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P Gustafson

Publications and source records attributed to P Gustafson.

At least 19 recordsLinked to original sources
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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