Biomedical subjects

Tomasz Burzykowski

Publications and source records attributed to Tomasz Burzykowski.

25 records · Page 2Linked to original sources

PubMed2002

Is there a minimum number of lymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0 colorectal carcinomas?

BACKGROUND AND OBJECTIVES: Because of the existing controversy, we searched for a cutoff value for the number of lymph nodes (LNs) to be examined in order to establish a reliable node-negative stage in colorectal carcinomas (CRCs). METHODS: From the SEER database, 8,574 T3N0M0 first, single, histologically confirmed, surgically treated CRCs, with at least 1 LN examined histologically, were considered. As a first approach, the relationships between number of examined LNs and 5- and 10-year overall survival (OS) rates, computed by the Kaplan-Meier method, were assessed. Next, multivariate analysis was performed; a proportional hazards model was fitted to the data and used to obtain a smoothed plot of the martingale residuals vs. the number of negative LNs. RESULTS: Both OS rates displayed an improvement with an increase of number of LNs examined. The smoothed plot of the martingale residuals against the number of negative LNs was reasonably linear. CONCLUSIONS: Both approaches suggest that there is no cutoff value for the number of LNs to be examined for an adequate nodal staging; for a reliable pN0 staging, as many LNs should be assessed as possible. However, qualitative features of lymph nodes (e.g., those identified by sentinel lymphadenectomy) may alter this recommendation.

Adenocarcinoma↗

PubMed2002

Post-surgery radiation in early breast cancer: survival analysis of registry data.

BACKGROUND AND PURPOSE: Overviews of randomized trials have shown a small survival advantage with post-surgery radiation in early breast cancer. The present study attempts to extend this observation through a systematic analysis of population data. MATERIALS AND METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER) data on 83,776 women with breast cancer diagnosed between 1988 and 1997, stage T1-T2, node negative or node positive. The analysis was performed using the proportional hazard models. RESULTS: Radiation was associated with a reduced mortality after breast-conserving surgery in node negative patients (hazard ratio 0.757; 95% confidence interval 0.709-0.809; using total mastectomy without radiation as reference) and in node positive patients (hazard ratio 0.777; 0.717-0.842), and after total mastectomy in node positive patients (hazard ratio 0.885; 0.815-0.961). Radiation was associated with an increased hazard ratio of 1.271 (1.080-1.496) after total mastectomy in node negative patients. Without radiation, breast-conserving surgery in node negative patients was associated with an increased hazard ratio (1.167; 1.036-1.314); a similar increase was not observed in node positive patients (hazard ratio 1.011; 0.884-1.155). In all cases, the best survival rates were found with combined breast-conserving surgery and radiation. CONCLUSION: The available data indicate that post-surgery radiation provides a survival advantage irrespective of the type of surgery in node positive patients. Likewise, survival advantage was observed with post-surgery radiation and breast-conserving procedure in node negative patients.

Adult↗

PubMed2002

Statistical challenges in the evaluation of surrogate endpoints in randomized trials.

The validation of surrogate endpoints has been studied by Prentice, who presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs proposed to replace the proportion explained by two quantities: (1). the relative effect, linking the effect of treatment on both endpoints, and (2). the adjusted association, an individual-level measure of agreement between both endpoints. In a multiunit setting, these quantities can be generalized to a trial-level measure of surrogacy and an individual-level measure of surrogacy. In this paper, we argue that such a multiunit approach should be adopted because it overcomes difficulties that necessarily surround validation efforts based on a single trial. These difficulties are highlighted.

Endpoint Determination↗

PubMedDate not supplied

Surrogate threshold effect: an alternative measure for meta-analytic surrogate endpoint validation.

In many therapeutic areas, the identification and validation of surrogate endpoints is of prime interest to reduce the duration and/or size of clinical trials. Buyse et al. [Biostatistics 2000; 1:49-67] proposed a meta-analytic approach to the validation. In this approach, the validity of a surrogate is quantified by the coefficient of determination Rtrial2 obtained from a model, which allows for prediction of the treatment effect on the endpoint of interest ('true' endpoint) from the effect on the surrogate. One problem related to the use of Rtial2 is the difficulty in interpreting its value. To address this difficulty, in this paper we introduce a new concept, the so-called surrogate threshold effect (STE), defined as the minimum treatment effect on the surrogate necessary to predict a non-zero effect on the true endpoint. One of its interesting features, apart from providing information relevant to the practical use of a surrogate endpoint, is its natural interpretation from a clinical point of view.

