n = 54). All but 6 patients underwent surgery; limb-sparing surgery of the primary tumor was performed in 89 patients. Twenty-four patients were given adjuvant radiotherapy; 11 received adjuvant chemotherapy. Inadequate local treatment was more common in patients treated outside the tumor center. Local recurrence occurred in 15 of 28 with inadequate local treatment and in 16 of 74 patients with adequate local treatment (20 of the 39 patients treated outside the center and 11 of the 63 patients treated at the center). At the latest follow-up visit, 32 patients had developed metastases, giving a 5-year metastasis-free survival rate of 0.72. In a multivariate analysis, tumor size larger than 5 cm and vascular invasion emerged as independent prognostic factors. Patients without these 2 factors had excellent survival. When compared with soft tissue sarcoma of the lower extremity or trunk wall, tumors in the upper extremity were smaller at the time of diagnosis and had a higher 5-year metastasis-free survival rate.

Adolescent↗
PubMed1999

Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients.

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.

Adolescent↗
PubMed1998

Flexible Bayesian modelling for survival data.

The analysis of failure time data often involves two strong assumptions. The proportional hazards assumption postulates that hazard rates corresponding to different levels of explanatory variables are proportional. The additive effects assumption specifies that the effect associated with a particular explanatory variable does not depend on the levels of other explanatory variables. A hierarchical Bayes model is presented, under which both assumptions are relaxed. In particular, time-dependent covariate effects are explicitly modelled, and the additivity of effects is relaxed through the use of a modified neural network structure. The hierarchical nature of the model is useful in that it parsimoniously penalizes violations of the two assumptions, with the strength of the penalty being determined by the data.

Bayes Theorem↗
PubMed1997

Flow cytometric S-phase fraction in soft-tissue sarcoma: prognostic importance analysed in 160 patients.

We could determine the S-phase fraction (SPF) by flow cytometric DNA analysis of paraffin archival material in 160 of 260 patients with soft-tissue sarcoma of extremity and trunk wall. The prognostic value of SPF was compared with other clinicopathological factors. The median follow-up time was 16 (6-31) years. In a univariate analysis, deep tumour location, increasing tumour size and histological malignancy grade, microscopic tumour necrosis, vascular invasion, DNA non-diploidy and high SPF (>3.0%) were associated with poor metastasis-free survival. In a multivariate analysis, microscopic tumour necrosis and high SPF were independently prognostic for metastasis. Used in combination with tumour size, microscopic tumour necrosis and vascular invasion, SPF could identify a group of patients with a 5-year metastasis-free survival rate of 0.97. This group constituted one-quarter of all patients. Patients with low SPF who did recur had a prolonged clinical course both as regards metastases and local recurrence. We conclude that SPF is a valuable adjunct in prognostication in soft-tissue sarcoma.

Adolescent↗
PubMed1997

Large hierarchical Bayesian analysis of multivariate survival data.

Failure times that are grouped according to shared environments arise commonly in statistical practice. That is, multiple responses may be observed for each of many units. For instance, the units might be patients or centers in a clinical trial setting. Bayesian hierarchical models are appropriate for data analysis in this context. At the first stage of the model, survival times can be modelled via the Cox partial likelihood, using a justification due to Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221). Thus, questionable parametric assumptions are avoided. Conventional wisdom dictates that it is comparatively safe to make parametric assumptions at subsequent stages. Thus, unit-specific parameters are modelled parametrically. The posterior distribution of parameters given observed data is examined using Markov chain Monte Carlo methods. Specifically, the hybrid Monte Carlo method, as described by Neal (1993a, in Advances in Neural Information Processing 5, 475-482; 1993b, Probabilistic inference using Markov chain Monte Carlo methods), is utilized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Overall cancer incidence not increased after prosthetic knee replacement: 14,551 patients followed for 66,622 person-years.

It is unknown whether patients as a consequence of prosthetic joint replacement are at a higher risk of developing cancer. We therefore analyzed cancer incidence following prosthetic knee replacement (TKR). The observed cancer incidence in 14,551 patients from the population-based Swedish Knee Arthroplasty Register who have undergone TKR because of osteoarthrosis (OA, n = 10,120) or rheumatoid arthritis (RA, n = 4431) were compared with the expected cancer incidence for a Swedish reference population. The cohort was followed for a total of 66,622 person-years. We followed 33% of the patients with OA and 59% of those with RA for more than 5 years. All patients who underwent TKR, whether for OA or for RA, had lower than expected total cancer incidence. We found a markedly low incidence of colorectal carcinoma, especially in patients with RA. Our results do not indicate an increased incidence of cancer following TKR.

Arthritis, Rheumatoid↗
PubMed1996

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↗
PubMed1996

Robustness considerations in Bayesian analysis.

All statistical analyses demand uncertain inputs or assumptions. This is especially true of Bayesian analyses. In addition to the usual concerns about the agreement of the data and model, a Bayesian must contemplate the effect of an uncertain prior specification. The degree to which inferences are robust to changes in the prior is of primary interest. This article discusses some robust techniques that have been suggested in the literature. One goal is to make apparent the relevance of some of these techniques to biostatistical work.

Adrenergic beta-Antagonists↗
PubMed1995

A Bayesian analysis of bivariate survival data from a multicentre cancer clinical trial.

I present an analysis of data from a clinical trial of new chemotherapies for colorectal cancer. I model participating clinical sites via random effects, to allow for heterogeneous patient responses across centres. Patient response is measured by both progression and survival times. The data suggest that patient responses are homogeneous before, but heterogeneous after, disease progression. For one new therapy, an increase in efficacy relative to standard therapy is detected before, but not after, progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

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↗