Biomarkers↗

PubMedDate not supplied

Statistical interaction in the survival analysis of early breast cancer using registry data: role of breast conserving surgery and radiotherapy.

PURPOSE: To identify subgroup effects that might influence the survival results of postoperative radiotherapy. PATIENTS AND METHODS: Women selected from the Surveillance, Epidemiology, and End Results database, aged 40-69 years, with non-metastasized T1-T2 breast carcinoma, in whom axillary lymph node dissection was performed. Subgroup analyses were performed using proportional hazards models with interactions. Joint significance of subgroups was evaluated with the Wald test. Event was death from any cause. RESULTS: Statistically significant interactions were found between type of surgery (breast-conserving [BCS] or mastectomy [ME]), radiotherapy [RT], T stage, and extent of nodal involvement, but not between treatments and nodal examination. For each treatment combination, ME-no RT, ME+RT, BCS-no RT, BCS+RT, the mortality hazard ratios were respectively: 1, 1.12, 1.11, 0.78 in T1, 0-3 positive nodes; 2.45, 2.77, 2.71, 1.92 in T2, 4+ nodes; 1.31, 1.38, 1.33, 1.19 in T2, 0-3+ nodes; and 3.41, 2.79, 3.44, 2.40 in T2, 4+ nodes. The corresponding joint tests showed: in the absence of radiotherapy, no significant survival disadvantage for breast-conserving surgery vs mastectomy; with radiotherapy, significant survival advantage for breast-conserving surgery irrespective of stage and for mastectomy in T2, 4+ nodes. For mastectomy in less advanced stages receiving radiotherapy, excess breast cancer deaths suggested undocumented adverse selection. The corresponding result was considered inconclusive. CONCLUSIONS: The analyses found subgroup effects that should be taken into account to interpret treatment results in breast cancer.

Adult↗

PubMedDate not supplied

Joint modelling of repeated measurements and event time: application to performance traits and survival of lambs bred in sub-humid tropics.

We considered the analysis of a study for Dorper, Red Maasai and crossbred lambs born over a period of 6 years at the Diani Estate, Kenya. The study was designed to compare survival and performance traits of genotypes with differing susceptibilities to helminthiasis. The available data include information on time to death and repeated measurements of body weight, packed cell volume (PCV) and faecal egg count (FEC) of the animals. In the paper, we consider joint modelling of the survival time and the repeated measurements. Such an approach allows to account for the possible association between the survival and repeated measurement processes. The advantages and limitations of the joint modelling are discussed and illustrated using the Diani Estate study data.

Animals↗

PubMedDate not supplied

Effect of the number of uninvolved nodes on survival in early breast cancer.

A high number of uninvolved axillary nodes was found by some authors to be associated with poor survival in node-negative breast cancer. We searched for confirmation and extend the investigation to node-positive cases, using population data from the SEER Program. Patients selected were women aged 40-69 years, diagnosed 1988-1997, T1-T2 breast cancer, undergoing axillary dissection with 4-35 nodes examined. Survivals were estimated by the product-limit method and were computed on pooled data. Results in node-negative patients (n=37,519) showed a 5-year overall survival from 92% (95% confidence interval: 88-95%) with 4 uninvolved nodes, to 93% (87-98%) with 34 uninvolved nodes. In node-positive patients (n=16,978), the 5-year survival increased from 50% (44-56%) with 0 uninvolved nodes, to 91% (82-100%) with 30 uninvolved nodes. Survival graphs indicated an improvement or a plateau with higher number of uninvolved nodes. The graphs also suggested that the ratio of involved and uninvolved nodes might be correlated with survival. We conclude that there was no evidence of poor outcome associated with a high number of uninvolved nodes. The incidental finding that ratio-based characterization of node involvement might be a prognostic factor will be further investigated.

Adult↗